Factors Influencing PROMIS Scores and Patient Reported Outcomes Following Surgical Intervention of Isolated Lisfranc Injury: Minimum 2 Year Follow-up.

Lisfranc injuries are rare but significant foot injuries, as they often result from polytrauma patients, and are often misdiagnosed, which further complicate their evaluation and contribute to their propensity towards disability. It is recommended that, on diagnosis, Lisfranc injuries be treated as soon as possible to decrease the risk of future chronic pain, disability, or osteoarthritis. Our study evaluated patients who completed the patient reported outcome measurement information systems (PROMIS) along with the foot function index (FFI) following operative fixation for Lisfranc injury. Fifty-one patients between 2010 and 2020 met inclusion criteria and were selected for this study, with completion. Utilizing the electronic medical record (EMR), patient charts were reviewed to obtain basic patient demographic information and comorbidities. Operative reports were reviewed to determine which procedure was performed for definitive fixation. Primary arthrodesis was associated with a significant decrease in complication rates (p = .025) when compared to ORIF. Females, arthrodesis, and procedures using a home run (HR) screw were independent risk factors for significantly higher reports of PROMIS pain interference. Arthrodesis also was associated with lower PROMIS pain interference scores. Arthrodesis and males exhibited higher scores in all FFI categories. Our results provide evidence that patient reported outcomes following Lisfranc surgery reported via PROMIS, FFI and VAS scores are independently influenced by patient demographics, comorbidities, and surgical variables. Analysis of potential associations between these patient characteristics and PROMIS and FFI scores provides evidence for physicians to manage patient expectations prior to operative treatment of a nonpolytraumatic Lisfranc injury.

Achilles tendon disorders: An overview of diagnosis and conservative treatment.

ABSTRACT: Achilles tendon-related pain affects up to 6% of the US population during their lifetime and is commonly encountered by primary care providers. An accurate diagnosis and early conservative management can improve patient quality of life and reduce unnecessary surgical consultations, saving healthcare dollars. Achilles tendon pathologies can be categorized into acute (pain lasting less than 6 weeks), chronic (pain lasting more than 6 weeks), and acute on chronic (worsening of pain with preexisting chronic Achilles tendon pathology). This article describes the diagnosis, conservative management, indications for imaging, and indications for surgical referral for acute and chronic Achilles tendon rupture, Achilles tendinitis, gastrocnemius strain, plantaris rupture, insertional Achilles tendinopathy, Haglund deformity, and noninsertional Achilles tendinopathy.

Drug-induced modulation of gp130 signalling prevents articular cartilage degeneration and promotes repair.

OBJECTIVE: Human adult articular cartilage (AC) has little capacity for repair, and joint surface injuries often result in osteoarthritis (OA), characterised by loss of matrix, hypertrophy and chondrocyte apoptosis. Inflammation mediated by interleukin (IL)-6 family cytokines has been identified as a critical driver of proarthritic changes in mouse and human joints, resulting in a feed-forward process driving expression of matrix degrading enzymes and IL-6 itself. Here we show that signalling through glycoprotein 130 (gp130), the common receptor for IL-6 family cytokines, can have both context-specific and cytokine-specific effects on articular chondrocytes and that a small molecule gp130 modulator can bias signalling towards anti-inflammatory and antidegenerative outputs. METHODS: High throughput screening of 170 000 compounds identified a small molecule gp130 modulator termed regulator of cartilage growth and differentiation (RCGD 423) that promotes atypical homodimeric signalling in the absence of cytokine ligands, driving transient increases in MYC and pSTAT3 while suppressing oncostatin M- and IL-6-mediated activation of ERK and NF-κB via direct competition for gp130 occupancy. RESULTS: This small molecule increased proliferation while reducing apoptosis and hypertrophic responses in adult chondrocytes in vitro. In a rat partial meniscectomy model, RCGD 423 greatly reduced chondrocyte hypertrophy, loss and degeneration while increasing chondrocyte proliferation beyond that observed in response to injury. Moreover, RCGD 423 improved cartilage healing in a rat full-thickness osteochondral defect model, increasing proliferation of mesenchymal cells in the defect and also inhibiting breakdown of cartilage matrix in de novo generated cartilage. CONCLUSION: These results identify a novel strategy for AC remediation via small molecule-mediated modulation of gp130 signalling.

Evolution in Casting Techniques: A Narrative Review of Casting Methods, Techniques, and Innovation.

Orthopedic casting has seen a remarkable evolution from ancient practices to cutting-edge innovations. Beginning with ancient Egyptian methods employing bark, linen, and bandages, casting techniques have progressed through historical milestones, including the adoption of plaster of Paris in the 19th century and the introduction of synthetic materials like fiberglass and thermoplastics in the 20th century. Historical progressions transitioned from primitive materials to more sophisticated techniques, such as resin-soaked bandages and starch-based casts. While thermoplastics showcased benefits like adjustability and comfort, widespread adoption faced hurdles due to cost and water resistance limitations. The emergence of 3D printing introduced patient-specific casts with improved ventilation but faced challenges in accessibility, cost, and immediate immobilization. FlexiOH presents as a groundbreaking foam cast by Orthoheal, offering customizable fit, lightweight design, improved ventilation, and moisture resistance. Its potential to reduce ER visits, enhance patient comfort, and streamline application procedures positions it as a promising technology for the future. This paper discusses each casting generation's advantages and drawbacks, highlighting the potential of innovative technologies like FlexiOH to revolutionize orthopedic casting practices, promising improved outcomes, reduced costs, and enhanced efficiency.

Variations in opioid prescribing after total joint arthroplasty: An Observational study.

Background: This study aimed to analyze the prescribing patterns of opioids by different categories of providers for postoperative pain after primary total hip and knee arthroplasty (THA, TKA) at a single institution. Methods: A retrospective review was conducted on 1774 patients who underwent primary THA or TKA between 2014 and 2019 at a single, level one academic trauma center. Patients were excluded for additional procedures within 90 days of the index surgery. Patient demographics, operative variables, and opioid prescriptions were collected and analyzed. Generalized linear models accounting for within-person correlations were used to model the association between patient age, prescriber, etiology, opioid category, and mean morphine milligram equivalent (MME) prescribed. Results: The mean MME prescribed per patient up to 90 days postoperatively was 1591. Significant variations were observed in prescribing habits based on patient gender, age, prescriber category, and drug type. Females were prescribed more MMEs than males (CI 8.58, 667.16; p = 0.0443) and patients 65 years or younger received higher MMEs compared to those above 65 (CI 231.11, 926.48; p = 0.0011). Non-orthopedic physicians prescribed higher MMEs than orthopedic surgeons (CI 402.76, 1219.48; p < 0.0001). Hydrocodone and oxycodone prescriptions had significantly higher MMEs than tramadol prescriptions (CI 446.33, 719.52; p < 0.0001 and CI 681.09, 1065.26; p < 0.0001, respectively). Conclusion: These findings suggest the need for standardized guidelines and interventions to address variations in opioid prescribing practices for postoperative pain control. Understanding baseline prescription habits can help guide efforts to optimize pain management and reduce opioid overprescribing in the surgical setting.

Patient-Reported Outcomes Following Open Broström-Gould Procedure: Minimum 5-Year Follow-Up.

Background: Ankle sprains are a common musculoskeletal injury among the general population and often involve the lateral ligament complex. Although the majority of ankle sprains are treated successfully with nonsurgical conservative measures, an estimated 5% to 20% of ankle injuries ultimately develop chronic lateral ankle instability (CAI). Multiple surgical treatment modalities for the lateral ankle complex exist, such as anatomical and nonanatomical reconstruction. The current gold standard for primary surgical repair is the Broström-Gould procedure. This is the first article to provide PROMIS scores following BG and the largest study with 5-year outcomes for an open BG. Methods: This was a descriptive study of a retrospective cohort of patients undergoing a BG with a minimum follow-up of 5 years. Patient-reported outcome instruments collected postoperatively were PROMIS Pain, Physical Function, Depression, and FAAM. Further preoperative clinic characteristics were analyzed to correlate with the final outcome. The electronic medical record was queried for Current Procedural Terminology (CPT) code 27698 (Broström-Gould) from January 2010 to June 2017. Surveys were conducted in the clinic and through phone interviews. Patient charts were reviewed to obtain basic patient demographic information including sex, age, race, and body mass index (BMI). The following preoperative variables were recorded: history of prior CAI procedures, history of major trauma, duration of symptoms, number of diagnosed ankle sprains, other collagen pathologies, generalized ligament laxity, participation in sports/activity level, peroneal subluxation, clinically diagnosed peroneus longus or brevis tendinopathy, deltoid ligament injury, anterior ankle impingement, and posterior ankle impingement. The PROMIS and Foot and Ankle Ability Measure (FAAM) scores were obtained with a combination of clinic and phone interviews. Data were aggregated in Microsoft Excel and entered in R (version 4.2.0) for statistical analysis. Results: Our results show that the minimum 5-year patient-reported PROMIS scores for patients following a Broström-Gould procedure are as follows: PROMIS physical function, 50.5; PROMIS pain interference, 48.2; and PROMIS depression, 38.2. This indicates, at a minimum, that patients 5 years removed from the procedure are within 1 SD of the general population in regard to PROMIS physical function and pain. Our patient-reported FAAM, activities of daily living, and FAAM sports scores were 59.6 and 13.0 respectively. Preoperative magnetic resonance imaging (MRI) findings were recorded. Arthroscopic examination was performed before lateral ligaments reconstruction for patients with intra-articular pathologies confirmed on MRI. Conclusion: The findings from our study offer evidence supporting the effectiveness of the Broström-Gould procedure to be associated with normal physical function, even 5 years after surgery. Furthermore, our research identified specific factors such as tobacco use, diabetes, and sports participation that independently correlated with reported outcome measures. These insights enable physicians to better manage patient expectations and tailor treatment strategies accordingly. Our study establishes a foundation for future prospective research endeavors that aim to leverage the PROMIS system for comprehensive outcome assessments. Level of Evidence: Level III, retrospective cohort study.

Anatomical Structures at Risk in Percutaneous Preparation Talonavicular Fusion.

BACKGROUND: The stability of the hindfoot greatly relies on the integrity of the talonavicular joint. Pathologies affecting this joint often necessitate fusion. Our study explores the risks posed to neurovascular and tendon structures during simulated percutaneous talonavicular joint preparation for fusion. METHODS: In 9 fresh cadaver specimens, the talonavicular joint was accessed through two portals. A 2-mm Shannon burr was employed for joint surface preparation with distraction provided by a pin-based distractor. Dissections were performed to assess potential damage to critical structures, including the dorsalis pedis artery, superficial and deep peroneal nerves, extensor hallucis longus (EHL), and tibialis anterior (TA) tendons. RESULTS: The dorsal portal site was found to be significantly closer to important structures compared to the medial portal site. The Shannon burr made contact with various structures, with a single transection identified for both deep and superficial peroneal nerve branches. During the dorsal portal site approach, potential injury to the EHL tendon was identified as concern. CONCLUSION: This study sheds light on the potential risks associated with percutaneous dorsal and medial joint preparation approaches using a Shannon burr.Level of Evidence:Level V, mechanism-based reasoning..

Anatomical Structures at Risk in Percutaneous Distal Bunionette Correction.

Bunionette deformity is an incredibly pervasive issue in our society with almost a quarter of individuals being affected by it. As it is so common, there are numerous techniques and approaches to correct the deformity. Currently, there is a growing trend that favors percutaneous osteotomy of the bunionette. As there are multiple osteotomy sites, there are anatomical considerations that must be made at each one. The purpose of this study was to investigate the anatomic structures at risk during distal osteotomy of bunionette deformity using a Shannon burr. Using 11 fresh cadaver specimens, the fifth metatarsal was accessed through a carefully marked portal. A Shannon burr was employed for the osteotomy. Dissections were performed to assess potential damage to critical structures, including the lateral dorsal cutaneous nerve (LDCN), abductor digiti minimi (ADM), and extensor digitorum longus (EDL). Measurements were taken from the osteotomy site to each structure. The distal osteotomy site was on average greater than 8 mm from the EDL and ADM, whereas it was 1.64 mm from the LDCN. The Shannon burr made contact with and transected the LDCN on 2 occasions. However, previous studies have highlighted potential anatomical variations of the LDCN that arise distally. The study underscored the challenges posed by minimally invasive approaches to treating bunionette deformity and highlighted the need for cautious consideration when using percutaneous methods.Level of Clinical Evidence: 5.

Femoral stem taper geometry and porous coating in cementless direct anterior primary total hip arthroplasty.

Objective: This study aims to compare the clinical outcomes and complications between a fully coated, dual-tapered hip stem versus a proximally coated, triple-tapered hip stem in patients undergoing cementless direct anterior (DA) primary total hip arthroplasty (THA). Methods: A retrospective analysis was conducted on patients who underwent primary THA with either a fully coated, dual-tapered hip stem or a proximally coated, triple-tapered stem with at least a 1-year follow up. Exclusion criteria included any patients that did not receive either femoral stem, those undergoing bilateral THA, those with a surgical approach other than DA, those with an indication other than osteoarthritis, avascular necrosis (AVN), or femoral neck fracture, and those that had a cemented femoral component. Complications and clinical outcomes were assessed. Statistical analyses were conducted to identify significant differences between the groups. Results: A total of 95 patients were included in the study. The average ages for the dual-tapered and triple-tapered stem cohorts were 63.6 and 59.5, respectively (p = 0.168). At 1-year follow-up, no significant differences were seen between the groups in terms of ambulatory status, ROM, and patient satisfaction (p = 0.414, p = 0.106, and p = 0.126). 6 (18 %) of the patients receiving the dual-tapered, fully coated hip stem had at least one complication while 8 (13 %) of the triple-tapered, proximally coated hip stem patients did (p = 0.550). Conclusion: Both hip stem cohorts demonstrated comparable clinical outcomes and complication rates in patients undergoing primary DA THA and we believe that either hip stem may be a reasonable choice for patients. Future studies with larger sample sizes and longer follow-up periods are warranted to validate these findings.

Revision Surgery for Recurrent Morton Neuroma with Use of a Collagen Conduit.

Background: Painful neuromas of the foot and ankle frequently pose a treatment dilemma because of persistent pain or recurrence after resection. Primary surgical treatment of painful neuromas includes simple excision with retraction of the residual nerve ending to a less vulnerable location1-4. The use of a collagen conduit for recurrent neuromas is advantageous, particularly in areas with minimal soft-tissue coverage options, and is a technique that has shown 85% patient satisfaction regarding surgical outcomes7. Additionally, the use of a collagen conduit limits the need for deep soft-tissue dissection and reduces the morbidity typically associated with nerve burial. Description: Specific steps include appropriate physical examination, preoperative planning, and supine patient positioning. The patient is placed supine with a lower-extremity bolster under the ipsilateral extremity in order to allow improved visualization of the plantar surface of the foot. A nonsterile tourniquet is placed on the thigh. The incision site is marked out, and a longitudinal plantar incision is made until proximal healthy nerve is identified-typically approximately 1 to 2 cm, but the incision can be extended up to 6 cm. The incision is made between the metatarsals, with blunt dissection carried down to the neuroma. The neuroma is sharply excised distally through healthy nerve, and a whip stitch is placed to facilitate the collagen conduit placement. The collagen conduit is passed dorsally into the intermetatarsal space and secured to the dorsal fascia of the foot. The wound is closed with 3-0 nylon horizontal mattress sutures. Postoperatively, a soft dressing is applied to the operative extremity, and patients are advised to be non-weight-bearing for two weeks. At two weeks, patients begin partial weight-bearing with use of a boot, and physical therapy is initiated. No antibiotics are necessary, and 300 mg of gabapentin is prescribed and tapered off by the six-week follow-up visit. Follow-ups are conducted at 2, 6, 12, 24, and fifty-two weeks. It is necessary to monitor for signs and symptoms of infection, surgical complications, and neuroma recurrence during follow-up appointments. Alternatives: Simple excision of the neuroma with proximal burial into muscle or bone is a common surgical technique. However, inadequate resection of the nerve or poor surgical technique can lead to recurrent neuromas. For neuromas not responding to simple excision, other techniques have been utilized, including cauterization, chemical agents, nerve capping, and muscle or bone burial5,6. The results of these techniques have varied, and none has gained clinical superiority over the other6. Rationale: A study analyzing the use of collagen conduits for painful neuromas of the foot and ankle has shown this technique to be a safe and successful alternative to the previously discussed methods of resection7. That study by Gould et al. found that 85% of patients had a substantial reduction in pain, with mean visual analog scale (VAS) pain scores reducing from 8 to 10 preoperatively to 0 to 4 postoperatively7. Moreover, alternative biological conduits, such as the greater saphenous vein, have proven to be costly in time and resources, as this structure is often utilized in cardiovascular bypass surgery and its harvest conveys a risk of iatrogenic nerve injury to the patient7.Numerous studies focusing on excision of recurrent Morton neuromas via a plantar approach have found variable success rates. Of the patients surveyed in those studies, 75% reported substantial pain improvement. However, <50% of these queried patients reported complete pain relief8,9. Studies analyzing the dorsal approach for revision Morton neuroma excision found similar success rates. Approximately 78% of patients reported good or excellent postoperative outcomes, and significant improvements were observed in patient postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores for pain interference, intensity, and global physical health10,11. One study comparing outcomes following plantar versus dorsal approaches for recurrent Morton neuroma found no significant difference in postoperative patient outcomes. That study suggested that surgeons utilize the approach with which they are most comfortable12. Gould et al. reported an 85% success rate with collagen conduit, which was similar to if not slightly improved compared with the other prior studies. The utilization of a collagen conduit technique thus offers comparable patient outcomes for patients with difficult neuromas7. Expected Outcomes: Recurrent neuroma resection with the use of a collagen conduit has proven to provide satisfactory patient outcomes regarding pain and neuritis symptoms7. The goal of any neuroma resection is to greatly diminish or entirely eliminate nerve pain. Based on the available evidence, there has been no proven clinical superiority of any particular technique over the others6. However, in the present example case, the location of the patient's neuroma in this video makes it 85% likely that the patient will report satisfactory outcomes and 50% likely that the patient will be entirely symptom-free7. At two weeks postoperatively, the patient reported well controlled pain, absence of burning or tingling sensation, full range of movement in the foot, and intact sensation throughout all major nerve distributions, including the saphenous; superficial peroneal nerve; deep peroneal nerve; and sural, medial, and lateral plantar nerves. However, sensation is absent distal to the site of a neuroma resection. Important Tips: Careful preoperative planting is of utmost importance.Ruling out other potential pathologies is necessary to ensure proper outcomes.Meticulous dissection should be carried out, with delicate handling of the proximal nerve ending.Excision of the nerve should be done sharply through the healthy portion of the nerve.Appropriate sizing of the nerve conduit (with a commercially available industry sizer) should be performed.The nerve conduit should be passed dorsally and secured to the dorsal fascia without any tension. Acronyms and Abbreviations: MRI = magnetic resonance imagingUS = ultrasoundVAS = visual analog scale.

Erector Spinae Plane Blocks for Circumferential Lumbar Spinal Fusion: Retrospective Cohort Study.

BACKGROUND: Circumferential lumbar spine fusions are extensive procedures that involve accessing the lumbar spine from multiple approaches. These surgeries often make postoperative pain control challenging, and efforts have been made to find alternative methods of analgesia that do not rely solely on opioids. The use of erector spinae plane (ESP) blocks has been found to be effective in controlling pain while decreasing narcotic requirements in patients undergoing thoracolumbar spine surgery. The purpose of this study is to evaluate the efficacy of ESP blocks for postoperative pain control and its effect on opioid consumption in patients undergoing circumferential lumbar spinal fusion. METHODS: A retrospective review was performed on patients undergoing 1- or 2-level elective anterior lumbar interbody fusion with open posterior decompression and posterolateral fusion. An analysis was performed to determine the effect of ESP blocks on hospital length of stay (LOS), pain scores using the visual analog scale, and opioid consumption using morphine milligram equivalents. RESULTS: 144 patients were included in the cohort analysis, of whom 36 patients received a preoperative ESP block and 108 did not. Demographic data, comorbidities, and number of levels fused were equally distributed between groups. Patients who received an ESP block had shorter LOS (3.0 vs 4.0 days, P = 0.005) and lower cumulative morphine milligram equivalent in the first 48 hours after surgery (123.7 vs 141.2, P = 0.05). Visual analog scale scores did not significantly differ between patients group except for on postoperative day 4 and at 12-month follow-up. CONCLUSIONS: The use of ESP blocks for patients undergoing 1- or 2-level circumferential fusion via an anterior lumbar interbody fusion with concomitant posterior open procedures was associated with decreased postoperative inpatient opioid requirements and LOS. This cohort study supports the growing body of evidence that ESP blocks are a useful adjunct for multimodal pain control. LEVEL OF EVIDENCE: 3 CLINICAL RELEVANCE: The data and results of this study provide clinical evidence supporting the use of ESP blocks in patients undergoing circumferential lumbar spine fusion procedures.

Factors and Radiographic Findings Influencing Patient-Reported Outcomes Following Maisonneuve Fractures.

BACKGROUND: This research adds to the literature by providing prognostic information for physicians and patients regarding the outcomes of operative management of Maisonneuve fractures (MFs). To date, this is the only cohort study of patient-reported outcomes measurement information systems (PROMIS) scores following surgical fixation of MF. Patient outcomes were compared focusing on the mean population with an inter-analysis using basic demographic information, radiographic findings, and patient comorbidities and their respective impact on PROMIS scores. METHODS: A total of 24 patients between 2012 and 2020 met the inclusion criteria and completed PROMIS surveys at a minimum of 18 months postoperatively. Patient charts were reviewed through the electronic medical record (EMR) for demographic information and comorbidities as well as operative variables. PROMIS scores for physical function (PF), pain interference (PI), and depression were obtained via follow-up visits and phone calls. The impact of categorical variables on complications was compared using Chi-Squared tests. Variables were analyzed with a type 3 SS test to stratify independent risk factors' effect on PROMIS scores and to account for confounding variables. RESULTS: PROMIS PF averaged 44.84 and was significantly affected by BMI>30 (p=.033), hypertension (HTN) (p=.026), patients with clinical anxiety or depression (p=.047), and subsequent screw removal (p=.041). PROMIS PI averaged a score of 54.57 and was significantly affected by BMI>30 (p=.0046), coronary artery disease (CAD) (p=.0123), patients with clinical anxiety or depression (p=.0206), and subsequent screw removal (p=.0039). PROMIS depression scores averaged 46.03 and were significantly affected by the presence of CAD (p=.049) and subsequent screw removal (p=.023). CONCLUSION: Patient-reported outcomes following MF surgery demonstrated PROMIS scores within +/- 1 standard deviation of the population-based control, and thus many patients can reasonably expect to return to a level of function comparable to the general population. Nonetheless, the significant effects of patient comorbidities and surgical variables ought to be evaluated and utilized as prognostic indicators when managing patient expectations prior to operative treatment of an MF injury.

Topical Antibiotic Powder and Nonunion Risk in Surgically Treated Tibial Plateau and Pilon Fractures.

INTRODUCTION: High-energy periarticular tibia fractures are challenging injuries with a significant risk of complications. Postoperative infection rates, although improved, remain unacceptable. Intrawound topical antibiotic (TA) application has been popularized to reduce postoperative infections. Although TA may minimize infections, it remains unclear whether TAs have any impact on the development of nonunion. Recent investigations of TA use in fracture care have questioned its efficacy in vivo and suggested a potentially deleterious effect on fracture healing. This study investigates the impact of TA on nonunion rates in surgically treated high-energy periarticular tibia fractures. METHODS: Retrospective analysis of surgically treated periarticular tibia fractures at a single Level 1 trauma center was conducted. Intervention in question was the clinical effect of intrawound TA powder application at definitive closure. A total of 222 high-energy periarticular tibia fractures were included, 114 with TA use and 108 without. The primary outcome was the occurrence of nonunion, with secondary outcomes being superficial and deep postoperative surgical site infections. RESULTS: Twenty-seven patients (12.1%) were diagnosed with nonunions (14 pilons and 13 plateaus). There was no statistically significant difference in nonunion rates among patients who received topical antibiotics (15.8%) versus the group of patients who did not (8.3%) ( P = 0.23). Odds of developing nonunion was significant for open injuries (odds ratio 6.16, P < 0.001) and patients with a provisional external fixator (odds ratio 8.72, P = 0.03) before definitive fixation. No notable difference in the number of superficial and deep infections was identified between groups. CONCLUSION: The use of TA in high-energy periarticular tibia fractures showed no statistically significant increase in nonunion rates but did not conclusively rule out nonunion as a possible effect of intrawound TA. Additional large-scale multicenter prospective studies are needed to confirm these findings. The current body of literature regarding high-energy periarticular tibia fractures does suggest that TAs lower the risk of postoperative infections, but the nonunion risk remains unclear. LEVEL OF EVIDENCE: Level III, Retrospective Cohort Study.

Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes.

Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation. Network analysis delineated five tissue-specific gene modules; these modules and chromatin state analysis defined broad similarities in gene expression during cartilage specification and maturation in vitro and in vivo, including early expression and progressive silencing of muscle- and bone-specific genes. Finally, ontogenetic analysis of freshly isolated and pluripotent stem cell-derived articular chondrocytes identified that integrin alpha 4 defines 2 subsets of functionally and molecularly distinct chondrocytes characterized by their gene expression, osteochondral potential in vitro and proliferative signature in vivo. These analyses provide new insight into human musculoskeletal development and provide an essential comparative resource for disease modeling and regenerative medicine.