A genome-scale deep learning model to predict gene expression changes of genetic perturbations from multiplex biological networks.

Systematic characterization of biological effects to genetic perturbation is essential to the application of molecular biology and biomedicine. However, the experimental exhaustion of genetic perturbations on the genome-wide scale is challenging. Here, we show TranscriptionNet, a deep learning model that integrates multiple biological networks to systematically predict transcriptional profiles to three types of genetic perturbations based on transcriptional profiles induced by genetic perturbations in the L1000 project: RNA interference, clustered regularly interspaced short palindromic repeat, and overexpression. TranscriptionNet performs better than existing approaches in predicting inducible gene expression changes for all three types of genetic perturbations. TranscriptionNet can predict transcriptional profiles for all genes in existing biological networks and increases perturbational gene expression changes for each type of genetic perturbation from a few thousand to 26 945 genes. TranscriptionNet demonstrates strong generalization ability when comparing predicted and true gene expression changes on different external tasks. Overall, TranscriptionNet can systemically predict transcriptional consequences induced by perturbing genes on a genome-wide scale and thus holds promise to systemically detect gene function and enhance drug development and target discovery.

Janus Membranes Patch Achieves High-Quality Tendon Repair: Inhibiting Exogenous Healing and Promoting Endogenous Healing.

The imbalance between endogenous and exogenous healing is the fundamental reason for the poor tendon healing. In this study, a Janus patch was developed to promote endogenous healing and inhibit exogenous healing, leading to improved tendon repair. The upper layer of the patch is a poly(dl-lactide-co-glycolide)/polycaprolactone (PLGA/PCL) nanomembrane (PMCP-NM) modified with poly(2-methylacryloxyethyl phosphocholine) (PMPC), which created a lubricated and antifouling surface, preventing cell invasion and mechanical activation. The lower layer is a PLGA/PCL fiber membrane loaded with fibrin (Fb) (Fb-NM), serving as a temporary chemotactic scaffold to regulate the regenerative microenvironment. In vitro, the Janus patch effectively reduced 92.41% cell adhesion and 79.89% motion friction. In vivo, the patch inhibited tendon adhesion through the TGF-ß/Smad signaling pathway and promoted tendon maturation. This Janus patch is expected to provide a practical basis and theoretical guidance for high-quality soft tissue repair.

Healthy Tendon Stem Cell-Derived Exosomes Promote Tendon-To-Bone Healing of Aged Chronic Rotator Cuff Tears by Breaking the Positive-Feedback Cross-Talk between Senescent Tendon Stem Cells and Macrophages through the Modulation of Macrophage Polarization.

The re-tear rate of rotator cuff tears (RCT) after surgical repair is high, especially in aged patients with chronic tears. Senescent tendon stem cells (s-TSCs) generally exist in aged and chronically torn rotator cuff tendons and are closely associated with impaired tendon-to-bone healing results. The present study found a positive feedback cross-talk between s-TSCs and macrophages. The conditioned medium (CM) from s-STCs can promote macrophage polarization mainly toward the M1 phenotype, whose CM reciprocally accelerated further s-TSC senescence. Additional healthy tendon stem-cells derived exosomes (h-TSC-Exos) can break this positive feedback cross-talk by skewing macrophage polarization from the M1 phenotype to the M2 phenotype, attenuating s-TSCs senescence. S-TSC senescence acceleration or attenuation effects induced by M1 or M2 macrophages are associated with the inhibition or activation of the bone morphogenetic protein 4 signaling pathway following RNA sequencing analysis. Using an aged-chronic rotator cuff tear rat model, it is found that h-TSC-Exos can shift the microenvironment in the tendon-to-bone interface from a pro-inflammatory to an anti-inflammatory type at the acute postoperative stage and improve the tendon-to-bone healing results, which are associated with the rejuvenated s-TSCs. Therefore, this study proposed a potential strategy to improve the healing of aged chronic RCT.

TMNP: a transcriptome-based multi-scale network pharmacology platform for herbal medicine.

One of the most difficult problems that hinder the development and application of herbal medicine is how to illuminate the global effects of herbs on the human body. Currently, the chemo-centric network pharmacology methodology regards herbs as a mixture of chemical ingredients and constructs the 'herb-compound-target-disease' connections based on bioinformatics methods, to explore the pharmacological effects of herbal medicine. However, this approach is severely affected by the complexity of the herbal composition. Alternatively, gene-expression profiles induced by herbal treatment reflect the overall biological effects of herbs and are suitable for studying the global effects of herbal medicine. Here, we develop an online transcriptome-based multi-scale network pharmacology platform (TMNP) for exploring the global effects of herbal medicine. Firstly, we build specific functional gene signatures for different biological scales from molecular to higher tissue levels. Then, specific algorithms are designed to measure the correlations of transcriptional profiles and types of gene signatures. Finally, TMNP uses pharmacotranscriptomics of herbal medicine as input and builds associations between herbs and different biological scales to explore the multi-scale effects of herb medicine. We applied TMNP to a single herb Astragalus membranaceus and Xuesaitong injection to demonstrate the power to reveal the multi-scale effects of herbal medicine. TMNP integrating herbal medicine and multiple biological scales into the same framework, will greatly extend the conventional network pharmacology model centering on the chemical components, and provide a window for systematically observing the complex interactions between herbal medicine and the human body. TMNP is available at http://www.bcxnfz.top/TMNP.

Characterization of the CT-based risk factors for concomitant patellofemoral instability in patients with anterior cruciate ligament injury.

OBJECTIVES: Underestimation of concomitant patellofemoral instability in patients with anterior cruciate ligament (ACL) injury has aroused extensive attention. However, the characteristics of the combined injury is not well recognized. Hence, we aimed to characterize the features of the combined injury, and determine the radiographic risk factors. METHODS: Fifteen radiological parameters were identified after discussion and pilot-tested. Radiographic measurements were compared using the analysis of variance model with Tukey post hoc analysis. A stepwise binomial logistic regression was performed and a nomogram model combining the significant risk factors was created. The model performance was validated by C-index, calibration plot, and decision curve. RESULTS: A total of 204 patients (mean [SD] age, 25.1 [6.7] years; 108 [52.9%] male) were included. The final model was updated through regression analysis using 4 parameters as significant risk factors: lateral femoral condyle ratio (OR (95% CI), 1.194 (1.023 to 1.409)), medial anterior tibial subluxation (mATS) (OR (95% CI), 1.234 (1.065 to 1.446)), medial posterior plateau tibial angle (mPPTA) (OR (95% CI), 1.266 (1.088 to 1.500)), and trochlear depth (OR (95% CI), 0.569 (0.397 to 0.784)). C-index for the nomogram was 0.802 (95% CI, 0.731 to 0.873) and was confirmed to be 0.784 through bootstrapping validation. Calibration plot established a good agreement between prediction and observation. Decision curve analysis showed that if threshold probability was over 10%, using the nomogram adds more benefit than either all or none scheme. CONCLUSIONS: Lateral femoral condyle ratio, mATS, mPPTA, and trochlear depth are strong adverse predictors of patellofemoral instability in patients with ACL injury. CLINICAL RELEVANCE: This study characterizes the radiological features of the combined injury. Patellofemoral instability should be noted when treating ACL injuries. KEY POINTS: • The radiological characteristics of the combined ACL injury and patellofemoral instability is not well recognized. • Lateral femoral condyle ratio, mATS, mPPTA, and trochlear depth are predominant risk factors for patellofemoral instability in patients with ACL injury. • Patellofemoral instability should be noted when treating ACL injuries.

Synthesis of sulfinamides via photocatalytic alkylation or arylation of sulfinylamine.

Sulfinamides are a versatile class of compounds that find applications in both organic synthesis and pharmaceuticals. Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. Commercially available potassium trifluoro(organo)borates and readily available sulfinyl amines are rationally used and converted to a series of alkyl or aryl sulfinamides in moderate to high yields. The reaction allows for the gram-scale preparation of sulfinamides. Moreover, sulfonimidamides, sulfonimidate esters and sulfonyl amides could be obtained in one pot.

Arthroscopic medial patellofemoral ligament reconstruction with polyethylene suture combined with medial retinaculum plication for the treatment of acute patellar dislocation in young and middle-aged patients with a follow-up of at least 2 years.

PURPOSE: The purpose of this study was to propose a surgical technique for arthroscopic medial patellofemoral ligament (MPFL) reconstruction with polyethylene suture combined with medial retinaculum plication and to evaluate the efficacy of this surgical technique in the treatment of acute patellar dislocation. METHODS: Clinical data of patients with acute patellar dislocations treated with arthroscopic MPFL reconstruction with polyethylene tape (FiberTape) combined with medial support band compression were analyzed retrospectively from January 2018 to January 2021. The mean age of the patients was 25.15 ± 4.66 years; the mean follow-up time was 27.5 (24-36) months. Clinical evaluation consisted of apprehension test results, patellar extrapolation test results, Lysholm score, Kujala score, and IKDC score, the Patellar lateral shift distance and patellar tilt angle (PTA) measured by CT scan. RESULTS: All patients had no recurrent patellar dislocation or subluxation after surgery, and the apprehension test was negative. In all patients, the Kujala score (36.0 ± 9.9 vs. 98.2 ± 3.1), the IKDC score (48.6 ± 7.0 vs. 90.6 ± 4.4) and the Lysholm score (32.8 ± 10.4 vs. 96.7 ± 3.1) had improved at the 24-month follow up (P < 0.05). In addition, PTA was significantly lower at the 12-month follow-up and 24-giving-month follow-up compared to the preoperative period (P < 0.05, Table 2). The patellar lateral shift distance decreased from 14.94 ± 6.11 mm preoperatively to 3.00 ± 1.40 mm (12-month follow up) and 3.26 ± 1.37 mm (24-month follow up), respectively. CONCLUSION: Arthroscopic MPFL reconstruction with polyethylene suture combined with medial retinaculum plication is a safe and reliable surgical technique for the treatment of acute patellar dislocation in young and middle-aged patients. LEVEL OF EVIDENCE: Level III, Therapeutic Study.

EditorialCommentary: In Situ Biceps Tenodesis Is Useful in the Treatment of Irreparable Rotator Cuff Tears.

For irreparable posterior superior rotator cuff tears (IPSRCTs), techniques other than reverse shoulder arthroplasty and tendon transfer are still under research; among these, reusing the long head of the biceps (LHB) is noteworthy. Various techniques of LHB reuse have been reported and can be divided into 3 biomechanical categories: restoration of the force chain of the rotator cuff, augmentation of the superior capsule, and combined force-chain restoration and superior capsule augmentation, among which in situ biceps tenodesis may be the simplest. LHB reuse for IPSRCTs is always combined with partial rotator cuff repair, and clinical studies have revealed that this combined treatment is effective in most cases. However, the structural and functional conditions of IPSRCTs vary. For each LHB reuse method, the most suitable conditions for its use should be explored. Likewise, for each specific rotator cuff tear condition, the best method for LHB reuse also needs to be explored. Studies of high level of evidence and long-term follow-up are needed.

Biomechanical Analysis Reveals Shoulder Instability With Bipolar Bone Loss Is Best Treated With Dynamic Anterior Stabilization for On-Track Lesions and With Remplissage for Off-Track Lesions.

PURPOSE: To compare the biomechanical effects of augmenting Bankart repair (BR) with either remplissage or dynamic anterior stabilization (DAS) in the treatment of anterior shoulder instability with on-track or off-track bipolar bone loss. METHODS: Eight fresh-frozen cadaveric shoulders were tested at 60° of glenohumeral abduction in the intact, injury, and repair conditions. Injury conditions included 15% glenoid bone loss with an on-track or off-track Hill-Sachs lesion as previously recommended. Repair conditions included isolated BR, BR with remplissage, and BR with DAS (long head of biceps transfer). The glenohumeral stability was assessed by measuring the anterior translation under 0, 10, 20, 30, 40, 50 N load and maximum load without causing instability at mid-range (60°) and end-range (90°) external rotation (ER). Maximum range of motion (ROM) was measured by applying a 2.2-N·m torque in passive ER and internal rotation. RESULTS: Isolated BR failed to restore native glenohumeral stability in both on-track and off-track bipolar bone loss models. Both remplissage and DAS significantly decreased the anterior instability in the bipolar bone loss models, showing better restoration than the isolated BR. In the on-track lesions, DAS successfully restored native glenohumeral stability and mobility, whereas remplissage significantly decreased anterior translation without load (-2.12 ± 1.07 mm at 90° ER, P = .003; -1.98 ± 1.23 mm at 60° ER, P = .015). In the off-track lesions, remplissage restored native glenohumeral stability but led to significant ROM limitation (-8.6° ± 2.3° for internal rotation, P < .001; -13.9° ± 6.2° for ER, P = .003), whereas DAS failed to restore native stability at 90° ER regarding the increased anterior translation under 50 N (4.10 ± 1.53 mm, P < .001) and decreased maximum load (-13.8 ± 9.2 N, P = .021). CONCLUSIONS: At time-zero, both remplissage and DAS significantly reduced residual anterior instability compared with isolated BR in the bipolar bone loss models and restored the native glenohumeral stability under most translational loads. However, remplissage could decrease the anterior translation without load for on-track lesions and may restrict ROM for off-track lesions, whereas DAS failed to restore native stability under high translational loads for off-track lesions. CLINICAL RELEVANCE: DAS could be recommended to treat on-track bipolar bone loss with less biomechanical adverse effects, whereas remplissage might be the preferred procedure to address off-track bipolar bone loss for better stability.

Double-Level Knee Derotational Osteotomy Yields Better Postoperative Outcomes Than Tibial Tubercle Transfer Combined With Medial Patellofemoral Ligament Reconstruction in Patients With Recurrent Patellar Instability and Severe Malrotation.

PURPOSE: To assess the postoperative outcomes of double-level knee derotational osteotomy (KDRO) combined with medial patellofemoral ligament reconstruction (MPFLR) and to compare it with tibial tuber transfer (TTT) and MPFLR without derotational osteotomy in patients with recurrent patellar instability and a marked torsional deformity. METHODS: From March 2020 to December 2021, patients with torsion deformity (combined femoral torsion [FT] and tibial torsion [TTn] ≥30°) were retrospectively included. The minimum follow-up time was 18 months. Patients who received KDRO and MPFLR were categorized as the KDRO group and patients who received a combined TTT and MPFLR were categorized as the control group. Preoperative and postoperative clinical symptoms, patient-reported outcomes (Kujala, visual analog scale, Lysholm, International Knee Documentation Committee, Tegner, and Knee Injury and Osteoarthritis Outcome scores), and imaging parameters (FT, TTn, patellar height, femoral trochlear dysplasia, congruence angle, patellar tilt angle, lateral patellar angle, lateral patellar translation, and tibial tubercle-trochlear groove distance) were analyzed. RESULTS: In all, 36 patients were included with 18 in KDRO group and 18 in control group. The mean follow-up time was 30 (range 21-39) months. At the latest follow-up, no patient experienced redislocation in either group. Except for the FT and TTn in the control group, postoperative imaging parameters were significantly reduced to the normal range. KDRO group had a lower patellar tilt angle (P = .043, effect size 0.64). All clinical scores in both groups significantly improved postoperatively. The KDRO group had better functional scores than control group except the KOOS daily living activities subscore and the KOOS sports and recreation subscore. More patients in the KDRO group met the minimal clinically important difference for most patient-reported outcomes than the control group. Eight patients (44%) in the control group complained of postoperative anterior knee pain, compared with 1 patient (6%) in the KDRO group (P = .018). CONCLUSIONS: KDRO combined with MPFLR was associated with better postoperative outcomes than TTT combined with MPFLR in patients with recurrent patellar instability and a torsion deformity. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

The Value of Minimal Clinically Important Difference, Substantial Clinical Benefit, and Patient-Acceptable Symptomatic State for Commonly Used Patient-Reported Outcomes in Recurrent Patellar Instability Patients After Medial Patellofemoral Ligament Reconstruction and Tibial Tubercle Transfer.

PURPOSE: To identify the minimal clinically important difference (MCID), substantial clinical benefit (SCB) and patient-acceptable symptomatic state (PASS) for commonly used patient-reported outcomes (PROs) in recurrent patellar instability patients after medial patellofemoral ligament reconstruction (MPFLR) and tibial tubercle transfer (TTT), and to determine the impact of potential prognostic factors on the likelihood of achieving these values. METHODS: From April 2015 to February 2021, patients who underwent MPFLR and TTT were retrospectively reviewed. PROs included Kujala, Knee Injury and Osteoarthritis Outcome (KOOS), Lysholm, International Knee Documentation Committee (IKDC), and Tegner score. Relevant anchor questions were provided. A distribution- or anchor-based method was adopted to determine the MCID, SCB, and PASS. Minimal detectable change (MDC) was included to confirm the validity. Univariate regression analyses were conducted to determine the potential prognostic factors. RESULTS: One hundred forty-two patients were included. The MCID were 9.1 (Kujala), 11.1 (Lysholm), 0.9 (Tegner), 9.9 (IKDC), 9.0 (KOOS-Pain), 10.8 (KOOS-Symptoms), 10.0 (KOOS-Activities of Daily Living [ADL]), 17.8 (KOOS-Sports and Recreation [Sports/Rec]), and 12.7 (KOOS-Quality of Life [QoL]). The SCB were 14.5 (Kujala), 12.5 (Lysholm), 1.5 (Tegner), 14.5 (IKDC), 13.9 (KOOS-Pain), 14.3 (KOOS-Symptoms), 18.4 (KOOS-ADL), 47.5 (KOOS-Sports/Rec), and 15.0 (KOOS-QoL). The PASSs were 85.5 (Kujala), 75.5 (Lysholm), 3.5 (Tegner), 73.2 (IKDC), 87.5 (KOOS-Pain), 73.2 (KOOS-Symptoms), 92.0 (KOOS-ADL), 77.5 (KOOS-Sports/Rec), and 53.1 (KOOS-QoL). All SCBs were valid except KOOS-QoL. All MCIDs were valid at the 95% confidence interval (CI) except KOOS scores, the majority of which were valid at the 90% CI. A younger age was an independent prognostic factor of reaching PASS for Lysholm, IKDC, Tegner, and KOOS-ADL score. A higher baseline score was a negative prognostic factor for achieving MCID or SCB but had a slightly positive influence on the achievement of PASS. CONCLUSIONS: This study established the MCID, SCB, and PASS for commonly used PROs and confirmed their validity in recurrent patellar instability patients after MPFLR and TTT. Younger age and lower baseline scores were prognostic factors of achieving MCID and SCB, whereas patients with higher baseline scores were more likely to report satisfaction. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic trial.

A Deep Learning Model Enhances Clinicians' Diagnostic Accuracy to More Than 96% for Anterior Cruciate Ligament Ruptures on Magnetic Resonance Imaging.

PURPOSE: To develop a deep learning model to accurately detect anterior cruciate ligament (ACL) ruptures on magnetic resonance imaging (MRI) and to evaluate its effect on the diagnostic accuracy and efficiency of clinicians. METHODS: A training dataset was built from MRIs acquired from January 2017 to June 2021, including patients with knee symptoms, irrespective of ACL ruptures. An external validation dataset was built from MRIs acquired from January 2021 to June 2022, including patients who underwent knee arthroscopy or arthroplasty. Patients with fractures or prior knee surgeries were excluded in both datasets. Subsequently, a deep learning model was developed and validated using these datasets. Clinicians of varying expertise levels in sports medicine and radiology were recruited, and their capacities in diagnosing ACL injuries in terms of accuracy and diagnosing time were evaluated both with and without artificial intelligence (AI) assistance. RESULTS: A deep learning model was developed based on the training dataset of 22,767 MRIs from 5 centers and verified with external validation dataset of 4,086 MRIs from 6 centers. The model achieved an area under the receiver operating characteristic curve of 0.987 and a sensitivity and specificity of 95.1%. Thirty-eight clinicians from 25 centers were recruited to diagnose 3,800 MRIs. The AI assistance significantly improved the accuracy of all clinicians, exceeding 96%. Additionally, a notable reduction in diagnostic time was observed. The most significant improvements in accuracy and time efficiency were observed in the trainee groups, suggesting that AI support is particularly beneficial for clinicians with moderately limited diagnostic expertise. CONCLUSIONS: This deep learning model demonstrated expert-level diagnostic performance for ACL ruptures, serving as a valuable tool to assist clinicians of various specialties and experience levels in making accurate and efficient diagnoses. LEVEL OF EVIDENCE: Level III, retrospective comparative case series.

Impact of sex and age on the lateralisation of the tibial tubercle in normal paediatric and adolescent populations.

PURPOSE: Numerous methods have been proposed to characterise tubercle lateralisation. However, their normal values and related changes remain unclear. Accordingly, it was aimed to determine the potential sex and age effects and determined the optimal individualised method of diagnosing lateralisation of the tibial tubercle in patients with recurrent patellar dislocation (RPD). METHODS: Measurements included the tibial tubercle-trochlear groove (TT-TG) distance, tibial tubercle-posterior cruciate ligament (TT-PCL) distance and tibial tubercle lateralisation (TTL); and the proximal tibial width (PTW), trochlear width (TW) and trochlear dysplasia index (TDI), for adjustment. A two-way analysis of variance was used to determine the effect of age, sex and their interaction within the normal group. When the age effect was statistically significant, a nonlinear regression was created. Areas under the receiver-operating characteristic curve (AUCs) were calculated to assess diagnostic accuracy. RESULTS: A total of 277 normal participants (mean [SD] age, 13.5 [2.6] years; 125 [45.1%] female) and 227 patients with RPD (mean [SD] age, 13.5 [2.6] years; 161 [58.1%] female) were analysed. It was found that in the normal group, in patients aged 7-10, TT-PCL distance (p = 0.006), TTL (p = 0.007) and TT-PCL/PTW (p < 0.001) were significantly larger in females than in males. A significant sex effect was also detected on TT-TG/TW (p = 0.014). TT-TG distance, TT-PCL distance, TTL and TT-PCL/PTW (in male patients) approached an established normal adult value of 12.3 mm, 20.9 mm, 0.64 and 0.28, respectively, with increasing age (p < 0.001). The AUC was greater for TT-TG/TDI and TT-TG/TW (p ≤ 0.01) and TT-TG/TDI outperformed TT-TG/TW in patients aged 15-18 (p = 0.004). CONCLUSIONS: Tubercle lateralisation increased with age and was affected by sex, with the exception of TT-TG distance and TT-TG/TDI. TT-TG/TDI is the optimal method of diagnosing a lateralized tibial tubercle in patients with RPD. These findings assist with the evaluation of tubercle lateralisation in that they provide a proper protocol for paediatric and adolescent populations with RPD; and thus, will help determine whether medial tubercle transfer should be included among the tailored surgical procedures considered for the treatment of patients with RPD. LEVEL OF EVIDENCE: Level III.

Anatomic double-bundle transtibial anterior cruciate ligament reconstruction restores graft length changes but leads to larger graft bending angles.

PURPOSE: The purpose of this study was to evaluate the femoral tunnel position using a modified anatomic transtibial (TT) double-bundle anterior cruciate ligament reconstruction (DBACLR) and to investigate the knee kinematics, graft length and graft bending angle following DBACLR. METHODS: Ten patients who underwent DBACLR using the modified TT technique were included in the study. All patients performed a single-legged lunge under a dual fluoroscopic imaging system to assess the 6 degrees of freedom tibiofemoral kinematics. Femoral tunnel position was evaluated via postoperative three-dimensional (3D) computed tomography. The area centroids of anteromedial (AM) and posterolateral (PL) bundles were determined on 3D knee models. The lengths of AM and PL bundles, as well as graft bending angle at the femoral tunnel aperture, were measured by created virtual fibres. RESULTS: The reconstructed knee rotated more externally compared with the contralateral knee between 0° and 60° (p ≤ 0.049). There is no significant difference in the length change of AM bundle (n.s.) and PL bundle (n.s.) between the two sides from 0° to 120° during the lunge motion. The maximum graft bending angle at the femoral tunnel aperture occurred at 0° of knee flexion, with the AM graft bending angle was 72.6° ± 9.0° and the PL graft bending angle was 90.3° ± 9.7°. CONCLUSION: The modified TT technique used in this study could achieve anatomical ACL reconstruction, restoring graft length change patterns compared to contralateral knees. However, residual rotational instability of the reconstructed knee was observed after DBACLR, despite achieving anatomic tunnel placement. Therefore, double-bundle reconstruction may not sufficiently address the persistent rotational instability of the knee. Additionally, larger graft bending angles at the femoral tunnel aperture were found with the modified TT technique. Therefore, further improvement to the TT technique should focus on reducing the graft's curvature while maintaining the anatomical properties of the knee joint. The findings of this study highlight the need for improved surgical techniques to address residual rotational instability and optimise graft curvature. These improvements are crucial for enhancing patient outcomes and long-term joint function following ACL reconstruction. LEVELS OF EVIDENCE: Level II.

One-pot cascade synthesis of dibenzothiophene-based heterobiaryls from dibenzothiophene-5-oxide.

A sulfoxide directed C-H metalation/boration/B2Pin2 mediated reduction/Suzuki coupling process to synthesize 4-substituted dibenzothiophene (DBT) in one-pot from dibenzothiophene-5-oxide (DBTO) was developed. A variety of DBT-based heterobiaryls were prepared in satisfactory to good yields. A mechanism was proposed. The application of this methodology was demonstrated by synthesizing a luminescent material.

Prevalence and a correlation analysis of discoid meniscus and femoral trochlear dysplasia.

BACKGROUND: Discoid meniscus (DM) and femoral trochlear dysplasia (FTD) are common knee disorders. Both as congenital malformation, whether there is a connection between them is unclear and the research on their prevalence in the general population is inadequate. This study aimed to investigate the prevalence of FTD and DM in the general population through a large sample size, and to explore the relationship between them. STUDY DESIGN: Retrospective study. METHODS: Patients undergoing knee magnetic resonance imaging (MRI) examinations at our outpatient clinic were screened and 1003 patients were enrolled in DM group with 989 patients in non-DM (NDM) group. The type of DM and FTD was classified with Watanabe classification and Dejour's classification, respectively. The prevalence of FTD and DM in the general population and the relationship between them were evaluated. RESULTS: The prevalence of DM and FTD was 10.0% and 14.5%, respectively. The overall percentage of FTD was higher in DM group (P < 0.001). The DM group has a higher percentage of all types of FTD except type D (P < 0.05), and a higher percentage of both low- and high-grade FTD (P < 0.001). There were 633 cases of type I DM and 370 cases of type II DM. The overall percentage of FTD was not significantly different between the two types (P = 0.106). No significant difference was detected for all types of FTD except type B (P < 0.05). The Type I DM group has a significant higher percentage of high-grade FTD than Type II group (P < 0.05). CONCLUSION: Patients with a DM are more likely to have FTD regardless of the type of DM, while those with a type I DM are more prone to have a high grade FTD.

Patella-Posterior Turning Point of the Distal Femur Distance Is a Potential Indicator for Diagnosing Patella Alta in Recurrent Patellar Dislocation Population.

PURPOSE: To introduce a simple patellar height measurement method (patella-posterior turning point of the distal femur [P-PTP] Distance) independent of patellar anatomy with standardized patient position, and tested the reliability, validity, and diagnostic accuracy compared with commonly used ratios in knee extension. METHODS: We retrospectively reviewed 418 computed tomography (CT) images of the knee joint in a group of patients who were diagnosed recurrent patellar dislocation (RPD). With the three-dimensional (3D) CT reconstructed knee, patellar height was qualitatively assessed by the patellar engagement with the femoral trochlea in terminal knee extension to divide RPD population into case (patella alta) and control group. With digitally reconstructed lateral radiographs, patellar height was measured with P-PTP distance (perpendicular distances between the distal edge of patella articular surface and posterior turning point of distal femur), and four commonly used ratios: Caton-Deschamps index, Modified Insall-Salvati index, Blackburne-Peel index, and Insall-Salvati index. An unpaired t-test was conducted to determine significant differences between groups. Correlation coefficient, intra- and inter-observer reliability, receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were also calculated. RESULTS: 198 knee images (198 patients) were included for final evaluation. Patella alta was present in 72 knees (36.3%) with RPD. The effect size was relatively large between the case and control group for P-PTP distance (d = -1.619; 95% CI, -1.948 to -1.286). P-PTP distance correlated moderately to strongly with four commonly used ratios (P < .001). Intraobserver and interobserver reliability was good for P-PTP distance. The AUC of the ROC curve was categorized as excellent for P-PTP distance, better than other measurements (P < .001), and the cutoff value was 4.2 mm with the highest sensitivity (86.11%) and specificity (84.92%). CONCLUSIONS: The measurement method, P-PTP distance, showed good intra-observer and inter-observer reliability, well correlated with commonly used ratios, and presented best diagnostic accuracy among commonly used ratios for predicting RPD. P-PTP distance might be a potential indicator for identifying patella alta in RPD patients when supine and knee extended. CLINICAL RELEVANCE: The measurement reported in this study may help in advancing clinical evaluation of patella alta, providing an alternative and simple method to measure patellar height. Standing or weight-bearing plain lateral radiographs obtained from the routine practice should be further assessed in the next step to further validate the method.

Arthroscopic Dynamic Anterior Stabilization Using Either Long Head of the Biceps or Conjoined Tendon Transfer for Anterior Shoulder Instability Results in a Similarly Low Recurrence Rate.

PURPOSE: To compare the clinical outcomes of arthroscopic dynamic anterior stabilization (DAS) between transferring the long head of the biceps (DAS-LHB) and the conjoined tendon (DAS-CT) for anterior shoulder instability with <15% glenoid bone loss. METHODS: From January 2016 to May 2019, a total of 63 patients who underwent DAS for recurrent anterior shoulder dislocation with <15% glenoid bone loss were included, comprising 33 patients in DAS-LHB group and 30 patients in DAS-CT group. Clinical outcomes were assessed preoperatively and at a minimum 3-year follow-up, including patient-reported outcomes, range of motion, and return to sports (RTS). Postoperative recurrent instability (including dislocation, subluxation, and subjective instability with a positive apprehension test), revisions and complications also were recorded. RESULTS: No significant demographic characteristics difference was detected between the DAS-LHB (26.3 ± 7.9 years) and DAS-CT groups (26.0 ± 6.7 years). At the latest follow-up, there were no significant differences between the 2 groups in functional scores: Oxford Shoulder Instability Score (14.8 ± 2.8 vs 15.2 ± 3.6), Rowe score (95.9 ± 6.5 vs 93.2 ± 10.2), visual analog scale for pain (0.8 ± 1.2 vs 0.7 ± 1.7), and American Shoulder and Elbow Surgeons (95 ± 8.8 vs 95.2 ± 9.1) (all P > .218). No significant difference was detected between groups in the rates of RTS (90.1% vs 86.7%, P = .700) and RTS at previous level (78.7% vs 73.3%, P = .258), respectively. No recurrent dislocation occurred in either group. One patient felt occasional subluxation in the DAS-LHB group, and one was positive for the apprehension test in each group. One patient presented with postoperative shoulder stiffness and underwent a secondary arthroscopic debridement in the DAS-CT group. CONCLUSIONS: Comparable rates of recurrence, complication, return to sports, and subjective shoulder function were observed between DAS-LHB and DAS-CT groups. LEVEL OF EVIDENCE: Level III, retrospective comparative therapeutic trial.

Patellar shift ratio (PSR) is the optimal measurement for characterising lateral patellar shift and a reliable predictor of recurrent patellar dislocation.

PURPOSE: To propose a new measurement, the patellar shift ratio (PSR), for characterising lateral patellar shift; to determine its diagnostic accuracy in predicting recurrent patellar dislocation (RPD); and to identify the effect of patellar tilt and morphology on shift measurements. METHODS: Variables including the PSR, bisect offset (BSO), BSO adjusted by trigonometric analysis, linear patellar displacement (LPD) distance and congruence angle were measured on axial computed tomography (CT). Furthermore, PSR was classified into grades determined by the threshold generated by receiver operating characteristic (ROC) curves. Youden's index was used to identify the ideal threshold on the curve. The area under the ROC curve (AUC) values and likelihood ratios were calculated to assess diagnostic performance in predicting RPD. Correlation analysis was conducted to identify the effects of lateral tilt and the Wiberg index on lateral shift. Intra- and interobserver reliability were evaluated using the intraclass correlation coefficient. RESULTS: The study included 54 RPD patients and 54 controls matched by sex and age. The threshold for PSR was 24.3% (sensitivity, 96.30%; specificity, 85.19%). AUCs were categorised as excellent for all protocols (P < 0.001). The positive likelihood ratio of the PSR for predicting RPD was 6.50. PSR was categorised in terms of lateral trochlear quadrants consisting of 25% increments. Lateral patellar tilt showed a strong positive correlation with BSO (P < 0.001); moderate correlations with PSR, LPD distance and adjusted BSO (P ≤ 0.001); and a weak correlation with congruence angle (P = 0.034). The Wiberg index presented a positive moderate correlation with BSO (P < 0.001), while no correlation was found with PSR, LPD distance, or congruence angle (n.s.). All parameters showed good repeatability (intraobserver) and reproducibility (interobserver). CONCLUSIONS: The PSR showed excellent diagnostic performance as indicated by likelihood ratios, measurement accuracy (being relatively resistant to the effects of tilt and the Wiberg index), and intra- and interobserver reliability. The optimal PSR threshold for predicting RPD risk was 24.3%, and the grade of PSR (normal, 1-4) was also a reliable and easily calculated predictor of RPD. This quantifying method to characterise lateral patellar shift is an alternative useful method for clinical assessments of RPD patients and for research on patellofemoral congruence. LEVEL OF EVIDENCE: Level III.

Sulcus depth, congruence angle, Wiberg index, TT-TG distance, and CDI are strong predictors of recurrent patellar dislocation.

PURPOSE: To characterize patellofemoral morphology, determine radiological cutoff values based on computed tomography (CT) images, and clarify predominant anatomic risk factors in young patients with recurrent patellar dislocation (RPD). METHODS: A total of 212 knees (age 23.0 ± 5.3 years, female: male = 110:102) with CT-confirmed RPD were enrolled for analysis. The control group was matched by age and sex (2:1). Patellofemoral and trochlear morphology, patellofemoral alignment, and other parameters were assessed by CT. Standardized methods were used for measurements. Receiver operating characteristic (ROC) curves and the areas under the ROC curve (AUCs) were used to assess accuracy in diagnosing RPD. The index of union (IU) was employed to identify a cutoff value for risk. A binary logistic regression model (Forward, LR) was constructed, and standardized coefficients were calculated to compare the relative strength of different predictors. Factors included in the model were employed to calculate distributions in the studied population. RESULTS: The majority of measurements showed a significant difference between the RPD and control groups when comparing mean values. The AUC value was favorable for sulcus depth and significantly better than that for other trochlear morphology parameters (P < 0.0001). Cutoff values were 0.58 for the Wiberg index, 153.3° for the sulcus angle, 3.6 mm for the sulcus depth, 1.94 for the trochlear width ratio, 16.2° for the lateral trochlear inclination, 17.2° for the patellar lateral tilt, 25.5° for the congruence angle, 1.2 for the patellar height [Caton-Deschamps index (CDI)], 6.1° for the knee rotation, and 16.4 mm for the tibial tubercle-trochlear groove (TT-TG) distance. A binary logistic regression model (χ2 = 20.826, P = 0.008) including the Wiberg index, sulcus depth, congruence angle, patellar height (CDI), and TT-TG distance was constructed for RPD (P ≤ 0.015), which showed excellent diagnostic performance, as indicated by an AUC of 0.989 (95% CI, 0.979 to 0.998). Sulcus depth showed the strongest relationship with RPD, followed by the congruence angle and Wiberg index, as indicated by the standardized coefficients - 1.43, 1.02, and 0.97, respectively. Eighty-seven percent of the RPD population had sulcus depth ≤ 3.6 mm. CONCLUSIONS: This study provides a systematic reference of cutoff values based on CT data. The combination of five anatomic risk factors (sulcus depth, congruence angle, Wiberg index, TT-TG distance, and CDI) may be an excellent predictor of RPD as initial risk assessment. Sulcus depth, as the most frequently observed anatomic risk factor, showed the best diagnostic performance among trochlear morphological parameters and the strongest relationship with RPD, followed by the congruence angle and Wiberg index. In clinical practice, the sulcus depth, congruence angle, Wiberg index, TT-TG distance, and CDI with the proposed cutoff values can be used in combination to evaluate RPD. When assessing trochlear morphology, sulcus depth is recommended as the best radiological parameter. LEVEL OF EVIDENCE: Level III.