Digital Commons Network^™

Transplanting Hepatitis B Surface Antigen-Positive Livers In The United States: Outcomes And Opportunities, Cameron Goff, Anjiya Shaikh, Donghee Kim, Aijaz Ahmed, Carl Berg, Susanna Naggie, Fasiha Kanwal, George Cholankeril, Tzu-Hao Lee

Faculty, Staff and Students Publications

Livers from donors with positive hepatitis B surface antigens (HBsAg+) have been used to expand the donor pool; however, outcome data are limited. We aim to evaluate survival following liver transplant (LT) from HBsAg+ donors. Using the United Network for Organ Sharing registry, we identified HBsAg+ donors used for LT from 2009 to 2020. We used Kaplan-Meier survival and Cox proportional hazards regression to compare post-LT survival in hepatitis B virus-negative recipients who utilized HBsAg+ donors to propensity-matched cohorts who utilized other types of donors. From 2009-2020, 70 patients received HBsAg+ livers, and 58 of them did not carry a …

High Risk Lung Nodule: A Multidisciplinary Approach To Diagnosis And Management, Anoop P Ayyappan, Quillan Huang, Steven Bujarski, Mohammad S Jafferji, Ravi Ghanta, Alexander N Hanania, Donald R Lazarus

Faculty, Staff and Students Publications

Pulmonary nodules are often discovered incidentally during CT scans performed for other reasons. While the vast majority of nodules are benign, a small percentage may represent early-stage lung cancer with the potential for curative treatments. With the growing use of CT for both clinical purposes and lung cancer screening, the number of pulmonary nodules detected is expected to increase substantially. Despite well-established guidelines, many nodules do not receive proper evaluation due to a variety of factors, including inadequate coordination of care and financial and social barriers. To address this quality gap, novel approaches such as multidisciplinary nodule clinics and multidisciplinary …

Hunger Extends Lifespan By Modulating Histone Proteins

Faculty, Staff and Students Publications

No abstract provided.

Publisher Correction: A Weakly Structured Stem For Human Origins In Africa, Eileen G Hoal, Marlo Möller, Brenna M Henn, Simon Gravel

Faculty, Staff and Students Publications

No abstract provided.

Effects Of Cathepsin S Inhibition In The Age-Related Dry Eye Phenotype, Wolfgang Haap, Tiago Santos-Ferreira, Christoph Ullmer, Zhiyuan Yu, Cintia S De Paiva

Faculty, Staff and Students Publications

PURPOSE: Aged C57BL/6J (B6) mice have increased levels of cathepsin S, and aged cathepsin S (Ctss-/-) knockout mice are resistant to age-related dry eye. This study investigated the effects of cathepsin S inhibition on age-related dry eye disease.

METHODS: Female B6 mice aged 15.5 to 17 months were randomized to receive a medicated diet formulated by mixing the RO5461111 cathepsin S inhibitor or a standard diet for at least 12 weeks. Cornea mechanosensitivity was measured with a Cochet-Bonnet esthesiometer. Ocular draining lymph nodes and lacrimal glands (LGs) were excised and prepared for histology or assayed by flow cytometry to quantify …

Fixation Strategy Does Not Affect Risk Of Growth Disturbance After Surgical Treatment Of Pediatric Tibial Spine Fracture, Julien T Aoyama, Theodore J Ganley, Peter D Fabricant, Daniel W Green, Scott D Mckay, Gregory A Schmale, R Justin Mistovich, Soroush Baghdadi, Yi-Meng Yen, Henry B Ellis, Aristides I Cruz

Faculty, Staff and Students Publications

PURPOSE: To characterize growth abnormalities after surgical treatment of tibial spine fractures and to investigate risk factors for these abnormalities.

METHODS: A retrospective analysis of children who underwent treatment of tibial spine fractures between January 2000 and January 2019 was performed, drawing from a multicenter cohort among 10 tertiary care children's hospitals. The entire cohort of surgically treated tibial spine fractures was analyzed for incidence and risk factors of growth disturbance. The cohort was stratified into those who were younger than the age of 13 years at the time of treatment in order to evaluate the risk of growth disturbance …

Machine Learning Driven Index Of Tumor Multinucleation Correlates With Survival And Suppressed Anti-Tumor Immunity In Head And Neck Squamous Cell Carcinoma Patients, Germán Corredor, Sirvan Khalighi, Zelin Zhang, Bolin Song, Cheng Lu, Reetoja Nag, Vidya Sankar Viswanathan, Michael Gilkey, Kailin Yang, Shlomo A Koyfman, Deborah J Chute, Patricia Castro, James S Lewis, Anant Madabhushi, Vlad C Sandulache

Faculty, Staff and Students Publications

OBJECTIVES: Matching treatment intensity to tumor biology is critical to precision oncology for head and neck squamous cell carcinoma (HNSCC) patients. We sought to identify biological features of tumor cell multinucleation, previously shown by us to correlate with survival in oropharyngeal (OP) SCC using a machine learning approach.

MATERIALS AND METHODS: Hematoxylin and eosin images from an institutional OPSCC cohort formed the training set (D

RESULTS: MuNI correlated with overall survival. A multivariable nomogram that included MuNI, age, race, sex, T/N stage, and smoking status yielded a C-index of 0.65, and MuNI was prognostic of overall survival (2.25, 1.07-4.71, 0.03), …

Deployment Of Cisplatin In Veterans With Oropharyngeal Cancer: Toxicity And Impact On Oncologic Outcomes, Anita L Sabichi, George Chen, Albert Chen, Samantha N Little, Andrew T Huang, David J Hernandez, Vlad C Sandulache

Faculty, Staff and Students Publications

OBJECTIVE: Cisplatin forms the backbone of systemic chemotherapy treatment for oropharyngeal squamous cell carcinoma (OPSCC). The ideal cisplatin dosing regimen remains yet to be fully defined for achieving optimal efficacy and toxicity profiles in patients with comorbidity.

METHODS: We retrospectively reviewed oncologic and toxicity data for patients with OPSCC treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who initiated curative intent, definitive chemo-radiation with one of three single agent regimens: high dose (HD) cisplatin, low dose (LD) cisplatin or cetuximab.

RESULTS: Patients with HPV-associated tumors and nonsmokers demonstrated improved overall and disease-free survival along …

Comparison Of Random Urine Protein/Creatinine Ratio With 24-Hour Urine Protein In Suspected Pre-Eclampsia, Sridevi Devaraj

Faculty, Staff and Students Publications

INTRODUCTION: Proteinuria is one of the classical criteria for the diagnosis of pre-eclampsia. The gold standard remains the measurement of 24-h urine protein which is time consuming and prone to preanalytical errors. Random urine protein creatinine ratio (UPCR) is endorsed by clinical practice guidelines as a faster alternative. The aim of this study was to evaluate the correlation between the 24-h urine protein excretion and UPCR in the identification of proteinuria in suspected preeclamptic patients.

METHOD: A total of 51 women with suspected pre-eclampsia from the maternal fetal clinic of our institution were retrospectively studied. The correlation between the UPCR …

Seladelpar Efficacy And Safety At 3 Months In Patients With Primary Biliary Cholangitis: Enhance, A Phase 3, Randomized, Placebo-Controlled Study, Kris V Kowdley, John M Vierling, Cynthia Levy, Andreas E Kremer, Ehud Zigmond, Pietro Andreone, Stuart C Gordon, Christopher L Bowlus, Eric J Lawitz, Richard J Aspinall, Daniel S Pratt, Karina Raikhelson, Maria S Gonzalez-Huezo, Michael A Heneghan, Sook-Hyang Jeong, Alma L Ladrón De Guevara, Marlyn J Mayo, George N Dalekos, Joost P H Drenth, Ewa Janczewska, Barbara A Leggett, Frederik Nevens, Victor Vargas, Eli Zuckerman, Christophe Corpechot, Eduardo Fassio, Holger Hinrichsen, Pietro Invernizzi, Palak J Trivedi, Lisa Forman, David E J Jones, Stephen D Ryder, Mark G Swain, Alexandra Steinberg, Pol F Boudes, Yun-Jung Choi, Charles A Mcwherter, Enhance Study Group

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).

APPROACH AND RESULTS: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events.

CONCLUSIONS: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver …

Worldwide Exploration Of Renal Replacement Outcomes Collaborative In Kidney Disease (We-Rock), Dana Y Fuhrman, Stephen M Gorga, Theresa Mottes, Nicholas Ollberding, Zaccaria Ricci, Natalja L Stanski, David T Selewski, Danielle E Soranno, Michael Zappitelli, Huaiyu Zang, Katja M Gist

Faculty, Staff and Students Publications

INTRODUCTION: Continuous renal replacement therapy (CRRT) is used for the symptomatic management of acute kidney injury (AKI) and fluid overload (FO). Contemporary reports on pediatric CRRT are small and single center in design. Large international studies evaluating CRRT practice and outcomes are lacking. Herein, we describe the design of a multinational collaborative.

METHODS: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) is an international collaborative of pediatric specialists whose mission is to improve short- and long-term outcomes of children treated with CRRT. The aims of this multicenter retrospective study are to describe the epidemiology, liberation patterns, …

Applying Normal Accident Theory To Ideological And Nation-State-Sponsored Cybercrimes, Thomas J. Holt, National Counterterrorism Innovation, Technology, And Education Center

Reports, Projects, and Research

This project aims to explore a new perspective on cyberattacks by applying normal accident theory, typically used to analyze complex system failures, to the realm of cybersecurity. The goal is to gain insights into the factors contributing to cyberattacks and identify potential strategies to prevent and mitigate them. Applying normal accident theory to cyberattacks reveals that while complete prevention is challenging, focusing on human and organizational aspects of cybersecurity can significantly reduce risks. Encouraging adherence to best practices and establishing cybersecurity audit and compliance entities are critical steps toward a more resilient cybersecurity landscape.

Relationships Between Burnout, Isolation, Secondary Trauma, And Self-Compassion In Mental Health Providers, Michael Underiner Psyd, Rodger K. Bufford, Mary Peterson Phd, Daniel Rodriquez Psyd

Faculty Publications - Doctor of Psychology (PsyD) Program

Burnout is a common challenge among mental health professionals It is the main catalyst for professional misconduct (Morse, et al., 2012) and common among mental health professionals (Prime, et al., 2020; Sampiao, et al, 2021; Simionato & Simpson, 2018). COVID-19 increased social isolation, decreased social support, and strained family systems among mental health practitioners increasing risk (Prime, et al., 2020; Sampaio, et al., 2021). Social distancing also diminished systemic resources and increased reliance on personal resources for coping. Ongoing vicarious trauma increased, thus fostering burnout (McBride, et al., 2020; Shoji et al., 2016). Self-compassion is proposed as a possible solution …

Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus In Children, Nicholas S Abend, Cristina Barcia Aguilar, Marta Amengual-Gual, Anne Anderson, Brian L Appavu, J Nicholas Brenton, Jessica Carpenter, Kevin E Chapman, Justice Clark, William D Gaillard, Marina Gaínza-Lein, Joshua Goldstein, Howard Goodkin, Zachary Grinspan, Rejean M Guerriero, Paul S Horn, Linda Huh, Robert Kahoud, Sarah A Kelley, Eric H Kossoff, Kush Kapur, Yi-Chen Lai, B Oyinkan Marquis, Tiffani Mcdonough, Mohamad A Mikati, Lindsey Morgan, Edward Novotny, Adam P Ostendorf, Eric T Payne, Juan Piantino, James Riviello, Tristan Sands, Carl E Stafstrom, Robert C Tasker, Dmitry Tchapyjnikov, Alejandra Vasquez, Mark S Wainwright, Angus Wilfong, Korwyn Williams, Tobias Loddenkemper

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children.

METHODS: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort. We explored clinical …

Variation In Early Anakinra Use And Short-Term Outcomes In Multisystem Inflammatory Syndrome In Children, Sara K Sexson Tejtel, Margaret M Newhams, Suden Kucukak, Hillary Crandall, Aline B Maddux, Courtney M Rowan, Natasha B Halasa, Helen A Harvey, Charlotte V Hobbs, Mark W Hall, Michele Kong, Cassyanne L Aguiar, Jennifer E Schuster, Julie C Fitzgerald, Aalok R Singh, Kari Wellnitz, Ryan A Nofziger, Natalie Z Cvijanovich, Elizabeth H Mack, Adam J Schwarz, Sabrina M Heidemann, Jane W Newburger, Laura D Zambrano, Angela P Campbell, Manish M Patel, Adrienne G Randolph, Mary Beth F Son, Overcoming Covid Investigators

Faculty, Staff and Students Publications

OBJECTIVE: Evidence regarding effectiveness of interleukin-1 receptor antagonism in multisystem inflammatory syndrome in children (MIS-C) is lacking. We characterized variation in initial treatment with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy.

METHODS: We conducted a retrospective cohort study of MIS-C cases in a US surveillance registry from November 2020 to December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0-1) were identified. We compared cases in patients ages 2-20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids versus anakinra plus IVIG and/or glucocorticoids on days …

Clinical And Laboratory Predictors Of Dehydration Severity In Children With Diabetic Ketoacidosis, Michael J Stoner, Kathleen M Brown, Julie K Mcmanemy, Jeffrey E Schunk, Kimberly S Quayle, Lise E Nigrovic, Arleta Rewers, Sage R Myers, Jonathan E Bennett, Maria Y Kwok, Cody S Olsen, T Charles Casper, Simona Ghetti, Nathan Kuppermann, Pediatric Emergency Care Applied Research Network (Pecarn) Fluid Study Group

Faculty, Staff and Students Publications

STUDY OBJECTIVE: Our primary objective was to characterize the degree of dehydration in children with diabetic ketoacidosis (DKA) and identify physical examination and biochemical factors associated with dehydration severity. Secondary objectives included describing relationships between dehydration severity and other clinical outcomes.

METHODS: In this cohort study, we analyzed data from 753 children with 811 episodes of DKA in the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation Study, a randomized clinical trial of fluid resuscitation protocols for children with DKA. We used multivariable regression analyses to identify physical examination and biochemical factors associated with dehydration severity, and we …

Food For Thought: Remission Of Perianal Pediatric Crohn's Disease On Specific Carbohydrate Diet Monotherapy, Richard Kellermayer

Faculty, Staff and Students Publications

There is growing interest among patients about the specific carbohydrate diet (SCD) as a treatment for Crohn's disease. In the meantime, deep remission in patients using SCD as their sole treatment has not been documented. We report a case with perianal and ileocolonic Crohn's disease in whom SCD monotherapy successfully induced and maintained not only clinical, but also endoscopic, radiographic and histologic (ie, deep mucosal remission) remission as well.

Interim Results From An Ongoing, Open-Label, Single-Arm Trial Of Odevixibat In Progressive Familial Intrahepatic Cholestasis, Pier Luigi Calvo, Piotr Czubkowski, Buket Dalgic, Lorenzo D'Antiga, Angelo Di Giorgio, Özlem Durmaz, Emmanuel Gonzalès, Tassos Grammatikopoulos, Girish Gupte, Winita Hardikar, Roderick H J Houwen, Binita M Kamath, Saul J Karpen, Florence Lacaille, Alain Lachaux, Elke Lainka, Kathleen M Loomes, Cara L Mack, Jan P Mattsson, Patrick Mckiernan, Quanhong Ni, Hasan Özen, Sanjay R Rajwal, Bertrand Roquelaure, Eyal Shteyer, Etienne Sokal, Ronald J Sokol, Nisreen Soufi, Ekkehard Sturm, Mary Elizabeth Tessier, Wendy L Van Der Woerd, Henkjan J Verkade, Jennifer M Vittorio, Terese Wallefors, Natalie Warholic, Qifeng Yu, Patrick Horn, Lise Kjems

Faculty, Staff and Students Publications

BACKGROUND & AIMS: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis.

METHODS: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up …

Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma: Pathogenesis And Treatment, Tim F Greten, Mathias Heikenwälder, Hashem B El-Serag, Richard S Finn, Scott L Friedman

Faculty, Staff and Students Publications

Nonalcoholic fatty liver disease (NAFLD), including its more severe manifestation, nonalcoholic steatohepatitis (NASH), has a global prevalence of 20-25% and is a major public health problem. Its incidence is increasing in parallel to the rise in obesity, diabetes and metabolic syndrome. Progression from NASH to NASH-related hepatocellular carcinoma (HCC) (~2% of cases per year) is influenced by many factors, including the tissue and immune microenvironment, germline mutations in PNPLA3, and the microbiome. NASH-HCC has unique molecular and immune traits compared with other aetiologies of HCC and is equally prevalent in men and women. Comorbidities associated with NASH, such as obesity …

The Sunbeam Birth Cohort: Protocol Design, Cynthia Visness, Patricia C Fulkerson, Alkis Togias, Wendy Davidson, Susan Perry, Sanaz Hamrah, Agustin Calatroni, Katina Robinson, Lars Dunaway, Carla M Davis, Sara Anvari, Susan M Leong-Kee, Gurjit Khurana Hershey, Emily Defranco, Ashley Devonshire, Haejin Kim, Christine Joseph, Brent Davidson, Noel K Strong, Angela J Tsuang, Marion Groetch, Julie Wang, Jennifer Dantzer, Kim Mudd, Abimbola Aina, Wayne Shreffler, Qian Yuan, Virginia Simmons, Donald Y M Leung, Jessica Hui-Beckman, Jania Arcia Ramos, Sharon Chinthrajah, Virginia Winn, Tina Sindher, Stacie M Jones, Nirvana A Manning, Amy M Scurlock, Edwin Kim, Alison Stuebe, James E Gern, Anne Marie Singh, Jennifer Krupp, Robert A Wood

Faculty, Staff and Students Publications

BACKGROUND: Food allergy (FA) and atopic dermatitis (AD) are common conditions that often present in the first year of life. Identification of underlying mechanisms and environmental determinants of FA and AD is essential to develop and implement effective prevention and treatment strategies. Objectives: We sought to describe the design of the Systems Biology of Early Atopy (SunBEAm) birth cohort.

METHODS: Funded by the National Institute of Allergy and Infectious Diseases (NIAID) and administered through the Consortium for Food Allergy Research (CoFAR), SunBEAm is a US population-based, multicenter birth cohort that enrolls pregnant mothers, fathers, and their newborns and follows them …

Predicting Postfire Sediment Yields Of Small Steep Catchments Using Airborne Lidar Differencing, James J. Guilinger, Efi Foufoula-Georgiou, Andrew B. Gray, James T. Randerson, Padhraic Smyth, Nicolas C. Barth, Michael L. Goulden

AES Faculty Publications and Presentations

Predicting sediment yield from recently burned areas remains a challenge but is important for hazard and resource management as wildfire impacts increase. Here we use lidar-based monitoring of two fires in southern California, USA to study the movement of sediment during pre-rainfall periods and postfire periods of flooding and debris flows over multiple storm events. Using a data-driven approach, we examine the relative importance of terrain, vegetation, burn severity, and rainfall amounts through time on sediment yield. We show that incipient fire-activated dry sediment loading and pre-fire colluvium were rapidly flushed out by debris flows and floods but continued erosion …

Should A Negative Microsurgical Testicular Sperm Extraction Be Repeated Routinely?, Larry I Lipshultz, John P Lindsey, Juan R Torres-Anguiano, Michael L Eisenberg

Faculty, Staff and Students Publications

No abstract provided.

Real-Time, Deep-Learning Aided Lensless Microscope, Jacob T Robinson

Faculty, Staff and Students Publications

Traditional miniaturized fluorescence microscopes are critical tools for modern biology. Invariably, they struggle to simultaneously image with a high spatial resolution and a large field of view (FOV). Lensless microscopes offer a solution to this limitation. However, real-time visualization of samples is not possible with lensless imaging, as image reconstruction can take minutes to complete. This poses a challenge for usability, as real-time visualization is a crucial feature that assists users in identifying and locating the imaging target. The issue is particularly pronounced in lensless microscopes that operate at close imaging distances. Imaging at close distances requires shift-varying deconvolution to …

Robotic Surgery And Hospital Reimbursement, Ali M Aral, Jessie Z Yu, Edward Reece, Sebastian Winocour

Faculty, Staff and Students Publications

The field of plastic surgery remains at the forefront of technological and surgical innovation. However, the promising applications of robotics in plastic surgery must be thoughtfully balanced with hospital finances and reimbursements. Robotic systems have been studied extensively across multiple surgical disciplines and across diverse health care systems. The results show that there may be equal or better patient outcomes than alternatives. In an era where fiscal responsibility in health care is a top priority, thoughtful budgeting and spending must be considered and revisited frequently to attain sustainable organizational models that ensure appropriate use of robotic technology.

Cognitive Ergonomics: A Review Of Interventions For Outpatient Practice

Faculty, Staff and Students Publications

Doctoring is difficult mental work, involving many cognitively demanding processes such as diagnosing, decision-making, parallel processing, communicating, and managing the emotions of others. According to cognitive load theory (CLT), working memory is a limited cognitive resource that can support a finite amount of cognitive load. While the intrinsic cognitive load is the innate load associated with a task, the extraneous load is generated by inefficiency or suboptimal work conditions. Causes of extraneous cognitive load in healthcare include inefficiency, distractions, interruptions, multitasking, stress, poor communication, conflict, and incivility. High levels of cognitive load are associated with impaired function and an increased …

Retrospective Review Of 181 Patients With Pathologic Vertebral Compression Fractures, Beatrice A Morrow, Brian G Smith, Nicole I Montgomery

Faculty, Staff and Students Publications

Background: Compression fractures are often associated with lower energy trauma and may occur in the setting of abnormal bone health associated with genetic disorders and endocrine disorders, neoplastic disease, infection, and inflammatory disorders. There is no significant series in the literature describing the prevalence or etiology of pathologic pediatric compression fractures.

Methods: IRB-approved retrospective study was performed at a tertiary children's hospital from 2012-2022. Patients < 18 years old diagnosed with atraumatic vertebral compression fractures were included and reviewed for demographics, underlying diagnosis/comorbidity, presentation, mobility, deformities, imaging data, treatments, and outcomes.

Results: 181 patients (54% Male) were included with mean age 14.17 years and follow-up of 20 months. A compression fracture was the presenting symptom of an underlying diagnosis in 32% of patients, and 21% of …

H3k36 Methylation Maintains Cell Identity By Regulating Opposing Lineage Programmes, Justin Langerman, Simona Cristea, Lai Ping Wong, Aaron J Huebner, Jocelyn Charlton, Weixian Deng, Chuck Haggerty, Ruslan I Sadreyev, Alexander Meissner, Franziska Michor, Kathrin Plath, Konrad Hochedlinger

Faculty, Staff and Students Publications

The epigenetic mechanisms that maintain differentiated cell states remain incompletely understood. Here we employed histone mutants to uncover a crucial role for H3K36 methylation in the maintenance of cell identities across diverse developmental contexts. Focusing on the experimental induction of pluripotency, we show that H3K36M-mediated depletion of H3K36 methylation endows fibroblasts with a plastic state poised to acquire pluripotency in nearly all cells. At a cellular level, H3K36M facilitates epithelial plasticity by rendering fibroblasts insensitive to TGFβ signals. At a molecular level, H3K36M enables the decommissioning of mesenchymal enhancers and the parallel activation of epithelial/stem cell enhancers. This enhancer rewiring …

Impact Of Prior Therapies And Subsequent Transplantation On Outcomes In Adult Patients With Relapsed Or Refractory B-Cell Acute Lymphoblastic Leukemia Treated With Brexucabtagene Autoleucel In Zuma-3, Bijal D Shah, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) …

Perceived Utility Of Intracranial Pressure Monitoring In Traumatic Brain Injury: A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis And Recommendations, Randall M. Chesnut, Michael Diringer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed.

OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion.

METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). …

Wildfire Risk Governance From The Bottom Up: Linking Local Planning Processes In Fragmented Landscapes, Matthew Hamilton, Max Nielsen-Pincus, Cody Evers

Environmental Science and Management Faculty Publications and Presentations

The growing scale of natural hazards highlights the need for models of governance capable of addressing risk across administrative boundaries. However, risk governance systems are often fragmented, decentralized, and sustained by informal linkages among local-level risk mitigation planning processes. Improving resilience to the effects of environmental change requires a better understanding of factors that contribute to these linkages. Using data on the patterns of participation of 10,199 individual stakeholders in 837 community wildfire protection plans (CWPPs) within the western U.S., we document the emergence of a locally clustered but spatially extensive wildfire risk governance network. Our evaluation of factors that …