Diseases Commons^™

An In Vivo Genome-Wide Crispr Screen Identifies The Rna-Binding Protein Staufen2 As A Key Regulator Of Myeloid Leukemia, Jeevisha Bajaj, Michael Hamilton, Yutaka Shima, Kendall Chambers, Kyle Spinler, Eric L Van Nostrand, Brian A Yee, Steven M Blue, Michael Chen, David Rizzeri, Charles Chuah, Vivian G Oehler, H Elizabeth Broome, Roman Sasik, James Scott-Browne, Anjana Rao, Gene W Yeo, Tannishtha Reya

Faculty, Staff and Students Publications

Aggressive myeloid leukemias such as blast crisis chronic myeloid leukemia and acute myeloid leukemia remain highly lethal. Here we report a genome-wide in vivo CRISPR screen to identify new dependencies in this disease. Among these, RNA-binding proteins (RBPs) in general, and the double-stranded RBP Staufen2 (Stau2) in particular, emerged as critical regulators of myeloid leukemia. In a newly developed knockout mouse, loss of Stau2 led to a profound decrease in leukemia growth and improved survival in mouse models of the disease. Further, Stau2 was required for growth of primary human blast crisis chronic myeloid leukemia and acute myeloid leukemia. Finally, …

The Comfort Of Destiny, Jeremy A Ross

The Texas Heart Institute Journal

No abstract provided.

Histologic Abnormalities Of The Ascending Aorta: Effects On Aortic Remodeling After Intracardiac Repair Of Tetralogy Of Fallot, Ujjwal Kumar Chowdhury, Lakshmi Kumari Sankhyan, Sheil Avneesh, Ruma Ray, Mani Kalaivani, Suruchi Hasija, Abhinavsingh Chauhan

The Texas Heart Institute Journal

We evaluated aortic tissue specimens from patients undergoing tetralogy of Fallot repair, to determine whether histologic abnormalities affect postsurgical aortic remodeling and other patient-related variables.

Using light microscopy, we studied full-thickness aortic wall tissue operatively excised from 118 consecutive patients undergoing intracardiac repair of tetralogy of Fallot. We performed multiple linear regression analysis to identify independent predictors of change in aortic root dimensions, which we measured with echocardiography after repair and every 3 months thereafter.

Thirty histologically normal specimens were used as controls. Elastic fiber fragmentation was found in 74.6% of the abnormal specimens, mucoid extracellular matrix accumulation in 49.2%, …

Speckle-Tracking Echocardiography In Cardio-Oncology And Beyond, Raymundo A Quintana, Linh P Bui, Rohit Moudgil, Nicolas Palaskas, Saamir Hassan, Jun-Ichi Abe, Elie Mouhayar, Syed Wamique Yusuf, Antonieta Hernandez, Jose Banchs

The Texas Heart Institute Journal

Speckle-tracking echocardiography has enabled clinicians to detect changes in myocardial function with more sensitivity than that afforded by traditional diastolic and systolic functional measurements, including left ventricular ejection fraction. Speckle-tracking echocardiography enables evaluation of myocardial strain in terms of strain (percent change in length of a myocardial segment relative to its length at baseline) and strain rate (strain per unit of time). Both measurements have potential for use in diagnosing and monitoring the cardiovascular side effects of cancer therapy. Regional and global strain measurements can independently predict outcomes not only in patients who experience cardiovascular complications of cancer and cancer …

Cofilin-1-Induced Actin Reorganization In Stored Platelets, Swapan K Dasgupta, Perumal Thiagarajan

Faculty, Staff and Students Publications

BACKGROUND: During platelet storage, there are extensive changes in cytoskeleton and phosphatidylserine exposure. The intrinsic mitochondrial pathway of apoptosis, activated in stored platelets, is a major mediator these changes. Cofilin-1 is an effector of actin reorganization. We examined the effect of cofilin-1 deficiency on cytoskeleton and phosphatidylserine exposure during storage and following activation of apoptosis.

METHODS AND RESULTS: We assessed actin filaments by Alexa-647-phalloidin and phosphatidylserine exposure by fluorescein isothiocyanate-lactadherin by fluorescence microscopy. In fresh platelets, actin filaments are distributed in the subcortical region, and they do not express phosphatidylserine in the outer surface. In stored platelets, there is retraction …

Provider Attitudes And Practice Patterns For Direct-Acting Antiviral Therapy For Patients With Hepatocellular Carcinoma, Nicole E Rich, Ju Dong Yang, Ponni V Perumalswami, Naim Alkhouri, Whitney Jackson, Neehar D Parikh, Neil Mehta, Reena Salgia, Andres Duarte-Rojo, Laura Kulik, Mina Rakoski, Adnan Said, Omobonike Oloruntoba, George N Ioannou, Maarouf A Hoteit, Andrew M Moon, Amol S Rangnekar, Sheila L Eswaran, Elizabeth Zheng, Janice H Jou, James Hanje, Anjana Pillai, Ruben Hernaez, Robert Wong, Steven Scaglione, Hrishikesh Samant, Devika Kapuria, Shaun Chandna, Russell Rosenblatt, Veeral Ajmera, Catherine T Frenette, Sanjaya K Satapathy, Parvez Mantry, Prasun Jalal, Binu V John, Oren K Fix, Michael Leise, Christina C Lindenmeyer, Avegail Flores, Nayan Patel, Z Gordon Jiang, Nyan Latt, Renumathy Dhanasekaran, Mobolaji Odewole, Sofia Kagan, Jorge A Marrero, Amit G Singal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC.

METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses …

Comparison Of Surgical Versus Transcatheter Aortic Valve Replacement For Patients With Aortic Stenosis At Low-Intermediate Risk, Mahin R Khan, Waleed T Kayani, Malalai Manan, Ahmad Munir, Ihab Hamzeh, Salim S Virani, Yochai Birnbaum, Hani Jneid, Mahboob Alam

Faculty, Staff and Students Publications

BACKGROUND: To compare safety and efficacy of transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (SAVR) in patients at low-intermediate risk, given the paucity of robust data.

METHODS: We performed an aggregate data meta-analysis of 7 randomized controlled trials (RCTs) and 6,778 patients comparing TAVR with SAVR for aortic stenosis (AS) in low-intermediate risk patients (Society of Thoracic Surgeons risk-score ≤8%) using the random-effects model. Primary outcome was all-cause mortality at 30-day, 1-year and 2-year of follow-up. Secondary outcomes included cardiac-mortality, stroke, acute kidney injury (AKI), atrial fibrillation (AF), permanent pacemaker (PPM) implantation, major-bleeding, moderate-severe paravalvular regurgitation (PVR) …

Tortuosity-Powered Microfluidic Device For Assessment Of Thrombosis And Antithrombotic Therapy In Whole Blood, David J Luna, Navaneeth K R Pandian, Tanmay Mathur, Justin Bui, Pranav Gadangi, Vadim V Kostousov, Shiu-Ki Rocky Hui, Jun Teruya, Abhishek Jain

Faculty, Staff and Students Publications

Accurate assessment of blood thrombosis and antithrombotic therapy is essential for the management of patients in a variety of clinical conditions, including surgery and on extracorporeal life support. However, current monitoring devices do not measure the effects of hemodynamic forces that contribute significantly to coagulation, platelet function and fibrin formation. This limits the extent to which current assays can predict clotting status in patients. Here, we demonstrate that a biomimetic microfluidic device consisting stenosed and tortuous arteriolar vessels would analyze blood clotting under flow, while requiring a small blood volume. When the device is connected to an inline pressure sensor …

Hepatitis B Virus Hbx Protein Mediates The Degradation Of Host Restriction Factors Through The Cullin 4 Ddb1 E3 Ubiquitin Ligase Complex, Marissa M Minor, F Blaine Hollinger, Adrienne L Mcnees, Sung Yun Jung, Antrix Jain, Joseph M Hyser, Karl-Dimiter Bissig, Betty L Slagle

Faculty, Staff and Students Publications

The hepatitis B virus (HBV) regulatory HBx protein is required for infection, and its binding to cellular damaged DNA binding protein 1 (DDB1) is critical for this function. DDB1 is an adaptor protein for the cullin 4A Really Interesting New Gene (RING) E3 ubiquitin ligase (CRL4) complex and functions by binding cellular DDB1 cullin associated factor (DCAF) receptor proteins that recruit substrates for ubiquitination and degradation. We compared the proteins found in the CRL4 complex immunoprecipitated from uninfected versus HBV-infected hepatocytes from human liver chimeric mice for insight into mechanisms by which HBV and the cell interact within the CRL4 …

A Case Of Pacemaker Syndrome Mimicking A Heart Failure Exacerbation, Seline Haci, Som Aftabizadeh, Senthil Thambidorai, Karan Gupta, Ahsan Khan, Aman Patel, Kimberly Wilson, Anand Subramanian

Cardiology

No abstract provided.

Case Series Of Anca Vasculitis As Prognostic Marker For Severity Or Relapse Of Glomerulonephritis., Jake N. Cho, Venkat Chitumalla, Izuchukwu Nwakoby

Nephrology

No abstract provided.

A Case Series Of Hyponatremia And Management In Hospitalized Patients, Jake N. Cho, Rebecca Ong, Izuchukwu Nwakoby

Nephrology

No abstract provided.

Computer Aided Detection Of Tuberculosis On Chest Radiographs: An Evaluation Of The Cad4tb V6 System, Keelin Murphy, Shifa Salman Habib, Syed Mohammad Asad Zaidi, Saira Khowaja, Aamir Khan, Jaime Melendez, Ernst T. Scholten, Farhan Amad, Steven Schalekamp, Maurits Verhagen

Community Health Sciences

There is a growing interest in the automated analysis of chest X-Ray (CXR) as a sensitive and inexpensive means of screening susceptible populations for pulmonary tuberculosis. In this work we evaluate the latest version of CAD4TB, a commercial software platform designed for this purpose. Version 6 of CAD4TB was released in 2018 and is here tested on a fully independent dataset of 5565 CXR images with GeneXpert (Xpert) sputum test results available (854 Xpert positive subjects). A subset of 500 subjects (50% Xpert positive) was reviewed and annotated by 5 expert observers independently to obtain a radiological reference standard. The …

Predictors Of Poor Quality Of Life After Primary Lower Limb Deep Venous Thrombosis: A Perspective From A Developing Nation, Nadeem Ahmed Siddiqui, Muhammad Asad Moosa, Fareed A. Shaikh, Noman Shahzad, Shahid Nazir, Ziad Sophie

Department of Surgery Docs

Objective: We aimed to determine predictors of poor long term quality of life, using the VEINES Quality of Life (QOL) questionnaire, in patients with lower limb deep venous thrombosis (DVT).
Material and Methods: This study included adult patients with primary lower limb DVT between January 2007 and December 2017. Post thrombotic syndrome (PTS) was assessed using the Villalta score and Quality of Life (QoL) by the VEINES quality of life questionnaire.
Results: Our study included 125 patients, 57 (45.6%) of whom were males. The patient population's median age was 41 years (IQR: 34-47 years). The median follow …

Thrombotic, Inflammatory, And Hif-Regulated Genes And Thrombosis Risk In Polycythemia Vera And Essential Thrombocythemia, Radhika Gangaraju, Jihyun Song, Soo Jin Kim, Tsewang Tashi, Brandi N Reeves, Krishna M Sundar, Perumal Thiagarajan, Josef T Prchal

Faculty, Staff and Students Publications

Thrombosis is a major cause of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET). The pathophysiology of thrombosis in these disorders remains unclear, and we hypothesized that upregulation of thrombotic, inflammatory, and hypoxia-inducible factor (HIF)-regulated genes may play a role in it. We performed unbiased RNA sequencing in granulocytes and platelets of PV patients and found differential expression of several thrombotic, inflammatory, and HIF-regulated genes. The expression of many of these genes positively correlated with JAK2 expression and JAK2V617F allelic burden. We then validated these findings by quantitative polymerase chain reaction analyses of selected gene transcripts in …

Trends In The Sources Of Endophthalmitis At Kresge Eye Institute, Anita Vaishampayan, Kresge Eye Institute

Medical Student Research Symposium

Purpose

Endophthalmitis is a defined as a purulent inflammation of the intraocular fluids, namely the vitreous and aqueous humor. Endophthalmitis most commonly develops from infection, but can also be acquired from inflammatory and neoplastic conditions. We sought to determine these sources at our institute and to look for trends in our urban population.

Methods

A retrospective chart review of patients who attended the Kresge Eye Institute in Detroit, MI between 2003 to 2018 was performed. Patient list was identified from our EMR using the diagnoses codes related endophthalmitis. Information gathered included demographics, type of tissue/fluid cultured, the presumed source of …

Management Of Childhood Migraine By Headache Specialist Versus Non-Headache Specialists, Kelly Valentini, Radhika Gutta, Gunjanpreet Kaur, Ahmad Farooqi, Lalitha Sivaswamy

Medical Student Research Symposium

This study aims to compare the management practices of a headache specialist with non-headache specialists in the treatment of pediatric migraine. The use of appropriate rescue medications and prophylactic agents, application of neuro-imaging, and short-term outcomes are compared in children treated by the two groups of physicians. A retrospective cohort study was conducted utilizing the electronic medical records of children 3-18 years of age with migraine, who were evaluated at a tertiary care children’s hospital from 2016-2018. Of the 849 patients that met the study criteria, 469 were classified as having chronic migraine or high-frequency episodic migraine and were followed …

Comparison Of Pre- And Post-Operative Shoulder Muscle Emg Profiles In Reverse Total Shoulder Arthroplasty Patients, Emily Lau, Sreten Franovic, Noah Kuhlmann, Eric C. Makhni Md, Stephanie Muh Md

Medical Student Research Symposium

Background: Deltoid muscle function is central in reverse total shoulder arthroplasty (RTSA) function; however, there is limited information available regarding changes in deltoid activity before and after surgery. Few tests exist to evaluate specific muscle metrics pre and post operatively. Surface Electromyographic (EMG) is non-invasive and allows for observation of motions with multifaceted analysis of movement with minimal patient demand. Understanding the changes in shoulder muscle activation, namely in the deltoid, in patients pre and post-RTSA can further advance understanding of the procedure and rehabilitation efforts.

Methods: Nine individuals were recruited for this study: all patients underwent RTSA by a …

Inflammatory Markers In Bicuspid Transcatheter Aortic Valve Replacement, Molly N. Pantelic, Paul Nona, Dee Dee Wang

Medical Student Research Symposium

Background

Aortic stenosis (AS) has a prevalence of 2%. Valve replacement is the definitive treatment for AS, with transcatheter aortic valve replacement (TAVR) offering a minimally invasive alternative to surgery.

Bicuspid aortic valve (BAV) is the most common congenital cardiac abnormality. BAV patients are predisposed to AS, and comprise a distinct, younger TAVR patient population. Given limited prior work on inflammatory markers for TAVR risk assessment, this study sought to investigate if white blood cell count (WBC) correlates with BAV TAVR patient severity and post-TAVR outcomes.

Methods

A single-center retrospective analysis was performed on patients with BAV who underwent TAVR …

Atrx Loss In Pediatric Glioma Results In Epigenetic Dysregulation Of G2/M Checkpoint Maintenance And Sensitivity To Atm Inhibition, Brendan Mullan, Tingting Qin, Ruby Siada, Carla Danussi, Jacqueline Brosnan-Cashman, Drew Pratt, Taylor Garcia, Viveka Nand Yadav, Xinyi Zhao, Meredith Morgan, Sriram Venneti, Alan Meeker, Alnawaz Rehemtulla, Pedro Lowenstein, Maria Castro, Carl Koschmann

Medical Student Research Symposium

ATRX is a histone chaperone protein recurrently mutated in pediatric glioma. The mechanism which mediates the proliferative advantage of ATRX loss in pediatric glioma remains unexplained. Recent data revealed a distinct pattern of DNA binding sites of the ATRX protein using ChIP-seq in mouse neuronal precursor cells (mNPCs). Using the ATRX peaks identified in p53^-/- mNPCs, we confirmed that ATRX binding sites were significantly enriched in gene promoters (p < 0.0001) and CpG islands (p < 0.0001) compared with random regions. Gene set enrichment (GSE) analysis identified that cell cycle and regulation of cell cycle were among the most significantly enriched gene sets (p=2.52e-16 and 1.61e-9, respectively). We found that ATRX loss resulted in dysfunction of G2/M checkpoint maintenance: (1) ATRX-deficient pediatric glioblastoma (GBM) cells exhibited a seven-fold increase in mitotic index at 16 hours after sub-lethal radiation, and (2) murine GBM cells with ATRX knockdown demonstrated impaired pChk1 signaling on western blot at multiple time points after radiation compared to controls (p=0.0187). Notably, the ATM signaling (pChk2) remained intact in those cells, suggesting a potential therapeutic target. ATRX-deficient mouse cells were uniquely sensitive to ATM inhibitors at 1 uM alongside 8 Gy radiation compared to controls with intact ATRX (AZD0156: p=0.0027 and AZD01390: p=0.0436). Mice intra-cranially implanted with ATRX-deficient GBM cells showed improved survival (n=10, p=0.0018) when treated with AZD0156 combined with radiation. Our findings suggest that ATRX loss in glioma results in unique sensitivity to ATM inhibition via epigenetic dysregulation of G2/M checkpoint maintenance.

Post-Surgical Pyoderma Gangrenosum After Breast Surgery: A Case Series, Jahan Tajran, Daniella Anderson, Arif Chaudhry, Dennis Hammond

Medical Student Research Symposium

Background:

Pyoderma gangrenosum (PG) is a rare inflammatory cutaneous disorder that is thought to be due to innate immune system dysfunction, specifically of neutrophils. PG has been well documented in patients with autoimmune disorders like Ulcerative Colitis and Rheumatoid Arthritis. PG can also present in surgical patients, imitating a potential wound infection and necrotizing fasciitis. Although PG is a diagnosis of exclusion, prompt recognition is essential to attaining desired aesthetic outcomes, especially with breast involvement. We present a case series of four patients who developed PG following breast surgery. We analyze each patient’s medical history, symptoms, wound progression and management …

Quality Improvement In Ibd Care: The Influence Of A Qi Specific Conference For Fellows, Olayinka Afolabi, Alexis Faber, Raya Kutaimy, Paul Naylor, Murray Ehrinpreis

Medical Student Research Symposium

Given the complexity of management of inflammatory bowel disease (IBD), medical societies such as the American Gastroenterological Association (AGA) and Crohn’s and Colitis Foundation of America (CCFA) have established measures aimed at defining quality of care. In 2011, the AGA proposed 10 quality metrics for IBD, eight of these measures relate to outpatient management and two focus on inpatient management. Our objective was to evaluate compliance with these measures in our own general GI practice and determine whether a GI conference discussing quality improvement (QI) in 2017 was effective.

Long-Term Outcomes Of Bleb Needling Following Primary Glaucoma Filtering Surgery In Primary Open Angle Glaucoma, Bryen Turco, Vaama Patel, Chaesik Kim, Justin Tannir, Lauren Keshishian, Anju Goyal, Mark Juzych, Bret Hughes, Faisal Ridha Al-Timimi

Medical Student Research Symposium

Purpose: To determine the long-term success rate of bleb needling in a predominantly African American population and to identify factors associated with success.

Methods: We conducted a retrospective, observational clinical study in patients with primary open angle glaucoma. Patients who underwent a primary trabeculectomy, with or without an express shunt placement, and then subsequently had a bleb needling procedure were selected for this study. Patients were followed every three months for a period of two years. Failure criteria included achieving an intraocular pressure (IOP) of greater than 20 mmHg or greater than 80% of the pre-needling value on …

Traditional Funeral And Burial Rituals And Ebola Outbreaks In West Africa: A Narrative Review Of Causes And Strategy Interventions, Chulwoo Park

Faculty Publications

Introduction: In West Africa, traditional funerals and burials have proven main contributors to the spread of infectious diseases, such as Ebola, plague, the Marburg virus, and others. Although the World Health Organization has provided guidelines for the safe burial process after learning of the culture of the afterlife in Ebola-affected areas, little effort has been made to integrate theoretical interventions and models for changing West Africans’ funeral behavior. This research was conducted to study 1) the background of traditional burial rituals, 2) interventions to contain Ebola outbreaks in West Africa, and 3) a strategic approach to future disease outbreak in …

Gut Microbial Protein Expression In Response To Dietary Patterns In A Controlled Feeding Study: A Metaproteomic Approach, Sheng Pan, Meredith A J Hullar, Lisa A Lai, Hong Peng, Damon H May, William S Noble, Daniel Raftery, Sandi L Navarro, Marian L Neuhouser, Paul D Lampe, Johanna W Lampe, Ru Chen

Faculty, Staff and Students Publications

Although the gut microbiome has been associated with dietary patterns linked to health, microbial metabolism is not well characterized. This ancillary study was a proof of principle analysis for a novel application of metaproteomics to study microbial protein expression in a controlled dietary intervention. We measured the response of the microbiome to diet in a randomized crossover dietary intervention of a whole-grain, low glycemic load diet (WG) and a refined-grain, high glycemic load diet (RG). Total proteins in stools from 9 participants at the end of each diet period (

Metastatic Spinal Cord Compression Mimicking Cauda Equina Syndrome Illustrating Importance Of Adequate Diagnostic Imaging, Jonathan L. Holt, Joseph Hill, Farzin Farhandnejad, Karyn Doddy, Se Won Lee

Physical Medicine & Rehabilitation

See additional files.

Worsening Weakness After Posterior Cervical Decompression And Fusion; The Challenge In Diagnosis, Steven D. Kim, Joseph Hill, Farzin Farhandnejad, Karyn Doddy

Physical Medicine & Rehabilitation

See additional files.

Unmasking Severe Hypotension After Intermittent Catheter For Distended Bladder In A Patient With Cervical Spinal Cord Injury, Dennis Nguyen, Neal Ekpoudia, Ellsworth Remson, Farzin Farhandnejad, Se Won Lee

Physical Medicine & Rehabilitation

See additional files.

Concussion, Anthony Shadiack

Sports Medicine

No abstract provided.

Ct Rapid Implementation In A 600+ Bed Hospital Serving 35 Counties In The Southeast, Christopher Burns Do, Adam Kassar Md, Jacob Beltz Md, Klie Hoffa, Peter Britt

Radiology

No abstract provided.