Association of Patient-Reported Outcomes Measurement Information System Measures With Injection and Surgical Treatment Response in Patients With De Quervain Tenosynovitis.

PURPOSE: Treatment of de Quervain tenosynovitis is largely empiric. Patient-Reported Outcomes Management Information System (PROMIS) scores at the time of diagnosis might provide insights into the probability of success of nonsurgical management and predict the necessity for surgical treatment. We aimed to identify which, if any, of the PROMIS metrics may be used to identify patients who will opt for surgery or be managed with injection alone. METHODS: Patients presenting to a tertiary academic medical center from 2014 to 2019, with a sole diagnosis of de Quervain tenosynovitis, were identified and separated by initial and most invasive treatment of either injection or surgery. These groups were then dichotomized using cut points of more than one SD from the mean on the PROMIS physical function and pain interference scales, and a logistic regression model was used to determine the odds ratio of surgical intervention. RESULTS: Patients who had low physical function or high pain interference had significantly increased odds of ultimately undergoing surgery. Age ranging from 40 to 60 years and female sex were also associated with increased odds of undergoing surgery. CONCLUSIONS: Patients who scored lower than 40 for physical function or higher than 60 for pain interference had significantly increased odds of eventually undergoing surgical release for de Quervain tenosynovitis. PROMIS scores may identify patients who are likely to fail steroid injections as a sole nonsurgical intervention and inform an individualized discussion about surgical management of this condition. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Diagnosis of Ulnar Neuropathy at the Elbow Using Ultrasound - A Comparison to Electrophysiologic Studies.

PURPOSE: Given the relatively high false negative rate of electrodiagnostic studies (EDX) in patients with clinically diagnosed ulnar neuropathy at the elbow (UNE), we sought to determine whether an alternative objective test could more effectively detect UNE. Additionally, we proposed to determine the relationship between the cross-sectional area (CSA) of the ulnar nerve on ultrasound (US), EDX, and clinical symptoms. METHODS: This was a retrospective study of patients presenting with symptomatic UNE. The performance characteristics of EDX versus ultrasound were calculated using the clinical diagnosis of UNE as the reference standard. Standard EDX studies and US of the ulnar nerve were analyzed. Maximal CSA of the ulnar nerve and EDX severity were analyzed for patients with each combination of US-positive/negative and EDX-positive/negative findings. RESULTS: Analysis was performed on 89 patients and 115 nerves with signs and symptoms of cubital tunnel syndrome. In total, 56 (49%) nerves were diagnosed as mild UNE, 32 (28%) nerves were diagnosed as moderate UNE, 17 (15%) nerves were diagnosed as severe UNE, and 10 (8%) nerves were negative for UNE by EDX. Maximal-maximal CSA was highly correlated with disease severity as determined by nerve conduction studies/electromyography. Compared with EDX+/US+, patients with EDX-/US+ showed higher rates of ulnar sensory loss and elbow tenderness with similar rates of positive Tinel and intrinsic muscle atrophy. In this sample of patients with clinically diagnosed UNE, 91.3% of the patients demonstrated positive EDX studies, whereas 94.8% had a positive US. CONCLUSIONS: Ultrasound is an alternative to EDX that could be incorporated clinically in the diagnosis and management of UNE. Ultrasound was able to consistently detect clinically positive cubital tunnel syndrome demonstrating its utility as a confirmatory or supplemental test to the clinical assessment if one is required. Ultrasound additionally may be able to better identify patients with early stages of UNE with negative EDX findings. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

Reduction Loss After Distal Radius Fracture Fixation With Locked Volar Plates.

Distal radius fractures are among the most common injuries in the upper extremity. While many studies have looked at the maintenance of reduction with volar locking plates, there is a paucity of literature comparing the ability of different plates to maintain reduction over time. This study reviews the ability of various plates to maintain radiographic reduction at union after distal radius fracture treatment. Loss of some aspect of fracture reduction was routinely observed following locked volar plating regardless of implant. However, choice of implant did have a significant impact on final radiographic alignment, particularly with respect to volar tilt and ulnar variance. Yet, selecting between a fixed angle versus a variable angle was not found to make a difference in maintaining reduction. The authors recommend that surgeons take these findings into consideration when selecting a volar locking plate. (Journal of Surgical Orthopaedic Advances.

Staphylococcal persistence due to biofilm formation in synovial fluid containing prophylactic cefazolin.

Antibiotic prophylaxis is standard for patients undergoing surgical procedures, yet despite the wide use of antibiotics, breakthrough infections still occur. In the setting of total joint arthroplasty, such infections can be devastating. Recent findings have shown that synovial fluid causes marked staphylococcal aggregation, which can confer antibiotic insensitivity. We therefore asked in this study whether clinical samples of synovial fluid that contain preoperative prophylactic antibiotics can successfully eradicate a bacterial challenge by pertinent bacterial species. This study demonstrates that preoperative prophylaxis with cefazolin results in high antibiotic levels. Furthermore, we show that even with antibiotic concentrations that far exceed the expected bactericidal levels, Staphylococcus aureus bacteria added to the synovial fluid samples are not eradicated and are able to colonize model implant surfaces, i.e., titanium pins. Based on these studies, we suggest that current prophylactic antibiotic choices, despite high penetration into the synovial fluid, may need to be reexamined.

Endoscopic Carpal Tunnel Release With Monitored Anesthesia Care Versus Local Anesthesia: Analysis of Operative Times and Patient-Reported Outcomes.

Purpose: Carpal tunnel syndrome is the most common peripheral nerve compressive neuropathy in clinical practice. Patients who fail nonsurgical management are indicated for carpal tunnel release (CTR), which can be performed open or endoscopically. Efforts have been made to utilize local anesthesia instead of monitored anesthesia care (MAC) for endoscopic release. This study seeks to compare perioperative surgical times and postoperative outcomes in patients undergoing endoscopic CTR with local anesthesia versus MAC. Methods: This is a 6-year retrospective study of 1,036 patients undergoing isolated endoscopic CTR with MAC (n = 607) versus local (n = 429) anesthesia within an outpatient surgical center. A combination of chi-square and t tests was used to compare the patient characteristics, operative details, and outcomes. Results: The local cohort demonstrated significantly shorter postoperative time to discharge (15.9 ± 9.8 vs 53.8 ± 11.0 minutes; P < .05), total time spent in surgical center (83.2 ± 18.7 vs 129.3 ± 20.7 minutes; P < .05), shorter total operating room time (26.7 ± 4.3 vs 29.0 ± 4.1 minutes; P < .05) and tourniquet time (12.4 ± 2.5 vs 13.1 ± 2.1 minutes; P < .05). Preoperative and postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores were similar between the cohorts (P > .05); however, PROMIS pain interference improved to a higher degree between pre- and post-op in the local group (-1.5 vs -0.8; P = .02). Early and late surgical complications were similar between the groups (P > .05). Conclusions: Patients within the MAC cohort demonstrated longer postoperative time to discharge and total time in the surgical center. The MAC cohort had longer operating room and tourniquet time, albeit not clinically significant. Surgical complications and PROMIS scores were similar between the two groups. Our findings suggest that local anesthesia is a safe and effective option for endoscopic CTR and may offer advantages in cost and convenience for patients. Type of study/level of evidence: Retrospective cohort study/therapeutic III.

Pharmacological Antagonism of Ccr2+ Cell Recruitment to Facilitate Regenerative Tendon Healing.

Successful tendon healing requires sufficient deposition and remodeling of new extracellular matrix at the site of injury, with this process mediating in part through fibroblast activation via communication with macrophages. Moreover, resolution of healing requires clearance or reversion of activated cells, with chronic interactions with persistent macrophages impairing resolution and facilitating the conversion the conversion to fibrotic healing. As such, modulation of the macrophage environment represents an important translational target to improve the tendon healing process. Circulating monocytes are recruited to sites of tissue injury, including the tendon, via upregulation of cytokines including Ccl2, which facilitates recruitment of Ccr2+ macrophages to the healing tendon. Our prior work has demonstrated that Ccr2-/- can modulate fibroblast activation and myofibroblast differentiation. However, this approach lacked temporal control and resulted in healing impairments. Thus, in the current study we have leveraged a Ccr2 antagonist to blunt macrophage recruitment to the healing tendon in a time-dependent manner. We first tested the effects of Ccr2 antagonism during the acute inflammatory phase and found that this had no effect on the healing process. In contrast, Ccr2 antagonism during the late inflammatory/ early proliferative period resulted in significant improvements in mechanical properties of the healing tendon. Collectively, these data demonstrate the temporally distinct impacts of modulating Ccr2+ cell recruitment and Ccr2 antagonism during tendon healing and highlight the translational potential of transient Ccr2 antagonism to improve the tendon healing process.

Clinical and Radiographic Outcomes Following Volar-Locked Plating Versus Dorsal Bridge Plating for Distal Radius Factures.

Purpose: Distal radius fractures (DRFs) indicated for operative intervention are most commonly treated with volar-locked plating (VLP); however, dorsal bridge plating (DBP) has been used as an alternative fixation method. The purpose of this study was to use a propensity score to match and compare the radiographic and clinical outcomes of patients undergoing isolated VLP or DBP for DRFs. Methods: We performed a retrospective, propensity score-matched analysis of patients undergoing isolated VLP or DBP treatment for isolated DRFs from 2015 to 2022 at a single level-1 trauma center. Patients were propensity score-matched by a total of eight demographic and comorbidity factors, AO Foundation/Orthopedic Trauma Association classification, and preoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores. Our primary outcomes included postoperative complications, wrist and forearm range of motion (ROM), grip strength, and radiographic measurements, including radial height, radial inclination, volar tilt, and articular step-off. Results: Overall, 415 DBP and 2075 VLP were successfully propensity score-matched and included in this study. Grip strength and ROM measurements at the 6-month follow-up, including wrist flexion, wrist extension, forearm pronation, forearm supination, radial deviation, and ulnar deviation, were increased in the VLP compared with DBP (P < .05). Complication rates among both the groups were relatively low; however, the rates of malunion and nonunion were significantly higher among the DBP group (P < .05). Radial height, radial inclination, and articular step-off were improved in the VLP group compared with the DBP group (P < .05); however, volar tilt was similar between groups. PROMIS upper extremity and physical function were significantly higher among the VLP group (P < .05). No significant difference was noted in PROMIS pain interference between the groups. Conclusions: When compared with DBP, patients undergoing VLP are more likely to have improved clinical and radiographic outcomes. Although improvement in wrist and forearm ROM and radiographic parameters is statistically significant, it may not be clinically relevant. Type of study/level of evidence: Therapeutic III.

Ultrasound Assessment of the Ulnar Nerve Around the Elbow and Diagnosis of Cubital Tunnel Syndrome, Clinical Outcomes.

BACKGROUND: There is increased interest in ultrasound (US) for the diagnosis of cubital tunnel syndrome (CuTS). We hypothesize that ulnar nerve cross-sectional area (CSA) correlates with disease severity and electrodiagnostic studies (EDX). METHODS: ARetrospective review was performed at a tertiary medical center. One hundred seventeen patients (166 ulnar nerves) were evaluated. Maximum CSA at 3 points around the elbow (proximal, groove, and distal) and EDX results (American Board of Electrodiagnostic Medicine-certified physiatrist's interpretations) were collected. RESULTS: US was positive (CSA > 0.1 cm2) in 95/117 cases (81.20%) versus 84/117 (71.79%) positive for EDX. CuTS patients treated surgically had significantly greater (0.13 cm2, standard deviation [SD] 0.038) preoperative CSA than non-operative patients (0.10 cm2, SD 0.033) (p = .003). CSA increased as EDX increased in severity; mild (0.116 cm2, SD 0.031), moderate (0.121 cm2, SD 0.035), and severe (0.163 cm2, SD 0.047) with a significant difference between the mild and severe groups (P = .001) and between the moderate and severe groups (p = .01). Significant differences were seen between patients with positive US and EDX studies compared to those with negative US and EDX in the average physical function scores (57.26, SD 8.57 versus 43.18, SD 7.70; p < .001); average sleep scores (50.14, SD 9.53 versus 56.62, SD 7.31; p = .02); average physical function scores (43.04, SD 8.68 versus 57.08, SD 6.34; p < .001) and average depression scores (49.10, SD 10.88 versus 45.043, SD 7.06; p = .02). CONCLUSIONS: US is a reliable tool for diagnosis and surgical decision-making for CuTS. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic/III.

Epitenon-derived cells comprise a distinct progenitor population that contributes to both tendon fibrosis and regeneration following acute injury.

Flexor tendon injuries are common and heal poorly owing to both the deposition of function- limiting peritendinous scar tissue and insufficient healing of the tendon itself. Therapeutic options are limited due to a lack of understanding of the cell populations that contribute to these processes. Here, we identified a bi-fated progenitor cell population that originates from the epitenon and goes on to contribute to both peritendinous fibrosis and regenerative tendon healing following acute tendon injury. Using a combination of genetic lineage tracing and single cell RNA-sequencing (scRNA-seq), we profiled the behavior and contributions of each cell fate to the healing process in a spatio-temporal manner. Branched pseudotime trajectory analysis identified distinct transcription factors responsible for regulation of each fate. Finally, integrated scRNA-seq analysis of mouse healing with human peritendinous scar tissue revealed remarkable transcriptional similarity between mouse epitenon- derived cells and fibroblasts present in human peritendinous scar tissue, which was further validated by immunofluorescent staining for conserved markers. Combined, these results clearly identify the epitenon as the cellular origin of an important progenitor cell population that could be leveraged to improve tendon healing.

Where Does Ultrasound Fit in the Diagnostic Algorithm for Cubital Tunnel Syndrome?

BACKGROUND: Ultrasound (US) has emerged as a promising supplement to electrodiagnostic studies (EDX) in the diagnosis of cubital tunnel syndrome (CuTS) and has potential to be performed by novice operators. Our objective is to understand the discrepancies in assessment between the two modalities and to assess the utility of US in CuTS diagnosis by a novice operator. METHODS: Patients who presented to a single tertiary academic medical center and clinically diagnosed with CuTS were prospectively enrolled. Electrodiagnostic studies were performed along with US measurements of the cross-sectional area (CSA) of the ulnar nerve by both a board-certified physiatrist and novice operator. Electrodiagnostic study and US outcomes were compared among four diagnostic impression groups: EDX-/US-, EDX+/US-, EDX-/US+, and EDX+/US+. RESULTS: Sixteen patients were classified as abnormal by both EDX and US, 14 were classified abnormal by US only, 3 were classified abnormal by EDX only, and 6 were classified normal by both EDX and US (P = .008, K = 0.14). The EDX+/US+ group had a significantly reduced sensory amplitude compared with the EDX-/US+ (P = .04) group. Diagnostic classifications between a board-certified physiatrist and novice operator were in moderate agreement (K = 0.58, P = .08). CONCLUSIONS: Ultrasound detected a greater proportion of patients as abnormal than EDX. A subset of patients with clinical diagnoses of CuTS had normal sensory amplitudes but increased maximum nerve CSAs. Competency in US may be easily acquired with minimal training, suggesting its potential to be extended for use by other members of the health care team.

Initial PROMIS Scores Correlate With Operative and Nonoperative Management of Lateral Epicondylitis.

BACKGROUND: Lateral epicondylitis (LE) is a common source of elbow pain. Treatment options include physical therapy (PT), corticosteroid injection, or surgery, but the efficacy of each remains unclear. In this study, we compare Patient-Reported Outcomes Measurement Information System (PROMIS) scores between patients treated both operatively and nonoperatively for LE. METHODS: Patients presenting to a tertiary academic medical center from February 2015 to December 2018 with a diagnosis of LE were identified. Those with initial and follow-up PROMIS physical function (PF), pain interference (PI), and Depression scores were included and stratified according to treatment. Single-factor analysis of variance testing was used to compare PROMIS scores between intervention types. RESULTS: In all, 982 patients were initially identified with the diagnosis of LE and documented PROMIS scores. Initial treatment consisted of 266 patients receiving formal PT, 238 patients receiving injections, 20 patients undergoing surgery, and 296 patients receiving no formal treatment. At final follow-up, 235 (44.8%) patients had been treated with isolated PT, 237 (45.1%) with injections, and 52 (9.9%) with surgery. Patients who underwent formal PT had the highest initial PF scores when compared with all other interventions. Patients who underwent operative management had higher initial PI scores than those who pursued nonoperative management. CONCLUSIONS: Patient-Reported Outcomes Measurement Information System PF and PI may be useful for determining which treatment course patients suffering from LE are likely to pursue. Pain as a limiting factor in daily living may be a better indication for operative management as opposed to physical metrics.

Vancomycin bonded to bone grafts prevents bacterial colonization.

Infection is an important medical problem associated with the use of bone allografts. To retard bacterial colonization, we have recently reported on the modification of bone allografts with the antibiotic vancomycin (VAN). In this report, we examine the ability of this antibiotic-modified allograft to resist bacterial colonization and biofilm formation. When antibiotic was coupled to the allograft, a uniform distribution of the antibiotic was apparent. Following challenges with Staphylococcus aureus for 6 h, the covalently bonded VAN decreased colonization as a function of inoculum, ranging from 0.8 to 2.0 log(10) CFU. Furthermore, the VAN-modified surface resisted biofilm formation, even in topographical niches that provide a protected environment for bacterial adhesion. Attachment of the antibiotic to the allograft surface was robust, and the bonded VAN was stable whether incubated in aqueous media or in air, maintaining levels of 75 to 100% of initial levels over 60 days. While the VAN-modified allograft inhibited the Gram-positive S. aureus colonization, in keeping with VAN's spectrum of activity, the VAN-modified allograft was readily colonized by the Gram-negative Escherichia coli. Finally, initial toxicity measures indicated that the VAN-modified allograft did not influence osteoblast colonization or viability. Since the covalently tethered antibiotic is stable, is active, retains its specificity, and does not exhibit toxicity, it is concluded that this modified allograft holds great promise for decreasing bone graft-associated infections.

Development of a Murine Model of Pyogenic Flexor Tenosynovitis.

BACKGROUND: Pyogenic flexor tenosynovitis is a debilitating infection of the hand flexor tendon sheath with high morbidity despite standard treatments of empiric antibiotics with irrigation and debridement. In vivo studies in the available literature have used avian models, but these models are difficult to scale and maintain. The purpose of this study was to demonstrate the plausibility of a murine model of pyogenic flexor tenosynovitis utilizing bioluminescence imaging and tissue analysis at harvest. METHODS: A 2-µL inoculate of bioluminescent Xen29 Staphylococcus aureus or sterile phosphate-buffered saline solution (sPBS) was administered to the tendon sheath of 36 male C57BL/6J mice. The infectious course was monitored by bioluminescence imaging (BLI) via an in vivo imaging system, gross anatomic deformity, and weight change. The infected hind paws were harvested at 4 time points: 24 hours, 72 hours, 1 week, and 2 weeks for histological analysis using Alcian blue, hematoxylin, and Orange-G staining. Two-way analysis of variance with the Sidak multiple comparison test was used to assess differences in bioluminescence and weight at each time point. RESULTS: The infected cohort displayed significantly elevated bioluminescence values, had reductions in weight, and exhibited swelling of the infected digit throughout the course of infection. By day 4, most infected mice saw a substantial decrease in BLI signal intensity; however, 2 infected mice exhibited persistent BLI intensity through day 14. Histological analysis of the infected cohort showed tissue disorganization and the presence of a cellular infiltrate in and around the flexor tendon sheath. CONCLUSIONS: A murine model of pyogenic flexor tenosynovitis is possible and can serve as an experimental platform for further investigation of the pathophysiology of pyogenic flexor tenosynovitis. CLINICAL RELEVANCE: This animal model can be utilized in elucidating the basic molecular and/or cellular mechanisms of pyogenic flexor tenosynovitis while simultaneously evaluating novel therapeutic strategies.

Clinical utilization of species-specific immunoassays for identification of Staphylococcus aureus and Streptococcus agalactiae in orthopedic infections.

Staphylococcus aureus and Streptococcus agalactiae (Group B streptococcus, GBS) are common causes of deep musculoskeletal infections (MSKI) and result in significant patient morbidity and cost to the healthcare system. One of the major challenges with MSKI is the lack of faithful diagnostics to correctly identify the primary pathogen, as standard culture-based assays are prone to false positives in the case of polymicrobial infections, and false negatives due to limitations in sample acquisition and antibiotic use before presentation. To improve upon our current diagnostic methods for MSKI, we developed a multiplex immunoassay for antigen-specific IgGs in serum (Luminex), and medium enriched for newly synthesized antibodies (MENSA) for anti-S. aureus and GBS generated from cultured peripheral blood mononuclear cells (PBMCs) of orthopedic infection patients undergoing surgical treatment. Samples were obtained from 110 MSKI patients: 80 diabetic foot ulcer, 21 periprosthetic joint infection, 5 septic arthritis, 2 spine, 1 hand, and 1 fracture-related infection (FRI). Anti-S. aureus and anti-GBS antibody titers were compared to culture results to assess their concordance in identifying the pathogens. Immunoassay, particularly MENSA, showed high diagnostic potential for monomicrobial S. aureus and GBS orthopedic infections (AUC > 0.95). MENSA also demonstrated diagnostic potential for GBS polymicrobial orthopedic infection and for GBS DFU (AUC > 0.83 for both). Serum showed high diagnostic potential for S. aureus PJI (AUC > 0.95). Taken together, these findings support the development of species-specific immunoassays for the identification of causal pathogens in active MSKI, especially in conjunction with standard culture.

Bacterial colonization of bone allografts: establishment and effects of antibiotics.

BACKGROUND: Bone grafts are frequently used to supplement bone stock and to establish structural stability. However, graft-associated infection represents a challenging complication leading to increased patient morbidity and healthcare costs. QUESTIONS/PURPOSES: We therefore designed this study to (1) determine if increasing initial S. aureus inoculation of bone allograft results in a proportionate increase in colonization; (2) assess if antibiotics decrease colonization and if antibiotic tethering to allograft alters its ability to prevent bacterial colonization; and (3) determine if covalent modification alters the allograft topography or its biological properties. METHODS: Allograft bone and vancomycin-modified bone (VAN-bone) was challenged with different doses of S. aureus for times out to 24 hours in the presence or absence of solution vancomycin. Bacterial colonization was assessed by fluorescence, scanning electron microscopy (SEM), and by direct colony counting. Cell density and distribution of osteoblast-like cells on control and modified allograft were then compared. RESULTS: Bacterial attachment was apparent within 6 hours with colonization and biofilm formation increasing with time and dose. Solution vancomycin failed to prevent bacterial attachment whereas VAN-bone successfully resisted colonization. The allograft modification did not affect the attachment and distribution of osteoblast-like cells. CONCLUSIONS: Allograft bone was readily colonized by S. aureus and covered by a biofilm with especially florid growth in natural topographic niches. Using a novel covalent modification, allograft bone was able to resist colonization by organisms while retaining the ability to allow adhesion of osteoblastic cells. CLINICAL RELEVANCE: Generation of allograft bone that can resist infection in vivo would be important in addressing one of the most challenging problems associated with the use of allograft, namely infection.

A Comparison of PROMIS Physical Function and Pain Interference Scores in Patients With Carpal Tunnel Syndrome: Research Collection Versus Routine Clinical Collection.

Background: There is a concern that patients may answer patient-reported outcome (PRO) questionnaires differently depending on the purpose-clinical care or research (eg, "Hawthorne effect"). We sought to determine whether Patient-Reported Outcomes Management Information System (PROMIS) scores differ at the same clinic visit based on whether a patient was completing the PRO tool for study or clinical care purposes. Methods: Patients presenting to one surgeon at an academic medical center hand clinic were asked to complete PROMIS Physical Function (PF) and Pain Interference (PI) questionnaires as part of routine care. Those diagnosed with carpal tunnel syndrome from February 2015 to April 2017 were then asked to participate in a clinical research project, which had them complete PROMIS PF and PROMIS PI again. Data from those who completed both routine and research PROs at each visit were compared. Between the 2 settings, test-retest reliability was determined using Pearson correlation coefficients (r), and internal consistency was evaluated using Cronbach α. Results: A total of 128 unique office visits representing 67 patients fit our inclusion criteria. There was a strong correlation between PROMIS PF and PI in the research and patient care setting (PF: r = 0.82, P < .01; PI: r = 0.83, P < .01). Both domains had a Cronbach α of 0.90. The PROMIS PF scores were not different between the 2 groups (P = .19), but the PROMIS PI scores were slightly different (P < .01). Conclusions: Patients appear to be consistent when completing PROMIS for both clinical care and research, supporting the idea that data obtained in either setting are generalizable and appropriate for research purposes.

NF-κB activation persists into the remodeling phase of tendon healing and promotes myofibroblast survival.

Although inflammation is necessary during the early phases of tissue repair, persistent inflammation contributes to fibrosis. Acute tendon injuries often heal through a fibrotic mechanism, which impedes regeneration and functional recovery. Because inflammation mediated by nuclear factor κB (NF-κB) signaling is implicated in this process, we examined the spatial, temporal, and cell type-specific activation profile of canonical NF-κB signaling during tendon healing. NF-κB signaling was maintained through all phases of tendon healing in mice, including the remodeling phase, and tenocytes and myofibroblasts from the Scleraxis (Scx) lineage were the predominant populations that retained NF-κB activation into the late stages of repair. We confirmed persistent NF-κB activation in myofibroblasts in human tendon scar tissue. Deleting the canonical NF-κB kinase, IKKß, in Scx-lineage cells in mice increased apoptosis and the deposition of the matrix protein periostin during the late stages of tendon repair, suggesting that persistent NF-κB signaling may facilitate myofibroblast survival and fibrotic progression. Consistent with this, myofibroblasts in human tendon scar samples displayed enhanced prosurvival signaling compared to control tissue. Together, these data suggest that NF-κB may contribute to fibrotic tendon healing through both inflammation-dependent and inflammation-independent functions, such as NF-κB-mediated cell survival.