Musculoskeletal Diseases Commons^™

Mri-Based Deep Learning Radiomics Model For Automated Classification Of Disc Degeneration In The Lumbar Spine, Shiv Patil, Om Gandhi, Mert Karabacak, Matthew Carr, Konstantinos Margetis

Student Papers, Posters & Projects

Disc degeneration in the lumbar spine is a major cause of low back pain (LBP). The accurate grading of disc degeneration on magnetic resonance imaging (MRI) is critical for clinical management and patient selection for spine surgery. This study aims to develop and evaluate machine learning (ML) models that combine features from deep learning (DL) and radiomics for the automated prediction of Pfirrmann grade (PG), a measure of disc degeneration, using multi-parametric lumbar spine MRI. Sagittal T1, T2, and T2 SPACE MRIs of 218 patients with LBP were acquired from the SPIDER dataset. For each intervertebral disc and available sequence, …

Expert Consensus On Osteoporosis Risk Management In Patients With Sleep Disorders, Siqi Leng, Jinming Yang, Yuming Jin, Jie Shi, Ye Zhang, Junying Zhou, Lusi Tan, Taomei Li, Peiyan Ni, Kejia Hu, Yuan Shi, Jiamin Liao, Yun Li, Pei Xue, Christian Benedict, Alexandros N. Vgontzas, Michael Furian, Talant Sooronbaev, Naima Covassin, Virend K. Somers, Zhoulong Yu, Hongqiang Sun, Xiao Tan, Jihui Zhang, Yun Kwok Wing, Yue Leng, Larry D. Sanford, Michael V. Vitiello, Katie L. Stone, Rong Ren, Lin Lu, Xiangdong Tang

Department of Biomedical and Translational Sciences Faculty Publications

A rate-limiting step in the prevention and early intervention of osteoporosis is identifying its asymptomatic onset. Accumulating evidence shows that sleep disorders are associated with an increased risk of osteoporosis. Given their early detectable and modifiable nature, integrating sleep disorder management into osteoporosis prevention and care pathways offers a novel approach for enhancing skeletal health. This expert consensus represents a collaborative effort by specialists in sleep medicine and orthopedics from across the world, integrating epidemiological, mechanistic, and interventional evidence to provide general guidance for prevention and clinical practice, and to foster multidisciplinary collaboration in the management of sleep disorders and …

P-15 Peptide Enhanced Bone Graft Improves Time To Fusion In Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study, James S. Harrop, Michael P. Steinmetz, John E. O'Toole, Christopher D Chaput, Rick C. Sasso, K. Brandon Strenge, Greg Maislin, Jeffrey P. Mullin, Thomas B. Freeman, Anthony Guanciale, Howard Lantner, Michael E. Janssen, David G. Schwartz, John M. Small, Wellington K. Hsu, Paul M. Arnold

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Prospective, multicenter, single-blind, randomized, and controlled pivotal study.

OBJECTIVE: Compare time-to-fusion in patients treated with P-15L (PearlMatrix TM P-15 peptide enhanced bone graft) versus local autograft over 24 months and evaluate changes in pain and quality of life at 24 months relative to baseline.

SUMMARY OF BACKGROUND DATA: P-15L, an FDA-designated breakthrough device, is a composite bone graft with P-15, a 15-amino acid polypeptide that promotes cellular adhesion, proliferation, and differentiation to support bone formation.

METHODS: Patients (22-80 y) with degenerative disc disease were randomized to the investigational (P-15L) or control (local autograft) group during single-level transforaminal lumbar …

Does Preoperative Arthritis Affect The Outcomes Of Superior Capsular Reconstruction? A Systematic Review, Tae-Hoon Park, Hyungsuk Kim, Sukil Kim, Jongin Lee, Gerald R. Williams, Hyun Seok Song

Rothman Institute Papers

BACKGROUND: The optimal indications for superior capsular reconstruction (SCR) in cases of massive irreparable rotator cuff tears (RCTs) accompanied by degenerative arthritis remain controversial.

METHODS: A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Embase (Elsevier), and Google Scholar. Studies were included if they documented Hamada grade and reported clinical and radiographic outcomes after SCR for irreparable RCTs. American Shoulder and Elbow Surgeons (ASES) score, visual analog scale for pain (pVAS), active range of motion, and acromiohumeral distance (AHD) were analyzed.

RESULTS: In all 7 studies, there was no consistent …

A Computer Vision And Machine Learning Approach To Classify Views In Distal Radius Radiographs, Rohan Vemu, Dion Birhiray, Bassem Darwish, Raven Hollis, Sai Unnam, Srikhar Chilukuri, Lorenzo Deveza

Faculty, Staff and Students Publications

Advances in computer vision and machine learning have augmented the ability to analyze orthopedic radiographs. A critical but underexplored component of this process is the accurate classification of radiographic views and localization of relevant anatomical regions, both of which can impact the performance of downstream diagnostic models. This study presents a deep learning object detection model and mobile application designed to classify distal radius radiographs into standard views-anterior-posterior (AP), lateral (LAT), and oblique (OB)- while localizing the anatomical region most relevant to distal radius fractures. A total of 1593 deidentified radiographs were collected from a single institution between 2021 and …

Development Of Emerin Mrna Lipid Nanoparticles To Rescue Myogenic Differentiation., Nicholas Marano, Liza Elif Guner, Rachel S Riley, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Emery-Dreifuss muscular dystrophy 1 (EDMD1) arises from mutations in EMD. Most EDMD1 patients lack detectable emerin expression. They experience symptoms such as skeletal muscle wasting, joint contractures, and cardiac conduction defects. Currently, physicians rely on treating patient symptoms without addressing the underlying cause-lack of functional emerin protein. Thus, there is a need for therapeutic approaches that restore emerin protein expression to improve patient outcomes. One way would be to deliver emerin mRNA or protein directly to affected tissues to restore tissue homeostasis. Here, we evaluated the utility of lipid nanoparticles (LNPs) to deliver emerin mRNA to diseased cells. LNPs …

Discontinuation Rates And Predictors Of Medical Cannabis Cessation For Chronic Musculoskeletal Pain, Mohammad Khak, Sina Ramtin, Juliet Chung, Asif M. Ilyas, Ari Greis

Rothman Institute Papers

Medical cannabis (MC) is increasingly used as a treatment for chronic musculoskeletal pain, but there is limited data on factors influencing its discontinuation. This study aims to investigate the rates of MC discontinuation and explore factors influencing it in patients with chronic musculoskeletal pain. A retrospective analysis was conducted on 78 patients certified for medical cannabis over a 2 year period. Patient demographics, pain origin, and Global Physical Health (GPH) and Global Mental Health (GMH) scores were collected before intervention. Discontinuation rates were measured at three-month and one-year follow-up. Statistical analyses, including Fisher's Exact Test and two-sample t-tests, were performed …

Which Systemic Responses Should We Evolve To Help Surgeons Navigate Their Regret Experiences?, Ryan X Lam, Ruhi Thapar, Eric J Silberfein, Lorenzo R Deveza

Faculty, Staff and Students Publications

Regret in surgical practice is typically construed as resulting from the commission or the omission of a specific action at a specific decision point, which leads to a deleterious outcome. This article suggests a need to expand this conception of surgical regret to better account for surgeons' regret experiences arising from factors beyond their control. The commentary accompanying the case investigates these external sources of regret, such as resource limitations or professional interpersonal dynamics that prevent a desired outcome from being realized. It also discusses the normative value of addressing surgeons' experiences of regret, especially as a catalyst to facilitate …

Palovarotene In Fibrodysplasia Ossificans Progressiva: Review And Perspective, Vincent Verheij, Robert Diecidue, Esmée Botman, Joseph Harrington, Nobuhiko Haga, Alberto Hidalgo-Bravo, Patricia Delai, Vrisha Madhuri, Mona Al Mukaddam, Keqin Zhang, Tae-Joon Cho, Rolf Morhart, Richard Keen, Carmen De Cunto, Clive Friedman, Zvi Grunwald, Michael Zasloff, J. Coen Netelenbos, Edward Hsiao, Frederick Kaplan, Robert Pignolo, Christiaan Scott, Elisabeth Marelise Eekhoff

Department of Oral and Maxillofacial Surgery Faculty Papers

INTRODUCTION: Palovarotene is a retinoic acid receptor gamma agonist that was studied in phase-2 and phase-3 clinical trials for the inhibition of new heterotopic ossification (HO) in fibrodysplasia ossificans progressiva (FOP). Despite numerous setbacks and regulatory delays, palovarotene is now the first approved FOP treatment in the U.S.A., Canada and Australia but remains unapproved in Europe where concerns surrounding the drug and its path to regional market authorization persist.

AREAS COVERED: The developmental history of palovarotene and an overview of the clinical trials and the regulatory approval journey are discussed by global FOP experts.

EXPERT OPINION: While post hoc analyses …

Diagnosis And Management Of Cardiometabolic Disease After Spinal Cord Injury: Identifying Gaps In Physician Training And Practices, Chinenye Christa Nnoromele, Du Pham, Felicia Skelton, Ryan Solinsky

Faculty, Staff and Students Publications

CONTEXT: Cardiometabolic disease (CMD) frequently occurs in individuals with spinal cord injury (SCI), with growing awareness surrounding the expansive scope of this problem. As CMD has significant morbidity and mortality, early guidelines-based screening and management have been established. However, the extent to which these guidelines have been adopted are unclear.

OBJECTIVE: Describe physicians' screening and management pattern for CMD in patients with SCI, as compared to SCI-specific CMD screening guidelines, and elucidate variables linked to screening and management patterns.

METHODS: SCI medicine-boarded physicians were surveyed on screening timing for CMD following acute SCI, along with their practice pattern and comfort …

Transcutaneous Electrical Nerve Stimulation For Fibromyalgia-Like Syndrome In Patients With Long-Covid: A Pilot Randomized Clinical Trial, Alejandro Zulbaran-Rojas, Rasha O Bara, Myeounggon Lee, Miguel Bargas-Ochoa, Tina Phan, Manuel Pacheco, Areli Flores Camargo, Syed Murtaza Kazmi, Mohammad Dehghan Rouzi, Dipaben Modi, Fidaa Shaib, Bijan Najafi

Faculty, Staff and Students Publications

This study investigated the effect of Transcutaneous Electrical Nerve Stimulation (TENS) for fibromyalgia-like symptoms including chronic widespread musculoskeletal pain, fatigue, and/or gait impairment in twenty-five individuals with long-COVID. Participants were randomized to a high dose (intervention group, IG) or low dose (placebo group, PG) TENS device. Both groups received daily 3-5 h of TENS therapy for 4-weeks. The Brief Pain Inventory assessed functional interference from pain (BPI-I), and pain severity (BPI-S). The global fatigue index (GFI) assessed functional interference from fatigue. Wearable technology measured gait parameters during three 30-feet consecutive walking tasks. At 4-weeks, the IG exhibited a greater decrease …

Successful Management Of Pre-Existing Psoriatic Arthritis Through Targeting The Il-23/Il-17 Axis In Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy: A Case Series, Yuanteng Jeff Li, Pavlos Msaouel, Matthew Campbell, Patrick Hwu, Adi Diab, Sang T Kim

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with cancer. However, these therapies are associated with adverse events including de novo immune-related adverse events or flare of pre-exiting autoimmune disorders. Up to 80% of patients with cancer and pre-existing psoriasis (PsO) or psoriatic arthritis (PsA) experience PsO/PsA flare after initiating ICIs. Targeting the interleukin (IL)-17/IL-23 axis is a mainstream of the PsO/PsA treatment. However, whether this treatment can effectively control PsO/PsA with ICI exposure while preserving anti-tumour efficacy remains unknown.

CASE REPORTS: We report three patients with PsA and cancer, who received ICIs for their cancer treatment. …

Whole Genome And Reverse Protein Phase Array Landscapes Of Patient Derived Osteosarcoma Xenograft Models, Chia-Chin Wu, Licai Huang, Zhongting Zhang, Zhenlin Ju, Xingzhi Song, E Anders Kolb, Wendong Zhang, Jonathan Gill, Min Ha, Malcolm A Smith, Peter Houghton, Christopher L Morton, Raushan Kurmasheva, John Maris, Yael Mosse, Yiling Lu, Richard Gorlick, P Andrew Futreal, Hannah C Beird

Faculty, Staff and Student Publications

Osteosarcoma is the most common primary bone malignancy in children and young adults, and it has few treatment options. As a result, there has been little improvement in survival outcomes in the past few decades. The need for models to test novel therapies is especially great in this disease since it is both rare and does not respond to most therapies. To address this, an NCI-funded consortium has characterized and utilized a panel of patient-derived xenograft models of osteosarcoma for drug testing. The exomes, transcriptomes, and copy number landscapes of these models have been presented previously. This study now adds …

Editorial Comment: Diversity And Disparities In Orthopaedic Surgery: Update 2024, Kimberly J Templeton, Melvyn A Harrington

Faculty, Staff and Students Publications

No abstract provided.

Low Skeletal Muscle Mass Is Associated With Inferior Preoperative And Postoperative Shoulder Function In Elderly Rotator Cuff Tear Patients, Yang Yang, Binbin Zheng, Xiaofang Lin, Mengqin Zhang, Yongzhi Ye, Haixiao Chen, Xiaobo Zhou

Faculty, Staff and Student Publications

BACKGROUND: The age-related loss of skeletal muscle mass is an important characteristic of sarcopenia, an increasingly recognized condition with systemic implications. However, its association with shoulder function in elderly patients with rotator cuff tears (RCT) remains unknown. This study aimed to investigate the relationship between low skeletal muscle mass and shoulder function in elderly RCT patients.

METHODS: A retrospective analysis was conducted on RCT patients who underwent chest computed tomography (CT) scans for clinical evaluation. Preoperative CT scan images of the chest were used to calculate the cross-sectional area (CSA) of thoracic muscle at the T4 level. The medical records …

Leukocyte Immunoglobulin-Like Receptor B1 (Lilrb1) Protects Human Multiple Myeloma Cells From Ferroptosis By Maintaining Cholesterol Homeostasis, Miao Xian, Qiang Wang, Liuling Xiao, Ling Zhong, Wei Xiong, Lingqun Ye, Pan Su, Chuanchao Zhang, Yabo Li, Robert Z Orlowski, Fenghuang Zhan, Siddhartha Ganguly, Youli Zu, Jianfei Qian, Qing Yi

Faculty, Staff and Student Publications

Multiple myeloma (MM) is a hematologic malignancy characterized by uncontrolled proliferation of plasma cells in the bone marrow. MM patients with aggressive progression have poor survival, emphasizing the urgent need for identifying new therapeutic targets. Here, we show that the leukocyte immunoglobulin-like receptor B1 (LILRB1), a transmembrane receptor conducting negative immune response, is a top-ranked gene associated with poor prognosis in MM patients. LILRB1 deficiency inhibits MM progression in vivo by enhancing the ferroptosis of MM cells. Mechanistic studies reveal that LILRB1 forms a complex with the low-density lipoprotein receptor (LDLR) and LDLR adapter protein 1 (LDLRAP1) to facilitate LDL/cholesterol …

Vertebral Hu Value And The Pectoral Muscle Index Based On Chest Ct Can Be Used To Opportunistically Screen For Osteoporosis, Xiong-Yi Wang, Sheng Pan, Wei-Feng Liu, Yi-Ke Wang, Si-Min Yun, You-Jia Xu

Faculty, Staff and Student Publications

BACKGROUND: Existing studies have shown that computed tomography (CT) attenuation and skeletal muscle tissue are strongly associated with osteoporosis; however, few studies have examined whether vertebral HU values and the pectoral muscle index (PMI) measured at the level of the 4th thoracic vertebra (T4) are strongly associated with bone mineral density (BMD). In this study, we demonstrate that vertebral HU values and the PMI based on chest CT can be used to opportunistically screen for osteoporosis and reduce fracture risk through prompt treatment.

METHODS: We retrospectively evaluated 1000 patients who underwent chest CT and DXA scans from August 2020-2022. The …

Effect Of Aspirin Versus Low-Molecular-Weight Heparin Thromboprophylaxis On Medication Satisfaction And Out-Of-Pocket Costs: A Secondary Analysis Of A Randomized Clinical Trial, Nathan N O'Hara, Katherine P Frey, Deborah M Stein, Joseph F Levy, Gerard P Slobogean, Renan Castillo, Reza Firoozabadi, Madhav A Karunakar, Joshua L Gary, William T Obremskey, Rachel B Seymour, Joseph Cuschieri, C Daniel Mullins, Robert V O'Toole, Metrc

Faculty, Staff and Student Publications

BACKGROUND: Current guidelines recommend low-molecular-weight heparin for thromboprophylaxis after orthopaedic trauma. However, recent evidence suggests that aspirin is similar in efficacy and safety. To understand patients' experiences with these medications, we compared patients' satisfaction and out-of-pocket costs after thromboprophylaxis with aspirin versus low-molecular-weight heparin.

METHODS: This study was a secondary analysis of the PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT) trial, conducted at 21 trauma centers in the U.S. and Canada. We included adult patients with an operatively treated extremity fracture or a pelvic or acetabular fracture. Patients were randomly assigned to receive 30 mg of low-molecular-weight heparin (enoxaparin) …

Mapping Sca1 Regional Vulnerabilities Reveals Neural And Skeletal Muscle Contributions To Disease, Lisa Duvick, W Michael Southern, Kellie A Benzow, Zoe N Burch, Hillary P Handler, Jason S Mitchell, Hannah Kuivinen, Udaya Gadiparthi, Praseuth Yang, Alyssa Soles, Carrie A Sheeler, Orion Rainwater, Shannah Serres, Erin B Lind, Tessa Nichols-Meade, Yun You, Brennon O'Callaghan, Huda Y Zoghbi, Marija Cvetanovic, Vanessa C Wheeler, James M Ervasti, Michael D Koob, Harry T Orr

Duncan NRI Faculty and Staff Publications

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced disease phenotypes, we developed a floxed conditional knockin mouse (f-ATXN1146Q/2Q) with mouse Atxn1 coding exons replaced by human ATXN1 exons encoding 146 glutamines. f-ATXN1146Q/2Q mice manifested SCA1-like phenotypes including motor and cognitive deficits, wasting, and decreased survival. Central nervous system (CNS) contributions to disease were revealed using f-ATXN1146Q/2Q;Nestin-Cre mice, which showed improved rotarod, open field, and Barnes maze performance by 6-12 weeks of age. In contrast, …

Reliability And Validity Of The Promis-29 Health Profile In Ankylosing Spondylitis Patients: A Cross-Sectional Study, Mark C Hwang, Cynthia Bell, Yvette Farran, Alexis Ogdie, Charles Green, John Reveille

Faculty, Staff and Student Publications

The Patient-Reported Outcomes Measurement Information System 29-Item Health Profile (PROMIS-29) is a generic measure of health-related quality of life that is not well-studied in Ankylosing Spondylitis (AS) patients. Our objective was to investigate the reliability and validity of the PROMIS-29 in AS. About 169 consecutive AS patients were enrolled from 2017 to 2022 with 167/169 patients fully completing the PROMIS-29 in this cross-sectional study. Test-retest reliability and internal consistency was assessed using intraclass correlation coefficients (ICC) and Cronbach alpha, respectively. We studied structural validity with confirmatory factor analysis (CFA) of our hypothesized and general population models. We evaluated model fit …

Potential Value Of A Rapid Syndromic Multiplex Pcr For The Diagnosis Of Native And Prosthetic Joint Infections: A Real-World Evidence Study, Stéphanie Pascual, Brooklyn Noble, Nusreen Ahmad-Saeed, Catherine Aldridge, Simone Ambretti, Sharon Amit, Rachel Annett, Shaan Ashk O'Shea, Anna Maria Barbui, Gavin Barlow, Lucinda Barrett, Mario Berth, Alessandro Bondi, Nicola Boran, Sara E Boyd, Catarina Chaves, Martin Clauss, Peter Davies, Ileana T Dianzo-Delgado, Jaime Esteban, Stefan Fuchs, Lennart Friis-Hansen, Daniel Goldenberger, Andrej Golle, Juha O Groonroos, Ines Hoffmann, Tomer Hoffmann, Harriet Hughes, Marina Ivanova, Peter Jezek, Gwennan Jones, Zeynep Ceren Karahan, Cornelia Lass-Flörl, Frédéric Laurent, Laura Leach, Matilde Lee Horsbøll Pedersen, Caroline Loiez, Maureen Lynch, Robert J Maloney, Martin Marsh, Olivia Milburn, Shanine Mitchell, Luke S P Moore, Lynn Moffat, Marianna Murdjeva, Michael E Murphy, Deepa Nayar, Giacomo Nigrisoli, Fionnuala O'Sullivan, Büşra Öz, Teresa Peach, Christina Petridou, Mojgan Prinz, Mitja Rak, Niamh Reidy, Gian Maria Rossolini, Anne-Laure Roux, Patricia Ruiz-Garbajosa, Kordo Saeed, Llanos Salar-Vidal, Carlos Salas Venero, Mathyruban Selvaratnam, Eric Senneville, Peter Starzengruber, Ben Talbot, Vanessa Taylor, Rihard Trebše, Deborah Wearmouth, Birgit Willinger, Marjan Wouthuyzen-Bakker, Brianne Couturier, Florence Allantaz

Faculty, Staff and Student Publications

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the …

Ccdc50 Promotes Tumor Growth Through Regulation Of Lysosome Homeostasis, Penghui Jia, Tian Tian, Zibo Li, Yicheng Wang, Yuxin Lin, Weijie Zeng, Yu Ye, Miao He, Xiangrong Ni, Ji'an Pan, Xiaonan Dong, Jian Huang, Chun-Mei Li, Deyin Guo, Panpan Hou

Faculty, Staff and Student Publications

The maintenance of lysosome homeostasis is crucial for cell growth. Lysosome-dependent degradation and metabolism sustain tumor cell survival. Here, we demonstrate that CCDC50 serves as a lysophagy receptor, promoting tumor progression and invasion by controlling lysosomal integrity and renewal. CCDC50 monitors lysosomal damage, recognizes galectin-3 and K63-linked polyubiquitination on damaged lysosomes, and specifically targets them for autophagy-dependent degradation. CCDC50 deficiency causes the accumulation of ruptured lysosomes, impaired autophagic flux, and superfluous reactive oxygen species, consequently leading to cell death and tumor suppression. CCDC50 expression is associated with malignancy, progression to metastasis, and poor overall survival in human melanoma. Targeting CCDC50 …

Garetosmab In Fibrodysplasia Ossificans Progressiva: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial, Maja Di Rocco, Eduardo Forleo-Neto, Robert J Pignolo, Richard Keen, Philippe Orcel, Thomas Funck-Brentano, Christian Roux, Sami Kolta, Annalisa Madeo, Judith S Bubbear, Jacek Tabarkiewicz, Małgorzata Szczepanek, Javier Bachiller-Corral, Angela M Cheung, Kathryn M Dahir, Esmée Botman, Pieter G Raijmakers, Mona Al Mukaddam, Lianne Tile, Cynthia Portal-Celhay, Neena Sarkar, Peijie Hou, Bret J Musser, Anita Boyapati, Kusha Mohammadi, Scott J Mellis, Andrew J Rankin, Aris N Economides, Dinko Gonzalez Trotter, Gary A Herman, Sarah J O'Meara, Richard Delgizzi, David M Weinreich, George D Yancopoulos, E Marelise W Eekhoff, Frederick S Kaplan

Faculty, Staff and Student Publications

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths …

Myc Regulates Csf1 Expression Via Microrna 17/20a To Modulate Tumor-Associated Macrophages In Osteosarcoma, Bikesh K Nirala, Tajhal D Patel, Lyazat Kurenbekova, Ryan Shuck, Atreyi Dasgupta, Nino Rainusso, Cristian Coarfa, Jason T Yustein

Faculty, Staff and Students Publications

Osteosarcoma (OS) is the most common primary bone tumor of childhood. Approximately 20%-30% of OSs carry amplification of chromosome 8q24, which harbors the oncogene c-MYC and correlates with a poor prognosis. To understand the mechanisms that underlie the ability of MYC to alter both the tumor and its surrounding tumor microenvironment (TME), we generated and molecularly characterized an osteoblast-specific Cre-Lox-Stop-Lox-c-MycT58A p53fl/+ knockin genetically engineered mouse model (GEMM). Phenotypically, the Myc-knockin GEMM had rapid tumor development with a high incidence of metastasis. MYC-dependent gene signatures in our murine model demonstrated significant homology to the human hyperactivated MYC OS. We established that …

Estrogen-Related Receptor Signaling In Skeletal Muscle Fitness, Danesh Sopariwala, Hao Nguyen, Vihang Narkar

Faculty, Staff and Student Publications

Skeletal muscle is a highly plastic tissue that can alter its metabolic and contractile features, as well as regenerative potential in response to exercise and other conditions. Multiple signaling factors including metabolites, kinases, receptors, and transcriptional factors have been studied in the regulation of skeletal muscle plasticity. Recently, estrogen-related receptors (ERRs) have emerged as a critical transcriptional hub in control of skeletal muscle homeostasis. ERRα and ERRγ - the two highly expressed ERR sub-types in the muscle respond to various extracellular cues such as exercise, hypoxia, fasting and dietary factors, in turn regulating gene expression in the skeletal muscle. On …

Achondroplasia Natural History Study (Clarity): 60-Year Experience In Orthopedic Surgery From Four Skeletal Dysplasia Centers, Nickolas J Nahm, W G Stuart Mackenzie, William G Mackenzie, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Janet M Legare, Mary Ellen Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria Elena Serna, Cory J Smid, Julie Hoover-Fong, Michael B Bober

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this study was to describe the frequency and risk factors for orthopedic surgery in patients with achondroplasia. CLARITY (The Achondroplasia Natural History Study) includes clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the United States from 1957 to 2018. Data were entered and stored in a Research Electronic Data Capture (REDCap) database.

RESULTS: Information from one thousand three hundred and seventy-four patients with achondroplasia were included in this study. Four hundred and eight (29.7%) patients had at least one orthopedic surgery during their lifetime and 299 (21.8%) patients underwent multiple procedures. …

Achondroplasia Natural History Study (Clarity): 60-Year Experience In Orthopedic Surgery From Four Skeletal Dysplasia Centers, Nickolas J Nahm, W G Stuart Mackenzie, William G Mackenzie, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Janet M Legare, Mary Ellen Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria Elena Serna, Cory J Smid, Julie Hoover-Fong, Michael B Bober

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this study was to describe the frequency and risk factors for orthopedic surgery in patients with achondroplasia. CLARITY (The Achondroplasia Natural History Study) includes clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the United States from 1957 to 2018. Data were entered and stored in a Research Electronic Data Capture (REDCap) database.

RESULTS: Information from one thousand three hundred and seventy-four patients with achondroplasia were included in this study. Four hundred and eight (29.7%) patients had at least one orthopedic surgery during their lifetime and 299 (21.8%) patients underwent multiple procedures. …

Achondroplasia Natural History Study (Clarity): 60-Year Experience In Orthopedic Surgery From Four Skeletal Dysplasia Centers, Nickolas J Nahm, W G Stuart Mackenzie, William G Mackenzie, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Janet M Legare, Mary Ellen Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria Elena Serna, Cory J Smid, Julie Hoover-Fong, Michael B Bober

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this study was to describe the frequency and risk factors for orthopedic surgery in patients with achondroplasia. CLARITY (The Achondroplasia Natural History Study) includes clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the United States from 1957 to 2018. Data were entered and stored in a Research Electronic Data Capture (REDCap) database.

RESULTS: Information from one thousand three hundred and seventy-four patients with achondroplasia were included in this study. Four hundred and eight (29.7%) patients had at least one orthopedic surgery during their lifetime and 299 (21.8%) patients underwent multiple procedures. …

2022 American College Of Rheumatology Guideline For Vaccinations In Patients With Rheumatic And Musculoskeletal Diseases, Anne R Bass, Eliza Chakravarty, Elie A Akl, Clifton O Bingham, Leonard Calabrese, Laura C Cappelli, Sindhu R Johnson, Lisa F Imundo, Kevin L Winthrop, Reuben J Arasaratnam, Lindsey R Baden, Roberta Berard, S Louis Bridges, Jonathan T L Cheah, Jeffrey R Curtis, Polly J Ferguson, Ida Hakkarinen, Karen B Onel, Grayson Schultz, Vidya Sivaraman, Benjamin J Smith, Jeffrey A Sparks, Tiphanie P Vogel, Eleanor Anderson Williams, Cassandra Calabrese, Joanne S Cunha, Joann Fontanarosa, Miriah C Gillispie-Taylor, Elena Gkrouzman, Priyanka Iyer, Kimberly S Lakin, Alexandra Legge, Mindy S Lo, Megan M Lockwood, Rebecca E Sadun, Namrata Singh, Nancy Sullivan, Herman Tam, Marat Turgunbaev, Amy S Turner, James Reston

Faculty, Staff and Students Publications

OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs).

METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review …

Effect Of Nintedanib In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease And Risk Factors For Rapid Progression, Dinesh Khanna, Toby M Maher, Elizabeth R Volkmann, Yannick Allanore, Vanessa Smith, Shervin Assassi, Michael Kreuter, Anna-Maria Hoffmann-Vold, Masataka Kuwana, Christian Stock, Margarida Alves, Steven Sambevski, Christopher P Denton

Faculty, Staff and Student Publications

Objective: To investigate the rate of decline in forced vital capacity (FVC), and the effect of nintedanib on the rate of decline in FVC, in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD) who had risk factors for rapid decline in FVC.

Methods: The SENSCIS trial enrolled subjects with SSc and fibrotic ILD of ≥10% extent on high-resolution CT. The rate of decline in FVC over 52 weeks was analysed in all subjects and in those with early SSc (< 18 months since first non-Raynaud symptom), elevated inflammatory markers (C reactive protein ≥6 mg/L and/or platelets ≥330×109/L) or significant skin fibrosis (modified Rodnan skin score (mRSS) 15-40 or mRSS ≥18) at baseline.

Results: In the placebo group, the rate of decline in FVC was numerically greater in subjects with < 18 months since first non-Raynaud symptom (-167.8 mL/year), elevated inflammatory markers (-100.7 mL/year), mRSS 15-40 (-121.7 mL/year) or mRSS ≥18 (-131.7 mL/year) than in all subjects (-93.3 mL/year). Nintedanib reduced the rate of FVC decline across subgroups, with a numerically greater effect in patients with these risk factors for rapid FVC decline.

Conclusion: In the …