Faculty Bibliography

A key pathological feature of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) is the loss of nuclear localization and accumulation of cytoplasmic inclusions of TAR-DNA binding protein 43 (TDP-43). TDP-43 is a nucleic acid-binding protein involved in transcriptional repression, mRNA splicing, and the regulation of retrotransposable elements (RTEs) and endogenous retroviruses (ERVs). RTEs/ERVs are mobile virus-like genetic elements that constitute about 45% of our genome and encode the capacity to replicate through an RNA intermediate and insert cDNA copies at de novo chromosomal locations. A causal role of RTEs/ERVs has been demonstrated in Drosophila in mediating both intracellular toxicity of TDP-43 and the intercellular spread of toxicity from glia to neurons. RTEs/ERVs are inappropriately expressed in postmortem tissues from ALS, FTD, and Alzheimer's Disease (AD) patients, but the role of RTEs/ERVs has not yet been examined in a vertebrate model of TDP-43 pathology. We utilized established transgenic mouse models that overexpress moderate levels of human wild-type TDP-43 or a mutant version with a specific ALS-causal Q331K amino acid substitution, together with a LINE-1-EGFP retrotransposon indicator line. We found that TDP-43 animals exhibit broad expression of RTEs/ERVs with LINE-1 retrotransposition in glia and neurons in the motor cortex. Expression begins with onset of neurological phenotypes, earlier in hTDP-43-Q331K animals and later in hTDP-43-WT. The LINE-1-EGFP retrotransposition reporter transiently labels spatially clustered groups of neurons and glia at the time of onset of motor symptoms, while EGFP-labeled neurons undergo cell death and are therefore lost over time. Unlabeled cells also die as a function of distance from the clusters of LINE-1-EGFP labeled neurons and glial cells. Together, these findings support the hypothesis that TDP-43 pathology triggers RTE/ERV expression in the motor cortex, that such expression marks cells for programmed cell death, with cell non-autonomous effects on nearby neurons and glial cells.

BACKGROUND & AIMS/OBJECTIVE:This study assessed the economic and health impact of colorectal cancer (CRC) screening programs for average-risk individuals aged 45 years and older. METHODS:A 10-year Markov model simulated disease progression, comparing multitarget stool RNA test (mt-sRNA, ColoSense), two mt-sDNA tests (Cologuard and Cologuard Plus), a blood-based test (cfDNA, Shield), and a fecal immunochemical test (FIT). Clinical inputs leveraged age-weighted sensitivity and specificity from independent studies. Outcomes were compared with a colonoscopy-based program and no screening. Model calibration and validation used previously reported Cancer Intervention Surveillance Modeling Network (CISNET) models. RESULTS:Among molecular tests, mt-sRNA detected the most advanced adenomas, referred the most individuals to surveillance, and prevented the highest number of CRC cases and deaths. At real-world adherence of 60%, mt-sRNA reduced CRC cases and deaths by 1% and 14% compared with FIT; by 21% and 19% compared with mt-sDNA; by 28% and 23% compared with mt-sDNA+; and by 80% and 86% compared with cfDNA. For all adherence levels, FIT ($25/test) was the most cost-effective strategy. For triennial molecular tests ($509/test), mt-sRNA was the most cost-effective strategy. Relative to the mt-sRNA program, the cost to prevent a CRC case was 30% (mt-sDNA), 45% (mt-sDNA+), and 642% (cfDNA) more expensive. Relative to the mt-sRNA program, the cost to prevent a CRC death was 30% (mt-sDNA), 41% (mt-sDNA+), and 1040% (cfDNA) more expensive. CONCLUSIONS:FIT was the most cost-effective strategy for preventing CRC cases and deaths. At real-world adherence of 60%, mt-sRNA demonstrated the greatest clinical benefit and was more cost-effective than other molecular strategies.

The rise of artificial intelligence (AI)-driven tools like ChatGPT is transforming professional fields, including pathology. This study provides early insights into how pathology trainees and practicing pathologists are integrating AI into their training and clinical practice. To assess adoption, usage patterns, perceptions, and challenges related to AI-driven tools, including large language models and vision-language models, among pathology professionals. The study also explores future directions for AI integration. A cross-sectional, anonymous survey was distributed electronically to pathology residents, fellows, and attending pathologists through the Accreditation Council for Graduate Medical Education program director registry, professional organizations, and social media (X, Reddit, LinkedIn, and The Pathologist email listserv). The survey included multiple-choice, Likert-scale, and open-ended questions on AI familiarity, usage, perceived benefits/risks, and institutional policies. Data were analyzed using descriptive and inferential statistics, with qualitative responses categorized thematically. A total of 268 respondents participated, primarily residents (41%), attendings (39%), and fellows (7%), representing 23 countries (65% from the USA). Most were affiliated with academic medical centers (72%) and aged 25-44. Whereas 73% reported some familiarity with AI, actual use was limited, 31% reported rare use and 29% no use at all, especially among residents and attendings. ChatGPT was the most used tool (84%), applied mainly for document drafting (57%), research (54%), and administrative tasks (34%). Diagnostic use was minimal. Top concerns included accuracy (81%), over-reliance (65%), and data security (63%). Only 10% reported having clear institutional AI guidelines. Familiarity was strongly associated with usage frequency (p < 0.00001). AI is increasingly used in non-diagnostic areas of pathology but adoption remains cautious. Significant gaps in clinical application, trust, and institutional support persist. Clear guidelines, targeted education, and robust validation are essential for safe, effective AI integration into pathology practice and training.

BACKGROUND:Regenerative medicine is an evolving medical subspecialty dedicated to enhancing the body's natural healing mechanisms to repair or replace damaged tissues. By using autologous or allogeneic biologics, it offers the potential to restore function where conventional therapies have shown limited success. While this field holds great promise and continues to generate enthusiasm among both patients and clinicians, it remains in early stages of clinical validation. Therefore, it must be approached with careful optimism and responsible application, ensuring that its presentation, promotion, and use in clinical settings are grounded in evidence and ethical standards. OBJECTIVE:To provide updated, evidence-based recommendations for the role of regenerative therapies in managing moderate to severe chronic low back pain. METHODS:A multidisciplinary panel of experts, convened by the American Society of Interventional Pain Physicians (ASIPP), systematically reviewed the current evidence and incorporated patient perspectives to develop practical, evidence-informed recommendations. The process included defining key clinical questions, reviewing the literature, formulating evidence-based statements, and reaching consensus through structured discussions and formal voting. RESULTS:A total of 35 authors contributed to the development of these guidelines, with 33 experts participating in the formal consensus process. Altogether, 19 recommendations were generated, with all of them achieving 100% agreement. These recommendations were informed by a comprehensive review of systematic reviews, randomized controlled trials (RCTs), and observational studies encompassing a broad range of regenerative therapies.Evidence was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to determine certainty levels. Both qualitative and quantitative analyses were applied to synthesize the best available data, resulting in evidence-based recommendations summarized below.Intradiscal Injections (PRP): Evidence Level: III, Fair; Consensus-Based Clinical Recommendation: ModerateIntradiscal Injections (BMAC): Evidence Level: III, Fair; Consensus-Based Clinical Recommendation: ModerateEpidural Injections (PRP): Evidence Level: III, Fair; Consensus-Based Clinical Recommendation: ModerateFacet Joint Injections (PRP and MSCs): Evidence Level: IV, Limited; Consensus-Based Clinical Recommendation: Moderate Sacroiliac Joint Injections (PRP): Evidence Level: IV, Limited; Consensus-Based Clinical Recommendation:  Low Functional Spine Unit Injections Evidence Level: Very Low; Consensus-Based Clinical Recommendation:Low. LIMITATIONS/CONCLUSIONS:The primary limitation of these guidelines is the scarcity of high-quality studies, with much of the available evidence derived from small or heterogeneous trials. PRECAUTIONS/UNASSIGNED:Regenerative therapies should be considered only after a thorough diagnostic evaluation confirming clinical necessity. Treatment decisions must account for the patient's medical condition, preferences, and expectations. Patients should be fully informed about the nature, potential benefits, risks, and costs of regenerative treatments, most of which are not covered by commercial insurance.These therapies may be used alone or in conjunction with other evidence-based modalities, such as structured exercise, physical therapy, behavioral therapy, or conventional medical management. Clinicians must follow all applicable U.S. Food and Drug Administration (FDA) regulations and adhere to safety and ethical standards outlined in these guidelines. CONCLUSION/CONCLUSIONS:Based on current evidence, lumbar intradiscal injections of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) are supported by Level III evidence. Lumbar epidural PRP injections are also supported by Level III evidence, while PRP injections for lumbar facet joints and sacroiliac joints are supported by Level IV evidence. Given the emerging status of biologic therapies and the limited quality of existing studies, the panel provides moderate, consensus-based recommendations for the use of all biologics in the lumbar spine.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Hand-sewn (HS) microsuturing is limited by tremor and fatigue. Robotic systems may improve performance, but quantitative comparisons remain limited. This study evaluates the precision of robot-assisted vs manual suturing during end-to-side microanastomosis. METHODS:Under simulation, microsurgical robot-assisted and HS sutures for end-to-side microanastomosis were performed by a single surgeon. One thousand four hundred and ninety-four total frames were assessed within 4 videos. Each robotic clip was paired with a corresponding HS clip. Tracker software extracted 2-dimensional positional data. Motion trajectories were smoothed using Savitzky-Golay filtering for an ideal suture trajectory. Deviation from an ideal path was quantified using Euclidean distance. Mean and SD of path deviation were calculated. Group comparisons were made as fold-change reductions and standardized effect sizes (Cohen d) to quantify the magnitude of observed differences. RESULTS:Robotic-assisted sutures demonstrated significantly lower mean path deviation and variability than HS sutures, particularly for the dominant (right) hand, with consistently large effect sizes for the right hand (all = 1.2, r = 0.5) and smaller for the left hand (d = 0.36-0.71, r = 0.18-0.33). CONCLUSION/CONCLUSIONS:Robotic microsuturing with microsurgical assistant significantly improves path fidelity, particularly in dominant-hand tasks. Manual sutures showed larger deviations between the ideal suture and raw data, supporting robotic integration into cerebrovascular neurosurgery and warranting study in live models.

The aim of this study was to provide a review for orthopedic surgeons on the care of para athletes. The article focuses on common patient populations that present to orthopedic surgeons, including individuals with spinal cord injuries and related disorders, limb deficiencies, and neuromuscular conditions. The most common types of injuries affecting these para athletes will be discussed, as well as strategies for injury prevention and treatment. This review article also dives into the historical origins of para sports and discusses how treatment can potentially influence classification levels for para athletes. Orthopedic surgeons should encourage their patients with disabilities to participate in para sports, understand the types of injuries they may be at risk of based on disability and sports-specific factors, and work to help keep para athletes successfully competing in the sports they love.

Since the beginning of documented medical history, amputation procedures, limb loss, and the myriad creative solutions attempted to care for these individuals have been reported. With the coalescence of multiple World Wars resulting in an ever-increasing number of individuals with limb loss and advancing medical technology, a need to innovate in this field has always been present. The complexity of the hand and upper extremity in self-care, communication, vocation, and exercise results in more demands of prostheses to mimic or replace these functions as opposed to the lower extremity, which is focused mostly on weight bearing and ambulation. As such, this need has pushed technological advances past the simpler passive or body-powered prostheses alone, now with externally powered and hybrid devices revolutionizing the way these appliances were implemented in everyday life. Despite the ever-advancing field of prosthetic technology, upper and lower extremity amputees alike still battle common challenges of pain, phantom limb sensation, and lack of prosthetic control and sensation. Targeted muscle reinnervation and regenerative peripheral nerve interface offer new surgical solutions to some of these challenges and are proving invaluable. As technology and surgical options continue to advance at an ever-rapid pace, a more thoughtful and individualized approach to the care of upper extremity limb loss is available. In this study, we review the history and evolution of upper extremity prostheses and discuss considerations in making optimal surgical and prosthetic decisions for upper extremity amputees.

Genetics is a burgeoning field within adult reconstructive surgery. Genome-wide sequencing has identified genetic variants found to be associated with not only the development of osteoarthritis but also arthroplasty-related complications, such as aseptic loosening, prosthetic joint infection, arthrofibrosis, and postoperative pain. Examples include newer technology, such as next-generation sequencing, in diagnosing culture-negative prosthetic joint infection. Genetics drives new therapeutic technologies, such as gene therapy, gene-editing, and bacteriophage treatment. Although still rare, a handful of phase 3 clinical trials of gene therapy for osteoarthritis have begun to demonstrate efficacy with low-risk profiles. As the field continues to grow, public and professional buy-in as well as cost present challenges.

BACKGROUND:The objective of this study was to survey a cross-section of US female orthopaedic surgeons evaluating their education and attitudes on radiation safety and adherence to safety recommendations. METHODS:An online survey was distributed to female orthopaedic surgery faculty through the Forum, a society for women in orthopaedic surgery, and through internal institutional education networks (residency and fellowship programs). The first component of the survey gathered demographic information including practice setting, US state, and years in practice. The second component was a 10-question knowledge assessment. The third component captured personal experiences among respondents including satisfaction with radiation safety training, radiation safety practices, and level of concern regarding exposure risk. Responses from 66 participants from differing geographic locations were collected using Research Electronic Data Capture. RESULTS:Sixty-six female orthopaedic surgeons from 21 states completed the survey. Regular dosimeter usage was reported by 24.2% of respondents, and 36.4% of respondents reported always having well-fitted radiation protective equipment provided. The majority (56.1%) stated that they worry about the risks of radiation to their health. Regarding their radiation safety training, 60.6% of respondents rated their training as unsatisfactory or extremely unsatisfactory, and 90.9% of respondents stated that they think training efforts for radiation safety can improve. CONCLUSIONS:Female orthopaedic surgeons demonstrated an inadequate knowledge of adherence to radiation safety protocols and the majority expressed concern with long-term radiation exposure, particularly regarding health and pregnancy risk. To enhance radiation safety awareness and adherence among female orthopaedic surgeons, strategies should be tailored to this demographic, fostering confidence in their knowledge of radiation exposure and bolstering safety measures.