Clinical and genetic characteristics of three patients with congenital insensitivity to pain with anhidrosis: Case reports and a review of the literature.

BACKGROUND: Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss-of-function mutations of the NTRK1 gene, affecting the autonomic and sensory nervous system. Clinical manifestation is varied and includes recurrent fever, pain insensitivity, anhidrosis, self-mutilating behavior, and intellectual disability. METHODS: Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing. RESULTS: CIPA symptoms including recurrent fever, pain insensitivity, and anhidrosis manifested at the age of 1 year (age range: 0.3-8 years). Two patients exhibited self-mutilation tendencies, intellectual disability, and developmental delay. Four NTRK1 (NM_002529.3) mutations, c.851-33T>A (p.?), c.2020G>T (p.Asp674Tyr), c.2303C>T (p.Pro768Leu), and c.574-156_850+1113del (exons 5-7 del) were identified. Two patients exhibited early onset and severe phenotype, being homozygous for c.851-33T>A (p.?) mutations and compound heterozygous for c.851-33T>A (p.?) and c.2020G>T (p.Asp674Tyr) mutation of NTRK1. The third patient with compound heterozygous mutations of c.2303C>T (p.Pro768Leu) and c.574-156_850+1113del (exons 5-7 del) displayed a late onset and milder clinical manifestation. CONCLUSION: All three patients exhibited variable phenotypes and disease severity. This research enriches our understanding of clinical and genetic aspects of CIPA, highlighting variable phenotypes and disease severity.

Reliability and modality analysis of patellar height measurement in pediatric knee.

Introduction: Various measurement methods and imaging technique are in use to measure patellar height in pediatric patients. However, there is no gold standard as to which measurement method and modality are the most reliable for pediatric patients. Therefore, the aim of this study was to determine the inter-observer reliability, intra-observer reliability, and applicability of various patellar height measurement methods in pediatric knee. Additionaly, we analyzed the reliability across different imaging modalities. Methods: Total 450 pediatric patients (age: 5-18 years) were evaluated using lateral knee radiographs and magnetic resonance imaging (MRI). The patellar height ratios were measured using five methods. Five methods were Insall-Salvati (IS), Koshino-Sugimoto (KS), Blackburne-Peel (BP), modified Insall-Salvati (MIS), and Caton-Deschamps (CD). The patients were categorized into two age groups: P (ages 5-13) and Q (ages 14-18). Each measurement was conducted twice by two raters. The intra-observer reliability, inter-observer reliability and inter-modality reliability were calculated. In addition, applicability was defined as the possibility to apply each measurement method to each age group. Results: The KS method showed the highest inter-observer reliability and intra-observer reliability when using MRI for both age groups. The inter-observer reliability and intra-observer reliability of the IS for lateral knee radiographs was highest among all observers for group Q. The CD method showed the highest inter-observer reliability in group P, while the KS showed the highest intra-observer reliability in group P using lateral radiographs. The KS method showed the highest inter-modality reliability in group P, while the IS showed the highest inter-modality reliability in group Q. The KS method was applicable to all patients when using lateral knee radiography, and the IS method was applicable to all patients when using MRI. Conclusions: Our results show that the reliability of various measurement method and imaging technique differed based on pediatric knee age group when measuring patellar height. Therefore, in the case of pediatric patients, reliability measurement methods and imaging techniques according to the patient's age should be applied.

Evaluating the Clinical Utility of Brachial Plexus Block for Reducing Opioid Exposure in Pediatric Elbow Fracture Surgery: A Retrospective Cohort Study.

Background and Objectives: Reducing opioid exposure in common pediatric surgeries is of paramount importance. This study aimed to assess the efficacy of regional nerve blocks in reducing opioid exposure while preserving high success rates. Materials and Methods: We conducted a retrospective matched cohort study (1:1) including patients with elbow fractures < 12 years old who underwent treatment with percutaneous pinning. Patients were divided into general-anesthesia (GA) and GA-followed-by-supraclavicular-brachial-plexus-block (GA-SCB) groups. The primary outcome was the number of patients administered postoperative rescue opioids. The secondary outcomes included intraoperative and postoperative opioid administration, the time to first request for rescue analgesia, pain scores, block success rate, block performing time, and block-related complications. Results: In a total of 478 patients, 363 underwent percutaneous pinning, and 86 were cohort-matched (GA: n = 43, GA-SCB: n = 43). On the first postoperative day, 34 (79.0%) patients in the GA group were administered postoperative rescue opioids, compared with 12 (27.9%) in the GA-SCB group (p < 0.001). All the patients in the GA-SCB group were opioid-free during the intraoperative period. No SCB-associated complications were observed. Total opioid consumption was significantly lower in the GA-SCB group than in the GA group until the first postoperative day (GA vs. GA-SCB, 3.2 ± 3.0 mg vs. 0.9 ± 1.8 mg, p < 0.001). Conclusions: SCB application in pediatric patients who underwent elbow fracture surgery significantly reduced opioid exposure and had a high success rate when performed using ultrasound guidance by an expert. Furthermore, the complication risk and surgical delay were minimal.

Micellized protein transduction domain-bone morphogenetic protein-2 accelerates bone healing in a rat tibial distraction osteogenesis model.

The clinical application of growth factors such as recombinant human bone morphogenetic protein-2 (rh-BMP-2), for functional bone regeneration remains challenging due to limited in vivo efficacy and adverse effects of previous modalities. To overcome the instability and short half-life of rh-BMP-2 in vivo, we developed a novel osteogenic supplement by fusing a protein transduction domain (PTD) with BMP-2, effectively creating a prodrug of BMP-2. In this study, we first created an improved PTD-BMP-2 formulation using lipid nanoparticle (LNP) micellization, resulting in downsizing from micrometer to nanometer scale and achieving a more even distribution. The micellized PTD-BMP-2 (mPTD-BMP-2) demonstrated improved distribution and aggregation profiles. As a prodrug of BMP-2, mPTD-BMP-2 successfully activated Smad1/5/8 and induced mineralization with osteogenic gene induction in vitro. In vivo pharmacokinetic analysis revealed that mPTD-BMP-2 had a much more stable pharmacokinetic profile than rh-BMP-2, with a 7.5-fold longer half-life. The in vivo BMP-responsive element (BRE) reporter system was also successfully activated by mPTD-BMP-2. In the in vivo rat tibia distraction osteogenesis (DO) model, micro-computed tomography (micro-CT) scan findings indicated that mPTD-BMP-2 significantly increased bone volume, bone surface, axis moment of inertia (MOI), and polar MOI. Furthermore, it increased the expression of osteogenesis-related genes, and induced bone maturation histologically. Based on these findings, mPTD-BMP-2 could be a promising candidate for the next-generation osteogenesis drug to promote new bone formation in DO surgery. STATEMENT OF SIGNIFICANCE: This study introduces micellized bone morphogenetic protein-2 (mPTD-BMP-2), a next-generation osteogenic supplement that combines protein transduction domain (PTD) and nano-sized micelle formulation technique to improve transduction efficiency and stability. The use of PTD represents a novel approach, and our results demonstrate the superiority of mPTD-BMP-2 over rh-BMP-2 in terms of in vivo pharmacokinetic profile and osteogenic potential, particularly in a rat tibial model of distraction osteogenesis. These findings have significant scientific impact and potential clinical applications in the treatment of bone defects that require distraction osteogenesis. By advancing the field of osteogenic supplements, our study has the potential to contribute to the development of more effective treatments for musculoskeletal disorders.

Sterile Silicone Ring Tourniquets in Limb Surgery: A Prospective Clinical Trial in Pediatric Patients Undergoing Orthopedic Surgery.

Sterile silicone ring tourniquets (SSRTs) reduce intraoperative bleeding and provide a wide surgical view. Moreover, they reduce the risk of contamination and are cheaper than conventional pneumatic tourniquets. Our study describes the perioperative outcomes of sterile silicone ring tourniquet placement in pediatric patients undergoing orthopedic surgery. We prospectively recruited 27 pediatric patients aged < 18 years who underwent 30 orthopedic surgeries between March and September 2021. Following complete surgical draping, all operations were initiated by placing SSRTs. We investigated the demographic and clinical characteristics of these patients, details of the tourniquet used, and intra- and postoperative outcomes of tourniquet placement. Owing to the narrowness of tourniquet bands and tourniquet placement at the proximal ends of the extremities, wide surgical fields were achieved, without limiting joint range of motion. Bleeding control was effective. Tourniquets were applied and removed rapidly and safely, regardless of limb circumference. None of the patients experienced postoperative pain, paresthesia, skin problems at the application site, surgical site infections, ischemic problems, or deep vein thrombosis. SSRTs effectively reduced intraoperative blood loss and facilitated wide operative fields in pediatric patients with various limb sizes. These tourniquets allow quick, safe, and effective orthopedic surgery for pediatric patients.

Acceleration of bone formation by octacalcium phosphate composite in a rat tibia critical-sized defect.

Background: The osteogenic capabilities and biodegradability of octacalcium phosphate (OCP) composites make them unique. Despite the excellent characteristics of OCP, their use is limited due to handling difficulties. In this study, we aimed to evaluate and compare three types of OCPs (cemented OCP (C-OCP), C-OCP with collagen (OCP/Col), and synthetic OCP (S-OCP) with alginate (OCP/Alg)) versus commercially available ß-tricalcium phosphate (ß-TCP) regarding their potential to accelerate bone formation in defective rat tibias. Methods: The specimens with OCP composite were manufactured into 5 â€‹mm cubes and inserted into the segmental defects of rat tibias fixed with an external fixator. In addition, 3 â€‹mm-hole defects in rat tibias were evaluated to compare the graft material properties in different clinical situations. Serial X-ray studies were evaluated weekly and the tibias were harvested at postoperative 6 weeks or 8 weeks for radiologic evaluation. Histological and histomorphometric analyses were performed to evaluate the acceleration of bone formation. Results: In the critical-defect model, OCP/Alg showed bone bridges between segmentally resected bone ends that were comparable to those of ß-TCP. However, differences were observed in the residual graft materials. Most ß-TCP was maintained until 8 weeks postoperatively; however, OCP/Alg was more biodegradable. In addition calcification in the ß-TCP occurred at the directly contacted area between graft particles and bony ingrowth was observed in the region adjacent resected surface of tibia. In contrast, no direct bony ingrowth was observed in OCP-based materials, but osteogenesis induced from resected surface of tibia was more active. In the hole-defect model, OCP/Col accelerated bone formation. ß-TCP and OCP/Alg showed similar patterns with relatively higher biodegradability. In histology, among the OCP-based materials, directly contacted new bone was formed only in OCP/Alg group. The new bone formation in the periphery area of graft materials was much more active in the OCP-based materials, and the newly formed bone showed a thicker trabecular and more mature appearance than the ß-TCP group. Conclusions: In this study, OCP/Alg was equivalent to ß-TCP in the acceleration of bone formation with better biodegradability appropriate for clinical situations in different circumstances. Our OCP/Col composite showed fast degradation, which makes it unsuitable for use in mechanical stress conditions in clinical orthopedic settings. The Translational Potential of this Article: In our research, we compared our various manufactured OCP composites to commercially available ß-TCP in critical-defect rat tibia model. OCP/Col showed acceleration in hole-defect model as previous studies in dental field but in our critical-sized defect model it resorbed fast without acceleration of bony union. OCP/Alg showed matched results compared to ß-TCP and relatively fast resorption so we showed market value in special clinical indication depending on treatment strategy. This is the first OCP composite study in orthopaedics with animal critical-sized tibia bone study and further study should be considered for clinical application based on this study.

Competitive Hybridization of a Microarray Identifies CMKLR1 as an Up-Regulated Gene in Human Bone Marrow-Derived Mesenchymal Stem Cells Compared to Human Embryonic Fibroblasts.

Mesenchymal stem cells (MSCs) have been widely applied to the regeneration of damaged tissue and the modulation of immune response. The purity of MSC preparation and the delivery of MSCs to a target region are critical factors for success in therapeutic application. In order to define the molecular identity of an MSC, the gene expression pattern of a human bone marrow-derived mesenchymal stem cell (hBMSC) was compared with that of a human embryonic fibroblast (hEF) by competitive hybridization of a microarray. A total of 270 and 173 genes were two-fold up- and down-regulated with FDR < 0.05 in the hBMSC compared to the hEF, respectively. The overexpressed genes in the hBMSC over the hEF, including transcription factors, were enriched for biological processes such as axial pattern formation, face morphogenesis and skeletal system development, which could be expected from the differentiation potential of MSCs. CD70 and CD339 were identified as additional CD markers that were up-regulated in the hBMSC over the hEF. The differential expression of CD70 and CD339 might be exploited to distinguish hEF and hBMSC. CMKLR1, a chemokine receptor, was up-regulated in the hBMSC compared to the hEF. RARRES2, a CMKLR1 ligand, stimulated specific migration of the hBMSC, but not of the hEF. RARRES2 manifested as ~two-fold less effective than SDF-1α in the directional migration of the hBMSC. The expression of CMKLR1 was decreased upon the osteoblastic differentiation of the hBMSC. However, the RARRES2-loaded 10% HA-silk scaffold did not recruit endogenous cells to the scaffold in vivo. The RARRES2−CMKLR1 axis could be employed in recruiting systemically delivered or endogenous MSCs to a specific target lesion.

Osteonecrosis in Korean Paediatric and Young Adults with Acute Lymphoblastic Leukaemia or Lymphoblastic Lymphoma: A Nationwide Epidemiological Study.

Osteonecrosis (ON) is a serious complication of acute lymphocytic leukaemia (ALL) or lymphoblastic lymphoma (LBL) treatment, and there is little information regarding ON in Korean paediatric and young adult patients. This retrospective cohort study assessed the cumulative incidence of and risk factors for ON using national health insurance claims data from 2008 to 2019 in 4861 ALL/LBL patients. The Kaplan-Meier method was used to estimate the cumulative incidence of ON according to age groups; the Cox proportional hazard regression model was used to identify risk factors related to ON development after diagnosing ALL/LBL. A cause-specific hazard model with time-varying covariates was used to assess the effects of risk factors. Overall, 158 (3.25%) patients were diagnosed with ON, among whom 23 underwent orthopaedic surgeries. Older age, radiotherapy (HR = 2.62, 95% confidence interval (CI) 1.87-3.66), HSCT (HR = 2.40, 95% CI 1.74-3.31), steroid use and anthracycline use (HR = 2.76, CI 1.85-4.14) were related to ON in the univariate analysis. In the multivariate analysis, age and steroid and asparaginase use (HR = 1.99, CI 1.30-3.06) were factors associated with ON. These results suggest that Korean patients with ALL/LBL who used steroids and asparaginase should be closely monitored during follow-up, even among young adult patients.

Evaluation of age group and sex differences in the measurement of patellar height of pediatric knee in a Korean population.

Introduction: Various methods based on bony landmarks are used to determine patellar height. This study analyzed five methods for patellar height measurement on lateral knee radiographs, namely, the Insall-Salvati, Koshino-Sugimoto, Blackburne-Peel, modified Insall-Salvati, and Caton-Deschamps methods. Methods: Overall, 425 pediatric participants (221 males, 204 females; age range 5-18 years) were included and were divided equally into three age groups (A, 5-10 years; B, 11-13 years; and C, 13-18 years). For the comparison of the applicability of each method, the applicable probabilities for each age group and sex-based differences were analyzed using logistic regression techniques. Intra-rater reliability and inter-rater variability were analyzed by two trained raters. Results: The Koshino-Sugimoto method was applicable to all patients. The 80% applicable age of female patients was lower than that of male patients for the Blackburne-Peel (male = 11.9, female = 11) and Caton-Deschamps (male = 11.9, female = 11.1) methods. However, in the Insall-Salvati (male = 12, female = 12.1) and modified Insall-Salvati (male = 12.6, female = 13.1) methods, the 80% applicable age in male patients was lower than that in female patients. The Koshino-Sugimoto method showed the highest variability in group B, while the Insall-Salvati showed the highest variability in group C. In terms of intra-observer reliability, the Caton-Deschamps method showed the same reliability as the Insall-Salvati method, in group C. Conclusions: Our results demonstrated differences in the reliability, variability, and applicability of patellar height measurement methods according to age group. The applicability of patellar height measurement methods also differed according to sex. Therefore, based on age group and sex, different methods should be used for patellar height measurement in pediatric patients.

Correlation of Femoral Trochlear Dysplasia With Anterior Cruciate Ligament Injury in Skeletally Immature Patients.

BACKGROUND: Reports of anterior cruciate ligament (ACL) injury in patients with skeletal immaturity have been increasing. Variations in knee joint anatomy have been linked to ACL injury risk factors. PURPOSE: To identify associations between ACL injury, patella alta, and femoral trochlear dysplasia in patients with skeletal immaturity by using magnetic resonance imaging (MRI). STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: This retrospective study included 231 patients with skeletal immaturity-116 with acute complete noncontact ACL injury and 115 without ACL injury (controls)-who underwent knee MRI. Cases of femoral trochlear dysplasia were divided into 4 types according to the Dejour classification scheme. Patellar height and patellar tendon length were measured via sagittal MRI, and the Insall-Salvati ratio (ISR) was calculated. RESULTS: In the ACL injury group, 56 (48.3%) knees exhibited trochlear dysplasia, including 51 (91.1%) that were Dejour type A; and in the control group, 12 (10.4%) knees exhibited trochlear dysplasia, 12 (100%) Dejour type A. The prevalence of femoral trochlear dysplasia was significantly higher in the ACL injury group than in the control group (P < .001). The ISR was not significantly different between the ACL injury and control groups (0.9 ± 0.2 vs 1 ± 0.2 mm; P = .16). The correlation between ISR >1.2 and presence of ACL injury was not significant. CONCLUSION: Femoral trochlear dysplasia was associated with ACL injury in patients with skeletal immaturity. In particular, Dejour type A femoral trochlear dysplasia was correlated with ACL injury patients with skeletal immaturity. Also, the possibility of ACL damage exists in patients with skeletal immaturity and femoral trochlear dysplasia.

Anatomic Differences in the Sagittal Knee Joint Are Associated With ACL Injury: Results From a Skeletally Immature Korean Population.

BACKGROUND: Differences in tibiofemoral articular morphology are associated with risks of anterior cruciate ligament (ACL) injury. PURPOSE: To determine whether bony and cartilaginous morphological characteristics are related to ACL injury in pediatric patients and to investigate any differences according to sex. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 200 skeletally immature Korean patients from a single institution were included in this study; 100 patients had an ACL injury, and 100 had an intact ACL. Condylar morphology and tibial slopes were evaluated and compared between the groups, and differences between sexes were evaluated in the ACL-injured group. RESULTS: The lateral femoral curvature was significantly greater and the lateral and medial tibial curvatures were significantly smaller in the ACL-injured group than in the intact group (P < .01 for all). In addition, the lateral and medial femoral curvatures as well as the lateral tibial curvature were significantly smaller in female than in male patients (P < .01 for all). Both the medial and lateral tibial slopes were greater in the ACL-injured versus intact group (medial slope, 5.5° vs 5.0°; lateral slope, 3.0° vs 1.3°, respectively); this difference was statistically significant for lateral tibial slope (P = .026). No sex-based differences were found for medial or lateral tibial slope. CONCLUSION: Femoral and tibial curvatures as well as lateral tibial slope were significantly different between the ACL-injured and ACL-intact patients, and the lateral tibial curvature was significantly smaller in female than in male patients. Medial and lateral tibial slopes were not associated with a significant difference in ACL injury between male and female patients.

Significant Changes in Serum MicroRNAs after High Tibial Osteotomy in Medial Compartmental Knee Osteoarthritis: Potential Prognostic Biomarkers.

High tibial osteotomy (HTO) is an effective alternative for medial compartmental knee osteoarthritis (OA). Circulating microRNAs (miRNAs) are known to serve as OA-related biomarkers. The present study investigated the differential expression of serum miRNAs before and after HTO to identify potential miRNAs as prognostic biomarkers. miRNA-polymerase chain reaction (PCR) arrays were used to screen for miRNAs in the serum at preoperative and 6-month postoperative time points from six patients, and the differentially expressed miRNAs identified in the profiling stage were validated using real-time PCR at post-operative months 6 and 18 in 27 other HTO-treated patients. Among 84 miRNAs involved in the inflammatory process, three (miR-19b-3p, miR-29c-3p, and miR-424-5p) showed differential expression patterns in the profiling stage (p = 0.011, 0.015, and 0.021, respectively). Levels of these three and four other miRNAs (miR-140-3p, miR-454-3p, miR-let-7e-5p, and miR-885-5p) known to be related to OA progression were evaluated in the serum of 27 patients. Only four miRNAs (miR-19b-3p, miR-140-3p, miR-454-3p, and miR-let-7e-5p) were significantly upregulated at postoperative month 6 (p = 0.003, 0.005, 0.004, and 0.004, respectively), and only miR-140-3p was significantly upregulated up to 18 months after operation (p = 0.003). Together, this study reveals the significantly upregulated serum miRNAs after HTO as potential prognostic biomarkers; however, further studies are warranted to elucidate their clinical implications.

Anatomic Relationship of the Femoral Neurovascular Bundle in Patients With Congenital Femoral Deficiency.

BACKGROUND: Congenital femoral deficiency (CFD) is a rare condition that affects the morphology of the hip and surrounding soft tissues. Bony deformity and distorted muscular anatomy are well known, but no studies have described the relationship of the femoral neurovascular (NV) bundle to surgically relevant anatomic landmarks. The authors compared the location of the femoral NV bundle on the affected side in patients with CFD with the unaffected side. The authors hypothesized that the bundle on the pathologic side would be in an abnormal position relative to the unaffected side. METHODS: Thirty-three patients diagnosed with unilateral CFD who had undergone preoperative magnetic resonance imaging of the pelvis were included in our study. The authors identified the femoral NV bundle on the axial cuts and measured its distance from the anterior superior iliac spine (ASIS), anterior inferior iliac spine (AIIS), and lesser trochanter (LT). Anatomic percent change and absolute measurements were then compared and correlated with associated boney deformities and the Paley classification. RESULTS: The distance from the femoral NV bundle to the ASIS, AIIS, and LT was significantly different compared with the unaffected side. The AIIS absolute distance and AIIS percent change significantly correlated with the neck-shaft angle of the proximal femur. CONCLUSIONS: In patients with CFD, the femoral NV bundle seems to be further from the LT and closer to the AIIS on the affected side when compared with the unaffected side. magnetic resonance imaging may be helpful to understand the course of the femoral NV bundle before reconstruction in patients with CFD; however, the authors recommend identification of the femoral NV bundle before transection of the proximal rectus femoris tendon to provide safe surgical care. LEVEL OF EVIDENCE: Level IV-case-control study of diagnostic studies.

Biomechanical effect of tibial slope on the stability of medial unicompartmental knee arthroplasty in posterior cruciate ligament-deficient knees.

AIMS: Unicompartmental knee arthroplasty (UKA) has become a popular method of treating knee localized osteoarthritis (OA). Additionally, the posterior cruciate ligament (PCL) is essential to maintaining the physiological kinematics and functions of the knee joint. Considering these factors, the purpose of this study was to investigate the biomechanical effects on PCL-deficient knees in medial UKA. METHODS: Computational simulations of five subject-specific models were performed for intact and PCL-deficient UKA with tibial slopes. Anteroposterior (AP) kinematics and contact stresses of the patellofemoral (PF) joint and the articular cartilage were evaluated under the deep-knee-bend condition. RESULTS: As compared to intact UKA, there was no significant difference in AP translation in PCL-deficient UKA with a low flexion angle, but AP translation significantly increased in the PCL-deficient UKA with high flexion angles. Additionally, the increased AP translation became decreased as the posterior tibial slope increased. The contact stress in the PF joint and the articular cartilage significantly increased in the PCL-deficient UKA, as compared to the intact UKA. Additionally, the increased posterior tibial slope resulted in a significant decrease in the contact stress on PF joint but significantly increased the contact stresses on the articular cartilage. CONCLUSION: Our results showed that the posterior stability for low flexion activities in PCL-deficient UKA remained unaffected; however, the posterior stability for high flexion activities was affected. This indicates that a functional PCL is required to ensure normal stability in UKA. Additionally, posterior stability and PF joint may reduce the overall risk of progressive OA by increasing the posterior tibial slope. However, the excessive posterior tibial slope must be avoided.Cite this article: Bone Joint Res 2020;9(9):593-600.

Femoral trochlear morphology is associated with anterior cruciate ligament injury in skeletally immature patients.

PURPOSE: Knee joint morphology is a known contributor to anterior cruciate ligament (ACL) injury, and the shape of the distal femur condyle is one of the associated factors. However, the relationship between femoral trochlear morphology and ACL injury is unclear, especially in pediatric patients. Therefore, the present study aimed to evaluate the effect of femoral trochlear morphology on ACL injury in pediatric patients and investigate the possibility of gender differences. METHODS: In total, 116 skeletally immature children aged 3-18 years with primary ACL injuries were matched with a control group of 116 skeletally immature children. Lateral trochlear inclination, trochlear facet asymmetry, trochlear depth, and sulcus angle were evaluated using magnetic resonance imaging (MRI). Differences between patient groups and gender were investigated. Receiver-operating characteristic (ROC) curves were constructed to obtain the sensitivity and specificity of all parameters. RESULTS: A significant difference was observed in the sulcus angle and trochlear inclination between the ACL injury and control groups (p < 0.05). No significant difference was observed between the ACL injury and control groups with respect to the anatomic patellar instability risk factors. All parameters showed an area under the curve of 0.6 in the ROC analysis, indicative of failure of the diagnostic test. CONCLUSIONS: There was a significant association between femoral trochlear morphology and increased risk of ACL injury in pediatric patients. No gender difference was found except in the trochlear depth. It was showed that the difference in trochlear morphology should be considered between normal children and pediatric patients with ACL injury to increase the awareness regarding ACL injuries. LEVEL OF EVIDENCE: III.

Evaluation of tibial rotational axis in total knee arthroplasty using magnetic resonance imaging.

Surgeon-dependent factors such as optimal implant alignment of the tibial component are thought to play a significant role in the outcome following primary total knee arthroplasty (TKA). In addition, tibial component malrotation is associated with pain, stiffness, and altered patellofemoral kinematics in TKA. However, measuring tibial component rotation after TKA is difficult. Therefore, the purpose of this study was to find a reliable method for positioning the tibial component in TKA. To investigate the morphology of the tibial plateau, 977 patients' knees (829 females and 148 males) were evaluated using MRI. The relationships between the femoral transepicondylar axis (TEA), Akagi line, posterior tibial margin (PTM), medial third of the tibial tubercle (MTT), and anatomical tibial axis (ATS) were investigated in this study. In addition, gender difference in tibial rotational alignment were evaluated. Relative to the TEA, the MTT and ATS were externally rotated by 0.5° ± 4.4° and 0.5° ± 5.4°, respectively, while Akagi line and PTM were internally rotated by 3.7° ± 4.5° and 9.9° ± 6.1°, respectively. Gender differences were found in MTT, Akagi line and ATS (P < 0.05). Our result showed that the rotational alignment led to notable variance between femoral and tibial components using fixed bone landmarks. The MTT and ATS axes showed the closest perpendicular aspect with projected TEA. And the MTT and Akagi axes showed the reduced variance. In addition, PTM is not a reliable landmark for rotation of the tibial component. Based on the results of this study, surgeons may choose the proper anteroposterior axis of the tibial component in order to reduce rotational mismatch and improve clinical outcomes.

Significant changes in synovial fluid microRNAs after high tibial osteotomy in medial compartmental knee osteoarthritis: Identification of potential prognostic biomarkers.

High tibial osteotomy (HTO) is a well-established treatment for medial compartmental knee osteoarthritis. Several microRNAs (miRNAs) are involved in osteoarthritis progression and are useful as osteoarthritis-related biomarkers. In this prospective study, we investigated differentially expressed microRNAs in the synovial fluid (SF) before and after HTO in patients with medial compartmental knee osteoarthritis to identify microRNAs that can be used as prognostic biomarkers. We used miRNA-PCR arrays to screen for miRNAs in SF samples obtained preoperatively and 6 months postoperatively from 6 patients with medial compartmental knee osteoarthritis who were treated with medial open wedge HTO. Differentially expressed miRNAs identified in the profiling stage were validated by real-time quantitative PCR in 22 other patients who had also been treated with HTO. All patients radiographically corresponded to Kellgren-Lawrence grade II or III with medial compartmental osteoarthritis. These patients were clinically assessed using a visual analogue scale and Western Ontario McMaster Universities scores. Mechanical axis changes were measured on standing anteroposterior radiographs of the lower limbs assessed preoperatively and at 6 months postoperatively. Among 84 miRNAs known to be involved in the inflammatory process, 14 were expressed in all SF specimens and 3 (miR-30a-5p, miR-29a-3p, and miR-30c-5p) were differentially expressed in the profiling stage. These 3 miRNAs, as well as 4 other miRNAs (miR-378a-5p, miR-140-3p, miR-23a-3p, miR-27b-3p), are related to osteoarthritis progression. These results were validated in the SF from 22 patients. Clinical and radiological outcomes improved after HTO in all patients, and only 2 miRNAs (miR-30c-5p and miR-23a-3p) were significantly differentially expressed between preoperative and postoperative 6-month SF samples (p = 0.006 and 0.007, respectively). Of these two miRNAs, miR-30c-5p correlated with postoperative pain relief. This study provides potential prognostic miRNAs after HTO and further investigations should be considered to determine clinical implications of these miRNAs.

Pharmacologic targeting of ß-catenin improves fracture healing in old mice.

ß-catenin protein needs to be precisely regulated for effective fracture repair. The pace of fracture healing slows with age, associated with a transient increase in ß-catenin during the initial phase of the repair process. Here we examined the ability of pharmacologic agents that target ß-catenin to improve the quality of fracture repair in old mice. 20 month old mice were treated with Nefopam or the tankyrase inhibitor XAV939 after a tibia fracture. Fractures were examined 21 days later by micro-CT and histology, and 28 days later using mechanical testing. Daily treatment with Nefopam for three or seven days but not ten days improved the amount of bone present at the fracture site, inhibited ß-catenin protein level, and increased colony forming units osteoblastic from bone marrow cells. At 28 days, treatment increased the work to fracture of the injured tibia. XAV939 had a more modest effect on ß-catenin protein, colony forming units osteoblastic, and the amount of bone at the fracture site. This data supports the notion that high levels of ß-catenin in the early phase of fracture healing in old animals slows osteogenesis, and suggests a pharmacologic approach that targets ß-catenin to improve fracture repair in the elderly.

Radiographic Assessment of Foot Alignment in Juvenile Hallux Valgus and Its Relationship to Flatfoot.

BACKGROUND: The relationship between juvenile hallux valgus (JHV) and flatfoot has not been clearly established. The aim of this study was to assess radiographic measurements in feet with JHV compared with matched controls and to investigate whether the foot alignment of JHV is related to flatfoot. METHODS: We retrospectively reviewed 163 patients with JHV as defined as hallux valgus angle greater than 20 degrees and intermetatarsal greater than angle than 10 degrees. Patients with open physes of the feet and who had weight-bearing radiographs of the feet were included. Another 55 normal participants served as controls. Patients with JHV were divided into 2 subgroups: Group 1 included patients with asymptomatic JHV and group 2 consisted of those treated with correctional surgery for painful JHV. Twelve radiographic indices were analyzed, including calcaneal pitch angle, tibiocalcaneal angle, talocalcaneal angle, naviculocuboid overlap, talonavicular coverage angle, lateral talo-first metatarsal angle, anteroposterior talo-first metatarsal angle, metatarsus adductus angle, hallux valgus angle, intermetatarsal angle, distal metatarsal articular angle, and first metatarsal cuneiform angle. The groups were compared by age, gender, and the above radiographic parameters. RESULTS: There was no significant difference in hindfoot alignment of patients with JHV and controls. Naviculocuboid overlap (P <.001), lateral talo-first metatarsal angle (P = .002), and metatarsus adductus angle (P = .004) were significantly greater in patients with JHV than in controls, whereas the anteroposterior talo-first metatarsal angle (P = .026) was significantly less. Symptomatic and asymptomatic JHV patient subsets showed no significant radiologic differences. CONCLUSION: Radiographic profiles in patients with JHV were inconsistent with regard to features of flatfoot, and foot alignment was unrelated to the presence of symptoms or degree of deformity in JHV. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

A comparative evaluation of tibial metaphyseal-diaphyseal angle changes between physiologic bowing and Blount disease.

The purpose of this study was to estimate the rate of spontaneous improvement in tibial metaphyseal-diaphyseal angle (TMDA) in physiologic bowing in comparison to that in Blount disease and to provide reference values of TMDA for monitoring patients with highly suspected to have Blount disease.We retrospectively reviewed patients with physiologic bowing meeting the following criteria:(1) TMDA greater than 9° before 36 months of age at initial evaluation;(2) two or more standing long bone radiographs available; and(3) follow-up conducted up to resolution of deformity.Patients with Blount disease had(1) more than 2 standing long bone radiographs obtained before 36 months of age and(2) underwent no treatment during the period in which these images were obtained.TMDA measurements were obtained from 174 patients with physiologic bowing and 32 patients with Blount disease. Rates of TMDA improvement were adjusted by multiple factors using a linear mixed model, with sex and laterality as fixed effects and age and individual patients as the random effects.In the physiologic bowing group, TMDA improved significantly, by 3° per 6 months and by 6° per year. Changes in TMDA were not significant in the Blount disease group.Knowing the rate of TMDA change can be helpful for physicians seeking to monitor infants with suspected as having Blount disease with a high TMDA and to avoid unnecessary repeat radiographic evaluations.