Are Generative Pretrained Transformer 4 Responses to Developmental Dysplasia of the Hip Clinical Scenarios Universal? An International Review.

OBJECTIVE: There is increasing interest in applying artificial intelligence chatbots like generative pretrained transformer 4 (GPT-4) in the medical field. This study aimed to explore the universality of GPT-4 responses to simulated clinical scenarios of developmental dysplasia of the hip (DDH) across diverse global settings. METHODS: Seventeen international experts with more than 15 years of experience in pediatric orthopaedics were selected for the evaluation panel. Eight simulated DDH clinical scenarios were created, covering 4 key areas: (1) initial evaluation and diagnosis, (2) initial examination and treatment, (3) nursing care and follow-up, and (4) prognosis and rehabilitation planning. Each scenario was completed independently in a new GPT-4 session. Interrater reliability was assessed using Fleiss kappa, and the quality, relevance, and applicability of GPT-4 responses were analyzed using median scores and interquartile ranges. Following scoring, experts met in ZOOM sessions to generate Regional Consensus Assessment Scores, which were intended to represent a consistent regional assessment of the use of the GPT-4 in pediatric orthopaedic care. RESULTS: GPT-4's responses to the 8 clinical DDH scenarios received performance scores ranging from 44.3% to 98.9% of the 88-point maximum. The Fleiss kappa statistic of 0.113 ( P = 0.001) indicated low agreement among experts in their ratings. When assessing the responses' quality, relevance, and applicability, the median scores were 3, with interquartile ranges of 3 to 4, 3 to 4, and 2 to 3, respectively. Significant differences were noted in the prognosis and rehabilitation domain scores ( P < 0.05 for all). Regional consensus scores were 75 for Africa, 74 for Asia, 73 for India, 80 for Europe, and 65 for North America, with the Kruskal-Wallis test highlighting significant disparities between these regions ( P = 0.034). CONCLUSIONS: This study demonstrates the promise of GPT-4 in pediatric orthopaedic care, particularly in supporting preliminary DDH assessments and guiding treatment strategies for specialist care. However, effective integration of GPT-4 into clinical practice will require adaptation to specific regional health care contexts, highlighting the importance of a nuanced approach to health technology adaptation. LEVEL OF EVIDENCE: Level IV.

Combination of tibial tubercle transfer, medial patellofemoral ligament reconstruction, trochleoplasty and lateral release for patellofemoral instability provides good middle- to long-term outcomes in adolescents.

PURPOSE: There are limited studies that have reported the middle- to long-term outcomes of combined procedures consisting of more than two procedures for patellofemoral instability. The current study aims to investigate and report the middle- to long-term outcomes of a combination procedure of tibial tubercle transfer, medial patellofemoral ligament reconstruction, trochleoplasty and lateral release for patellofemoral instability in patients aged 18 years and below. METHODS: In the cohort study, all patients aged 18 years old or younger who underwent a combination procedure of tibial tubercle transfer, medial patellofemoral ligament reconstruction, trochleoplasty and lateral release for recurrent patellofemoral instability were included. RESULTS: A total of 21 patients were included in the study. All patients had no further patellofemoral dislocation, pain and apprehension following the 4-in-1 surgery (p < 0.01). There was a significant improvement in the Kujala score from 36.1 (SD 12.9) pre-operatively to 93.1 (SD 3.6) post-operatively (p < 0.001). The patients also had a statistically significant improvement in their radiological factors, including the patellar tilt angle (p < 0.001), sulcus angle (p = 0.001), trochlear groove depth (p = 0.041), tibial tubercle-trochlear groove distance (p < 0.001) and Caton-Deschamps index (p = 0.001). CONCLUSION: A combination procedure of tibial tubercle transfer, medial patellofemoral ligament reconstruction, trochleoplasty and lateral release leads to good middle- to long-term subjective, functional and radiographic outcomes for patients with recurrent patellofemoral instability and underlying predisposing factors of increased TT-TG distance of more than 20 mm, Dejour B or D trochlear dysplasia and medial patellofemoral ligament rupture. LEVEL OF EVIDENCE: IV.

Small extracellular vesicles from mesenchymal stromal cells: the next therapeutic paradigm for musculoskeletal disorders.

Musculoskeletal disorders are one of the biggest contributors to morbidity and place an enormous burden on the health care system in an aging population. Owing to their immunomodulatory and regenerative properties, mesenchymal stromal/stem cells (MSCs) have demonstrated therapeutic efficacy for treatment of a wide variety of conditions, including musculoskeletal disorders. Although MSCs were originally thought to differentiate and replace injured/diseased tissues, it is now accepted that MSCs mediate tissue repair through secretion of trophic factors, particularly extracellular vesicles (EVs). Endowed with a diverse cargo of bioactive lipids, proteins, nucleic acids and metabolites, MSC-EVs have been shown to elicit diverse cellular responses and interact with many cell types needed in tissue repair. The present review aims to summarize the latest advances in the use of native MSC-EVs for musculoskeletal regeneration, examine the cargo molecules and mechanisms underlying their therapeutic effects, and discuss the progress and challenges in their translation to the clinic.

Lower re-rupture rates but higher complication rates following surgical versus conservative treatment of acute achilles tendon ruptures: a systematic review of overlapping meta-analyses.

PURPOSE: To systematically review and evaluate the current meta-analyses for the treatment of acute Achilles tendon rupture (AATR). This study can provide clinicians with a clear overview of the current literature to aid clinical decision-making and the optimal formulation of treatment plans for AATR. METHODS: Two independent reviewers searched PubMed and Embase on June 2, 2022 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Assessment of evidence was twofold: level of evidence (LoE) and quality of evidence (QoE). LoE was evaluated using published criteria by The Journal of Bone and Joint Surgery and the QoE by the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) scale. Pooled complication rates were highlighted for significance in favour of one treatment arm or no significance. RESULTS: There were 34 meta-analyses that met the eligibility criteria, with 28 studies of LoE 1, and the mean QoE was 9.8 ± 1.2. Significantly lower re-rupture rates were reported with surgical (2.3-5%) versus conservative treatment (3.9-13%), but conservative treatment was favoured in terms of lower complication rates. The re-rupture rates were not significantly different between percutaneous repair or minimally invasive surgery (MIS) compared to open repair, but MIS was favoured in terms of lower complication rates (7.5-10.4%). When comparing rehabilitation protocols following open repair (four studies), conservative treatment (nine studies), or combined (three studies), there was no significant difference in terms of re-rupture or obvious advantage in terms of lower complication rates between early versus later rehabilitation. CONCLUSION: This systematic review found that surgical treatment was significantly favoured over conservative treatment for re-rupture, but conservative treatment had lower complication rates other than re-rupture, notably for infections and sural nerve injury. Open repair had similar re-rupture rates to MIS, but lower complication rates; however, the rate of sural nerve injuries was lower in open repair. When comparing earlier versus later rehabilitation, there was no difference in re-rupture rates or obvious advantage in complications between open repair, conservative treatment, or when combined. The findings of this study will allow clinicians to effectively counsel their patients on the postoperative outcomes and complications associated with different treatment approaches for AATR. LEVEL OF EVIDENCE: IV.

Strategies to enhance immunomodulatory properties and reduce heterogeneity in mesenchymal stromal cells during ex vivo expansion.

Therapies using mesenchymal stromal cells (MSCs) to treat immune and inflammatory conditions are now at an exciting stage of development, with many MSC-based products progressing to phase II and III clinical trials. However, a major bottleneck in the clinical translation of allogeneic MSC therapies is the variable immunomodulatory properties of MSC products due to differences in their tissue source, donor heterogeneity and processes involved in manufacturing and banking. This variable functionality of MSC products likely contributes to the substantial inconsistency observed in the clinical outcomes of phase III trials of MSC therapies; several trials have failed to reach the primary efficacy endpoint. In this review, we discuss various strategies to consistently maintain or enhance the immunomodulatory potency of MSCs during ex vivo expansion, which will enable the manufacture of allogeneic MSC banks that have high potency and low variability. Biophysical and biochemical priming strategies, the use of culture additives such as heparan sulfates, and genetic modification can substantially enhance the immunomodulatory properties of MSCs during in vitro expansion. Furthermore, robust donor screening, the use of biomarkers to select for potent MSC subpopulations, and rigorous quality testing to improve the release criteria for MSC banks have the potential to reduce batch-to-batch heterogeneity and enhance the clinical efficacy of the final MSC product. Machine learning approaches to develop predictive models of individual patient response can enable personalized therapies and potentially establish correlations between in vitro potency measurements and clinical outcomes in human trials.

Clinical Outcomes of Patients with C3G or IC-MPGN Treated with the Factor D Inhibitor Danicopan: Final Results from Two Phase 2 Studies.

INTRODUCTION: C3 glomerulopathy (C3G) is an ultrarare, chronic and progressive nephropathy mediated by dysregulation of the alternative pathway of complement (AP), with poor prognosis and limited treatment options. Targeted inhibition of proximal AP through factor D (FD) blockade represents a rational treatment approach. We present two phase 2 proof-of-concept clinical studies of the orally active FD inhibitor danicopan in patients with C3G and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) (NCT03369236 and NCT03459443). METHODS: A double-blind, placebo-controlled study in patients with C3G and a single-arm, open-label study in patients with C3G or IC-MPGN treated with danicopan are reported. The studies evaluated pharmacokinetic/pharmacodynamic (PK/PD), efficacy, and safety outcomes. The co-primary endpoints were change from baseline in composite biopsy score and the proportion of patients with a 30% reduction in proteinuria relative to baseline at 6 or 12 months. RESULTS: Optimal systemic concentrations of danicopan were not achieved for complete and sustained inhibition of AP, although there was evidence that blockade of FD reduced AP activity shortly after drug administration. Consequently, limited clinical response was observed in key efficacy endpoints. While stable disease or improvement from baseline was seen in some patients, response was not consistent. The data confirmed the favorable safety profile of danicopan. CONCLUSION: While demonstrating a favorable safety profile, danicopan resulted in incomplete and inadequately sustained inhibition of AP, probably due to limitations in its PK/PD profile in C3G, leading to lack of efficacy. Complete and sustained AP inhibition is required for a clinical response in patients with C3G.

Orthopedic concerns of a child with short stature.

PURPOSE OF REVIEW: Pediatric short stature poses severe concerns to the patient, parents, and physicians. Management for pediatric short stature is still widely debated due to heterogenous etiological factors and treatment options. This review will address the approach to pediatric short stature, commonly within the subset of skeletal dysplasia resulting in disproportionate short stature. The following will be discussed: the etiology, clinical, and radiological evaluations, and management for pediatric short stature. RECENT FINDINGS: Early recognition of short stature and appropriate referrals is shown to benefit the patient and reduce parental concern. A multidisciplinary team, comprising an orthopedic surgeon, is fundamental to provide holistic care and ensure overall good quality of life. Advancements in clinical diagnostic tools and diversified treatment modalities today provides optimism in managing pediatric short stature. SUMMARY: Skeletal dysplasia can be treated with good prognosis if diagnosed and managed early. Thorough clinical, radiological, laboratory, and even genetic investigations are important to differentiate and manage various types of skeletal dysplasia. Our review will provide a comprehensive and up-to-date approach to skeletal dysplasia for pediatric orthopedic surgeons, and indications for physicians to refer patients with suspected short stature to pediatric orthopedic surgeons.

Limited evidence of adjuvant biologics with bone marrow stimulation for the treatment of osteochondral lesion of the talus: a systematic review.

PURPOSE: To evaluate the complication rates, continuous functional outcome scores, and return to play data following bone marrow stimulation (BMS) versus biologics ± BMS for the treatment of osteochondral lesion of the talus (OLT). METHODS: A systematic review was performed. The PubMed and Embase databases were searched using specific search terms and eligibility criteria according to the PRISMA guidelines. The level of evidence was assessed using published criteria by The Journal of Bone & Joint Surgery, and the quality of evidence using the Modified Coleman Methodology Score. Continuous variables were presented as mean ± standard deviation and categorical variables as frequencies (percentages). RESULTS: BMS versus BMS + hyaluronic acid (HA): no complications in either treatment arm were reported. The mean American Orthopaedic Foot and Ankle Society score was 43.5 to 67.3 points and 44.0 to 72.4 points, respectively. The mean 10 mm Visual Analogue Scale pain score was 7.7 to 3.8 points and 7.5 to 2.5 points, respectively. BMS versus BMS + concentrated bone marrow aspirate (CBMA): the pooled overall complication rate was 17/64 (26.6%) versus 11/71 (15.5%), respectively (non-significant). The pool revision rate was 15/64 (23.4%) versus 6/71 (8.5%), respectively (p = 0.016). There has been a notable poor reporting of complication rates for the use of ADSC and PRP as adjuvant biological therapies to BMS for the treatment of OLT. CONCLUSION: There was an overall limited comparative clinical evidence of adjuvant biologics with BMS versus BMS alone for the treatment of OLT. BMS + HA and BMS + CBMA can provide superior outcomes, albeit the currently limited evidence. Further studies are warranted to establish the true clinical superiority of the various biologics ± BMS versus BMS alone. These studies must also compare the various biologics against one another to determine, if any, the optimal biologic for OLT. Clinicians should counsel patients accordingly on these findings as required. LEVEL OF EVIDENCE: Level III.

Predictive Scoring for Recurrent Patellar Instability After a First-time Patellar Dislocation.

PURPOSE: Patellofemoral instability is a common acute knee injury seen in the pediatric population. First-time patellar dislocations usually undergo conservative management, but ~15% to 80% of patients experience recurrent instability. This study aims to develop a prediction model using radiographic parameters of the patellofemoral joint seen on computed tomography scans in different degrees of knee flexion, to determine the risk of recurrence after the first episode of patellofemoral instability. METHODS: A 12-year retrospective case-control study was performed. All patients in a single institution aged 18 years or younger who had a computed tomography patellar tracking scan performed for patellar instability were included. Predictors included in the score were determined through backward logistic regression and compared using receiver operating characteristic curve analysis. RESULTS: This study revealed that recurrent dislocation in first-time patellofemoral dislocation could be accurately predicted using the prediction score that consisted of age, tibial tubercle-trochlear groove distance and congruence angle at 10- and 20-degree flexion. The sensitivity of the score was 100% and specificity was 73.3%. Three diagnostic zones were identified and used to categorize patients into low-, intermediate-, and high-probability groups. CONCLUSION: This study presented a scoring system that incorporated radiographic knee kinematics in the risk assessment for recurrent patellofemoral instability for patient stratification. The scoring system could guide the decision for early surgical intervention after the first-episode patellofemoral dislocation for patients at high risk of recurrent patellofemoral dislocation.

Accuracy of biplanar linear radiography versus conventional radiographs when used for lower limb and implant measurements.

INTRODUCTION: The current standard of care for measuring lower extremity length and angular discrepancies is using a full-length standing anteroposterior radiograph. However, there has been increasing interest to use biplanar linear EOS imaging as an alternative. This study aims to compare lower extremity length and implant measurements between biplanar linear and conventional radiographs. MATERIALS AND METHODS: In this 5-year retrospective study, all patients who had a standing full-length anteroposterior and biplanar linear radiographs (EOS®) that include the lower extremities done within one year of each other were included. Patients who underwent surgery in between the imaging, underwent surgeries that could result in graduated length or angulated corrections and inadequate exposure of the lower extremity were excluded. Four radiographic segments were measured to assess lower limb alignment and length measurements. Height and width measurements of implants were performed for patients who had implants in both imaging. RESULTS: When comparing imaging and actual implant dimensions, biplanar linear radiographs were accurate in measuring actual implant height (median difference = - 0.14 cm, p = 0.66), and width (median difference = - 0.13 cm, p = 0.71). However, conventional radiographs were inaccurate in measuring actual implant height (median difference = 0.19 cm, p = 0.01) and width (median difference = 0.61 cm, p < 0.01). When comparing conventional and biplanar linear radiographs, there was statistically significant difference in all measurements. This includes anatomical femoral length (median difference = 3.53 cm, p < 0.01), mechanical femoral length (median difference = 3.89 cm, p < 0.01), anatomical tibial length (median difference = 2.34 cm, p < 0.01) and mechanical tibial length (median difference = 2.20 cm, p < 0.01). CONCLUSION: First, there is a significant difference in the lower extremity length when comparing conventional and biplanar linear radiographs. Second, biplanar linear radiographs are found to be accurate while conventional radiographs are not as accurate in implant measurements of length and width in the lower extremity.

Meniscoplasty leads to good mid-term to long-term outcomes for children and adolescents with discoid lateral meniscus.

PURPOSE: To date, there have been limited studies reporting the mid- to long-term outcomes of meniscoplasties for discoid lateral meniscus. The current study aims to evaluate the mid- to long-term outcomes of arthroscopic meniscoplasty for discoid lateral meniscus in children and adolescents. METHODS: In the study, all patients under the age of 21 years who had undergone arthroscopic meniscoplasty with or without meniscal repair or partial meniscectomy for symptomatic lateral discoid meniscus were included. All patients were then followed up for a minimum of 5 years (median 84 months; range 68-110 months). The Lysholm scores and Ikeuchi scores were collected pre-operatively and at final follow-up and were compared. RESULTS: A total of 24 knees were included in the study. The median duration of follow-up was 84.0 months (range 68-110 months). The Lysholm score improved from 53 (range 11-95) pre-operatively to 100.0 (range 60-100) at final follow-up (p < 0.001). Based on the Ikeuchi score pre-operatively, 15 knees were rated as poor (62.5%), 7 knees were rated as fair (29.2%), and 2 knees were rated as good (8.4%). The Ikeuchi score improved significantly at the final follow-up, such that 1 knee was rated as good (4.2%) and 23 knees were rated as excellent (95.8%) (p < 0.001). When analysing the effect of concomitant meniscal repair or partial meniscectomy on the outcomes at final follow-up, there was no apparent difference in the improvement in Lysholm score or Ikeuchi score when comparing between patients who had meniscoplasty alone and patients who had concomitant meniscal repair, as well as when comparing between patients who had meniscoplasty alone and patients who had concomitant partial meniscectomy. CONCLUSION: Meniscoplasty leads to good mid-term to long-term outcomes for children and adolescents with discoid lateral meniscus. Concomitant procedures such as meniscal repair or partial meniscectomy do not improve or worsen the mid- to long-term outcomes in these patients. LEVEL OF EVIDENCE: IV.

The incidence and risk factors of osteoarthritis following osteochondritis dissecans of the knees: a systematic review and meta-analysis.

PURPOSE: The current systematic review and meta-analysis aim to pool together the incidence and risk factors of osteoarthritis following osteochondritis dissecans of the knee. METHODS: The systematic review was conducted according to PRISMA guidelines. A search was conducted using PubMed and Cochrane Library with the keywords being "knee" and "osteochondritis dissecans" or "osteochondral lesion". All original human studies that reported the incidence or risk factors of osteoarthritis following osteochondritis dissecans of the knee were included. RESULTS: Nine studies with 496 patients were included. The incidence of osteoarthritis following osteochondritis dissecans is 0.39 (95% CI 0.19-0.59). Patients with a body mass index greater than 25 kg/m2 had a significantly increased risk of osteoarthritis. Fragment excision had an increased relative risk of 1.89 (95% CI 1.19-3.01) of osteoarthritis as compared to fragment preservation. Significant heterogeneity was identified when comparing between juvenile and adult osteochondritis dissecans. The size of the lesions moderated the between-study heterogeneity with regards to the incidence of osteoarthritis, with the relative risk of osteoarthritis in lesions bigger than 4 cm2 being 2.29 (95% CI 1.24-4.23). No other risk factors, including gender of the patient, location of osteochondritis dissecans, stability of osteochondritis dissecans, and surgical versus non-surgical management were significant risk factors. CONCLUSION: Significant risk factors for osteoarthritis were increased body mass index and fragment excision. Probable but inconclusive risk factors were the age of the patients and the size of the osteochondritis dissecans. The gender of the patient, location of osteochondritis dissecans, the stability of osteochondritis dissecans, and surgical versus non-surgical management of osteochondritis dissecans when appropriate were not significant risk factors.

The outcomes of subtalar arthroereisis in pes planus: a systemic review and meta-analysis.

INTRODUCTION: Subtalar arthroereisis has been increasingly accepted as a solution to manage symptomatic pes planus. However, despite the recent developments related to arthroereisis, no other published literature has aimed to review the outcomes in paediatric patients since 2010. This systematic review and meta-analysis, therefore, aims to evaluate the current outcomes of subtalar arthroereisis in the treatment of symptomatic pes planus among the paediatric population. MATERIALS AND METHODS: The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All studies reported on the clinical outcomes of subtalar arthroereisis in children aged 21 or younger were included. RESULTS: A total of 17 publications were included, with 1536 feet. The average duration of follow-up of the studies included in the review is 43.52 months. The studies consistently reported improvement in the radiological outcomes, approximating that of a normal population. Subtalar arthroereisis has shown to restore the collapsed medial longitudinal arch, supported by the decrease in Meary's angle to 5.267° (95% CI: 4.695°-5.839°, normal: 0°-10.0°) post-operatively and an increased calcaneal pitch of 15.70° (95% CI: 15.41°-15.99°, normal 18.0°-20.0°). Deformities associated with pes planus such as heel valgus was also significantly reduced, evident by the post-operative lateral talocalcaneal angle of 27.19° (95% CI: 26.44°-27.93°, normal: 25.0°-45.0°) and a post-operative Kite's angle of 18.13° (95% CI: 17.73°-18.52°, normal: 15.0°-30.0°). Subjectively, subtalar arthroereisis has generally resulted in an improvement in the grading of outcomes postoperatively from the patient's point of view. CONCLUSIONS: Subtalar arthroereisis could serve as a procedure to correct radiological abnormalities, as well as relieve pain in selected patients with symptomatic pes planus.

Quantitative Control of Gene-Engineered T-Cell Activity through the Covalent Attachment of Targeting Ligands to a Universal Immune Receptor.

Universal immune receptors represent a rapidly emerging form of adoptive T-cell therapy with the potential to overcome safety and antigen escape challenges faced by conventional chimeric antigen receptor (CAR) T-cell therapy. By decoupling antigen recognition and T-cell signaling domains via bifunctional antigen-specific targeting ligands, universal immune receptors can regulate T-cell effector function and target multiple antigens with a single receptor. Here, we describe the development of the SpyCatcher immune receptor, the first universal immune receptor that allows for the post-translational covalent attachment of targeting ligands at the T-cell surface through the application of SpyCatcher-SpyTag chemistry. The SpyCatcher immune receptor redirected primary human T cells against a variety of tumor antigens via the addition of SpyTag-labeled targeting ligands, both in vitro and in vivo. SpyCatcher T-cell activity relied upon the presence of both target antigen and SpyTag-labeled targeting ligand, allowing for dose-dependent control of function. The mutational disruption of covalent bond formation between the receptor and the targeting ligand still permitted redirected T-cell function but significantly compromised antitumor function. Thus, the SpyCatcher immune receptor allows for rapid antigen-specific receptor assembly, multiantigen targeting, and controllable T-cell activity.

Intra-Articular Injections of Mesenchymal Stem Cell Exosomes and Hyaluronic Acid Improve Structural and Mechanical Properties of Repaired Cartilage in a Rabbit Model.

PURPOSE: To compare the efficacy of mesenchymal stem cell (MSC) exosomes with hyaluronic acid (HA) against HA alone for functional cartilage regeneration in a rabbit osteochondral defect model. METHODS: Critical-size osteochondral defects (4.5-mm diameter and 1.5-mm depth) were created on the trochlear grooves in the knees of 18 rabbits and were randomly allocated to 2 treatment groups: (1) exosomes and HA combination and (2) HA alone. Three 1-mL injections of either exosomes and HA or HA alone were administered intra-articularly immediately after surgery and thereafter at 7 and 14 days after surgery. At 6 and 12 weeks, gross evaluation, histologic and immunohistochemical analysis, and scoring were performed. The functional biomechanical competence of the repaired cartilage also was evaluated. RESULTS: Compared with defects treated with HA, defects treated with exosomes and HA showed significant improvements in macroscopic scores (P = .032; P = .001) and histologic scores (P = .005; P < .001) at 6 and 12 weeks, respectively. Defects treated with exosomes and HA also demonstrated improvements in mechanical properties compared with HA-treated defects, with significantly greater Young's moduli (P < .05) and stiffness (P < .05) at 6 and 12 weeks. By 12 weeks, the newly-repaired tissues in defects treated with exosomes and HA composed mainly of hyaline cartilage that are mechanically and structurally superior to that of HA-treated defects and demonstrated mechanical properties that approximated that of adjacent native cartilage (P > .05). In contrast, HA-treated defects showed some repair at 6 weeks, but this was not sustained, as evidenced by significant deterioration of histologic scores (P = .002) and a plateau in mechanical properties from 6 to 12 weeks. CONCLUSIONS: This study shows that the combination of MSC exosomes and HA administered at a clinically acceptable frequency of 3 intra-articular injections can promote sustained and functional cartilage repair in a rabbit post-traumatic cartilage defect model, when compared with HA alone. CLINICAL RELEVANCE: Human MSC exosomes and HA administered in combination promote functional cartilage repair and may represent a promising cell-free therapy for cartilage repair in patients.

Medications in COVID-19 patients: summarizing the current literature from an orthopaedic perspective.

PURPOSE: The review aims to provide a summary of the current literature regarding common medications prescribed in orthopaedic surgery and their potential implications in COVID-19 patients. METHODS: A systematic review was performed using the PRISMA guidelines. All clinical studies, reviews, consensus and guidelines related to the above medications and COVID-19 were included. RESULTS: A total of 18 articles were included. The use of analgesia, anti-inflammatories, steroids, anticoagulants, antibiotics, vitamin B, vitamin C and vitamin D and their potential impact on COVID-19 patients were reported. CONCLUSION: Eight main recommendations were derived from the review. Firstly, paracetamol remains the first line of analgesia and antipyretic. Secondly, there is no need to avoid NSAIDs for COVID-19 patients. Thirdly, opioids have the potential for immunosuppression in addition to respiratory depression and, therefore, should be prescribed with care in COVID-19 patients. Fourthly, patients with conditions where steroids are proven to be efficacious can continue to receive their steroids; otherwise, systemic steroids are not recommended for COVID-19 patients. Fifthly, orthopaedic surgeons following up on COVID-19 patients who are using steroids should continue to follow them up for possible avascular necrosis. Sixthly, whenever possible, oral anticoagulation should be converted to parental heparin. Seventhly, common orthopaedic antibiotics including penicillin and clindamycin are safe to continue for COVID-19 patients. However, for COVID-19 patients, the antibiotics can potentially be switched to macrolides and tetracyclines if the organisms are sensitive. Lastly, prescription for vitamins B, C and D should continue as per usual clinical practice.

MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment.

Mesenchymal stem cell (MSC) therapies have demonstrated efficacy in cartilage repair in animal and clinical studies. The efficacy of MSC-based therapies which was previously predicated on the chondrogenic potential of MSC is increasingly attributed to the paracrine secretion, particularly exosomes. Exosomes are thought to function primarily as intercellular communication vehicles to transfer bioactive lipids, nucleic acids (mRNAs and microRNAs) and proteins between cells to elicit biological responses in recipient cells. For MSC exosomes, many of these biological responses translated to a therapeutic outcome in injured or diseased cells. Here, we review the current understanding of MSC exosomes, discuss the possible mechanisms of action in cartilage repair within the context of the widely reported immunomodulatory and regenerative potency of MSC exosomes, and provide new perspectives for development of an off-the-shelf and cell-free MSC therapy for treatment of cartilage injuries and osteoarthritis.

Hemiepiphysiodesis is a potentially effective surgical management for skeletally immature patients with patellofemoral instability associated with isolated genu valgum.

PURPOSE: Genu valgum is one of the well-known predisposing factors for patellofemoral instability. The study aims to investigate the outcomes of isolated hemiepiphysiodesis in the correction of genu valgum and in the management of recurrent patellofemoral instability. The hypothesis was that hemiepiphysiodesis alone would result in significant correction of genu valgum, thereby preventing recurrent patellofemoral instability. METHODS: In the cohort study, all skeletally immature patients who underwent isolated hemiepiphysiodesis for recurrent patellofemoral instability were included. All patients included in the study had a minimum of 1-year follow-up duration prior to the conclusion of the study. RESULTS: Sixteen of twenty knees had no further patellofemoral instability post-operatively. The change in the status of patellofemoral instability was statistically significant (p = 0.001), similar to the change in the tibiofemoral angle (p = 0.015) and patellar tilt angle (p = 0.002). Comparison between patients with and without patellofemoral instability post-operatively revealed that the pre-operative patellar tilt angle (p = 0.005) and tibiofemoral angle (p = 0.001), post-operative patellar tilt angle (p = 0.004) and tibiofemoral angle (p = 0.027) as well as the change in patellar tilt angle (p = 0.001) and tibiofemoral angle (p = 0.001) were all significant predictors of the outcomes of genu valgum. CONCLUSION: Hemiepiphysiodesis is a potentially effective surgical management for skeletally immature patients with patellofemoral instability associated with isolated genu valgum. This is especially for patients who are skeletally immature and have sufficient remaining years for their genu valgum to be corrected using hemiepiphysiodesis. These patients also tended to have less severe genu valgum and patellar tilt angle, which could be corrected using hemiepiphysiodesis with the remaining years of growth. LEVEL OF EVIDENCE: II.

A roundtable on responsible innovation with autologous stem cells in Australia, Japan and Singapore.

We report on a roundtable event hosted in Singapore that sought to identify some of the ethical and regulatory challenges in translating autologous cell-based interventions, particularly those claiming to involve stem cells, into safe and effective therapies and to propose some solutions to encourage responsible innovation with these products. Challenges are identified in the three areas of cell manufacturing and processing, innovative uses of autologous cells in clinical practice and standards of evidence. Proposed solutions are discussed within a co-operative model of statutory laws and regulations that can enable product development with autologous cells and professional codes and standards that can encourage ethical conduct in clinical practice. Future research should be directed toward establishing regional networks for the development of internationally consistent standards in manufacturing and ethical codes of conduct for innovating with stem cells, and other autologous cells, and fostering ongoing exchange between jurisdictions.

Patellar tracking should be taken into account when measuring radiographic parameters for recurrent patellar instability.

PURPOSE: To date, many radiographic parameters on patellar instability have their measurements taken statically, and have not been studied in various degrees of flexion according to the patellar tracking. There are also limited data regarding the use of these parameters in predicting recurrent patellar dislocation. The current study aims to review the radiographic parameters of the patellofemoral joint in different degrees of knee flexion and to correlate them with the presence of recurrent instability. METHODS: A 10-year retrospective study was conducted on all patients who had computed tomography patellar-tracking scan done for patellar instability when aged 18 years or younger. The computed tomography patellar-tracking scans were performed with the knee in extension, 10° flexion, and 20° flexion. The axial radiographic parameters were evaluated at the patellar equator, roman arch, and distal patellar pole. Sagittal and coronal parameters were noted. Radiographic parameters were then correlated with recurrent patellar instability. RESULTS: The femoral sulcus angle and trochlear groove depth at the distal patellar pole in 10° knee flexion (p value 0.04 and 0.03, respectively) and patellar equator in 20° knee flexion (p value 0.02 and 0.03, respectively) had the most significant clinical correlations with recurrent instability on multivariate analysis. Other radiographic parameters found to have significant clinical correlation on univariate analysis include the patellar tilt angle, congruence angle, femoral sulcus angle, trochlear groove depth, and Wiberg's classification. CONCLUSIONS: As per the knee dynamics, axial radiographic parameters had the most significant correlation with recurrent patellar instability when measured at the distal patellar pole in 10° knee flexion and at the patellar equator in 20° knee flexion. Future axial radiographic evaluation of patellofemoral instability should then be performed at these degrees of knee flexion and axial cuts. Trochlear dysplasia, as measured by the femoral sulcus angle and trochlear groove depth, was the most significant predictor of recurrent patellar instability in the skeletally immature. Wiberg's classification was also a novel factor found to have clinical correlation with patellofemoral instability. LEVEL OF EVIDENCE: III.