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Smith, Jay

https://orcid.org/0000-0002-1449-6639

Mayo Clinic

Mayo Clinic

Citations 43

A phase 1 clinical trial shows safe, sustained, AAV-mediated expression of IL-1Ra in the human osteoarthritic knee joint
Vega, Rodolfo E. De la , Sellon, Jacob L. , Smith, Jay , Wisniewski, Stephen, Jurisson, Mary L. , Frick, Matthew A., Scrabeck, Tyson L., Block, Julie B., Mills, Candee J. , Pohlkamp, Zachary W., Coenen, Michael J., Hawse, Gresin P. , Abdul, Temilola Y. , Conaghan, Philip G. , Keravala, Annahita, Robbins, Paul D. , Ghivizzani, Steven C. , Evans, Christopher H. , De La Vega, Rodolfo E , Wisniewski, Stephen J, Conaghan, Philip , Chalberg, Thomas W , Robbins, Paul D , Ghivizzani, Steven C , Evans, Christopher H , Block, Julie B.

Science Translational Medicine | June 4, 2025 | Volume: 17 | Issue: 801 | Pages: No page available

10.1126/scitranslmed.adu9804 Get It

Osteoarthritis (OA) is a major global health problem with no disease-modifying therapies. Interleukin-1 (IL-1) is a critical cytokine associated with the pathophysiology of OA and can be inhibited by IL-1 receptor antagonist (IL-1Ra). Here, we tested the delivery of a gene therapeutic encoding the human IL-1Ra to the knee in a phase 1, open-label clinical trial that enrolled nine patients with radiographic knee OA. The IL-1Ra gene was delivered by a self-complementary (sc)–recombinant adeno-associated virus (rAAV) serotype 2.5 (sc-rAAV2.5IL-1Ra) by intra-articular injection into an index knee at one of three doses: low [1 × 10 11 viral genomes (vg)], mid (1 × 10 12 vg), or high (1 × 10 13 vg). The primary outcome was safety. There were no serious adverse events (AEs) related to sc-rAAV2.5IL-1Ra. Two AEs occurred that were possibly related to the vector. Both were effusions with increased pain and resolved with conservative treatment. sc-rAAV2.5IL-1Ra did not cause changes in vital signs, physical findings, or clinical laboratory measures. Less than 1% of the injected dose of sc-rAAV2.5IL-1Ra vg was detected in circulation after 1 day and was cleared within a week. Titers of neutralizing antibodies to AAV2.5 rose in serum and synovial fluid. In all cases, IL-1Ra concentration increased in the synovial fluid, and IL-1Ra concentrations remained elevated after 1 year. Baseline pain and function scores improved during the study. Therefore, we found that intra-articular gene therapy with sc-rAAV2.5IL-1Ra was safe. The sustained increase in local IL-1Ra in human knee joints supports the further clinical examination of this therapy to provide therapeutic benefit in OA.
Recommended Musculoskeletal and Sports Ultrasound Terminology: A Delphi‐Based Consensus Statement
Hall, Mederic M. , Allen, Georgina , Allison, Sandra J. , Craig, Joseph G. , DeAngelis, Joseph P. , Delzell, Patricia B. , Finnoff, Jonathan T. , Gupta, Atul , Hoffman, Douglas F. , Nazarian, Levon N. , Onishi, Kentaro , Ray, Jeremiah W. , Smith, Jay , Tagliafico, Alberto , Allen, Georgina M , Allison, Sandra , Craig, Joseph , Frank, Rachel M , Gupta, Atul , Hoffman, Douglas F , Jacobson, Jon A , Narouze, Samer , Nazarian, Levon N , Onishi, Kentaro , Ray, Jeremiah W , Sconfienza, Luca M , Smith, Jay , Tagliafico, Alberto , Finnoff, Jonathan T , Jacobson, Jon A. , Narouze, Samer

Journal of Ultrasound in Medicine | February 1, 2022 | Volume: 41 | Issue: 10 | Pages: 2395-2412

10.1002/jum.15947 Get It

Objectives The current lack of agreement regarding standardized terminology in musculoskeletal and sports ultrasound presents challenges in education, clinical practice, and research. This consensus was developed to provide a reference to improve clarity and consistency in communication. Methods A multidisciplinary expert panel was convened consisting of 18 members representing multiple specialty societies identified as key stakeholders in musculoskeletal and sports ultrasound. A Delphi process was used to reach consensus which was defined as group level agreement >80%. Results Content was organized into seven general topics including: 1) General Definitions, 2) Equipment and Transducer Manipulation, 3) Anatomic and Descriptive Terminology, 4) Pathology, 5) Procedural Terminology, 6) Image Labeling, and 7) Documentation. Terms and definitions which reached consensus agreement are presented herein. Conclusions The historic use of multiple similar terms in the absence of precise definitions has led to confusion when conveying information between colleagues, patients, and third‐party payers. This multidisciplinary expert consensus addresses multiple areas of variability in diagnostic ultrasound imaging and ultrasound‐guided procedures related to musculoskeletal and sports medicine.
Ultrasound visualization of the thumb annular pulleys: A cadaveric validation study
Hoffman, Douglas F. , Hoefler, Amanda Honsvall , Bianchi, Stefano , Hoxie, Samuel C., Smith, Jay , Honsvall Hoefler, Amanda

PM&R | January 25, 2022 | Volume: 15 | Issue: 2 | Pages: 203-211

10.1002/pmrj.12769 Get It

AbstractBackgroundThe thumb annular pulley system is unique from the other digits and is integral to normal thumb function. Injuries to this pulley system can present a diagnostic challenge. No prior study has evaluated the ability of ultrasound (US) to evaluate all four thumb pulleys.ObjectiveTo validate the sonographic visualization of all four thumb pulleys.DesignProspective cadaveric laboratory investigation.SettingAcademic center procedural skills laboratory.ParticipantsTwelve unembalmed cadaveric hands from seven adult male donors ages 78‐89 years with body mass index 21.9‐26.6 kg/m2.InterventionsBased on anatomic descriptions, a single examiner used a standardized protocol and high‐frequency linear transducers to identify the A1, variable (Av), oblique (Ao), and A2 pulleys of the thumb in 10 cadaveric hands. As part of the validation process, the presumed Ao pulley was injected with diluted colored latex using US guidance. Two additional cadaveric specimens were dissected for detailed study of the thumb pulley system.Main Outcome MeasuresCorrelation between the four anatomic pulleys as revealed by dissection and the US findings, including identification of latex location with respect to the Ao pulley.ResultsUS correctly identified all four thumb pulleys as distinct anatomic structures and the sonographic appearance of the pulleys correlated with the dissection in all 10 specimens. Latex was observed in the Ao pulley in 100% of the cadavers.ConclusionsUltrasound can be used to accurately identify all four thumb pulleys, including distinct Ao and Av pulleys, and should be considered in the evaluation of thumb pulley injuries. This is the first study to validate the US visualization of the annular pulley system of the thumb.
The Turtle Neck Sign: Identification of Severe Retracted Distal Biceps Tendon Rupture
Boonrod, Artit , Harasymczuk, Michał , Ramazanian, Taghi , Boonrod, Arunnit, Smith, Jay , O’Driscoll, Shawn W. , Fitzsimmons, James S

Orthopaedic Journal of Sports Medicine | January 19, 2022 | Volume: 10 | Issue: 1 | Pages: No page available

10.1177/23259671211065030 Get It

Background: Chronic tendon retraction subsequent to distal biceps tendon rupture significantly increases repair difficulty and potential for tendon grafting. Biceps tendons that appear short or absent with magnetic resonance imaging (MRI) or that cannot be readily identified at surgery may erroneously be classified as irreparable. These apparent “absent” biceps tendons may actually be retracted and curled up inside the muscle, visually resembling the head-neck of a turtle retracted inside its shell (the “turtle neck sign”). When located, these tendons could be unfolded and repaired primarily. This type of tendon retraction seems to be associated with high-degree ruptures and larcertus fibrosus tears. Purpose: To test the hypothesis that tendon retractions with a turtle neck sign on MRI are more associated with high-degree ruptures and larcertus fibrosus tears versus tendon tears with simple linear retraction. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Retracted distal biceps tendon ruptures on sagittal MRI were categorized as linear retraction or curled-up (turtle neck) retraction. Retraction length, injury severity, and lacertus fibrosus tears were analyzed. Results: The authors retrospectively analyzed the patient records of 85 consecutive traumatic distal biceps tendon ruptures from 2003 to 2019; the final study cohort was 37 patients. Injury-to-surgery timing was as follows: <3 weeks, 43% (16 cases); 3 weeks to 3 months, 32% (12 cases); and >3 months, 24% (9 cases). Overall, 19 patients had linear retraction <7 cm (mean, 3.3 ± 1.9 cm) and 18 patients had a turtle neck retraction ≥7 cm (mean, 9.1 ± 1.6 cm). The injury-to-surgery time (median [± interquartile range]) was 27 days (±90 days) in the linear retraction group and 23 days (±65 days) in the turtle neck retraction group. The turtle neck retraction group had a significantly higher occurrence of abnormal hook test findings, complete distal biceps tendon rupture, and lacertus fibrosus tears compared with the linear retraction group (100% vs 58%, 100% vs 68%, and 100% vs 37%, respectively; P ≤ .02). However, significant repairability differences were not found. Conclusion: Highly retracted distal biceps turtle neck sign tendon ruptures occur frequently in association with high-degree ruptures and lacertus fibrosus tears. The presence of a turtle neck retraction did not affect reparability. Surgeons should be aware of this curled-up retraction to avoid mistaking it for an absent tendon or a muscle-tendon disruption.
Diagnostic Imaging of A2 Pulley Injuries: A Review of the Literature
Berrigan, William A. , White, William D. , Cipriano, Kevin , Wickstrom, Jordan , Smith, Jay , Hager, Nelson, White, William

Journal of Ultrasound in Medicine | August 3, 2021 | Volume: 41 | Issue: 5 | Pages: 1047-1059

10.1002/jum.15796 Get It

Injury to the A2 pulley is caused by high eccentric forces on the flexor‐tendon–pulley system. Accurate diagnosis is necessary to identify the most appropriate treatment options. This review summarizes the literature with respect to using ultrasound (US) to diagnose A2 pulley injuries, compares ultrasound to magnetic resonance imaging and computed tomography, and identifies current knowledge gaps. The results suggest that US should be used as the primary imaging modality given high accuracy, relatively low cost, ease of access, and dynamic imaging capabilities. Manual resistance is beneficial to accentuate bowstringing, but further research is needed to determine best positioning for evaluation.
American Medical Society for Sports Medicine Sports Ultrasound Curriculum for Sports Medicine Fellowships
Hall, Mederic M. , Bernhardt, David T., Hoffman, Douglas F. , Hrubes, Melody, Rao, Ashwin L., Ray, Jeremiah W. , Smith, Jay , Waterbrook, Anna L., Finnoff, Jonathan T. , Mautner, Kenneth

Clinical Journal of Sport Medicine | May 9, 2021 | Volume: 31 | Issue: 4 | Pages: e176-e187

10.1097/jsm.0000000000000944 Get It

Abstract: Sports ultrasound is commonly used by sports medicine physicians to enhance diagnostic and procedural accuracy. This expert consensus statement serves as an update to the 2015 American Medical Society for Sports Medicine recommended sports ultrasound curriculum for sports medicine fellowships. Although written in the context of the American sports medicine fellowship training model, we present a stepwise progression in both diagnostic and interventional sports ultrasound that may be applicable to the broader sports medicine community. The curriculum is divided into 12 units with each unit including didactic instructional sessions, practical hands-on instruction, independent scanning practice sessions, and mentored clinical experience. To assist with prioritization of learning, we have organized relevant pathology and procedures as essential, desirable, and optional. The expanded content can serve as an outline for continuing education postfellowship or for any physician to further advance their sports ultrasound knowledge and skill. We also provide updated scanning protocols, sample milestones, and a sample objective structured clinical examination (OSCE) to aid fellowships with implementation of the curriculum and ongoing assessment of fellow progress.
Local Anesthesia Prior to Ultrasound‐Guided Hip Joint Injections: A Double‐Blind Randomized Controlled Trial of Bacteriostatic Saline versus Buffered Lidocaine
Kruse, Ryan C. , Kindle, Brett J., Wisniewski, Steve J. , Presley, James T., Smith, Jay , Sellon, Jacob L. , Wisniewski, Steve, Presley, James, Presley, James

PM&R | September 27, 2020 | Volume: 13 | Issue: 8 | Pages: 811-818

10.1002/pmrj.12489 Get It

BackgroundUltrasound (US)‐guided hip joint injections are commonly performed for patients with suspected or known intra‐articular hip pain. Lidocaine is a well‐established local anesthetic used prior to hip joint injections, but it is often associated with discomfort during infiltration. Bacteriostatic saline is an alternative local anesthetic that has been shown to be less painful during infiltration for superficial injections.ObjectiveTo compare infiltrative pain and anesthetic efficacy of bacteriostatic saline (0.9% benzyl alcohol) with a standard local anesthetic (buffered 1% lidocaine) used for local anesthesia prior to US‐guided intra‐articular hip corticosteroid injections.DesignDouble‐blinded, randomized controlled trial.SettingTertiary care medical center.ParticipantsSixty eight patients age 18‐80 (mean 54.8) years referred for US‐guided intra‐articular hip corticosteroid injections.InterventionPatients were randomized to receive a US‐guided hip joint corticosteroid injection using either bacteriostatic saline or buffered 1% lidocaine for preinjection local anesthesia.Main Outcome MeasuresVisual Analog Scale (VAS) for pain (0‐100) during local anesthetic infiltration as well as during the intra‐articular injection. Adverse events were also recorded.ResultsThere were no significant differences between bacteriostatic saline and buffered lidocaine with respect to pain during local anesthetic infiltration or during the subsequent intra‐articular injection. Pain VAS during local anesthetic infiltration was 13.2 (95% confidence interval [CI] 7.8, 18.5) in the bacteriostatic saline group and 14.0 (95% CI 9.4, 18.5) in the buffered 1% lidocaine group (P = .82). Furthermore, pain VAS during the intra‐articular injection was 20.7 (95% CI 14.1, 27.3) in the bacteriostatic saline group and 15.7 (95% CI 10.9, 20.3) in the buffered 1% lidocaine group (P = .57). No adverse events occurred.ConclusionsBacteriostatic saline is a safe and comparably effective alternative to buffered 1% lidocaine for local anesthesia before US‐guided hip joint injections and may be considered for subcutaneous/periarticular anesthesia during similar musculoskeletal procedures.
Accuracy of Ultrasound Compared to Magnetic Resonance Imaging in the Diagnosis of Thumb Ulnar Collateral Ligament Injuries
Moore, Brittany J. , Iafrate, Julia L., Kakar, Sanjeev , Wisniewski, Stephen, Murthy, Naveen S. , Smith, Jay , Wisniewski, Stephen J, Kakar, Sanjeev , Murthy, Naveen S

Journal of Ultrasound in Medicine | September 24, 2020 | Volume: 40 | Issue: 6 | Pages: 1251-1257

10.1002/jum.15491 Get It

This prospective case series compared the accuracy of ultrasound (US) to magnetic resonance imaging (MRI) in differentiating complete displaced (CD) thumb ulnar collateral ligament (UCL) tears from nondisplaced injuries in 10 patients with suspected traumatic thumb UCL injuries. Ultrasound identified 100% (2 of 2) of MRI‐documented CD tears, both of which were further confirmed during surgical repair. Ultrasound identified the absence of CD tears in the remaining 8 patients. Although MRI is the reference standard imaging modality for characterizing thumb UCL injuries, ultrasound should be considered an accurate, cost‐effective, and alternative imaging modality to differentiate surgical versus nonsurgical thumb UCL injuries.
Sonoanatomy and Pathology of the Gluteus Minimus Tendon
Hoffman, Douglas F. , Sellon, Jacob L. , Moore, Brittany J. , Smith, Jay , Hoffman, Douglas F

Journal of Ultrasound in Medicine | November 9, 2019 | Volume: 39 | Issue: 4 | Pages: 647-657

10.1002/jum.15156 Get It

Gluteus minimus disorders are a potential source of greater trochanteric or anterior hip pain. Disorders of the gluteus minimus tendon most commonly occur in conjunction with gluteus medius tendon abnormalities but can also occur in isolation. Understanding the sonoanatomy of the gluteus minimus muscle‐tendon unit is a prerequisite for recognizing and characterizing gluteus minimus tendon disorders, which, in turn, guides treatment for patients with greater trochanteric or anterior hip pain syndromes.
Distribution of Sonographically Guided Injections of the Subgluteus Minimus and Medius Bursae in Cadaveric Model
Moore, Brittany J. , Johnson, Wade O. , Smith, Jay , Sellon, Jacob L. , Finnoff, Jonathan T.

Medicine & Science in Sports & Exercise | June 25, 2019 | Volume: 51 | Issue: 6S | Pages: 592-592

10.1249/01.mss.0000562280.50168.94 Get It