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Department of Medicine Faculty Papers

2022

Articles 1 - 30 of 43

Full-Text Articles in Medical Specialties

Comprehensive Review Of Cardiovascular Disease Risk In Nonalcoholic Fatty Liver Disease, Kevan Josloff, Jacob Beiriger, Adnan Khan, Richard J. Gawel, Richard S. Kirby, Aaron Kendrick, Abhinav K. Rao, Roy Wang, Michelle Schafer, Margaret Pearce, Kashyap Chauhan, Yash B. Shah, Gregary D. Marhefka, Dina Halegoua-De Marzio Nov 2022

Comprehensive Review Of Cardiovascular Disease Risk In Nonalcoholic Fatty Liver Disease, Kevan Josloff, Jacob Beiriger, Adnan Khan, Richard J. Gawel, Richard S. Kirby, Aaron Kendrick, Abhinav K. Rao, Roy Wang, Michelle Schafer, Margaret Pearce, Kashyap Chauhan, Yash B. Shah, Gregary D. Marhefka, Dina Halegoua-De Marzio

Department of Medicine Faculty Papers

Nonalcoholic Fatty Liver Disease (NAFLD) is a growing global phenomenon, and its damaging effects in terms of cardiovascular disease (CVD) risk are becoming more apparent. NAFLD is estimated to affect around one quarter of the world population and is often comorbid with other metabolic disorders including diabetes mellitus, hypertension, coronary artery disease, and metabolic syndrome. In this review, we examine the current evidence describing the many ways that NAFLD itself increases CVD risk. We also discuss the emerging and complex biochemical relationship between NAFLD and its common comorbid conditions, and how they coalesce to increase CVD risk. With NAFLD's rising …


Transradial-Transfistula Access For Cardiac Catheterization In Patients With Abandoned Hemodialysis Fistulas, Noah Q. Haroian, Michael P. Savage, David L. Fischman Nov 2022

Transradial-Transfistula Access For Cardiac Catheterization In Patients With Abandoned Hemodialysis Fistulas, Noah Q. Haroian, Michael P. Savage, David L. Fischman

Department of Medicine Faculty Papers

Guidelines consider radial access a relative contraindication in patients with end-stage renal disease as part of a vessel preservation strategy. Radial access distal to a hemodialysis fistula, what we term transradial-transfistula access, offers a solution to radially access this population without affecting their vessel preservation plan. (Level of Difficulty: Advanced.)


Pathogenicity And Impact Of Hla Class I Alleles In Aplastic Anemia Patients Of Different Ethnicities, Timothy S Olson, Benjamin F Frost, Jamie L Duke, Marian Dribus, Hongbo M Xie, Zachary D Prudowsky, Elissa Furutani, Jonas Gudera, Yash B Shah, Deborah Ferriola, Amalia Dinou, Ioanna Pagkrati, Soyoung Kim, Yixi Xu, Meilun He, Shannon Zheng, Sally Nijim, Ping Lin, Chong Xu, Taizo A Nakano, Joseph H Oved, Beatriz M Carreno, Yung-Tsi Bolon, Shahinaz M Gadalla, Steven Ge Marsh, Sophie Paczesny, Stephanie J Lee, Dimitrios S Monos, Akiko Shimamura, Alison A Bertuch, Loren Gragert, Stephen R Spellman, Daria V Babushok Nov 2022

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

Department of Medicine Faculty Papers

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


The Development Of A Mobile App-Focused Deduplication Strategy For The Apple Heart Study That Informs Recommendations For Future Digital Trials, Ariadna Garcia, Justin Lee, Vidhya Balasubramanian, Rebecca Gardner, Santosh E. Gummidipundi, Grace Hung, Todd Ferris, Lauren Cheung, Sumbul Desai, Christopher B. Granger, Mellanie True Hills, Peter Kowey, Divya Nag, John S. Rumsfeld, Andrea M. Russo, Jeffrey W. Stein, Nisha Talati, David Tsay, Kenneth W. Mahaffey, Marco V. Perez, Mintu P. Turakhia, Haley Hedlin, Manisha Desai Nov 2022

The Development Of A Mobile App-Focused Deduplication Strategy For The Apple Heart Study That Informs Recommendations For Future Digital Trials, Ariadna Garcia, Justin Lee, Vidhya Balasubramanian, Rebecca Gardner, Santosh E. Gummidipundi, Grace Hung, Todd Ferris, Lauren Cheung, Sumbul Desai, Christopher B. Granger, Mellanie True Hills, Peter Kowey, Divya Nag, John S. Rumsfeld, Andrea M. Russo, Jeffrey W. Stein, Nisha Talati, David Tsay, Kenneth W. Mahaffey, Marco V. Perez, Mintu P. Turakhia, Haley Hedlin, Manisha Desai

Department of Medicine Faculty Papers

An app-based clinical trial enrolment process can contribute to duplicated records, carrying data management implications. Our objective was to identify duplicated records in real time in the Apple Heart Study (AHS). We leveraged personal identifiable information (PII) to develop a dissimilarity score (DS) using the Damerau-Levenshtein distance. For computational efficiency, we focused on four types of records at the highest risk of duplication. We used the receiver operating curve (ROC) and resampling methods to derive and validate a decision rule to classify duplicated records. We identified 16,398 (4%) duplicated participants, resulting in 419,297 unique participants out of a total of …


Cladophialophora Bantiana Brain Abscess And Concurrent Pulmonary Cryptococcus Neoformans Infection In A Patient Twenty Years After Renal Transplantation, Daniel Tsang, Sara Haddad, Ziver Sahin, Chairut Vareechon, Mitchell Sternlieb, Tricia. Royer Nov 2022

Cladophialophora Bantiana Brain Abscess And Concurrent Pulmonary Cryptococcus Neoformans Infection In A Patient Twenty Years After Renal Transplantation, Daniel Tsang, Sara Haddad, Ziver Sahin, Chairut Vareechon, Mitchell Sternlieb, Tricia. Royer

Department of Medicine Faculty Papers

Recipients of solid organ transplants are at risk for a variety of infections due to their immunocompromised status. The types of infections are often correlated to the timing from their transplant. After about six to twelve months, transplant recipients remain at risk for typical community acquired pathogens, late viral infections, and fungal infections including atypical molds such as Cladophialophora bantiana. C. bantiana is a dematiaceous fungus that has a predilection for infecting the brain and is the most common cause of cerebral phaeohyphomycosis - a term used to describe infections caused by molds that produce dark cell walls. Patients with …


The Enigma Of Primary Hypertension In Childhood, Bonita Falkner Nov 2022

The Enigma Of Primary Hypertension In Childhood, Bonita Falkner

Department of Medicine Faculty Papers

Beginning in the 1970s, hypertension in children and adolescents has been defined as systolic and/or diastolic blood pressure (BP) that is equal to or greater than the 95th percentile of the normal BP distribution in healthy children. The definition of hypertension in adults is based on longitudinal data that links a BP level with an increased risk for subsequent adverse outcomes related to hypertension including heart failure, kidney failure, stroke, or death. The statistical definition of hypertension continues to be used in childhood because there have been no data that link a BP level in childhood with a heightened risk …


How I Perform Totally Endoscopic Robotic Mitral Valve Repair., Colin C Yost, Jake L Rosen, Meagan Wu, Caroline M Komlo, Jordan E Goldhammer, T Sloane Guy Nov 2022

How I Perform Totally Endoscopic Robotic Mitral Valve Repair., Colin C Yost, Jake L Rosen, Meagan Wu, Caroline M Komlo, Jordan E Goldhammer, T Sloane Guy

Department of Medicine Faculty Papers

A sixty-two-year-old male presented with significant symptoms related to severe mitral regurgitation with posterior leaflet flail and prolapse on transesophageal echocardiogram (TEE). Preoperative computed tomography (CT) angiography showed normal caliber thoracoabdominal aorta and patent access vessels. The patient underwent totally endoscopic robotic mitral valve repair (rMVr) with left atrial CryoMAZE procedure.


Accuracy Of Noninvasive Diagnostic Tests For The Detection Of Significant And Advanced Fibrosis Stages In Nonalcoholic Fatty Liver Disease: A Systematic Literature Review Of The Us Studies, Dhaval Gosalia, Vlad Ratziu, Filip Stanicic, Djurdja Vukicevic, Vladimir Zah, Nadege Gunn, Dina Halegoua-De Marzio, Tram Tran Oct 2022

Accuracy Of Noninvasive Diagnostic Tests For The Detection Of Significant And Advanced Fibrosis Stages In Nonalcoholic Fatty Liver Disease: A Systematic Literature Review Of The Us Studies, Dhaval Gosalia, Vlad Ratziu, Filip Stanicic, Djurdja Vukicevic, Vladimir Zah, Nadege Gunn, Dina Halegoua-De Marzio, Tram Tran

Department of Medicine Faculty Papers

Background: The purpose of this systematic literature review (SLR) was to evaluate the accuracy of noninvasive diagnostic tools in detecting significant or advanced (F2/F3) fibrosis among patients with nonalcoholic fatty liver (NAFL) in the US healthcare context.

Methods: The SLR was conducted in PubMed and Web of Science, with an additional hand search of public domains and citations, in line with the PRISMA statement. The study included US-based original research on diagnostic test sensitivity, specificity and accuracy.

Results: Twenty studies were included in qualitative evidence synthesis. Imaging techniques with the highest diagnostic accuracy in F2/F3 detection and differentiation were magnetic …


Retrospective Comparison Of Patients ≥ 80 Years With Atrial Fibrillation Prescribed Either An Fda-Approved Reduced Or Full Dose Direct-Acting Oral Anticoagulant, Roy Taoutel, Michael D. Ezekowitz, Usman A. Chaudhry, Carly Weber, Dana Hassan, Ed J. Gracely, Mohammed H. Kamareddine, Benjamin I. Horn, Glenn R. Harper Oct 2022

Retrospective Comparison Of Patients ≥ 80 Years With Atrial Fibrillation Prescribed Either An Fda-Approved Reduced Or Full Dose Direct-Acting Oral Anticoagulant, Roy Taoutel, Michael D. Ezekowitz, Usman A. Chaudhry, Carly Weber, Dana Hassan, Ed J. Gracely, Mohammed H. Kamareddine, Benjamin I. Horn, Glenn R. Harper

Department of Medicine Faculty Papers

Direct-acting oral anticoagulants (DOACs) represent the standard for preventing stroke and systemic embolization (SSE) in patients with atrial fibrillation (AF). There is limited information for patients ≥ 80 years. We report a retrospective analysis of AF patients ≥ 80 years prescribed either a US Food and Drug Administration (FDA)-approved reduced (n = 514) or full dose (n = 199) DOAC (Dabigatran, Rivaroxaban, or Apixaban) between January 1st, 2011 (first DOAC commercially available) and May 31st, 2017. The following multivariable differences in baseline characteristics were identified: patients prescribed a reduced dose DOAC were older (p < 0.001), had worse renal function (p = 0.001), were more often prescribed aspirin (p = 0.004) or aspirin and clopidogrel (p < 0.001), and more often had new-onset AF (p = 0.001). SSE and central nervous system (CNS) bleed rates were low and not different (1.02 vs 0 %/yr and 1.45 vs 0.44 %/yr) for the reduced and full dose groups, respectively. For non-CNS bleeds, rates were 10.89 vs 4.15 %/yr (p < 0.001, univariable) for the reduced and full doses, respectively. The mortality rate was 6.24 vs 1.75 %/yr (p = 0.001, univariable) for the reduced and full doses. Unlike the non-CNS bleed rate, mortality rate differences remained significant when adjusted for baseline characteristics. Thus, DOACs in patients ≥ 80 with AF effectively reduce SSE with a low risk of CNS bleeding, independent of DOAC dose. The higher non-CNS bleed rate and not the mortality rate is explained by the higher risk baseline characteristics in the reduced DOAC dose group. Further investigation of the etiology of non-CNS bleeds and mortality is warranted.


A Critical Review Of Medication Adherence In Hypertension: Barriers And Facilitators Clinicians Should Consider, Seyed Mehrdad Hamrahian, Omar H. Maarouf, Tibor Fülöp Oct 2022

A Critical Review Of Medication Adherence In Hypertension: Barriers And Facilitators Clinicians Should Consider, Seyed Mehrdad Hamrahian, Omar H. Maarouf, Tibor Fülöp

Department of Medicine Faculty Papers

Hypertension is a global public health problem, and its prevalence is increasing worldwide. Impacting all human societies and socioeconomic strata, it remains the major modifiable risk factor for global burden of cardiovascular disease all-cause mortality and the leading cause of loss of disability-adjusted life years. Despite increased awareness, the rate of blood pressure control remains unsatisfactory, particularly in low-to middle-income countries. Apparent treatment-resistant hypertension is associated with worse adverse health outcomes. It includes both true resistant and pseudo-resistant hypertension, which requires out-of-office blood pressure monitoring to exclude white-coat effect and confirmation of adherence to the agreed recommended antihypertensive therapy. The …


Sex-Specific Considerations In Degenerative Aortic Stenosis For Female-Tailored Transfemoral Aortic Valve Implantation Management, Giulia Masiero, Valeria Paradies, Anna Franzone, Barbara Bellini, Chiara De Biase, Nicole Karam, Francesca Sanguineti, Mamas A Mamas, Hélène Eltchaninoff, Chiara Fraccaro, Battistina Castiglioni, Tiziana Attisano, Giovanni Esposito, Alaide Chieffo Oct 2022

Sex-Specific Considerations In Degenerative Aortic Stenosis For Female-Tailored Transfemoral Aortic Valve Implantation Management, Giulia Masiero, Valeria Paradies, Anna Franzone, Barbara Bellini, Chiara De Biase, Nicole Karam, Francesca Sanguineti, Mamas A Mamas, Hélène Eltchaninoff, Chiara Fraccaro, Battistina Castiglioni, Tiziana Attisano, Giovanni Esposito, Alaide Chieffo

Department of Medicine Faculty Papers

The impact of sex on pathophysiological processes, clinical presentation, treatment options, as well as outcomes of degenerative aortic stenosis remain poorly understood. Female patients are well represented in transfemoral aortic valve implantation (TAVI) trials and appear to derive favorable outcomes with TAVI. However, higher incidences of major bleeding, vascular complications, and stroke have been reported in women following TAVI. The anatomical characteristics and pathophysiological features of aortic stenosis in women might guide a tailored planning of the percutaneous approach. We highlight whether a sex-based TAVI management strategy might impact on clinical outcomes. This review aimed to evaluate the impact of …


Sickle Cell Disease Chronic Joint Pain: Clinical Assessment Based On Maladaptive Central Nervous System Plasticity, Tiago Da Silva Lopes, Samir K. Ballas, Jamille Evelyn Rodrigues Souza Santana, Pedro De Melo-Carneiro, Lilian Becerra De Oliveira, Katia Nunes Sá, Larissa Conceição Dias Lopes, Wellington Dos Santos Silva, Rita Lucena, Abrahão Fontes Baptista Sep 2022

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

Department of Medicine Faculty Papers

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


Serpinb3 Drives Cancer Stem Cell Survival In Glioblastoma, Adam Lauko, Josephine Volovetz, Soumya M Turaga, Defne Bayik, Daniel J Silver, Kelly Mitchell, Erin E Mulkearns-Hubert, Dionysios C Watson, Kiran Desai, Manav Midha, Jing Hao, Kathleen Mccortney, Alicia Steffens, Ulhas Naik, Manmeet S Ahluwalia, Shideng Bao, Craig Horbinski, Jennifer S Yu, Justin D Lathia Sep 2022

Serpinb3 Drives Cancer Stem Cell Survival In Glioblastoma, Adam Lauko, Josephine Volovetz, Soumya M Turaga, Defne Bayik, Daniel J Silver, Kelly Mitchell, Erin E Mulkearns-Hubert, Dionysios C Watson, Kiran Desai, Manav Midha, Jing Hao, Kathleen Mccortney, Alicia Steffens, Ulhas Naik, Manmeet S Ahluwalia, Shideng Bao, Craig Horbinski, Jennifer S Yu, Justin D Lathia

Department of Medicine Faculty Papers

Despite therapeutic interventions for glioblastoma (GBM), cancer stem cells (CSCs) drive recurrence. The precise mechanisms underlying CSC resistance, namely inhibition of cell death, are unclear. We built on previous observations that the high cell surface expression of junctional adhesion molecule-A drives CSC maintenance and identified downstream signaling networks, including the cysteine protease inhibitor SerpinB3. Using genetic depletion approaches, we found that SerpinB3 is necessary for CSC maintenance, survival, and tumor growth, as well as CSC pathway activation. Knockdown of SerpinB3 also increased apoptosis and susceptibility to radiation therapy. SerpinB3 was essential to buffer cathepsin L-mediated cell death, which was enhanced …


Role Of Hla-I Structural Variants And The Polyreactive Antibodies They Generate In Immune Homeostasis, Mepur H Ravindranath, Fatiha El Hilali, Carly J Amato-Menker, Hajar El Hilali, Senthamil R Selvan, Edward J Filippone Sep 2022

Role Of Hla-I Structural Variants And The Polyreactive Antibodies They Generate In Immune Homeostasis, Mepur H Ravindranath, Fatiha El Hilali, Carly J Amato-Menker, Hajar El Hilali, Senthamil R Selvan, Edward J Filippone

Department of Medicine Faculty Papers

Cell-surface HLA-I molecules consisting of β2-microglobulin (β2m) associated heavy chains (HCs), referred to as Face-1, primarily present peptides to CD8+ T-cells. HCs consist of three α-domains, with selected amino acid sequences shared by all alleles of all six isoforms. The cell-surface HLA undergoes changes upon activation by pathological conditions with the expression of β2m-free HCs (Face-2) resulting in exposure of β2m-masked sequences shared by almost all alleles and the generation of HLA-polyreactive antibodies (Abs) against them. Face-2 may homodimerize or heterodimerize with the same (Face-3) or different alleles (Face-4) preventing exposure of shared epitopes. Non-allo immunized males naturally carry HLA-polyreactive …


Bone Health Management In The Continuum Of Prostate Cancer Disease, Ettickan Boopathi, Ruth Birbe, Sunday A. Shoyele, Robert B. Den, Thangavel Chellappagounder Sep 2022

Bone Health Management In The Continuum Of Prostate Cancer Disease, Ettickan Boopathi, Ruth Birbe, Sunday A. Shoyele, Robert B. Den, Thangavel Chellappagounder

Department of Medicine Faculty Papers

Prostate cancer (PCa) is the second-leading cause of cancer-related deaths in men. PCa cells require androgen receptor (AR) signaling for their growth and survival. Androgen deprivation therapy (ADT) is the preferred treatment for patients with locally advanced and metastatic PCa disease. Despite their initial response to androgen blockade, most patients eventually will develop metastatic castration-resistant prostate cancer (mCRPC). Bone metastases are common in men with mCRPC, occurring in 30% of patients within 2 years of castration resistance and in >90% of patients over the course of the disease. Patients with mCRPC-induced bone metastasis develop lesions throughout their skeleton; the 5-year …


Coronavirus Disease-19 Infection And Angioedema In African Americans: A Case Series, Jose Manuel Martinez Manzano, Otoniel Ysea-Hill, Brenda Chiang, Simone A Jarrett, Kevin Bryan Lo, Zurab Azmaiparashvili Sep 2022

Coronavirus Disease-19 Infection And Angioedema In African Americans: A Case Series, Jose Manuel Martinez Manzano, Otoniel Ysea-Hill, Brenda Chiang, Simone A Jarrett, Kevin Bryan Lo, Zurab Azmaiparashvili

Department of Medicine Faculty Papers

Rationale: Few case series have described the simultaneous development of angioedema in patients with coronavirus 19 disease (COVID-19). Most of these reports were described in at-risk patients for developing bradykinin angioedema. Therefore, we aim to describe 5 African American patients who developed simultaneous COVID-19 and angioedema.

Methods: This was a case series of hospitalized patients with simultaneous angioedema and COVID-19 infection in a single center from May 2020 to February 2022. We used descriptive statistics. The study was approved by the institutional review board.

Results: Their median age was 55 years (range 28-66); all patients were African American, and 3/5 …


Libretto-531: A Phase Iii Study Of Selpercatinib In Multikinase Inhibitor-Naïve, Lori J Wirth, Marcia S Brose, Rossella Elisei, Jaume Capdevila, Ana O Hoff, Mimi I Hu, Makoto Tahara, Bruce Robinson, Ming Gao, Meng Xia, Patricia Maeda, Eric Sherman Sep 2022

Libretto-531: A Phase Iii Study Of Selpercatinib In Multikinase Inhibitor-Naïve, Lori J Wirth, Marcia S Brose, Rossella Elisei, Jaume Capdevila, Ana O Hoff, Mimi I Hu, Makoto Tahara, Bruce Robinson, Ming Gao, Meng Xia, Patricia Maeda, Eric Sherman

Department of Medicine Faculty Papers

Selpercatinib is a first-in-class, highly selective and potent, central nervous system-active RET kinase inhibitor. In the phase I/II trial, selpercatinib demonstrated clinically meaningful antitumor activity with manageable toxicity in heavily pre-treated and treatment-naive patients with RET-mutant medullary thyroid cancer (MTC). LIBRETTO-531 (NCT04211337) is a multicenter, open-label, randomized, controlled, phase III trial comparing selpercatinib to cabozantinib or vandetanib in patients with advanced/metastatic RET-mutant MTC. The primary objective is to compare progression-free survival (per RECIST 1.1) by blinded independent central review of patients with progressive, advanced, multikinase inhibitor-naive, RET-mutant MTC treated with selpercatinib versus cabozantinib or vandetanib. …


Grk2 Regulates Adp Signaling In Platelets Via P2y1 And P2y12., Xuefei Zhao, Matthew Cooper, James V Michael, Yanki Yarman, Aiden Baltz, J Kurt Chuprun, Walter J Koch, Steven E. Mckenzie, Maurizio Tomaiuolo, Timothy J Stalker, Li Zhu, Peisong Ma Aug 2022

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

Department of Medicine Faculty Papers

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


Development Of The Centrifugal Blood Pump For A Hybrid Continuous Flow Pediatric Total Artificial Heart: Model, Make, Measure, Carson S Fox, Thomas Palazzolo, Matthew Hirschhorn, Randy M Stevens, Joseph Rossano, Steven W Day, Vakhtang Tchantchaleishvili, Amy L Throckmorton Aug 2022

Development Of The Centrifugal Blood Pump For A Hybrid Continuous Flow Pediatric Total Artificial Heart: Model, Make, Measure, Carson S Fox, Thomas Palazzolo, Matthew Hirschhorn, Randy M Stevens, Joseph Rossano, Steven W Day, Vakhtang Tchantchaleishvili, Amy L Throckmorton

Department of Medicine Faculty Papers

Clinically-available blood pumps and total artificial hearts for pediatric patients continue to lag well behind those developed for adults. We are developing a hybrid, continuous-flow, magnetically levitated, pediatric total artificial heart (TAH). The hybrid TAH design integrates both an axial and centrifugal blood pump within a single, compact housing. The centrifugal pump rotates around the separate axial pump domain, and both impellers rotate around a common central axis. Here, we concentrate our development effort on the centrifugal blood pump by performing computational fluid dynamics (CFD) analysis of the blood flow through the pump. We also conducted transient CFD analyses (quasi-steady …


Predictive Factors And Outcomes For Ibrutinib In Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter Cohort Study, Narendranath Epperla, Qiuhong Zhao, Sayan Mullick Chowdhury, Lauren Shea, Tamara K Moyo, Nishitha Reddy, Julia Sheets, David M Weiner, Praveen Ramakrishnan Geethakumari, Malathi Kandarpa, Ximena Jordan Bruno, Colin Thomas, Michael C Churnetski, Andrew Hsu, Luke Zurbriggen, Cherie Tan, Kathryn Lindsey, Joseph Maakaron, Paolo F Caimi, Pallawi Torka, Celeste Bello, Sabarish Ayyappan, Reem Karmali, Seo-Hyun Kim, Anna Kress, Shalin Kothari, Yazeed Sawalha, Beth Christian, Kevin A David, Irl Brian Greenwell, Murali Janakiram, Vaishalee P Kenkre, Adam J Olszewski, Jonathon B Cohen, Neil D. Palmisiano, Elvira Umyarova, Ryan A Wilcox, Farrukh T Awan, Juan Pablo Alderuccio, Stefan K Barta, Natalie S Grover, Nilanjan Ghosh, Nancy L Bartlett, Alex F Herrera, Geoffrey Shouse Jul 2022

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

Department of Medicine Faculty Papers

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


Addressing The Gap In Data Communication From Home Health Care To Primary Care During Care Transitions: Completeness Of An Interoperability Data Standard, Paulina Sockolow, Edgar Y Chou, Subin Park Jul 2022

Addressing The Gap In Data Communication From Home Health Care To Primary Care During Care Transitions: Completeness Of An Interoperability Data Standard, Paulina Sockolow, Edgar Y Chou, Subin Park

Department of Medicine Faculty Papers

In a future where home health care is no longer an information silo, patient information will be communicated along transitions in care to improve care. Evidence-based practice in the United States supports home health care patients to see their primary care team within the first two weeks of hospital discharge to reduce rehospitalization risk. We sought to identify a parsimonious set of home health care data to be communicated to primary care for the post-hospitalization visit. Anticipating electronic dataset communication, we investigated the completeness of the international reference terminology, Logical Observation Identifiers Names and Codes (LOINC), for coverage of the …


Breaking Barriers To Breast Reconstruction Among Socioeconomically Disadvantaged Patients At A Large Safety-Net Hospital, Anna E Meade, Samantha M Cummins, Jordyn T Farewell, Sofia Duque, Sydney K Mulqueen, Ashleigh Chuah, Andrew Y Zhang Jul 2022

Breaking Barriers To Breast Reconstruction Among Socioeconomically Disadvantaged Patients At A Large Safety-Net Hospital, Anna E Meade, Samantha M Cummins, Jordyn T Farewell, Sofia Duque, Sydney K Mulqueen, Ashleigh Chuah, Andrew Y Zhang

Department of Medicine Faculty Papers

Socioeconomic disparities remain prevalent among those who undergo breast reconstruction. At our institution, patients must meet certain criteria to become eligible for breast reconstruction. The purpose of this study was to determine the impact of socioeconomic factors on breast reconstruction eligibility, enrollment, choice, and completion at our large safety-net institution.

Methods: A retrospective chart review of patients who underwent partial or total mastectomy at a large safety-net hospital from 2016 to 2019 was completed. Surgical and demographic data were compared across varying socioeconomic factors.

Results: A total of 645 patients were included in the study. More patients of a racial …


Does Ligamentous Laxity Protect Against Chondral And Osteochondral Injuries In Patients With Patellofemoral Instability?, Lauren H Redler, Elizabeth R Dennis, Gabrielle M Mayer, Irene L Kalbian, Joseph T Nguyen, Beth E Shubin Stein, Sabrina M Strickland Jul 2022

Does Ligamentous Laxity Protect Against Chondral And Osteochondral Injuries In Patients With Patellofemoral Instability?, Lauren H Redler, Elizabeth R Dennis, Gabrielle M Mayer, Irene L Kalbian, Joseph T Nguyen, Beth E Shubin Stein, Sabrina M Strickland

Department of Medicine Faculty Papers

Background: Many patients undergoing medial patellofemoral ligament (MPFL) reconstruction for patellofemoral instability have chondral or osteochondral injuries requiring treatment.

Hypothesis: In patients undergoing MPFL reconstruction for patellofemoral instability, those with ligamentous laxity (LAX) would be less likely to have chondral or osteochondral defects requiring surgical intervention compared with those with no laxity (NLX).

Study Design: Cohort study; Level of evidence, 2.

Methods: Included were 171 patients with patellofemoral instability (32 men, 139 women; mean age, 22 years [range, 11-57 years]) who underwent MPFL reconstruction between 2005 and 2015. Patients with a Beighton-Horan score ≥5 were considered LAX (n = 96), …


Analyzing The Effect Of Interview Time And Day On Emergency Medicine Residency Interview Scores, Alanna O'Connell, Sean Greco, Tingting Zhan, Tracy Brader, Megan Crossman, Robin Naples, Anthony Sielicki, Megan Stobart Gallagher, Peter Tomaselli, Dimitrios Papanagnou Apr 2022

Analyzing The Effect Of Interview Time And Day On Emergency Medicine Residency Interview Scores, Alanna O'Connell, Sean Greco, Tingting Zhan, Tracy Brader, Megan Crossman, Robin Naples, Anthony Sielicki, Megan Stobart Gallagher, Peter Tomaselli, Dimitrios Papanagnou

Department of Medicine Faculty Papers

Background: When it comes to scheduling interviews, medical students may wonder if they need a strategy to increase their likelihood of matching. Previous studies examined the temporal effects of the residency interview on overall match rate; however, there are additional factors that affect the match process, including board examination scores and letters of recommendation. Only few studies have examined the effect interview time of day has on match success. The current study examines the impact date and time of interview during the interview season have on candidates' respective interview scores.

Methods: Interview data over a three-year period (i.e., three interview …


Tolerability And Feasibility Of At-Home Remotely Supervised Transcranial Direct Current Stimulation (Rs-Tdcs): Single-Center Evidence From 6,779 Sessions, Giuseppina Pilloni, Amy Vogel-Eyny, Matthew Lustberg, Pamela Best, Martin Malik, Lillian Walton-Masters, Allan George, Ibraheem Mirza, Lana Zhovtis, Abhishek Datta, Marom Bikson, Lauren Krupp, Leigh Charvet Apr 2022

Tolerability And Feasibility Of At-Home Remotely Supervised Transcranial Direct Current Stimulation (Rs-Tdcs): Single-Center Evidence From 6,779 Sessions, Giuseppina Pilloni, Amy Vogel-Eyny, Matthew Lustberg, Pamela Best, Martin Malik, Lillian Walton-Masters, Allan George, Ibraheem Mirza, Lana Zhovtis, Abhishek Datta, Marom Bikson, Lauren Krupp, Leigh Charvet

Department of Medicine Faculty Papers

Introduction: The ability to deploy transcranial direct current stimulation (tDCS) at home is a key usability advantage to support scaling for pivotal clinical trials. We have established a home-based tDCS protocol for use in clinical trials termed remotely supervised (RS)-tDCS.

Objective: To report the tolerability and feasibility of tDCS sessions completed to date using RS-tDCS in clinical trials.

Methods: We analyzed tolerability (i.e., adverse events, AEs) reported in six Class I/II/III trials using RS-tDCS to study symptom outcomes over 10 to 60 daily applications. Across the six clinical trials, 308 participants (18-78 years old) completed an average of 23 sessions …


Role Of Extracellular Vesicles In Glia-Neuron Intercellular Communication, Shahzad Ahmad, Rohit K Srivastava, Pratibha Singh, Ulhas P. Naik, Amit K Srivastava Apr 2022

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

Department of Medicine Faculty Papers

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


The Efficacy Of Low-Dose Aspirin In Pregnancy Among Women In Malaria-Endemic Countries, Melissa Bauserman, Sequoia I Leuba, Jennifer Hemingway-Foday, Tracy L Nolen, Janet Moore, Elizabeth M Mcclure, Adrien Lokangaka, Antoinette Tsehfu, Jackie Patterson, Edward A Liechty, Fabian Esamai, Waldemar A Carlo, Elwyn Chomba, Robert L Goldenberg, Sarah Saleem, Saleem Jessani, Marion Koso-Thomas, Matthew Hoffman, Richard Derman, Steven R Meshnick, Carl L Bose Apr 2022

The Efficacy Of Low-Dose Aspirin In Pregnancy Among Women In Malaria-Endemic Countries, Melissa Bauserman, Sequoia I Leuba, Jennifer Hemingway-Foday, Tracy L Nolen, Janet Moore, Elizabeth M Mcclure, Adrien Lokangaka, Antoinette Tsehfu, Jackie Patterson, Edward A Liechty, Fabian Esamai, Waldemar A Carlo, Elwyn Chomba, Robert L Goldenberg, Sarah Saleem, Saleem Jessani, Marion Koso-Thomas, Matthew Hoffman, Richard Derman, Steven R Meshnick, Carl L Bose

Department of Medicine Faculty Papers

Background: Low dose aspirin (LDA) is an effective strategy to reduce preterm birth. However, LDA might have differential effects globally, based on the etiology of preterm birth. In some regions, malaria in pregnancy could be an important modifier of LDA on birth outcomes and anemia.

Methods: This is a sub-study of the ASPIRIN trial, a multi-national, randomized, placebo controlled trial evaluating LDA effect on preterm birth. We enrolled a convenience sample of women in the ASPIRIN trial from the Democratic Republic of Congo (DRC), Kenya and Zambia. We used quantitative polymerase chain reaction to detect malaria. We calculated crude prevalence …


Alpha-Fetoprotein (Afp) And Afp-L3 Is Most Useful In Detection Of Recurrence Of Hepatocellular Carcinoma In Patients After Tumor Ablation And With Low Afp Level, Madison Force, Grace Park, Divya Chalikonda, Christopher G. Roth, Micah Cohen, Dina Halegoua-De Marzio, Hie-Won Hann Apr 2022

Alpha-Fetoprotein (Afp) And Afp-L3 Is Most Useful In Detection Of Recurrence Of Hepatocellular Carcinoma In Patients After Tumor Ablation And With Low Afp Level, Madison Force, Grace Park, Divya Chalikonda, Christopher G. Roth, Micah Cohen, Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a leading cause of mortality worldwide. While there are many risk factors for HCC including alcohol, obesity, and diabetes, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection still account for the majority of HCC worldwide. Globally, HBV is the leading risk factor for HCC. Patients with chronic hepatitis B (CHB) and advanced liver disease are at high risk for HCC. Screening for HCC is done routinely with ultrasound with or without alpha-fetoprotein (AFP) at six-month intervals. The combination of ultrasound and AFP has been …


Safety And Efficacy Of Colchicine In Covid-19 Patients: A Systematic Review And Meta-Analysis Of Randomized Control Trials, Farah Yasmin, Hala Najeeb, Abdul Moeed, Wardah Hassan, Mahima Khatri, Muhammad Sohaib Asghar, Ahmed Kunwer Naveed, Waqas Ullah, Salim Surani Apr 2022

Safety And Efficacy Of Colchicine In Covid-19 Patients: A Systematic Review And Meta-Analysis Of Randomized Control Trials, Farah Yasmin, Hala Najeeb, Abdul Moeed, Wardah Hassan, Mahima Khatri, Muhammad Sohaib Asghar, Ahmed Kunwer Naveed, Waqas Ullah, Salim Surani

Department of Medicine Faculty Papers

Background: Colchicine has been used an effective anti-inflammatory drug to treat gout diseases. Owing to its pharmacodynamic of inhibiting interleukins, it has been repurposed to target the cytokine storm post-SARS-CoV-2 invasion. The goal of this meta-analysis was to evaluate the safety profile of colchicine in COVID-19 patients using the gold-standard randomised-control trials.

Methods: Electronic databases (Pubmed, Google Scholar, and Cochrane) were systematically searched until June 2021 and RCTs were extracted. Outcomes of interest included all-cause mortality, COVID-19 severity, mechanical ventilation, C-reactive protein and D-dimer levels. Using a random-effects model, dichotomous outcomes were pooled using odds ratios (OR) through the generic …


Hepatitis B Virus-Associated Hepatocellular Carcinoma And Chronic Stress, Nicholas Noverati, Rukaiya Bashir, Dina Halegoua-De Marzio, Hie-Won Hann Apr 2022

Hepatitis B Virus-Associated Hepatocellular Carcinoma And Chronic Stress, Nicholas Noverati, Rukaiya Bashir, Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

The Hepatitis B virus is one of the most significant hepatocarcinogens globally. The carcinogenic mechanisms of this virus are complex, and may include interactions with the host's immune system. Certain factors, such as stress on the body, can also potentiate these mechanisms. Stress, although adaptive in an acute form, is deleterious to health when chronic and can both suppress and activate the host's defense system. In hepatocellular carcinoma, this can lead to tumor initiation and progression. Those that are more prone to stress, or exposed to situations that incite stress, may be at higher risk of developing cancer. Racial disparities, …