Intra-articular sustained-release of pirfenidone as a disease-modifying treatment for early osteoarthritis.

Osteoarthritis (OA) is a major clinical challenge, and effective disease-modifying drugs for OA are still lacking due to the complicated pathology and scattered treatment targets. Effective early treatments are urgently needed to prevent OA progression. The excessive amount of transforming growth factor ß (TGFß) is one of the major causes of synovial fibrosis and subchondral bone sclerosis, and such pathogenic changes in early OA precede cartilage damage. Herein we report a novel strategy of intra-articular sustained-release of pirfenidone (PFD), a clinically-approved TGFß inhibitor, to achieve disease-modifying effects on early OA joints. We found that PFD effectively restored the mineralization in the presence of excessive amount of TGFß1 (as those levels found in patients' synovial fluid). A monthly injection strategy was then designed of using poly lactic-co-glycolic acid (PLGA) microparticles and hyaluronic acid (HA) solution to enable a sustained release of PFD (the "PLGA-PFD + HA" strategy). This strategy effectively regulated OA progression in destabilization of the medial meniscus (DMM)- induced OA mice model, including preventing subchondral bone loss in early OA and subchondral bone sclerosis in late OA, and reduced synovitis and pain with cartilage preservation effects. This finding suggests the promising clinical application of PFD as a novel disease-modifying OA drug.

Establishment of a Mouse Degenerative Model of Patellar Tendinopathy with Upregulation of Inflammation.

There is no mouse model of patellar tendinopathy. This study aimed to establish a mouse inflammatory and degenerative patellar tendon injury model, which will facilitate research on patellar tendinopathy using advanced molecular tools including transgenic models. Collagenase at different doses (low dose (LD), medium dose (MD), high dose (HD)) or saline was injected over the mouse patellar tendon. At weeks 1, 2, 4, and 8 post-injection, the tendons were harvested for histology and further examined by micro-computed tomography (microCT) imaging at week 8. The optimal dose group and the saline group were further evaluated by immunohistochemical staining, gait pattern, and biomechanical properties. The histopathological score increased dose-dependently post-collagenase injection. Ectopic mineralization was observed and increased with collagenase dose. The LD group was selected for further analysis. The expression of IL-10, TNF-α, and MMP-1 significantly increased post-injection. The changes of limb idleness index (ΔLII) compared to preinjury state were significantly higher, while the ultimate load, stiffness, ultimate stress, and maximum Young's modulus were significantly lower in the LD group compared to the saline group. A mouse inflammatory degenerative model of patellar tendon injury resembling tendinopathy was established as indicated by the dose-dependent increase in tendon histopathology, ectopic calcification, decrease in biomechanical properties, and pain-associated gait changes.

Vitamin D as an intervention for improving quadriceps muscle strength in patients after anterior cruciate ligament reconstruction: study protocol for a randomized double-blinded, placebo-controlled clinical trial.

BACKGROUND: The goal of anterior cruciate ligament reconstruction (ACLR) is to restore the preinjury level of knee function to return to play (RTP). However, even after completing the rehabilitation programme, some patients may have persistent quadriceps muscle weakness affecting knee function which ultimately leads to a failure in returning to play. Vitamin D has been long recognized for its musculoskeletal effects. Vitamin D deficiency may impair muscle strength recovery after ACLR. Correcting vitamin D levels may improve muscle strength. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of vitamin D supplementation during the post-operative period on quadriceps muscle strength in anterior cruciate ligament (ACL)-injured patients. Patients aged 18-50 with serum vitamin D < 20 ng/ml, unilateral ACL injury, > 90% deficit in total quadriceps muscle volume on the involved leg compared with uninvolved leg, Tegner score 7 + , and no previous knee injury/surgery will be recruited. To assess patient improvement, we will perform isokinetic and isometric muscle assessments, ultrasound imaging for quadriceps thickness, self-reported outcomes, KT-1000 for knee laxity, biomechanical analysis, and Xtreme CT for bone mineral density. To investigate the effect of vitamin D status on quadriceps strength, blood serum samples will be taken before and after intervention. DISCUSSION: Patients with low vitamin D levels had greater quadriceps fibre cross-sectional area loss and impaired muscle strength recovery after ACL. The proposed study will provide scientific support for using vitamin D supplementation to improve quadriceps strength recovery after ACLR. TRIAL REGISTRATION: ClinicalTrials.gov NCT05174611. Registered on 28 November 2021.

Reconsidering "Critical" Bone Loss in Shoulder Instability: 17-Year Follow-Up Study following Arthroscopic Bankart Repair.

Background: Glenoid bone loss is a risk factor leading to the failure of arthroscopic Bankart repair. While 20-25% glenoid bone loss has long been considered the level to necessitate bony augmentation, recent studies indicate that 13.5% has a "subcritical" glenoid bone loss level, which is associated with decreased short- and medium-term functional scores. Few researchers worked on the long-term effect of "subcritical" or even less severe degrees of glenoid bone loss on redislocation rates and functional outcomes after arthroscopic Bankart repair. This study aimed to evaluate the effect of subcritical or less severe glenoid bone loss on redislocation rates and function after arthroscopic Bankart repair. Methods: A patient cohort who had undergone computed tomography (CT) of glenoid bone loss and arthroscopic Bankart repair over 15 years ago was reviewed. Western Ontario Shoulder Instability (WOSI) score, Single Assessment Numeric Evaluation (SANE) score, redislocation after operation, mechanism of recurrence, and revision details were reviewed. Results: Seventy-five patients were reassessed 17.6 ± 1.9 years following initial surgery. The age at enrolment was 26.8 ± 8.3 years. Twenty-two (29%) patients of the 75 patients had a redislocation on long-term follow-up, though this was not related to glenoid bone loss severity. The impaired functional score was found in patients with initial glenoid bone loss of 7% or more on long-term follow-up: WOSI (physical symptoms): 0.98 ± 2.00 vs 2.25 ± 4.01, p=0.04 and WOSI (total): 0.79 ± 1.43 vs 1.88 ± 3.56, p=0.04. Conclusions: At a mean of 17.5 years following arthroscopic Bankart repair, redislocation occurs in over a quarter of 75 patients, and they are not related to initial glenoid bone loss severity. Impaired functional outcome is apparent in patients with initial glenoid bone loss of >7%, though this impairment does not seem sufficiently severe to warrant an alternative treatment approach.

Serum vitamin D insufficiency is correlated with quadriceps neuromuscular functions in patients with anterior cruciate ligament injury: A preliminary study.

Background: This study aimed to investigate the correlations of serum vitamin D insufficiency with quadriceps neuromuscular function in patients with anterior cruciate ligament (ACL) injury. Methods: A cross-sectional study was conducted. Eighteen patients with a primary, unilateral ACL injury who had insufficient serum vitamin D concentrations (<30 ng/ml) were recruited for the study. Bilateral quadriceps neuromuscular function, including maximal strength, the speed of rapid contraction, and inhibition, were measured on an isokinetic dynamometer with the hip and the knee joint flexion at 90° and 45°, respectively. Quadriceps strength was measured by maximal voluntary isometric contractions (MVIC); the speed of rapid contraction was quantified by the rate of torque development (RTD), which was divided into the early (RTD0-50) and the late phase (RTD100-200); quadriceps inhibition was quantified by the central activation ratio (CAR). Serum vitamin D concentration was quantitatively determined by serum 25(OH)D concentration measured by the 25(OH)D ELISA kit. The Spearman rank correlation analysis was used to examine the correlation between the vitamin D concentration and bilateral quadriceps MVIC, RTD0-50, RTD100-200, and CAR, respectively. Results: The results of Spearman rank correlation analyses showed that the serum 25(OH)D concentration was significantly correlated with bilateral quadriceps MVIC (injured: r = 0.574, p = 0.013; uninjured: r = 0.650, p = 0.003) and RTD0-50 (r = 0.651, p = 0.003), and CAR (r = 0.662, p = 0.003) on the uninjured limb. However, no significant correlations were found between the serum 25(OH)D concentration and the other outcomes. Conclusions: The serum vitamin D concentration correlates with quadriceps neuromuscular function in patients with ACL injury who had vitamin D insufficiency.

Effect of eccentric isokinetic exercise on muscle strength and functional recovery after anterior cruciate ligament reconstruction.

Background: Previous studies have shown isokinetic exercise forms an important part in reconditioning the patients after anterior cruciate ligament reconstruction (ACLR) in regaining muscle strength and knee function. Although eccentric isokinetic training has been shown to enhance quadriceps muscle strength, the application toward benefiting patients after ACLR remains controversial. The present study aims to investigate the benefits of eccentric over concentric isokinetic exercises on knee muscle strength and its value in later stage of rehabilitation, including the return-to-sport. Methods: Thirty-six patients who had undergone ACLR for 4-to-6 months were assigned to receive either eccentric or concentric isokinetic training weekly for six weeks on top of their standardized post-operative exercise programme. The assessments include isokinetic test on the peak torques of quadriceps and hamstrings, single-leg hop test and ability to return-to-sport. Results: Both groups demonstrated significant gains on peak torques in quadriceps and hamstrings after training. At post-intervention, the peak torques for both quadriceps (p = 0.005) and hamstrings (p = 0.017) of the ACL-reconstructed limb from eccentric training were significantly higher than concentric training. The significant improvement was similarly demonstrated in the limb symmetry index (LSI) in hamstrings (p = 0.016) of the ACL-reconstructed limb from eccentric training. Moreover, eccentric group performed significantly better in single-leg hop tests (p = 0.042). Most importantly, eccentric group have higher percentages of return-to-sport (55.6 %) than concentric group (27.8 %). Conclusion: A 6-week course of eccentric isokinetic training was more effective than concentric isokinetic training in increasing quadriceps and hamstrings strength in terms of peak torques. Importantly, the better functional performance after the eccentric isokinetic exercise account for higher return-to-sport ratio.

Surgical accuracy of image-free versus image-based robotic-assisted total knee arthroplasty.

BACKGROUND: This study investigated the accuracy in achieving proper lower limb alignment and component positions after total knee replacement (TKR) with image-free and image-based robotic-assisted TKR. METHODS: A total of 129 patients (166 knees) suffering from end-stage knee arthritis who underwent TKA operated by robotic-assisted surgery between the years 2018 and mid-2021 were recruited. Radiological outcomes were compared between image-free and image-based robotic-assisted surgical systems. RESULTS: There were significant differences between the two robotic systems when comparing the mean planned component alignment and the mean measured alignment on radiographs, in which the image-free robotic-assisted system was more varus, whereas the image-based robotic-assisted system was more valgus for both the mean femoral and tibial component coronal alignment (p < 0.001). For tibial component sagittal alignment, the image-based group had a larger deviation from the planned posterior slope (p < 0.001). CONCLUSION: Image-free and image-based robotic assisted TKR had differing accuracy in femoral and tibial alignment.

Clinical effectiveness of pulsed electromagnetic field therapy as an adjunct treatment to eccentric exercise for Achilles tendinopathy: a randomised controlled trial.

BACKGROUND: The Achilles tendon is the largest and strongest tendon in the human body. Achilles tendinopathy (AT) is a common clinical problem with Achilles overuse. Eccentric exercise is often used as an initial treatment for these patients. Most patients with AT experienced moderate to severe pain, limiting the incentive to perform eccentric exercise. It is difficult for them to complete eccentric exercise for 3 months consecutively to obtain significant improvements. Using PEMF as an adjunct, there could be immediate pain relief and improved response to eccentric exercise by modulating the mechanical properties of the Achilles tendon. Participants may experience less pain while performing eccentric exercises to increase compliance with the rehabilitation programme. METHODS: This prospective randomised double-blinded, placebo-controlled trial aims to investigate the treatment effects of PEMF for participants with AT. All participants are randomised into two groups: the intervention group (n = 20; active PEMF treatment and eccentric exercise) and the control group (n = 20; sham treatment and eccentric exercise). Researchers perform self-reported, functional and ultrasonographic outcomes during baseline assessment, 4 weeks, 8 weeks follow-ups, and 3 and 6 months follow-ups after the commencement of the PEMF treatment. DISCUSSION: AT is a common clinical condition affecting athletes and sedentary populations. It is essential to investigate treatment adjuncts to improve rehabilitation outcomes for these patients. This trial may demonstrate the effectiveness of PEMF in relieving pain, improving function, and restoring mechanical changes of the tendon in participants with AT. TRIAL REGISTRATION: ClinicalTrials.gov NCT05316961. Registered on 7th April 2022.

Blockage of Osteopontin-Integrin ß3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice.

The knowledge of osteoarthritis (OA) has nowadays been extended from a focalized cartilage disorder to a multifactorial disease. Although recent investigations have reported that infrapatellar fat pad (IPFP) can trigger inflammation in the knee joint, the mechanisms behind the role of IPFP on knee OA progression remain to be defined. Here, dysregulated osteopontin (OPN) and integrin ß3 signaling are found in the OA specimens of both human and mice. It is further demonstrated that IPFP-derived OPN participates in OA progression, including activated matrix metallopeptidase 9 in chondrocyte hypertrophy and integrin ß3 in IPFP fibrosis. Motivated by these findings, an injectable nanogel is fabricated to provide sustained release of siRNA Cd61 (RGD- Nanogel/siRNA Cd61) that targets integrins. The RGD- Nanogel possesses excellent biocompatibility and desired targeting abilities both in vitro and in vivo. Local injection of RGD- Nanogel/siRNA Cd61 robustly alleviates the cartilage degeneration, suppresses the advancement of tidemark, and reduces the subchondral trabecular bone mass in OA mice. Taken together, this study provides an avenue for developing RGD- Nanogel/siRNA Cd61 therapy to mitigate OA progression via blocking OPN-integrin ß3 signaling in IPFP.

Effects of Gluteus Medius and Biceps Femoris Stimulation on Reduction of Knee Abduction Moment During a Landing Task.

Anterior cruciate ligament injury prevention should focus primarily on reduction of the knee abduction moment (KAM) in landing tasks. Gluteus medius and hamstring forces are considered to decrease KAM during landing. The effects of different muscle stimulations on KAM reduction were compared using 2 electrode sizes (standard 38 cm2 and half size 19 cm2) during a landing task. Twelve young healthy female adults (22.3 [3.6] y, 1.62 [0.02] m, 50.2 [4.7] kg) were recruited. KAM was calculated under 3 conditions of muscle stimulation (gluteus medius, biceps femoris, and both gluteus medius, and biceps femoris) using 2 electrode sizes, respectively versus no stimulation during a landing task. A repeated-measures analysis of variance determined that KAM differed significantly among stimulation conditions and post hoc analysis revealed that KAM was significantly decreased in conditions of stimulating either the gluteus medius (P < .001) or the biceps femoris (P < .001) with the standard electrode size, and condition of stimulating both gluteus medius and biceps femoris with half-size electrode (P = .012) when compared with the control condition. Therefore, stimulation on the gluteus medius, the biceps femoris, or both muscles could be implemented for the examination of anterior cruciate ligament injury potential.

Cross-cultural adaptation, reliability and validity of the Cantonese-Chinese Cumberland Ankle Instability Tool (CAIT-HK).

Acute lateral ankle sprains are common amongst athletes, and screening is essential in preventing these long-term sequelae. Self-reported questionnaires, such as the Cumberland Ankle Instability Tool (CAIT), may help identify individuals with chronic ankle instability. To date, a Cantonese-Chinese version of the CAIT does not exist. A cross-cultural adaptation and validation of the CAIT were carried out: 46 individuals who were native in Cantonese completed the Cantonese-Chinese version of the CAIT and Chinese Foot and Ankle Outcome Score. For the test-retest analysis, the intraclass correlation coefficient was 0.874. Internal consistency showed a Cronbach's ɑ value of 0.726. Construct validity against the FAOS was fair but statistically significant with a Spearman's correlation coefficient of 0.353, 0.460, 0.303, 0.369 and 0.493 for the categories of symptoms, pain, daily function, sports function, and quality of life, respectively. A cutoff score of 20.5 was determined to differentiate healthy individuals from those with chronic ankle instability for this study population. The original English CAIT was successfully translated, cross-culturally adapted and validated into Cantonese-Chinese.

Investigation on the site of coronal deformities in Hallux valgus.

Hallux valgus (HV) is a common foot deformity that is more prevalent in females, characterised by abnormal adduction of the first metatarsal (MT) and valgus deviation of the phalanx on the transverse plane. Increasing evidence indicates that HV is more than a 2D deformity but a 3D one with rotational malalignment. Pronation deformity is seen during clinical examination for HV patients, but the exact origin of this rotational deformity is still unknown. Some attribute it to first tarsometatarsal (TMT) joint rotation, while others attribute it to intra-metatarsal bony torsion. In addition, the correlation between the rotational and transverse plane deformity is inconclusive. Identifying the origin of the rotational deformity will help surgeons choose the optimal surgical procedure while also enhancing our understanding of the pathophysiology of HV. This study aims to (1) develop an objective method for measuring the first MT torsion and first TMT joint rotation; (2) investigate the exact location of the coronal deformity in HV; (3) investigate the relationship between the severity of deformity on the transverse and coronal planes as well as the correlation between deformity severity and foot function/symptoms in HV. Age-matched females with and without HV were recruited at the Foot and Ankle Clinic of the Department of Orthopaedics and Traumatology. Computed tomography was conducted for all subjects with additional weight-bearing dorsal-plantar X-ray examination for HV subjects. Demographic information of all subjects was recorded, with symptoms and functions related to HV evaluated. The intra-class correlation was used to explore the relationship between deformities on different planes and the deformity severity and functional outcomes, respectively. An Independent t-test was used to compare joint rotation and bone torsion degrees. TMT joint rotation is significantly correlated with foot function. HV patients had more TMT joint rotation but not MT torsion compared to normal controls. No relationship was found between the coronal rotation and the 1,2-intermetatarsal angle (IMA) or Hallux valgus angle (HVA) on the transverse plane. Our results indicate that coronal deformities in HV may originate from TMT joint rotation. In addition, the severity of the TMT joint coronal rotation correlates with worse foot function; thus, multi-plane assessment and examination will be necessary for more precise surgical correction.

Surgical accuracy and clinical outcomes of image-free robotic-assisted total knee arthroplasty.

BACKGROUND: The development of total knee arthroplasty (TKA) for knee osteoarthritis (OA) has a good reputation for its effectiveness in reducing joint pain and improving range of motion. We aimed to review our early results using the image-free robotic-assisted technology in knee arthroplasty. METHODS: A total of 71 patients suffering from end-stage OA knee receiving TKA operated by robotic-assisted surgery between the years 2018 and mid-2021 were recruited. Clinical and radiological outcomes were compared with age and sex-matched control group (conventional TKA). RESULTS: The radiological outcome showed significantly more postoperative lower limb alignment outliers in conventional side than robotic-assisted sides. Postoperative knee scores were similar among both groups. Robotic-assisted TKA required a longer implantation time but a shorter hospital stay. CONCLUSION: Robotic-assisted TKA achieved a lower rate of mechanical axis Outlier in the coronal and sagittal plane with a shorter hospital stay. Yet both methods achieve a similar functional outcome.

Comparative short-term effectiveness of non-surgical treatments for insertional Achilles tendinopathy: a systematic review and network meta-analysis.

BACKGROUND: The incidence of Achilles tendinopathy has risen over the past decades. Insertional Achilles tendinopathy is characterised by tissue degeneration of the Achilles tendon from its insertion in the calcaneus to up to 2 cm proximally. This clinical condition is accompanied by pain, loss of function and diminished exercise tolerance. Numerous conservative treatment modalities are available to participants with insertional Achilles tendinopathy, including eccentric exercises, extracorporeal shockwave therapy, laser therapy, cryotherapy, therapeutic ultrasound, and orthotics. Eccentric exercise and extracorporeal shockwave therapy may reduce pain in participants with non-calcified insertional Achilles tendinopathy. However, no specific treatment is recommended over another due to the low methodological quality of trials. Given the lack of standard or preferred non-surgical treatment and the potential risks of surgical treatment, there is an imminent need to reassess different non-surgical treatments based on the newest evidence. Thus, this systematic review aims to evaluate the clinical effectiveness of the various non-surgical treatments for insertional Achilles tendinopathy. METHODS: AMED EBSCOhost, CINAHL, EBSCOhost, EMBASE, PEDro, PubMed, Web of Science, and Clinicaltrials.gov were searched from 1992 to 14th October 2022, randomised controlled trials of adults with insertional Achilles tendinopathy investigating non-surgical treatments compared with each other or no treatment, placebo/sham control. Two reviewers independently screened and extracted the data. Random effects of network meta-analysis immediately after treatments were used to report comparative treatment effects. The surface under the cumulative ranking probabilities was calculated to assess the relative ranking of treatments. RESULTS: Nine trials (total n = 464 participants) were included. This review recommended the combination of eccentric exercise and soft tissue therapy to manage insertional Achilles tendinopathy. With the highest SUCRA values of 84.8, and the best mean rank of 1.9, Eccentric exercise plus soft tissue treatment ranked as the most effective treatment for short-term pain. CONCLUSIONS: This is the first NMA of non-surgical treatment focusing on short-term pain control for IAT which eccentric exercise plus soft-tissue therapy was found to be the most effective treatment combination. However, the overall confidence in non-surgical treatments from all included trials was very low. No recommendation of the best treatment option can be made from this review.

Bioactive Decellularized Tendon-Derived Stem Cell Sheet for Promoting Graft Healing After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Stem cell sheets provide a scaffold-free option for the promotion of graft healing after anterior cruciate ligament reconstruction (ACLR). However, cell viability, stability, and potential uncontrolled actions create challenges for clinical translation. The decellularization of cell sheets may overcome these problems as studies have shown that the natural extracellular matrix of stem cells is bioactive and can promote tissue repair. HYPOTHESIS: The decellularized tendon-derived stem cell (dTDSC) sheet can promote graft healing after ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: An optimized decellularization protocol was developed to decellularize the TDSC sheets. A total of 64 Sprague-Dawley rats underwent ACLR with or without the dTDSC sheet wrapping the tendon graft (n = 32/group). At 2 and 6 weeks after surgery, graft healing was assessed by micro-computed tomography, histology, and biomechanical testing. The accumulation of iNOS+ and CD206+ cells and the expression of metalloproteinase 1 (MMP-1), MMP-13, and tissue inhibitor of metalloprotease 1 (TIMP-1) were assessed by immunohistochemistry. RESULTS: The decellularization was successful, with the removal of 98.4% nucleic acid while preserving the collagenous proteins and bioactive factors. The expression of bone morphogenetic protein 2 (BMP-2) and VEGF in the dTDSC sheet was comparable with the TDSC sheet (P > .05). Micro-computed tomography showed significantly more tunnel bone formation in the dTDSC sheet group. The dTDSC sheet group demonstrated better graft osteointegration and higher integrity of graft midsubstance with significantly higher ultimate failure load (16.58 ± 7.24 vs 8.93 ± 2.45 N; P = .002) and stiffness (11.97 ± 5.21 vs 6.73 ± 2.20 N/mm; P = .027). Significantly fewer iNOS+ cells but more CD206+ cells, as well as lower MMP-1 and MMP-13 but higher TIMP-1 expression, were detected at the tendon-bone interface and graft midsubstance in the dTDSC sheet group. CONCLUSION: An optimized decellularization protocol for producing bioactive dTDSC sheets was developed. Wrapping tendon graft with a dTDSC sheet promoted graft healing after ACLR, likely via enhancing bone formation and angiogenesis by BMP-2 and VEGF, modulating macrophage polarization and MMP/TIMP expression, and physically protecting the tendon graft. CLINICAL RELEVANCE: dTDSC sheets alleviate the quality control and safety concerns of cell transplantation and can be used as a cell-free alternative for the promotion of graft healing in ACLR.

A novel image-based machine learning model with superior accuracy and predictability for knee arthroplasty loosening detection and clinical decision making.

Background: Loosening is the leading cause of total knee arthroplasty (TKA) revision. This is a heavy burden toward the healthcare system owing to the difficulty in diagnosis and complications occurring from the delay management. Based on automatic analytical model building, machine learning, may potentially help to automatically recognize the risk of loosening based on radiographs alone. The aim of this study was to build an image-based machine-learning model for detecting TKA loosening. Methods: Image-based machine-learning model was developed based on ImageNet, Xception model and a TKA patient X-ray image dataset. Based on a dataset with TKA patient clinical parameters, another system was then created for developing the clinical-information-based machine learning model with random forest classifier. In addition, the Xception Model was pre-trained on the ImageNet database with python and TensorFlow deep learning library for the prediction of loosening. Class activation maps were also used to interpret the prediction decision made by model. Two senior orthopaedic specialists were invited to assess loosening from X-ray images for 3 attempts in setting up comparison benchmark. Result: In the image-based machine learning loosening model, the precision rate and recall rate were 0.92 and 0.96, respectively. While for the accuracy rate, 96.3% for visualization classification was observed. However, the addition of clinical-information-based model, with precision rate of 0.71 and recall rate of 0.20, did not further showed improvement on the accuracy. Moreover, as class activation maps showed corresponding signals over bone-implant interface that is loosened radiographically, this confirms that the current model utilized a similar image recognition pattern as that of inspection by clinical specialists. Conclusion: The image-based machine learning model developed demonstrated high accuracy and predictability of knee arthroplasty loosening. And the class activation heatmap matched well with the radiographic features used clinically to detect loosening, which highlighting its potential role in assisting clinicians in their daily practice. However, addition of clinical-information-based machine-learning model did not offer further improvement in detection. As far as we know, this is the first report of pure image-based machine learning model with high detection accuracy. Importantly, this is also the first model to show relevant class activation heatmap corresponding to loosening location. Translational potential: The finding in this study indicated image-based machine learning model can detect knee arthroplasty loosening with high accuracy and predictability, which the class activation heatmap can potentially assist surgeons to identify the sites of loosening.

Associations of patient characteristics, rate of torque development, voluntary activation of quadriceps with quadriceps strength, and knee function before anterior cruciate ligament reconstruction.

Good preoperative knee function (KF) and quadriceps strength (QS) relate to good prognoses after anterior cruciate ligament reconstruction (ACLR). This study aimed to investigate the associations between patient characteristics, rate of torque development (RTD), voluntary activation (VA) of the quadriceps against preoperative KF and QS. A cross-sectional study was conducted. Forty patients with a primary, unilateral ACL injury who had finished the preoperative rehabilitation and scheduled for an ACLR were included. KF was evaluated using the International Knee Documentation Committee score. QS was measured by maximal voluntary isometric contractions. RTD was divided into the early (RTD0-50) and the late (RTD100-200) phases. Quadriceps VA was measured using the superimposed burst technique. Our results showed that patients with poor preoperative KF had more deficits in RTD0-50 (P = 0.025), higher BMI(P = 0.043), and more meniscus injuries (MI) (P = 0.001) than those with good KF. Patients with asymmetrical QS showed lower BMI (P = 0.020) and shorter time from injury (TFI) (P = 0.027) than those with symmetrical QS. Additionally, a higher pre-injury Tegner score combined with greater RTD100-200 contributed to greater QS on the injured limb (R2 = 0.357, P = 0.001). To conclude, BMI, TFI, concomitant MI, pre-injury physical activity level, and quadriceps RTD are related to QS and KF before ACLR.

Effect of pulsed electromagnetic field as an intervention for patients with quadriceps weakness after anterior cruciate ligament reconstruction: a double-blinded, randomized-controlled trial.

BACKGROUND: The ultimate goal of anterior cruciate ligament reconstructions (ACLR) is to fulfil the return-to-play (RTP) criteria. Quadriceps muscle strength is one of the key determinants for a patient's successful return-to-play after ACLR. Quadriceps muscle atrophy can persist beyond the completion of the rehabilitation program in almost half the patients and the reason behind this is still unknown. There are emerging evidences showing that pulsed electromagnetic field (PEMF) can modulate mitochondrial activities for muscle gain. PEMF exposure on top of regular exercise training may promote muscle regeneration and tissue healing. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of PEMF treatment during the postoperative period on quadriceps muscle strength in ACL injured patient. Adult patients (aged 18-30) with a unilateral ACL injury, total quadriceps muscle volume is equal or more than 7% deficit on involved leg compared with uninvolved leg, sporting injury with a Tegner score of 7+, and both knees without a history of injury/prior surgery will be recruited. To estimate the improvement of patients, isokinetic muscle assessment, ultrasound imaging and MRI for quadriceps muscle thickness, self-reported outcomes with questionnaires, KT-1000 for knee laxity and biomechanical analysis, and Xtreme CT for bone mineral density will be performed. To investigate the mechanism of PEMF therapy on increasing quadriceps strength, samples of blood serum will be drawn before and after intervention. DISCUSSION: This is the first trial evaluating the effects of PEMF on quadriceps muscle recovery after ACLR. The proposed study addresses a huge research gap by evaluating practical use of PEMF as part of rehabilitation. The proposed study will provide much needed scientific support in the use of this noninvasive treatment modality to facilitate recovery of quadriceps strength after PEMF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05184023. Registered on 5 January 2022.