Medical Specialties Commons^™

Promoting Resilience In Stress Management For Adolescents With Type 1 Diabetes: A Randomized Clinical Trial, Joyce P Yi-Frazier, Marisa E Hilliard, Maeve B O'Donnell, Chuan Zhou, Britney M Ellisor, Samantha Garcia Perez, Brenda Duran, Yuliana Rojas, Faisal S Malik, Daniel J Desalvo, Catherine Pihoker, Miranda C Bradford, Samantha Scott, Sridevi Devaraj, Abby R Rosenberg

Faculty, Staff and Students Publications

IMPORTANCE: Type 1 diabetes (T1D) requires demanding self-management health behaviors, and adolescents with T1D are at risk for poor psychosocial and medical outcomes. Developing resilience skills may help adolescents with T1D and elevated distress navigate common stressors and achieve positive outcomes.

OBJECTIVE: To test the efficacy of the Promoting Resilience in Stress Management (PRISM) intervention on levels of hemoglobin A1c (HbA1c), diabetes distress, self-management behaviors, resilience, and quality of life among adolescents.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, parallel, 1:1 randomized clinical trial that followed up 172 participants for 12 months was conducted from January 1, 2020, to November …

Eculizumab For Management Of Hyperhemolysis Syndrome In Pediatric Patients With Sickle Cell Disease: A Single-Center Case Series, Ajibike Lapite, Saleh Bhar, Titilope Fasipe

Faculty, Staff and Students Publications

Chronic hemolytic anemia and vascular occlusion are hallmarks of sickle cell disease (SCD). Blood transfusions are critical for supportive and preventive management of SCD complications. Patients with SCD are at risk for hyperhemolysis syndrome (HHS), a subtype of delayed hemolytic transfusion reactions. HHS management includes intravenous immunoglobulin, corticosteroids, and avoidance of further transfusions. Not all patients respond to first-line agents. Eculizumab, which blocks terminal complement activation, has been proposed as second-line management of HHS. We describe two patients who received eculizumab for refractory HHS. In our experience, eculizumab is a safe and effective option for refractory pediatric HHS.

Predicting Wait Time For Pediatric Kidney Transplant: A Novel Index, Alexandra Alvarez, Ashley Montgomery, Nhu Thao Nguyen Galván, Eileen D Brewer, Abbas Rana

Faculty, Staff and Students Publications

BACKGROUND: Over one thousand pediatric kidney transplant candidates are added to the waitlist annually, yet the prospective time spent waiting is unknown for many. Our study fills this gap by identifying variables that impact waitlist time and by creating an index to predict the likelihood of a pediatric candidate receiving a transplant within 1 year of listing. This index could be used to guide patient management by giving clinicians a potential timeline for each candidate's listing based on a unique combination of risk factors.

METHODS: A retrospective analysis of 3757 pediatric kidney transplant candidates from the 2014 to 2020 OPTN/UNOS …

Use Of Pancreatic Endotherapy In Patients With Chronic Pancreatitis: Results From A Multicenter Cohort Study In The United States, Samuel Han, Darwin L Conwell, Jeffrey J Easler, Yunlong Yang, Dana K Andersen, William E Fisher, Evan L Fogel, Chris Forsmark, Phil A Hart, Steven J Hughes, Liang Li, Stephen J Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Although pancreatic endotherapy (PET) is commonly used for treating adverse events of chronic pancreatitis, data on the frequency and factors associated with the use of PET are limited. Our aim was to define the use of and factors predictive for receiving PET in a well-characterized chronic pancreatitis cohort.

METHODS: This is a cross-sectional analysis of data from PROCEED, a multicenter U.S. cohort study of chronic pancreatitis. PET modalities primarily consisted of ERCP. A treatment course was defined as the number of sessions performed for a specific indication. A repeat course was defined as PET >1 year after …

Muscle Mitochondrial Function Is Impaired In Adults With Type 1 Diabetes, Daniel Gottlieb, Layla A Abushamat, Kristen J Nadeau, Judith G Regensteiner, Jane E B Reusch, Kalie L Tommerdahl, John Rice, Leslie A Knaub, Cynthia M F Monaco, Thomas J Hawke, Christopher G R Perry, Melanie G Cree, Irene E Schauer

Faculty, Staff and Students Publications

Aims: Type 1 diabetes has been associated with mitochondrial dysfunction. However, the mechanism of this dysfunction in adults remains unclear.

Methods: A secondary analysis was conducted using data from several clinical trials measuring in-vivo and ex-vivo mitochondrial function in adults with type 1 diabetes (n = 34, age 38.8 ± 14.6 years) and similarly aged controls (n = 59, age 44.6 ± 13.9 years). In-vivo mitochondrial function was assessed before, during, and after isometric exercise with 31phosphorous magnetic resonance spectroscopy. High resolution respirometry of vastus lateralis muscle tissue was used to assess ex-vivo measures.

Results: In-vivo data showed higher rates …

A Community Health Worker Led Diabetes Self-Management Education Program: Reducing Patient And System Burden, Laura Porterfield, Xiaoying Yu, Victoria Warren, Michael E Bowen, Carolyn Smith-Morris, Elizabeth M Vaughan

Faculty, Staff and Students Publications

Aims: Conduct a secondary analysis of the TIME (Telehealth-supported, Integrated Community Health Workers (CHWs), Medication access, diabetes Education) made simple trial (SIMPLE) to evaluate healthcare utilization and explore variables that may have influenced HbA1c.

Methods: Participants (N = 134 [67/group]) were low-income, uninsured Hispanics with or at risk for type 2 diabetes mellitus. We included in-person and telehealth clinician visits, other visits, missed visits, orders placed, and guideline-adherence (e.g., vaccinations, quarterly HbA1c for uncontrolled diabetes). Using multivariable models, we explored for associations between HbA1c changes and these measures.

Results: The control arm had higher missed visits rates (intervention: 45 %; …

Pediatric Mental Health Emergency Department Visits From 2017 To 2022: A Multicenter Study, Jennifer A Hoffmann, Camille P Carter, Cody S Olsen, David Ashby, Kamali L Bouvay, Susan J Duffy, James M Chamberlain, Sofia S Chaudhary, Nicolaus W Glomb, Jacqueline Grupp-Phelan, Maya Haasz, Erin P O'Donnell, Mohsen Saidinejad, Bashar S Shihabuddin, Leah Tzimenatos, Neil G Uspal, Joseph J Zorc, Lawrence J Cook, Elizabeth R Alpern

Faculty, Staff and Students Publications

Background: The COVID-19 pandemic adversely affected children's mental health (MH) and changed patterns of MH emergency department (ED) utilization. Our objective was to assess how pediatric MH ED visits during the COVID-19 pandemic differed from expected prepandemic trends.

Methods: We retrospectively studied MH ED visits by children 5 to < 18 years old at nine U.S. hospitals participating in the Pediatric Emergency Care Applied Research Network Registry from 2017 to 2022. We described visit length by time period: prepandemic (January 2017-February 2020), early pandemic (March 2020-December 2020), midpandemic (2021), and late pandemic (2022). We estimated expected visit rates from prepandemic data using multivariable Poisson regression models. We calculated rate ratios (RRs) of observed to expected visits per 30 days during each pandemic time period, overall and by sociodemographic and clinical characteristics.

Results: We identified 175,979 pediatric MH ED visits. Visit length exceeded 12 h for 7.3% prepandemic, 8.4% early pandemic, 15.0% midpandemic, and 19.2% late pandemic visits. During the early pandemic, observed visits per 30 days decreased relative to expected rates (RR 0.80, 95% confidence interval [CI] 0.78-0.84), were similar to expected …

Sensory Symptoms Across The Lifespan In People With Cerebral Palsy, Ariel M Lyons-Warren, Danielle Guez-Barber, Sruthi P Thomas, Evelyne K Tantry, Aditya Mahat, Bhooma Aravamuthan

Faculty, Staff and Students Publications

Background: To estimate the prevalence of sensory symptoms in people with cerebral palsy (CP) across the lifespan.

Methods: In this cross-sectional study, the self-reported Sensory Processing Scale Inventory (SPS-I) was administered via Research Electronic Data Capture (REDCap) between February 1, 2022, and August 15, 2022, to people with CP or their caregivers enrolled in the online MyCP Community Registry. We determined the association between SPS-I scores and age (Pearson correlation) and functional status as assessed using five validated functional classification systems for CP (analysis of variance [ANOVA]). We hypothesized that sensory symptoms would differ between younger and older individuals with …

A Content Analysis Of Self-Report Child Anxiety Measures, Minjee Kook, Jane W Clinger, Eric Lee, Sophie C Schneider, Eric A Storch, Andrew G Guzick

Faculty, Staff and Students Publications

A clear understanding of the item content of psychological assessments is critical but often overlooked. This study describes the content overlap of seven commonly used and psychometrically validated measures of anxiety among children and adolescents. Symptom codes were created for all items across measures and items were sorted by these codes, which all fell into specific symptom categories. We conducted two analyses of all items: a "bottom-up" content categorization approach, which used symptom categories that were developed during this study, and a "top-down" DSM-5 categorization which mapped items onto symptoms of anxiety disorders in the DSM-5. Findings reveal a weak …

Comparison Of Open Thoracoabdominal Repair For Chronic Aortic Dissections And Aneurysms, Ian O Cook, Susan Y Green, Kimberly R Rebello, Qianzi Zhang, Veronica A Glover, Rodrigo Zea-Vera, Marc R Moon, Scott A Lemaire, Joseph S Coselli

Faculty, Staff and Students Publications

Objective: Aortic dissection is common in patients undergoing open surgical repair of thoracoabdominal aortic aneurysms (TAAAs). Most often, dissection is chronic and is associated with progressive aortic dilatation. Because contemporary outcomes in chronic dissection are not clearly understood, we compared patient characteristics and outcomes after open TAAA repair between patients with chronic dissection and those with non-dissection aneurysm.

Methods: We retrospectively analyzed data from 3470 open TAAA repairs performed in a single practice. Operations were for non-dissection aneurysm in 2351 (67.8%) and chronic dissection in 1119 (32.2%). Outcomes included operative mortality and adverse events, a composite variable comprising operative death …

Fathers In The United States Are Getting Older, Larry I Lipshultz, Blair T Stocks

Faculty, Staff and Students Publications

No abstract provided.

Asynchronous Online Training Increased Knowledge, Confidence, And Intent To Screen And Treat Substance Use Disorders Among Primary Care Clinicians Practicing In Texas, Roger Zoorob, Sung In Kim-Vences, Jacqueline M Hirth, Kylie Schaper, Larissa Grigoryan, Sandra Gonzalez, Alicia Kowalchuk

Faculty, Staff and Students Publications

Introduction: Despite increasing prevalence of substance use disorders (SUD), few patients are diagnosed and treated in primary care settings. This study evaluated changes in knowledge, confidence, and intention to implement screening and brief intervention (SBI) and SUD treatment after clinicians participated in an asynchronous online education course.

Methods: A self-selected sample of primary care clinicians in Texas participated in online SBI and SUD education March 2021-July 2023. Baseline and post-training surveys evaluated changes in knowledge, confidence, and intent to implement SBI and SUD treatment. Changes were compared using paired t-tests. Multivariable linear regression examined factors potentially associated with confidence and …

A Rare Variant In Mrc2 Associated With Familial Supraventricular Tachycardia And Wolff-Parkinson-White Syndrome, Adam S Potter, Christina Y Miyake, Claudia Gonzaga-Jauregui, Yuriana Aguilar-Sanchez, Mohit M Hulsurkar, Satadru K Lahiri, Lucia M Moreira, Neelam Mehta, Mahshid S Azamian, James R Lupski, Svetlana Reilly, Seema R Lalani, Xander H T Wehrens

Faculty, Staff and Students Publications

Background: Accessory pathways are a common cause of supraventricular tachycardia (SVT) and can lead to sudden cardiac death in otherwise healthy children and adults when associated with Wolff-Parkinson-White syndrome. The goal of this study was to identify genetic variants within a large family with structurally normal hearts affected by SVT and Wolff-Parkinson-White syndrome and determine causality of the gene deficit in a corresponding mouse model.

Methods: Whole exome sequencing performed on 2 distant members of a 3-generation family in which multiple members were affected by SVT or Wolff-Parkinson-White pattern (preexcitation) on ECG identified MRC2 as a candidate gene. Serial electrocardiograms, …

Molecular And Physiological Changes In The Spacex Inspiration4 Civilian Crew, Christopher W Jones, Eliah G Overbey, Jerome Lacombe, Adrian J Ecker, Cem Meydan, Krista Ryon, Braden Tierney, Namita Damle, Matthew Mackay, Evan E Afshin, Jonathan Foox, Jiwoon Park, Theodore M Nelson, Mir Suhail Mohamad, Syed Gufran Ahmad Byhaqui, Burhan Aslam, Ummer Akbar Tali, Liaqun Nisa, Priya V Menon, Chintan O Patel, Sharib A Khan, Doug J Ebert, Aaron Everson, Michael C Schubert, Nabila N Ali, Mallika S Sarma, Jangkeun Kim, Nadia Houerbi, Kirill Grigorev, J Sebastian Garcia Medina, Alexander J Summers, Jian Gu, John A Altin, Ali Fattahi, Mohammad I Hirzallah, Jimmy H Wu, Alexander C Stahn, Afshin Beheshti, Remi Klotz, Veronica Ortiz, Min Yu, Laura Patras, Irina Matei, David Lyden, Ari Melnick, Neil Banerjee, Sean Mullane, Ashley S Kleinman, Michael Loesche, Anil S Menon, Dorit B Donoviel, Emmanuel Urquieta, Jaime Mateus, Ashot E Sargsyan, Mark Shelhamer, Frederic Zenhausern, Eric M Bershad, Mathias Basner, Christopher E Mason

Faculty, Staff and Students Publications

Human spaceflight has historically been managed by government agencies, such as in the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first all-civilian crew to low Earth orbit, which included the youngest American astronaut (aged 29), new in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables and immune profiling), ocular alignment measurements and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular …

Trajectory Of C-Reactive Protein And Incident Heart Failure In Black Adults: The Jackson Heart Study, Arsalan Hamid, Wondwosen K Yimer, Adebamike A Oshunbade, Muhammad Shahzeb Khan, Daisuke Kamimura, Rodney K Kipchumba, Ambarish Pandey, Donald Clark, Robert J Mentz, Ervin R Fox, Jarett D Berry, R Brandon Stacey, Amil Shah, Adolfo Correa, Salim S Virani, Javed Butler, Michael E Hall

Faculty, Staff and Students Publications

Background: Increased hsCRP (high-sensitivity C-reactive protein), a marker of inflammation, is associated with incident cardiovascular events. We aim to determine whether the baseline or trajectory of hsCRP levels over time predicts incident heart failure (HF) hospitalization.

Methods: JHS (Jackson Heart Study) participants' (n=3920 Black adults) hsCRP levels were measured over 3 visits (from 2000 to 2013). We assessed the association of hsCRP at baseline (visit 1) with incident HF hospitalization using Cox proportional hazards models. Furthermore, we assessed the association of the trajectory of hsCRP over repeated measurements (visits 1-3) with incident HF using joint models. Hazard ratios are reflective …

Individual Variation In The Distribution Of Apolipoprotein B Levels Across The Spectrum Of Ldl-C Or Non-Hdl-C Levels, Ahmed Sayed, Eric D Peterson, Salim S Virani, Allan D Sniderman, Ann Marie Navar

Faculty, Staff and Students Publications

Importance: Although apolipoprotein B (apoB) is a superior marker of lipid-related risk compared with low-density lipoprotein cholesterol (LDL-C), few data exist to translate the goals and thresholds from LDL-C to their apoB equivalent. In addition, although current American College of Cardiology/American Heart Association guidelines provide a relative indication for apoB measurement among individuals with hypertriglyceridemia, whether discordance is limited to those subgroups is unknown.

Objectives: To assess the variability in apoB level across the spectrum of LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) levels and evaluate whether discordance between apoB and LDL-C or non-HDL-C is limited to specifiable subgroups.

Design, setting, …

An Innovative Approach To Aligning Healthcare With What Matters Most To Patients: A Hybrid Type 1 Trial Protocol Of Patient Priorities Care For Older Adults With Multiple Chronic Conditions, Aanand D Naik, Mackenzie L Shanahan, Lilian Dindo, Marcia C Mecca, Jennifer Arney, Amber B Amspoker, Sheena Wydermyer, Jack Banks, Richard L Street, Lea Kiefer, Maria Zenoni, Tracey Rosen, Raquel D Gonzalez, Angela Catic, Terri R Fried

Faculty, Staff and Students Publications

Background: Providing healthcare for older adults with multiple chronic conditions (MCC) is challenging. Polypharmacy and complex treatment plans can lead to high treatment burden and risk for adverse events. For clinicians, managing the complexities of patients with MCC leaves little room to identify what matters and align care options with patients' health priorities. New care approaches are needed to navigate these challenges. In this clinical trial, we evaluate implementation and effectiveness outcomes of an innovative, structured, patient-centered care approach (Patient Priorities Care; PPC) for reducing treatment burden and aligning health care decisions with the health priorities of older adults with …

Validation Of Electronic Diagnostic Codes For Rapid Eye Movement Sleep Behavior Disorder, Melissa B Jones, Carlos H Schenck, Mehrnaz Azarian, Ricardo E Jorge, Amir Sharafkhaneh, Javad Razjouyan

Faculty, Staff and Students Publications

We investigated the accuracy of International Classification of Diseases (ICD) codes for the identification of veterans with rapid eye movement sleep behavior disorder. The charts of 139 randomly sampled veterans with ≥ 1 ICD-9 and ICD-10 code(s) for rapid eye movement sleep behavior disorder were reviewed for documentation of a suspected, previous, or current diagnosis; clinical symptoms; and/or empiric treatments for this disorder. Notably, 71 (51.1%) patients with rapid eye movement sleep behavior disorder electronic diagnoses had not undergone polysomnography, and 29 (20.9%) had polysomnography reports without commentary on rapid eye movement sleep without atonia. Sleep centers are therefore encouraged …

Safety And Efficacy Outcomes Of Early Cessation Of Anti-Pd1 Therapy In Patients 80 Years Or Older: A Retrospective Cohort Study, Kylie Fletcher, Alessio Cortellini, Teja Ganta, Roma Kankaria, Haocan Song, Fei Ye, Rebecca Irlmeier, Neha Debnath, Anwaar Saeed, Maluki Radford, Asrar Alahmadi, Akiva Diamond, Christopher Hoimes, Carolyn J Presley, Dwight H Owen, Sarah Abou Alaiwi, Amin H Nassar, Giuseppe Lamberti, Fabiana Perrone, Sebastiano Buti, Raffaele Giusti, Marco Filetti, Vito Vanella, Domenico Mallardo, Tamara A Sussman, Domenico Galetta, Foteini Kalofonou, Ella Daniels, Paolo A Ascierto, David J Pinato, Caroline Nebhan, Stephanie Berg, Toni K Choueiri, Thomas U Marron, Yinghong Wang, Abdul Rafeh Naqash, Douglas B Johnson

Faculty, Staff and Students Publications

Older patients have similar immune checkpoint inhibitor efficacy and rates of adverse events as younger patients, but appear to have decreased tolerability, particularly in the oldest patient cohort (>80 years), often leading to early cessation of therapy. We aimed to determine whether early discontinuation impacts efficacy of anti-PD-1 therapy in patients ≥80 years old. In this retrospective, multicenter, international cohort study, we examined 773 patients with 4 tumor types who were at least 80 years old and treated with anti-PD-1 therapy. We determined response rate, overall survival (OS), and progression-free survival (PFS) in patients who discontinued therapy early (< 12 months) for reasons other than progression or death. We used descriptive statistics for demographics, response, and toxicity rates. Survival statistics were described using Kaplan Meier curves. Median (range) age at anti-PD-1 initiation was 83.0 (75.8-97.0) years. The cancer types included were melanoma (n = 286), non-small cell lung cancer (NSCLC) (n = 345), urothelial cell carcinoma (UCC) (n = 108), and renal cell carcinoma (RCC) (n = 34). Of these, 102 met the primary endpoint of < 12 months to discontinuation for reasons other than death or progression. Median PFS and OS, respectively, for these patients were 34.4 months and 46.6 months for melanoma, 15.8 months and 23.4 months for NSCLC, and 10.4 months and 15.8 months for UCC. This study suggests geriatric patients who have demonstrated therapeutic benefit and discontinued anti-PD-1 therapy at less than 12 months of duration for reasons other than progression may have durable clinical benefit without additional therapy.

Deletion Of Mipep In Adipocytes Protects Against Obesity And Insulin Resistance By Boosting Muscle Metabolism, Alexis Diaz-Vegas, Kristen C Cooke, Harry B Cutler, Belinda Yau, Stewart W C Masson, Dylan Harney, Oliver K Fuller, Meg Potter, Søren Madsen, Niamh R Craw, Yiju Zhang, Cesar L Moreno, Melkam A Kebede, G Gregory Neely, Jacqueline Stöckli, James G Burchfield, David E James

Faculty, Staff and Students Publications

Mitochondria facilitate thousands of biochemical reactions, covering a broad spectrum of anabolic and catabolic processes. Here we demonstrate that the adipocyte mitochondrial proteome is markedly altered across multiple models of insulin resistance and reveal a consistent decrease in the level of the mitochondrial processing peptidase miPEP.

OBJECTIVE: To determine the role of miPEP in insulin resistance.

METHODS: To experimentally test this observation, we generated adipocyte-specific miPEP knockout mice to interrogate its role in the aetiology of insulin resistance.

RESULTS: We observed a strong phenotype characterised by enhanced insulin sensitivity and reduced adiposity, despite normal food intake and physical activity. Strikingly, …

Histone Serotonylation Regulates Ependymoma Tumorigenesis, Hsiao-Chi Chen, Peihao He, Malcolm Mcdonald, Michael R Williamson, Srinidhi Varadharajan, Brittney Lozzi, Junsung Woo, Dong-Joo Choi, Debosmita Sardar, Emmet Huang-Hobbs, Hua Sun, Siri M Ippagunta, Antrix Jain, Ganesh Rao, Thomas E Merchant, David W Ellison, Jeffrey L Noebels, Kelsey C Bertrand, Stephen C Mack, Benjamin Deneen

Faculty, Staff and Students Publications

Bidirectional communication between tumors and neurons has emerged as a key facet of the tumor microenvironment that drives malignancy1,2. Another hallmark feature of cancer is epigenomic dysregulation, where alterations in gene expression influences cell states and interactions with the tumor microenvironment3. Ependymoma (EPN) is a pediatric brain tumor that relies on epigenomic remodeling to engender malignancy4,5; how these epigenetic mechanisms intersect with extrinsic neuronal signaling during EPN tumor progression is unknown. Here we show that activity of serotonergic neurons regulates EPN tumorigenesis, while serotonin itself also serves as an activating …

Low Vitamin D Levels In Patients With Symptoms Of Gastroparesis: Relationships With Nausea And Vomiting, Gastric Emptying And Gastric Myoelectrical Activity, Kenneth L Koch, Henry P Parkman, Katherine P Yates, Mark L Van Natta, Madhusudan Grover, Gianrico Farrugia, Thomas L Abell, Richard W Mccallum, Irene Sarosiek, Braden Kuo, Robert J Shulman, Laura Miriel, James Tonascia, Pankaj J Pasricha

Faculty, Staff and Students Publications

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied.

AIMS: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp.

METHODS: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and …

Structure Of Adenylyl Cyclase 5 In Complex With Gβγ Offers Insights Into Adcy5-Related Dyskinesia, Yu-Chen Yen, Yong Li, Chun-Liang Chen, Thomas Klose, Val J Watts, Carmen W Dessauer, John J G Tesmer

Faculty, Staff and Student Publications

The nine different membrane-anchored adenylyl cyclase isoforms (AC1-9) in mammals are stimulated by the heterotrimeric G protein, Gαs, but their response to Gβγ regulation is isoform specific. In the present study, we report cryo-electron microscope structures of ligand-free AC5 in complex with Gβγ and a dimeric form of AC5 that could be involved in its regulation. Gβγ binds to a coiled-coil domain that links the AC transmembrane region to its catalytic core as well as to a region (C1b) that is known to be a hub for isoform-specific regulation. We confirmed the Gβγ interaction with both purified proteins and cell-based …

Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial, Jason L Sperry, Francis X Guyette, Bedda L Rosario-Rivera, Matthew E Kutcher, Lucy Z Kornblith, Bryan A Cotton, Chad T Wilson, Kenji Inaba, Eva V Zadorozny, Laura E Vincent, Ashley M Harner, Emily T Love, Joseph E Doherty, Joseph Cuschieri, Aaron E Kornblith, Erin E Fox, Yu Bai, Marcus K Hoffman, Catherine P Seger, Jay Hudgins, Sheila Mallett-Smith, Matthew D Neal, Christine M Leeper, Philip C Spinella, Mark H Yazer, Stephen R Wisniewski, Cold Stored Platelet For Hemorrhagic Shock (Crisp-Hs) Study Group

Faculty, Staff and Student Publications

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock.

BACKGROUND: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury.

METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus …

Parkinson’S Disease Variant Detection And Disclosure: Pd Generation, A North American Study, Lola Cook, Jennifer Verbrugge, Tae-Hwi Schwantes-An, Jeanine Schulze, Tatiana Foroud, Anne Hall, Karen S Marder, Ignacio F Mata, Niccolò E Mencacci, Martha A Nance, Michael A Schwarzschild, Tanya Simuni, Susan Bressman, Anne-Marie Wills, Hubert H Fernandez, Irene Litvan, Kelly E Lyons, Holly A Shill, Carlos Singer, Thomas F Tropea, Nora Vanegas Arroyave, Janfreisy Carbonell, Rossy Cruz Vicioso, Linn Katus, Joseph F Quinn, Priscila D Hodges, Yan Meng, Samuel P Strom, Cornelis Blauwendraat, Katja Lohmann, Cynthia Casaceli, Shilpa C Rao, Kamalini Ghosh Galvelis, Anna Naito, James C Beck, Roy N Alcalay

Faculty, Staff and Students Publications

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's …

Fetal Malrotation With Midgut Volvulus: Prenatal Diagnosis And Planning, Jai Sidpra, Sniya Sudhakar, Asthik Biswas, Flavia Massey, Valentina Turchetti, Tracy Lau, Edward Cook, Javeria Raza Alvi, Hasnaa M Elbendary, Jerry L Jewell, Antonella Riva, Alessandro Orsini, Aglaia Vignoli, Zara Federico, Jessica Rosenblum, An-Sofie Schoonjans, Matthias De Wachter, Ignacio Delgado Alvarez, Ana Felipe-Rucián, Nourelhoda A Haridy, Shahzad Haider, Mashaya Zaman, Selina Banu, Najwa Anwaar, Fatima Rahman, Shazia Maqbool, Rashmi Yadav, Vincenzo Salpietro, Reza Maroofian, Rajan Patel, Rupa Radhakrishnan, Sanjay P Prabhu, Klaske Lichtenbelt, Helen Stewart, Yoshiko Murakami, Ulrike Löbel, Felice D'Arco, Emma Wakeling, Wendy Jones, Eleanor Hay, Sanjay Bhate, Thomas S Jacques, David M Mirsky, Matthew T Whitehead, Maha S Zaki, Tipu Sultan, Pasquale Striano, Anna C Jansen, Maarten Lequin, Linda S De Vries, Mariasavina Severino, Andrew C Edmondson, Lara Menzies, Philippe M Campeau, Henry Houlden, Amy Mctague, Stephanie Efthymiou, Kshitij Mankad

Faculty, Staff and Students Publications

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals; the largest single cohort to date. Core clinical features were developmental delay or …

Treatment Of Large Intracranial Aneurysms Using The Woven Endobridge (Web): A Propensity Score-Matched Analysis, Basel Musmar, Hamza Salim, Nimer Adeeb, Assala Aslan, Bahaa Aljeradat, Jose Diestro, Rachel Mclellan, Oktay Algin, Sherief Ghozy, Mahmoud Dibas, Sovann Lay, Adrien Guenego, Leonardo Renieri, Nicole Cancelliere, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Kevin Premat, Markus Möhlenbruch, Michael Kral, Justin Vranic, Charlotte Chung, Mohamed Salem, Ivan Lylyk, Paul Foreman, Jay Vachhani, Hamza Shaikh, Vedran Župančić, Muhammad Hafeez, Joshua Catapano, Muhammad Waqas, Vincent Tutino, Mohamed Ibrahim, Marwa Mohammed, M. Ozgur Ozates, Giyas Ayberk, James Rabinov, Yifan Ren, Clemens Schirmer, Mariangela Piano, Anna Kühn, Caterina Michelozzi, Stéphanie Elens, Robert Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie Nawka, Marios Psychogios, Christian Ulfert, Julian Spears, Brian Jankowitz, Jan-Karl Burkhardt, Ricardo Domingo, Thien Huynh, Juan Carlos Martinez-Gutierrez, Muhammed Essibayi, Sunil Sheth, Gary Spiegel, Rabih Tawk, Boris Lubicz, Pietro Panni, Ajit Puri, Guglielmo Pero, Erez Nossek, Eytan Raz, Monika Killer-Oberfalzer, Christoph Griessenauer, Hamed Asadi, Adnan Siddiqui, Allan Brook, David Altschul, Andrew Ducruet, Felipe Albuquerque, Robert Regenhardt, Christopher Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Mohammad A Aziz-Sultan, Stavropoula Tjoumakaris, Frédéric Clarençon, Nicola Limbucci, Hugo Cuellar-Saenz, Pascal Jabbour, Vitor Pereira, Aman Patel, Adam Dmytriw

Department of Neurosurgery Faculty Papers

The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence …

Iatrogenic Atrial Septal Defect After Mitraclip Transcatheter Edge-To-Edge Repair: To Close Or Not To Close??, Mariem Abdelsalam, Raghad Younus, Lamis F Abdalla, Abdelkader Almanfi

The Texas Heart Institute Journal

The evolution of percutaneous procedures that use transseptal puncture to treat left-sided structural heart disease has led to the emergence of iatrogenic atrial septal defects as a potential complication. These defects can result in hemodynamic decompensation and worsening clinical outcomes. Some iatrogenic atrial septal defects require immediate closure, others do not. This case report presents 2 patients who underwent transcatheter edge-to-edge mitral valve repair with transseptal puncture and required iatrogenic atrial septal defect closure (1 immediate and 1 delayed). The goal of this report is to highlight iatrogenic atrial septal defect assessment and the possible need for closure after transseptal …

Potential S1 Nerve Root Blocks Associated With Sacroiliac Joint Injections, Andrew Ng, Jesse Lou, Dajie Wang

Department of Anesthesiology Faculty Papers

BACKGROUND: Sacroiliac (SI) joint dysfunction is a common cause of lower back pain. The diagnosis of SI joint pain remains challenging. Sacroiliac joint injection remains the gold standard of diagnosis of SI joint pain as well as providing therapeutic effect. One complication related to SI joint injection is temporary numbness and weakness of the leg.

OBJECTIVES: To evaluate the anatomy of the SI joint and the flow of the contrast in the sacroiliac joint and to understand how local anesthetic can affect the nerve roots and cause temporary weakness and numbness of the leg.

METHODS: Patients who underwent SI joint …

Adaptive Fine-Tuning Based Transfer Learning For The Identification Of Mgmt Promoter Methylation Status, Erich Schmitz, Yunhui Guo, Jing Wang

Faculty, Staff and Student Publications

Background. Glioblastoma Multiforme (GBM) is an aggressive form of malignant brain tumor with a generally poor prognosis. O 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been shown to be a predictive bio-marker for resistance to treatment of GBM, but it is invasive and time-consuming to determine methylation status. There has been effort to predict the MGMT methylation status through analyzing MRI scans using machine learning, which only requires pre-operative scans that are already part of standard-of-care for GBM patients. Purpose. To improve the performance of conventional transfer learning in the identification of MGMT promoter methylation status, we developed a 3D SpotTune …