Medicine and Health Sciences Commons^™

Huntington Study Group's Neuropsychology Working Group: Implementing Non-Motor Diagnostic Criteria, Ciaran M Considine, M Agustina Rossetti, Victor A Del Bene, Kendra Anderson, Sharlet A Anderson, Andrea S Celka, Mary C Edmondson, Amelia L Nelson-Sheese, Adam Piccolino, Antonio L Teixeira, Julie C Stout

Faculty, Staff and Student Publications

Background: The clinical diagnosis of manifest Huntington's disease (HD) relies on a high level of clinical confidence (99% confidence) of HD-consistent motor signs. Longitudinal data have reliably identified cognitive and behavioral dysfunction predating clinical motor diagnosis by up to 15 years. Reliance on motor signs to establish a diagnosis of HD increases risk of early misdiagnosis or delayed diagnosis. Clinical neuropsychologists are uniquely positioned to advise on the clinical application of the Movement Disorder Society Task Force's recently proposed non-motor diagnostic criteria for HD.

Objectives: To provide (1) a recommended clinical approach toward non-motor diagnostic criteria in persons with HD …

Relapse Recovery In Relapsing-Remitting Multiple Sclerosis: An Analysis Of The Combirx Dataset, Marcus W Koch, Ester Moral, Luis Brieva, Jop Mostert, Eva Mm Strijbis, Jacynthe Comtois, Pavle Repovic, James D Bowen, Jerry S Wolinsky, Fred D Lublin, Gary Cutter

Faculty, Staff and Student Publications

BACKGROUND: Clinical relapses are the defining feature of relapsing forms of multiple sclerosis (MS), but relatively little is known about the time course of relapse recovery.

OBJECTIVE: The aim of this study was to investigate the time course of and patient factors associated with the speed and success of relapse recovery in people with relapsing-remitting MS (RRMS).

METHODS: Using data from CombiRx, a large RRMS trial (clinicaltrials.gov identifier NCT00211887), we measured the time to recovery from the first on-trial relapse. We used Kaplan-Meier survival analyses and Cox regression models to investigate the association of patient factors with the time to …

Relationship Between Occupational Safety And Health Policy Principles, Organizational Action On Work-Related Stress And The Psychosocial Work Environment In Italy, Stavroula Leka, Luis Torres, Aditya Jain, Cristina Di Tecco, Simone Russo, Sergio Iavicoli

Faculty, Staff and Student Publications

BACKGROUND: It is acknowledged that legislation acts as a motivator for organizational action on psychosocial risks. Our study aims to provide evidence on the relationship between key occupational safety and health (OSH) policy principles and organizational action on work-related stress, and, in turn, with reported employee job demands and resources and their experience of work-related stress. We focus on Italy where specific legislation and practices on work-related stress were introduced in 2008 which are underpinned by these key OSH policy principles.

METHODS: Secondary analysis of the Italian samples from the employer ESENER-2 and employee 6th EWCS surveys was conducted, using …

Systematic Review And Meta-Analysis Of The Association Between Radiation Therapy Treatment Volume And Patient Outcomes, Jerry Ye Aung Kyaw, Alice Rendall, Erin F Gillespie, Tom Roques, Laurence Court, Yolande Lievens, Alison C Tree, Chris Frampton, Ajay Aggarwal

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Purpose: Evidence of a volume-outcome association in cancer surgery has shaped the centralization of cancer services; however, it is unknown whether a similar association exists for radiation therapy. The objective of this study was to determine the association between radiation therapy treatment volume and patient outcomes.

Methods and materials: This systematic review and meta-analysis included studies that compared outcomes of patients who underwent definitive radiation therapy at high-volume radiation therapy facilities (HVRFs) versus low-volume facilities (LVRFs). The systematic review used Ovid MEDLINE and Embase. For the meta-analysis, a random effects model was used. Absolute effects and hazard ratios (HRs) were …

Outcome Of Philadelphia Chromosome-Positive Chronic Myeloid Leukemia In The United States Since The Introduction Of Imatinib Therapy–The Surveillance, Epidemiology, And End Results Database, 2000–2019, Koji Sasaki, Fadi G Haddad, Nicholas J Short, Nitin Jain, Ghayas Issa, Elias Jabbour, Hagop Kantarjian

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Background: Since the introduction of BCR::ABL1 tyrosine kinase inhibitors (TKIs) in 2000, the treatment of Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) has improved significantly.

Methods: This study aimed to evaluate Ph-positive CML outcomes in the TKI therapy era, considering factors like age, ethnicity, and income. Using the Surveillance, Epidemiology, and End Results (SEER) database, 2857 patients with Ph-positive CML diagnosed from 2000 to 2019 were analyzed.

Results: The overall 5-year survival rates in Ph-positive CML increased to above 80%, compared with pre-TKIs historical data reporting 5-year overall survival (OS) rates of less than 50%. The 5-year OS rate was …

An Update On The Management Of Advanced Phase Chronic Myeloid Leukemia, Nicholas J Short, Jayastu Senapati, Elias Jabbour

Faculty, Staff and Student Publications

Purpose of review: While most patients with chronic myeloid leukemia (CML) present in a chronic phase and are expected to have a normal life expectancy, some patients present with or progress to a more aggressive accelerated phase (AP) or blast phase (BP) of CML. Herein, we discuss the diagnostic considerations of advanced phase CML and review its contemporary management.

Recent findings: Later-generation, more potent BCR::ABL1 tyrosine kinase inhibitors (TKIs) such as ponatinib may result in superior outcomes in patients with advanced phase CML. For CML-BP, combination approaches directed against the blast immunophenotype appear superior to TKI monotherapy. The role of …

Evaluation Of Potential Role Of R-Loop And G-Quadruplex Dna In The Fragility Of C-Myc During Chromosomal Translocation Associated With Burkitt's Lymphoma, Nitu Kumari, Kohal Das, Shivangi Sharma, Sumedha Dahal, Sagar Sanjiv Desai, Urbi Roy, Anju Sharma, Meghana Manjunath, Vidya Gopalakrishnan, S T Retheesh, Saniya M Javadekar, Bibha Choudhary, Sathees C Raghavan

Faculty, Staff and Student Publications

t(8;14) translocation is the hallmark of Burkitt's lymphoma and results in c-MYC deregulation. During the translocation, c-MYC gene on chromosome 8 gets juxtaposed to the Ig switch regions on chromosome 14. Although the promoter of c-MYC has been investigated for its mechanism of fragility, little is known about other c-MYC breakpoint regions. We have analyzed the translocation break points at the exon 1/intron 1 of c-MYC locus from patients with Burkitt's lymphoma. Results showed that the breakpoint region, when present on a plasmid, could fold into an R-loop confirmation in a transcription-dependent manner. Sodium bisulfite modification assay revealed significant single-strandedness …

The Risk Index As A Basis For Risk/Benefit Analyses And Protocol Optimization In Diagnostic Nuclear Imaging, Juan C Ocampo Ramos, Lukas M Carter, Justin L Brown, Harry Marquis, Carlos F Uribe, Pat B Zanzonico, Wesley E Bolch, Adam L Kesner

Faculty, Staff and Student Publications

Background: Potential risk associated with low-dose radiation exposures is often expressed using the effective dose (E) quantity. Other risk-related quantities have been proposed as alternatives. The recently introduced risk index (RI) shares similarities with E but expands the metric to incorporate medical imaging-appropriate risks factors including patient-specific size, age, and sex.

Purpose: The aim of this work is to examine the RI metric for quantifying stochastic radiation risk and demonstrate its applications in nuclear imaging. The advantages in this improved metric may help the field progress toward stratified risk consideration in the course of patient management, improve efforts for procedure …

Droid: Dose-Ranging Approach To Optimizing Dose In Oncology Drug Development, Beibei Guo, Ying Yuan

Faculty, Staff and Student Publications

In the era of targeted therapy, there has been increasing concern about the development of oncology drugs based on the "more is better" paradigm, developed decades ago for chemotherapy. Recently, the US Food and Drug Administration (FDA) initiated Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development. To accommodate this paradigm shifting, we propose a dose-ranging approach to optimizing dose (DROID) for oncology trials with targeted drugs. DROID leverages the well-established dose-ranging study framework, which has been routinely used to develop non-oncology drugs for decades, and bridges it with established oncology dose-finding designs to …

Corrigendum To “Epstein-Barr-Virus-Positive Large B-Cell Lymphoma Associated With Breast Implants: An Analysis Of Eight Patients Suggesting A Possible Pathogenetic Relationship” [Modern Pathology 34 (2021) 2154–2167], L Jeffrey Medeiros, Mario L Marques-Piubelli, Valentina F I Sangiorgio, Roberto Ruiz-Cordero, Francisco Vega, Andrew L Feldman, Jennifer R Chapman, Mark W Clemens, Kelly K Hunt, Mark G Evans, Christine Khoo, Stephen Lade, Mark Silberman, Jerzy Morkowski, Edward M Pina, Daniel C Mills, Christopher M Bates, Winston B Magno, Aliyah R Sohani, Beth A Sieling, Joseph M O'Donoghue, Chris M Bacon, Neill Patani, Despina Televantou, Suzanne D Turner, Laura Johnson, Fiona Macneill, Andrew C Wotherspoon, Swaminathan P Iyer, Luis E Malpica, Keyur P Patel, Jie Xu, Roberto N Miranda

Faculty, Staff and Student Publications

No abstract provided.

The Clinicopathologic Features And Molecular Signatures Of Blastoid High-Grade B Cell Lymphoma, Not Otherwise Specified, Lianqun Qiu, Pei Lin, Mahsa Khanlari, Jie Xu, Evan N Cohen, Sofia Garces, Roberto N Miranda, Wei Wang, Hong Fang, Carlos E Bueso-Ramos, L Jeffrey Medeiros, Shaoying Li

Faculty, Staff and Student Publications

A small subset of high-grade B-cell lymphoma (HGBL) with blastoid morphology remains poorly understood. We assessed 55 cases of blastoid HGBL, not otherwise specified (NOS) and compared their clinicopathologic characteristics with those of 81 non-blastoid HGBL-NOS and 62 blastoid HGBL with MYC and BCL2, with or without BCL6 rearrangements (double/triple-hit lymphoma [D/THL]). Patients with blastoid HGBL-NOS showed similar clinicopathologic features to patients with blastoid D/THLs and non-blastoid HGBL-NOS, except more frequently with a history of low-grade B-cell lymphoma, bone marrow involvement, and BCL2 rearrangement (P < .05) compared to the latter. MYC rearrangement (MYC-R), detected in 40% of blastoid HGBL-NOS, was associated with aggressive clinicopathologic features and poorer overall survival, even worse than that of blastoid D/THL (P < .05). Transcriptome profiling revealed a distinct gene expression pattern with differentially expressed genes enriched in MYC and P53-targeted genes in MYC-R blastoid HGBL-NOS. Fifty-two percent of blastoid HGBL-NOS had a double hit-like signature, similar to non-blastoid HGBL-NOS (P = .73). The overall survival of the blastoid HGBL-NOS group was similar to that of the blastoid D/THL group but appeared poorer than that of its non-blastoid counterparts (P = .07). Taken together, blastoid HGBL-NOS is an aggressive B-cell lymphoma that shares overlapping clinicopathologic and genetic features with non-blastoid HGBL-NOS. MYC-R in patients with blastoid HGBL-NOS identifies a highly aggressive subgroup with distinct aggressive clinicopathologic features, unique molecular signatures, and a dismal clinical outcome.

Radiation-Induced Innate Neutrophil Response In Tumor Is Mediated By The Cxcls/Cxcr2 Axis, Faya Zhang, Oscar Mulvaney, Erica Salcedo, Subrata Manna, James Z Zhu, Tao Wang, Chul Ahn, Laurentiu M Pop, Raquibul Hannan

Faculty, Staff and Student Publications

The early events that lead to the inflammatory and immune-modulatory effects of radiation therapy (RT) in the tumor microenvironment (TME) after its DNA damage response activating the innate DNA-sensing pathways are largely unknown. Neutrophilic infiltration into the TME in response to RT is an early innate inflammatory response that occurs within 24-48 h. Using two different syngeneic murine tumor models (RM-9 and MC-38), we demonstrated that CXCR2 blockade significantly reduced RT-induced neutrophilic infiltration. CXCR2 blockade showed the same effects on RT-induced tumor inhibition and host survival as direct neutrophil depletion. Neutrophils highly and preferentially expressed CXCR2 compared to other immune …

Firearm Injury Prevention, Kelsey A B Gastineau, Sandra Mckay

Faculty, Staff and Student Publications

Firearms are the leading cause of death for US youth, overtaking motor vehicle collisions in 2020. Approximately 65% are due to homicide, 30% are due to suicide, 3.5% are due to unintentional injuries, 2% are undetermined intent, and 0.5% are from legal interventions. In homes with firearms, the likelihood of unintentional death, suicide, and homicide is three to four times higher than those without firearms. Secure storage of firearms, having them locked, unloaded, and separate from ammunition can prevent unintentional firearm injuries.

Comparative Study Between Antegrade Flexible Ureteroscopy And Reterograde Intrarenal Surgery In The Management Of Impacted Upper Ureteric Stones 15 Cm Or Larger, Ahmed Mohey, Ahmed A Abdelfattah, Ahmed E Mohammed, Abdelmoniem Marzouk, Amr S El-Dakhakhny

Faculty, Staff and Student Publications

OBJECTIVE: To prospectively investigate the safety and efficacy of antegrade flexible ureteroscopy (FURS) with the following criteria (supine, ultrasonic guided puncture through lower calyx with 14 fr tract, tubeless) versus retrograde intrarenal surgery (RIRS) in the management of large impacted upper ureteric stones ≥ 1.5 cm.

PATIENTS AND METHODS: This study recruited 61 patients with single large impacted upper ureteric stone of ≥ 1.5 cm. The patients were randomly allocated to two groups. Group A, included 31 patients who treated by antegrade FURS, all patients were put in supine modified galadako Valdivia position and the renal access is reached by …

The Application Of Simultaneous Mainstem Bronchus Dilation With Pulmonary Artery Stenting In The Context Of Hypoplastic Left Heart Syndrome, Sylwia Hasterok, Thomas G Scott, Devin G Roller, Adam Spencer, Arun B Dutta, Kizhakke M Sathyan, Daniel E Frigo, Michael J Guertin, Daniel Gioeli

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The clinical success of combined androgen deprivation therapy (ADT) and radiotherapy (RT) in prostate cancer created interest in understanding the mechanistic links between androgen receptor (AR) signaling and the DNA damage response (DDR). Convergent data have led to a model where AR both regulates, and is regulated by, the DDR. Integral to this model is that the AR regulates the transcription of DDR genes both at a steady state and in response to ionizing radiation (IR). In this study, we sought to determine which immediate transcriptional changes are induced by IR in an AR-dependent manner. Using PRO-seq to quantify changes …

Genome-Wide Significant Risk Loci For Mood Disorders In The Old Order Amish Founder Population, Elizabeth M Humphries, Kwangmi Ahn, Rachel L Kember, Fabiana L Lopes, Evelina Mocci, Juan M Peralta, John Blangero, David C Glahn, Fernando S Goes, Peter P Zandi, Peter Kochunov, Cristopher Van Hout, Alan R Shuldiner, Toni I Pollin, Braxton D Mitchell, Maja Bucan, L Elliot Hong, Francis J Mcmahon, Seth A Ament

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Genome-wide association studies (GWAS) of mood disorders in large case-control cohorts have identified numerous risk loci, yet pathophysiological mechanisms remain elusive, primarily due to the very small effects of common variants. We sought to discover risk variants with larger effects by conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish (OOA, n = 1,672). Our analysis revealed four genome-wide significant risk loci, all of which were associated with >2-fold relative risk. Quantitative behavioral and neurocognitive assessments (n = 314) revealed effects of risk variants on sub-clinical depressive symptoms and information processing speed. Network …

Sonographic Characteristics And Pathology Correlation Of Breast Imaging Reporting And Data System (Bi-Rads) Category 4 Lesions, Poonum Khan, Imrana Masroor, Muhammad S Alam, Abdus Salam, Yasir Ali, Muhammad Salman Khan

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Introduction: The Breast Imaging-Reporting and Database System (BI-RADS) category 4 is designated for breast lumps that do not display the typical features of malignancy but still raise enough suspicion to warrant a recommendation for a biopsy, as malignancy cannot be ruled out through imaging alone. The main objective of this study was to investigate the sonographic characteristics and pathology correlation of BI-RADS 4 breast lesions and determine the positive predictive rate of BI-RADS 4 lesions in diagnosing breast cancer, using histopathology as the gold standard.

Methods: This was a cross-sectional study conducted at the Department of Radiology, Aga Khan University …

Cortical Thickness Is Related To Variability In Heritage Bilingual Language Proficiency, My V H Nguyen, Kelly A Vaughn, Hannah Claussenius-Kalman, Pilar Archila-Suerte, Arturo E Hernandez

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Research suggests that bilingual experience is associated with gray matter changes, such that initial language gains are associated with expansion and language expertise is associated with renormalization. Previous studies on language proficiency development primarily focused on between-subjects, quasiexperimental comparisons of monolinguals and bilinguals. This study proposes a new paradigm to examine language expertise and cortical thickness within heritage bilinguals (

Genomic Profiles And Clinical Outcomes Of Penile Squamous Cell Carcinoma With Elevated Tumor Mutational Burden, Andrea Necchi, Philippe E Spiess, Tiago Costa De Padua, Roger Li, Petros Grivas, Richard S P Huang, Douglas I Lin, Natalie Danziger, Jeffrey S Ross, Joseph M Jacob, Rebecca A Sager, Alina Basnet, Gerald Li, Ryon P Graf, Dean C Pavlick, Gennady Bratslavsky

Faculty, Staff and Student Publications

IMPORTANCE: Tumor mutational burden (TMB) is a putative biomarker of efficacy for immune checkpoint inhibitor (ICI) therapies of solid tumors, but not specifically for penile squamous cell carcinoma (PSCC).

OBJECTIVE: To characterize biomarker features and ICI therapy outcomes associated with high TMB in PSCC in the routine clinical practice setting.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, 397 PSCC cases were analyzed to identify genomic alterations in more than 300 cancer-associated genes and genomic signatures, including TMB, using a hybrid capture-based comprehensive genomic profiling assay. Tumor mutational burden was categorized as low ([mut/Mb]), high (10-19 mut/Mb), or very high …

Evaluation Of The Quality Of Thyroidectomy-Related Posts On A Video-Based Social Media Platform, Yun J Kim, Matthew Lin, Ryan J Davis, Oluwatobiloba Ayo-Ajibola, Daniel Kwon, Kevin Hur

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate the quality of thyroidectomy-related posts on TikTok, the fastest-growing social media platform worldwide.

METHODS: Videos posted from April 2020 to September 2022 were queried on TikTok using the search terms "thyroidsurgery," "thyroidectomy," and "thyroidremoval." Two reviewers recorded thematic, demographic, and performance data of these posts. The DISCERN instrument was used to evaluate the quality and reliability of the information contained in the videos. Descriptive statistics were used to characterize post-submitter demographics and video content. Simple and multiple linear regression analyses were used to evaluate the association between DISCERN scores and video characteristics. Univariate analysis of variance was …

Will You Go The Distance? A Satisfaction Survey Of Telemedicine In Sexual Medicine, Gal Saffati, Taher Naeem, Jordan Kassab, Daniela Orozco Rendon, Charles Green, Larry I Liphsultz, Mohit Khera

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BACKGROUND: The success of telemedicine depends on patient satisfaction with the care that they receive, which is impacted by the ease of use of the technology, quality of the connection, and perceived effectiveness of care.

AIM: The study sought to evaluate patient satisfaction with telemedicine services in a high-volume andrology clinic.

METHODS: We included all patients who had a telemedicine appointment between January 1, 2020, and August 22, 2022. Demographic information was gathered, and a satisfaction survey was conducted using REDCap software. Data were grouped into 2 age categories, with ≥50 years as the cutoff (19-50 years; >50 years). The …

“Be Sustainable”: Eosc-Life Recommendations For Implementation Of Fair Principles In Life Science Data Handling, Romain David, Arina Rybina, Jean-Marie Burel, Jean-Karim Heriche, Pauline Audergon, Jan-Willem Boiten, Frederik Coppens, Sara Crockett, Katrina Exter, Sven Fahrner, Maddalena Fratelli, Carole Goble, Philipp Gormanns, Tobias Grantner, Björn Grüning, Kim Tamara Gurwitz, John M Hancock, Henriette Harmse, Petr Holub, Nick Juty, Geoffrey Karnbach, Emma Karoune, Antje Keppler, Jessica Klemeier, Carla Lancelotti, Jean-Luc Legras, Allyson L Lister, Dario Livio Longo, Rebecca Ludwig, Bénédicte Madon, Marzia Massimi, Vera Matser, Rafaele Matteoni, Michaela Th Mayrhofer, Christian Ohmann, Maria Panagiotopoulou, Helen Parkinson, Isabelle Perseil, Claudia Pfander, Roland Pieruschka, Michael Raess, Andreas Rauber, Audrey S Richard, Paolo Romano, Antonio Rosato, Alex Sánchez-Pla, Susanna-Assunta Sansone, Ugis Sarkans, Beatriz Serrano-Solano, Jing Tang, Ziaurrehman Tanoli, Jonathan Tedds, Harald Wagener, Martin Weise, Hans V Westerhoff, Rudolf Wittner, Jonathan Ewbank, Niklas Blomberg, Philip Gribbon

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The main goals and challenges for the life science communities in the Open Science framework are to increase reuse and sustainability of data resources, software tools, and workflows, especially in large-scale data-driven research and computational analyses. Here, we present key findings, procedures, effective measures and recommendations for generating and establishing sustainable life science resources based on the collaborative, cross-disciplinary work done within the EOSC-Life (European Open Science Cloud for Life Sciences) consortium. Bringing together 13 European life science research infrastructures, it has laid the foundation for an open, digital space to support biological and medical research. Using lessons learned from …

Empagliflozin In Patients Admitted To Hospital With Covid-19 (Recovery): A Randomised, Controlled, Open-Label, Platform Trial, Recovery Collaborative Group

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BACKGROUND: Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

METHODS: In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge …

Behavioral Or Neuropsychiatric Symptoms Of Alzheimer’S Disease: From Psychopathology To Pharmacological Management, Antonio Lucio Teixeira, Natalia Pessoa Rocha, Jennifer Gatchel

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Neuropsychiatric or behavioral symptoms of dementia encompass a series of disorders, such as anxiety, depression, apathy, psychosis, and agitation, all commonly present in individuals living with dementia. While they are not required for the diagnosis of Alzheimer's disease (AD), they are ubiquitously present in all stages of the disease, contributing to negative clinical outcomes, including cognitive decline, functional disability, and caregiver burden. Neuropsychiatric symptoms have been conceptualized not only as risk factors but as clinical markers of decline along the AD spectrum. The concept of "mild behavioral impairment", the behavioral correlate of mild cognitive impairment, has been proposed within this …

The Hidden Impact Of Orthopedic Surgeries: Examining The Psychological Consequences, Emily R Erwin, Keisha S Ray, Shuyang Han

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Orthopedic surgery is commonly considered "quality of life care," as most orthopedic procedures have been shown to provide excellent pain relief and successful surgical outcomes for patients. Although orthopedic surgeries continue to improve patients' functional outcomes through modern surgical techniques and preoperative psychological screening, variation in patient function persists in current studies. Sub-optimal function in patients has been shown to be associated with emotional health burdens, such as anxiety and depression. Previous research has found that preoperative psychological conditions could negatively affect patients' functional outcomes. However, these studies were limited in that they did not examine novel psychological repercussions in …

Ezh2 Cooperates With Brd4-Nut To Drive Nut Carcinoma Growth By Silencing Key Tumor Suppressor Genes, Yeying Huang, R Taylor Durall, Nhi M Luong, Hans J Hertzler, Julianna Huang, Prafulla C Gokhale, Brittaney A Leeper, Nicole S Persky, David E Root, Praju V Anekal, Paula D L M Montero Llopis, Clement N David, Jeffery L Kutok, Alejandra Raimondi, Karan Saluja, Jia Luo, Cynthia A Zahnow, Biniam Adane, Kimberly Stegmaier, Catherine E Hawkins, Christopher Ponne, Quan Le, Geoffrey I Shapiro, Madeleine E Lemieux, Kyle P Eagen, Christopher A French

Faculty, Staff and Student Publications

NUT carcinoma (NC) is an aggressive carcinoma driven by the BRD4-NUT fusion oncoprotein, which activates chromatin to promote expression of pro-growth genes. BET bromodomain inhibitors (BETi) are a promising treatment for NC that can impede BRD4-NUT’s ability to activate genes, but the efficacy of BETi as monotherapy are limited. Here, we demonstrated that EZH2, which silences genes through establishment of repressive chromatin, is a dependency in NC. Inhibition of EZH2 with the clinical compound tazemetostat (taz) potently blocked growth of NC cells. Epigenetic and transcriptomic analysis revealed that taz reversed the EZH2-specific H3K27me3 silencing mark and restored expression of multiple …

Resuscitative Endovascular Balloon Occlusion Of The Aorta And Resuscitative Thoracotomy Are Associated With Similar Outcomes In Traumatic Cardiac Arrest, Ezra Y Koh, Erin E Fox, Charles E Wade, Thomas M Scalea, Charles J Fox, Ernest E Moore, Bryan C Morse, Kenji Inaba, Eileen M Bulger, David E Meyer

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Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive alternative to resuscitative thoracotomy (RT) for patients with hemorrhagic shock. However, the potential benefits of this approach remain subject of debate. The aim of this study was to compare the outcomes of REBOA and RT for traumatic cardiac arrest.

Methods: A planned secondary analysis of the United States Department of Defense-funded Emergent Truncal Hemorrhage Control study was performed. Between 2017 and 2018, a prospective observational study of noncompressible torso hemorrhage was conducted at six Level I trauma centers. Patients were dichotomized by REBOA or RT, and baseline …

Transcarotid Stenting Of Extracranial Carotid Artery Aneurysm With Covered Stents And Flow Reversal, S Taha Zaidi, Mitchell J George, Tommaso Cambiaghi, Naveed Saqib, Daniel Miles, Shihuan Wang, Stuart Harlin

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Introduction: An extracranial carotid artery aneurysm (ECAA) is a rare pathology comprising < 1% of all arterial aneurysms. The etiology includes trauma, previous surgery, radiation, and infection. Treatment of ECAAs has evolved from open repair to endovascular repair with stenting. Reports of endovascular repair describe the transfemoral approach; however, little more than case reports are available describing the transcarotid approach for ECAAs. In this study, we describe a cohort of patients who safely underwent transcarotid repair of ECAAs.

Methods: We performed a retrospective medical record review of all cases of transcarotid stenting using covered stents for a carotid aneurysm within 11 different hospitals within the Memorial Hermann Health System from December 2019 through December 2022. Technical success is defined as coverage of the aneurysm with no endoleak. We report the patient demographics, clinical presentation, intraoperative metrics, and outcomes.

Results: Seven patients underwent transcarotid covered stent placement using flow reversal for neurologic protection. Their average age was 65 years, and four of the seven patients were men. …

Guidelines For Prehospital Management Of Traumatic Brain Injury 3rd Edition: Executive Summary, Gregory W J Hawryluk, Al Lulla, Randy Bell, Andy Jagoda, Halinder S Mangat, Bentley J Bobrow, Jamshid Ghajar

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Prehospital care markedly influences outcome from traumatic brain injury, yet it remains highly variable. The Brain Trauma Foundation's guidelines informing prehospital care, first published in 2002, have sought to identify and disseminate best practices. Many of its recommendations relate to the management of airway, breathing and circulation, and infrastructure for this care. Compliance with the second edition of these guidelines has been associated with significantly improved survival. A working group developed evidence-based recommendations informing assessment, treatment, and transport decision-making relevant to the prehospital care of brain injured patients. A literature search spanning May 2005 to January 2022 supplemented data contained …

Nurse Care Management For Opioid Use Disorder Treatment: The Proud Cluster Randomized Clinical Trial, Paige D Wartko, Jennifer F Bobb, Denise M Boudreau, Abigail G Matthews, Jennifer Mccormack, Amy K Lee, Hongxiang Qiu, Onchee Yu, Noorie Hyun, Abisola E Idu, Cynthia I Campbell, Andrew J Saxon, David S Liu, Andrea Altschuler, Jeffrey H Samet, Colleen T Labelle, Mohammad Zare-Mehrjerdi, Angela L Stotts, Jordan M Braciszewski, Mark T Murphy, Douglas Dryden, Julia H Arnsten, Chinazo O Cunningham, Viviana E Horigian, José Szapocznik, Joseph E Glass, Ryan M Caldeiro, Rebecca C Phillips, Mary Shea, Gavin Bart, Robert P Schwartz, Jennifer Mcneely, Jane M Liebschutz, Judith I Tsui, Joseph O Merrill, Gwen T Lapham, Megan Addis, Katharine A Bradley, Proud Trial Collaborators, Megan M Ghiroli, Leah K Hamilton, Yong Hu, Jennifer S Lahue, Amy M Loree, Sean M Murphy, Thomas F Northrup, Dikla Shmueli-Blumberg, Angela J Silva, Zoe M Weinstein, Mark Tinfook Wong, Rachael P Burganowski

Faculty, Staff and Student Publications

Importance: Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments.

Objective: To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization.

Design, setting, and participants: The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention …