Medical Specialties Commons^™

Heat Shock Factor 1 Directly Regulates Transsulfuration Pathway To Promote Prostate Cancer Proliferation And Survival, J Spencer Hauck, David Moon, Xue Jiang, Mu-En Wang, Yue Zhao, Lingfan Xu, Holly Quang, William Butler, Ming Chen, Everardo Macias, Xia Gao, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

There are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and is an actionable target. In this manuscript, we identify that HSF1 regulates the conversion of homocysteine to cystathionine in the transsulfuration pathway by altering levels of cystathionine-β-synthase (CBS). We find that HSF1 directly binds the CBS gene and upregulates CBS mRNA levels. Targeting CBS decreases PCa growth and induces tumor cell death while benign prostate cells are largely unaffected. Combined inhibition of HSF1 and CBS results in more pronounced inhibition of PCa cell …

Features Of Acute Covid-19 Associated With Post-Acute Sequelae Of Sars-Cov-2 Phenotypes: Results From The Impacc Study, Al Ozonoff, Naresh Doni Jayavelu, Shanshan Liu, Esther Melamed, Carly E Milliren, Jingjing Qi, Linda N Geng, Grace A Mccomsey, Charles B Cairns, Lindsey R Baden, Joanna Schaenman, Albert C Shaw, Hady Samaha, Vicki Seyfert-Margolis, Florian Krammer, Lindsey B Rosen, Hanno Steen, Caitlin Syphurs, Ravi Dandekar, Casey P Shannon, Rafick P Sekaly, Lauren I R Ehrlich, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez Sesma, Viviana Simon, Harm Van Bakel, Seunghee Kim-Schulze, David A Hafler, Ofer Levy, Monica Kraft, Chris Bime, Elias K Haddad, Carolyn S Calfee, David J Erle, Charles R Langelier, Walter Eckalbar, Steven E Bosinger, Bjoern Peters, Steven H Kleinstein, Elaine F Reed, Alison D Augustine, Joann Diray-Arce, Holden T Maecker, Matthew C Altman, Ruth R Montgomery, Patrice M Becker, Nadine Rouphael

Faculty, Staff and Students Publications

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B …

Gene Regulation And Speciation In A Migratory Divide Between Songbirds, Matthew I M Louder, Hannah Justen, Abigail A Kimmitt, Koedi S Lawley, Leslie M Turner, J David Dickman, Kira E Delmore

Faculty, Staff and Students Publications

Behavioral variation abounds in nature. This variation is important for adaptation and speciation, but its molecular basis remains elusive. Here, we use a hybrid zone between two subspecies of songbirds that differ in migration - an ecologically important and taxonomically widespread behavior---to gain insight into this topic. We measure gene expression in five brain regions. Differential expression between migratory states was dominated by circadian genes in all brain regions. The remaining patterns were largely brain-region specific. For example, expression differences between the subspecies that interact with migratory state likely help maintain reproductive isolation in this system and were documented in …

Appelmans Protocol – A Directed In Vitro Evolution Enables Induction And Recombination Of Prophages With Expanded Host Range, Thao Nguyen Vu, Justin Ryan Clark, Eris Jang, Roshan D'Souza, Le Phuong Nguyen, Naina Adren Pinto, Seongjun Yoo, Ricardo Abadie, Anthony William Maresso, Dongeun Yong

Faculty, Staff and Students Publications

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) present significant healthcare challenges due to limited treatment options. Bacteriophage (phage) therapy offers potential as an alternative treatment. However, the high host specificity of phages poses challenges for their therapeutic application. To broaden the phage spectrum, laboratory-based phage training using the Appelmans protocol was employed in this study. As a result, the protocol successfully expanded the host range of a phage cocktail targeting CRAB. Further analysis revealed that the expanded host range phages isolated from the output cocktail were identified as recombinant derivatives originating from prophages induced from encountered bacterial strains. These findings …

Combinatorial Effects Of Ion Channel Mis-Splicing As A Cause Of Myopathy In Myotonic Dystrophy, Larissa Nitschke, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder caused by an unstable expanded CTG repeat located in the 3'-UTR of the DM1 protein kinase (DMPK) gene. The pathogenic mechanism results in misregulated alternative splicing of hundreds of genes, creating the dilemma of establishing which genes contribute to the mechanism of DM1 skeletal muscle pathology. In this issue of the JCI, Cisco and colleagues systematically tested the combinatorial effects of DM1-relevant mis-splicing patterns in vivo and identified the synergistic effects of mis-spliced calcium and chloride channels as a major contributor to DM1 skeletal muscle impairment. The authors further demonstrated …

Novel Techniques In Imaging Congenital Heart Disease: Jacc Scientific Statement, Ritu Sachdeva, Aimee K Armstrong, Rima Arnaout, Lars Grosse-Wortmann, B Kelly Han, Luc Mertens, Ryan A Moore, Laura J Olivieri, Anitha Parthiban, Andrew J Powell

Faculty, Staff and Students Publications

Recent years have witnessed exponential growth in cardiac imaging technologies, allowing better visualization of complex cardiac anatomy and improved assessment of physiology. These advances have become increasingly important as more complex surgical and catheter-based procedures are evolving to address the needs of a growing congenital heart disease population. This state-of-the-art review presents advances in echocardiography, cardiac magnetic resonance, cardiac computed tomography, invasive angiography, 3-dimensional modeling, and digital twin technology. The paper also highlights the integration of artificial intelligence with imaging technology. While some techniques are in their infancy and need further refinement, others have found their way into clinical workflow …

Time To Continuous Renal Replacement Therapy Initiation And 90-Day Major Adverse Kidney Events In Children And Young Adults, Katja M Gist, Shina Menon, Pilar Anton-Martin, Amee M Bigelow, Gerard Cortina, Akash Deep, Sara De La Mata-Navazo, Ben Gelbart, Stephen Gorga, Isabella Guzzo, Kenneth E Mah, Nicholas J Ollberding, H Stella Shin, Sameer Thadani, Amanda Uber, Huaiyu Zang, Michael Zappitelli, David T Selewski, We-Rock Investigators

Faculty, Staff and Students Publications

IMPORTANCE: In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown.

OBJECTIVE: To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO;

DESIGN, SETTING, AND PARTICIPANTS: This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young …

Navigating The Observation Zone: Do Risk Scores Help Stratify Patients With Indeterminate High-Sensitivity Cardiac Troponins?, Nicklaus P Ashburn, James K Mccord, Anna C Snavely, Robert H Christenson, Fred S Apple, Richard M Nowak, William F Peacock, Christopher R Defilippi, Simon A Mahler

Faculty, Staff and Students Publications

No abstract provided.

Injectable Hydrogel Electrodes As Conduction Highways To Restore Native Pacing, Gabriel J Rodriguez-Rivera, Allison Post, Mathews John, Skylar Buchan, Drew Bernard, Mehdi Razavi, Elizabeth Cosgriff-Hernandez

Faculty, Staff and Students Publications

There is an urgent clinical need for a treatment regimen that addresses the underlying pathophysiology of ventricular arrhythmias, the leading cause of sudden cardiac death. The current report describes the design of an injectable hydrogel electrode and successful deployment in a pig model with access far more refined than any current pacing modalities allow. In addition to successful cardiac capture and pacing, analysis of surface ECG tracings and three-dimensional electroanatomic mapping revealed a QRS morphology comparable to native sinus rhythm, strongly suggesting the hydrogel electrode captures the deep septal bundle branches and Purkinje fibers. In an ablation model, electroanatomic mapping …

Il-12 Reprograms Car-Expressing Natural Killer T Cells To Long-Lived Th1-Polarized Cells With Potent Antitumor Activity, Elisa Landoni, Mark G Woodcock, Gabriel Barragan, Gabriele Casirati, Vincenzo Cinella, Simone Stucchi, Leah M Flick, Tracy A Withers, Hanna Hudson, Giulia Casorati, Paolo Dellabona, Pietro Genovese, Barbara Savoldo, Leonid S Metelitsa, Gianpietro Dotti

Faculty, Staff and Students Publications

Human natural killer T cells (NKTs) are innate-like T lymphocytes increasingly used for cancer immunotherapy. Here we show that human NKTs expressing the pro-inflammatory cytokine interleukin-12 (IL-12) undergo extensive and sustained molecular and functional reprogramming. Specifically, IL-12 instructs and maintains a Th1-polarization program in NKTs in vivo without causing their functional exhaustion. Furthermore, using CD62L as a marker of memory cells in human NKTs, we observe that IL-12 maintains long-term CD62L-expressing memory NKTs in vivo. Notably, IL-12 initiates a de novo programming of memory NKTs in CD62L-negative NKTs indicating that human NKTs circulating in the peripheral blood possess an intrinsic …

Gambian Mothers Lack Obstetric Danger Sign Knowledge, But Educational Intervention Shows Promise, Kara Shannon, Jocelyn Burridge, Brodus Franklin, Sheena Bhushan, Susan Hilsenbeck, Elena V Petrova, James N'Dow, Ibezimako Iwuh, Sharmila Anandasabapathy, Jeffrey P Wilkinson

Faculty, Staff and Students Publications

BACKGROUND: The Gambia has the 12th highest maternal mortality rate in the world, with 80% of deaths resulting from avoidable causes. Unawareness of pregnancy danger signs (DS) has been shown to be a barrier to seeking obstetric care, while app-based education intervention has shown promise.

OBJECTIVE: We aim to assess patient awareness of DS, identify barriers to awareness, and evaluate potential for implementing smartphone-based technologies for education.

METHODS: A cross-sectional semi-structured survey was administered to Gambian women (n = 100) across five hospitals/health centers. Data and informed consent were collected via an online survey portal. Analysis included bivariate analysis and …

Proton Pump Inhibitors: Rational Use And Use-Reduction - The Windsor Workshop, Peter Kahrilas, Foteini Anastasiou, Albert J Bredenoord, Hashem B El Serag, Joachim Labenz, Juan Mendive, Edoardo V Savarino, Daniel Sifrim, Mihaela Udrescu, Rena Yadlapati, A Pali Hungin

Faculty, Staff and Students Publications

BACKGROUND: Despite deprescribing initiatives to curb overutilization of proton pump inhibitors (PPIs), achieving meaningful reductions in PPI use is proving a challenge.

SUMMARY: An international group of primary care doctors and gastroenterologists examined the literature surrounding PPI use and use-reduction to clarify: (i) what constitutes rational PPI prescribing; (ii) when and in whom PPI use-reduction should be attempted; and (iii) what strategies to use when attempting PPI use-reduction.

KEY MESSAGES: Before starting a PPI for reflux-like symptoms, patients should be educated on potential causes and alternative approaches including dietary and lifestyle modification, weight loss, and relaxation strategies. When commencing a …

Differences In Prediagnostic Serum Metabolomic And Lipidomic Profiles Between Cirrhosis Patients With And Without Incident Hepatocellular Carcinoma, Hannah Powell, Cristian Coarfa, Elisa Ruiz-Echartea, Sandra L Grimm, Omar Najjar, Bing Yu, Luis Olivares, Michael E Scheurer, Christie Ballantyne, Abeer Alsarraj, Emad Mohamed Salem, Aaron P Thrift, Hashem B El Serag, Salma Kaochar

Faculty, Staff and Students Publications

BACKGROUND: Early detection of hepatocellular carcinoma (HCC) is crucial for improving patient outcomes, but we lack robust clinical biomarkers. This study aimed to identify a metabolite and/or lipid panel for early HCC detection.

METHODS: We developed a high-resolution liquid chromatography mass spectrometry (LC-MS)-based profiling platform and evaluated differences in the global metabolome and lipidome between 28 pre-diagnostic serum samples from patients with cirrhosis who subsequently developed HCC (cases) and 30 samples from patients with cirrhosis and no HCC (controls). We linked differentially expressed metabolites and lipids to their associated genes, proteins, and transcriptomic signatures in publicly available datasets. We used …

Concurrent Hbsag And Anti-Hbs Induced By A Pres Deletion Mutant In A Chronic Hepatitis B Patient, Wen Wu, Yingjian Chen, F Blaine Hollinger, Xiangyan Huang

Faculty, Staff and Students Publications

This study analyzed the origins of concurrent hepatitis B surface antigen (HBsAg) and HBsAg antibodies (anti-HBs) in a patient with chronic hepatitis B virus (HBV) infection. The levels of serological markers of HBV infection were determined by enzyme-linked immunosorbent assay (ELISA). The preS/S gene was analyzed by gene amplification and sequencing. The tests revealed that HBsAg and anti-HBs coexisted in this patient with mixed infections of the full-length preS/S virus strain and preS1 183 bp deletion mutant, and both the mutant and the anti-HBs were no longer present after one year, which means that the mutant strain was cleared by …

Trends In Cardiovascular Disease-Related Mortality In Texas, Muhammad Shariq Usman, Adeena Jamil, Zainali Chunawala, Mahboob Alam, Vijay Nambi, Layla A Abushamat, Arunima Misra, Salim S Virani, Christie M Ballantyne, George E Taffet, Khurram Nasir, Sachin Goel, Sadeer Al-Kindi, Javed Butler, Abdul Mannan Khan Minhas

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular disease (CVD) is associated with high mortality in the United States, but the burden of CVD mortality is unevenly distributed between demographic and geographic subgroups, with poor characterization of state-specific trends. In this study, the disparities in CVD-related mortality trends in Texas and the United States from 1999 to 2019 were assessed.

METHODS: Trends in CVD-related mortality were evaluated through analysis of the Multiple Causes of Death Files from the National Center for Health Statistics. Crude and age-adjusted mortality rates (AAMRs) per 100,000 population with associated annual percentage changes were determined. Joinpoint regression was used to assess trends …

Clinical Utility Of Plasma Microbial Cell-Free Dna Sequencing In Determining Microbiologic Etiology Of Infectious Syndromes In Solid Organ Transplant Recipients, Jesal R Shah, Muhammad Rizwan Sohail, Todd Lasco, John A Goss, Mayar Al Mohajer, Sarwat Khalil

Faculty, Staff and Students Publications

BACKGROUND: Metagenomic next-generation sequencing (mNGS) is increasingly being used for microbial detection in various infectious syndromes. However, data regarding the use of mNGS in solid organ transplant recipients (SOTR) are lacking.

OBJECTIVES: To describe and analyze real-world clinical impact of mNGS using plasma microbial cell-free DNA (mcfDNA) in SOTR.Design: Retrospectively reviewed all adult SOTR who underwent mNGS testing using plasma mcfDNA at Baylor St Luke's Medical Center from March 2017 to February 2023.

METHODS: Clinical impact (positive, neutral, and negative) was assessed using standardized objective criteria. Three Infectious Diseases physicians independently performed clinical adjudication to determine the correlation of mcfDNA …

Clinical Utility Of Metagenomic Next-Generation Sequencing In Fever Of Undetermined Origin, Marilyne Daher, Roumen Iordanov, Mayar Al Mohajer, M Rizwan Sohail, Kristen Andrews Staggers, Ahmed Mufeed Hamdi

Faculty, Staff and Students Publications

BACKGROUND: Metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool increasingly used in the field of infectious diseases. Little guidance is available regarding its appropriate use in different patient populations and clinical syndromes. We aimed to review the clinical utility of mNGS in patients with a specific clinical syndrome and identify factors that may increase its utility.

METHODS: We retrospectively reviewed charts of 72 non-immunocompromised adults hospitalized with the clinical syndrome of 'fever of undetermined origin' and underwent mNGS testing. Standardized criteria from a previously published study were used to determine the clinical impact of mNGS testing. We applied logistic …

The Impact Of The Filmarray Meningitis/Encephalitis Panel On Empiric Antibiotic Prescriptions In Patients With Suspected Community-Acquired Meningitis, Aaron Pathak, Caitlynn Pham, Sabra Shay, Todd Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

The BioFire® FilmArray® meningitis/encephalitis (FA/ME) panel provides rapid testing for common cerebrospinal fluid pathogens. We compared empiric antibiotic utilization between patients with suspected community-acquired meningitis with and without an FA/ME panel ordered. No significant differences in antibiotic use were found.

Comparing The Effects Of Two Initial Specimen Diversion Techniques On Blood Culture Contamination Rates And Clinical Outcomes-A Multicenter Study, Anthony Febres-Aldana, Patrycja Ashley, Eva Amenta, Megan Duffey, Theresa Sepulveda, Corina Lopez, Sabra Shay, Miriam Barrett, Todd Lasco, Takei Pipkins, Margaret Reed, Bradley Lembcke, Mayar Al Mohajer

Faculty, Staff and Students Publications

Although the initial specimen diversion device (ISDD) has been shown to reduce blood culture contamination (BCC) rates, its impact on clinical outcomes remains unclear. This multicenter study showed that ISDD significantly decreased BCC. However, there was no reduction in length of stay, days of therapy, or central line-associated bloodstream infections.

Comparison Of Complication Types In Patients Receiving Vesicant Intravenous Antimicrobials Or Vasopressors Via Midlines And Peripherally Inserted Central Catheters, Bryan Grigg, Nishant Varghese, Christi Knapp, Sabra L Shay, Geraldine Jones, James P Herlihy, Prasad Manian, Bradley Lembcke, Mayar Al Mohajer

Faculty, Staff and Students Publications

We assessed adverse events in hospitalized patients receiving selected vesicant antibiotics or vasopressors administered through midline catheters or peripherally inserted central catheters (PICC). The rates of catheter-related bloodstream infections, thrombosis, and overall events were similar across the two groups, while occlusion was higher in the PICC group.

Detection Of Invasive Bartonella Infections With Next-Generation Sequencing Of Microbial Cell-Free Dna, Fernando H Centeno, Ahmed M Hamdi, Todd M Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

We report 9 patients with invasive Bartonella infections, including 5 with endocarditis, who were diagnosed with microbial cell-free DNA next-generation sequencing and Bartonella serology studies. Diagnosis with plasma mcfDNA NGS enabled a faster clinical and laboratory diagnosis in 8 patients. Prompt diagnosis impacted antibiotic management in all 9 patients.

The Impact Of Direct Inoculation Of Ascites Into Blood Culture Bottles On Ascites Culture Positivity, Tyler Brehm, Todd Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

OBJECTIVE: Assess whether direct inoculation of ascites into blood culture bottles would improve ascites culture yield.

DESIGN: Pre-post-study.

SETTING: The study was performed at a quaternary academic medical center in Houston, Texas, including all inpatient and emergency department encounters.

PATIENTS: Ascites cultures collected from November 2020 to December 2022 were reviewed and screened for spontaneous bacterial peritonitis. Patients were excluded if a prior ascites culture from the same patient was already included in the study or if there was evidence of secondary bacterial peritonitis.

INTERVENTION: In the pre-intervention period, ascites cultures were collected into a sterile container and inoculated onto/into …

Creating A Plasma Coordination Center To Support Covid-19 Outpatient Trials Across A National Network Of Hospital Blood Banks, Anusha Yarava, Christi Marshall, David E Reichert, Aaron Ye, Preeti Khanal, Sanford H Robbins, Bruce S Sachais, David Oh, Ryan A Metcalf, Kathleen Conry-Cantilena, Karen King, Meredith Reyes, Jill Adamski, Marisa B Marques, Minh-Ha Tran, Elizabeth S Allen, Daniel Pach, Neil Blumberg, Rhonda Hobbs, Tammon Nash, Aarthi G Shenoy, Giselle S Mosnaim, Yuriko Fukuta, Bela Patel, Sonya L Heath, Adam C Levine, Barry R Meisenberg, Shweta Anjan, Moises A Huaman, Janis E Blair, Judith S Currier, James H Paxton, William Rausch, Kevin Oei, Matthew Abinante, Donald N Forthal, Martin S Zand, Seble G Kassaye, Edward R Cachay, Kelly A Gebo, Shmuel Shoham, Arturo Casadevall, Nichol A Mcbee, Daniel Amirault, Ying Wang, Erica Hopkins, David M Shade, Oliver Layendecker, Sabra L Klein, Han-Sol Park, John S Lee, Patrizio Caturegli, Jay S Raval, Daniel Cruser, Alyssa F Ziman, Jonathan Gerber, Thomas J Gniadek, Evan M Bloch, Aaron A R Tobian, Daniel F Hanley, David J Sullivan, Karen Lane

Faculty, Staff and Students Publications

INTRODUCTION: In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

METHODS: A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

RESULTS: We performed 1,351 transfusions in …

A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment Of Drug-Resistant Tuberculosis, Nika Zielinski, Dragos Baiceanu, Antonela Dragomir, Jan Heyckendorf, Elmira Ibraim, Niklas Köhler, Christoph Leschczyk, Cristina Popa, Andrea Rachow, Jens Sachsenweger, Patricia Sanchez Carballo, Dagmar Schaub, Hajo Zeeb, Begna Tulu, Andrew R Dinardo, Christoph Lange, Maja Reimann

Faculty, Staff and Students Publications

BACKGROUND: Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation.

OBJECTIVE: We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy.

METHODS: Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was …

Impact Of Successful Recanalization And Clinical Outcomes Of Patients With Acute Ischemic Stroke With 5 Or More Thrombectomy Passes, Kazutaka Uchida, Mohammad-Mahdi Sowlat, Hidetoshi Matsukawa, Sameh Samir Elawady, Ali Alawieh, Conor Cunningham, Sami Al Kasab, Ilko Maier, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M Starke, Marios-Nikos Psychogios, Amir Shaban, Adam Arthur, Hugo Cuellar, Jonathan A Grossberg, Daniele G Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Joshua Osbun, Roberto Crosa, Charles Matouk, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Richard Williamson, Pedro Navia, Peter Kan, Reade De Leacy, Shakeel Chowdhry, Mohamad Ezzeldin, Shinichi Yoshimura, Alejandro M Spiotta, Stroke Thrombectomy And Aneurysm Registry (Star) Collaborators

Faculty, Staff and Students Publications

Background: As the number of thrombectomy passes increases during endovascular therapy (EVT) for acute stroke, neurointerventionalists must weigh the risks of potential complications against the risk of failing to recanalize the affected vessel. Thus, we investigated the effectiveness and safety of EVT for patients with acute stroke in which ≥5 EVT passes were performed.

Methods: This retrospective cohort study from January 2013 to December 2022 included 31 thrombectomy-capable centers. Patients in whom ≥5 EVT passes were made were included in the analysis. The patients with successful recanalization defined as modified Thrombolysis in Cerebral Infarction ≥2b at 5, 6, 7, or …

Gut Pathobiont Enrichment Observed In A Population Predisposed To Dementia, Type 2 Diabetics Of Mexican Descent Living In South Texas, Lisa M Matz, Nisarg S Shah, Laura Porterfield, Olivia M Stuyck, Michael D Jochum, Rakez Kayed, Giulio Taglialatela, Randall J Urban, Shelly A Buffington

Faculty, Staff and Students Publications

Type 2 diabetes (T2D) is a common forerunner of neurodegeneration and accompanying dementia, including Alzheimer's Disease (AD), yet the mechanisms underlying this comorbidity remain unresolved. Individuals of Mexican descent living in South Texas have increased prevalence of comorbid T2D and early onset AD, despite low incidence of the APOE-ε4 risk variant among the population and an absence of a similar predisposition among relatives residing in Mexico - suggesting a role for environmental factors in coincident T2D and AD susceptibility. We therefore sought to test if differences in gut community structure could be observed in this population prior to any AD …

Posttransplantation Late Complications Increase Over Time For Patients With Scid: A Primary Immune Deficiency Treatment Consortium (Pidtc) Landmark Study, Hesham Eissa, Monica S Thakar, Ami J Shah, Brent R Logan, Linda M Griffith, Huaying Dong, Roberta E Parrott, Richard J O'Reilly, Jasmeen Dara, Neena Kapoor, Lisa Forbes Satter, Sharat Chandra, Malika Kapadia, Shanmuganathan Chandrakasan, Alan Knutsen, Soma C Jyonouchi, Lyndsay Molinari, Ahmad Rayes, Christen L Ebens, Pierre Teira, Blachy J Dávila Saldaña, Lauri M Burroughs, Sonali Chaudhury, Deepak Chellapandian, Alfred P Gillio, Fredrick Goldman, Harry L Malech, Kenneth Desantes, Geoff D E Cuvelier, Jacob Rozmus, Ralph Quinones, Lolie C Yu, Larisa Broglie, Victor Aquino, Evan Shereck, Theodore B Moore, Mark T Vander Lugt, Talal I Mousallem, Joeseph H Oved, Morna Dorsey, Hisham Abdel-Azim, Caridad Martinez, Jacob H Bleesing, Susan Prockop, Donald B Kohn, Jeffrey J Bednarski, Jennifer Leiding, Rebecca A Marsh, Troy Torgerson, Luigi D Notarangelo, Sung-Yun Pai, Michael A Pulsipher, Jennifer M Puck, Christopher C Dvorak, Elie Haddad, Rebecca H Buckley, Morton J Cowan, Jennifer Heimall

Faculty, Staff and Students Publications

Background: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT).

Objective: We investigated outcomes of HCT for severe combined immunodeficiency (SCID).

Methods: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers. Eligibility criteria included survival to at least 2 years after HCT without need for subsequent cellular therapy. CLE were defined as either conditions present at any time before 2 years from HCT that remained unresolved (chronic), …

Welcoming 2024: Supporting Students' Well-Being, Eric A Storch, Rick Yang

Faculty, Staff and Students Publications

No abstract provided.

Klebsiella Pneumoniae Carbapenemase Variant 44 Acquires Ceftazidime-Avibactam Resistance By Altering The Conformation Of Active-Site Loops, Zhizeng Sun, Hanfeng Lin, Liya Hu, Neetu Neetu, Banumathi Sankaran, Jin Wang, B V Venkataram Prasad, Timothy Palzkill

Faculty, Staff and Students Publications

Klebsiella pneumoniae carbapenemase 2 (KPC-2) is an important source of drug resistance as it can hydrolyze and inactivate virtually all β-lactam antibiotics. KPC-2 is potently inhibited by avibactam via formation of a reversible carbamyl linkage of the inhibitor with the catalytic serine of the enzyme. However, the use of avibactam in combination with ceftazidime (CAZ-AVI) has led to the emergence of CAZ-AVI-resistant variants of KPC-2 in clinical settings. One such variant, KPC-44, bears a 15 amino acid duplication in one of the active-site loops (270-loop). Here, we show that the KPC-44 variant exhibits higher catalytic efficiency in hydrolyzing ceftazidime, lower …

Inhibition Of Src-3 As A Potential Therapeutic Strategy For Aggressive Mantle Cell Lymphoma, Imani Bijou, Yang Liu, Dong Lu, Jianwei Chen, Shelby Sloan, Lapo Alinari, David M Lonard, Bert W O'Malley, Michael Wang, Jin Wang

Faculty, Staff and Students Publications

Mantle cell lymphoma (MCL) has a poor prognosis and high relapse rates despite current therapies, necessitating novel treatment regimens. Inhibition of SRC-3 show effectiveness in vivo and in vitro in other B cell lymphomas. Additionally, previous studies have shown that SRC-3 is highly expressed in the lymph nodes of B cell non-Hodgkin's lymphoma patients, suggesting SRC-3 may play a role in the progression of B cell lymphoma. This study aimed to investigate novel SRC-3 inhibitors, SI-10 and SI-12, in mantle cell lymphoma. The cytotoxic effects of SI-10 and SI-12 were evaluated in vitro and demonstrated dose-dependent cytotoxicity in a panel …