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Hydrogels are promising materials for biomedical applications, particularly in drug delivery and tissue engineering. This study highlights thermoresponsive hydrogels, specifically poly(lactic- co -glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-PLGA triblock copolymers, and introduces a feed rate-controlled polymerization (FRCP) method. By utilizing an organic catalyst and regulating the monomer feed rate, the sequence distribution of PLGA within the triblock copolymer is controlled. Various analyses, including 13 C NMR and rheological measurements, were conducted to investigate the impact of sequence distribution. Results show that altering sequence distribution significantly influences the sol-gel transition, hydrophobicity-hydrophilicity balance, and drug release profile. Increased sequence uniformity lowers the glass transition temperature, raises the sol-gel transition temperature due to enhanced hydrophilicity, and promotes a more uniform drug (curcumin) distribution within the PLGA domain, resulting in a slower release rate. This study emphasizes the importance of PLGA sequence distribution in biomedical applications and the potential of FRCP to tailor thermoresponsive hydrogels for biomedical advancements.

Background: The subtalar joint movement between the talus and calcaneus is restricted in patients with talocalcaneal coalition (TCC). When the motion of the subtalar joint is restricted, shock absorption in the foot decreases, leading to pain during walking. Resection methods to maintain subtalar motion by removing abnormal unions have been proposed. The purpose of this study was to analyze the joint kinematics of patients who underwent TCC resection and to quantitatively evaluate the results of the surgery based on the measured kinematics., Methods: Joint kinematics of five patients with TCC were obtained using a biplane fluoroscopic imaging system and an intensity-based two-/three-dimensional registration method. The joint kinematics of the tibiotalar and subtalar joints and the tibiocalcaneal motion during the stance phase of walking were obtained. From the kinematics of the hindfoot joints, the inversion/eversion range of motion (ROM) of the patients before and after resection was statistically analyzed using the Wilcoxon signed-rank test to test whether TCC resection improved the ROM., Results: During the loading response period, the eversion ROM of the subtalar joint and tibiocalcaneal motion significantly increased postoperatively. In addition, a significant postoperative increase was observed in the subtalar and tibiocalcaneal inversion ROM during the pre-swing period., Significance: TCC resection surgery increased the ROM of the subtalar joint, which in turn contributed to the increase in tibiocalcaneal ROM. Increased subtalar and tibiocalcaneal ROM could result in increased shock attenuation and may be a contributing factor to pain relief during walking., Competing Interests: Declaration of Competing Interest No conflict., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Accurate postoperative assessment of varying mechanical properties is crucial for customizing patient-specific treatments and optimizing rehabilitation strategies following Achilles tendon (AT) rupture and reconstruction surgery. This study introduces a wireless, chip-less, and immune-tolerant in vivo strain-sensing suture designed to continuously monitor mechanical stiffness variations in the reconstructed AT throughout the healing process. This innovative sensing suture integrates a standard medical suturing thread with a wireless fiber strain-sensing system, which incorporates a fiber strain sensor and a double-layered inductive coil for wireless readout. The winding design of Au nanoparticle-based fiber electrodes and a hollow core contribute to the fiber strain sensor's high sensitivity (factor of 6.2 and 15.1 pF for revised sensitivity), negligible hysteresis, and durability over 10,000 stretching cycles. To ensure biocompatibility and immune tolerance during extended in vivo periods, an antibiofouling lubricant layer was applied to the sensing suture. Using this sensing system, we successfully monitored the strain responses of the reconstructed AT in an in vivo porcine model. This facilitated the postoperative assessment of mechanical stiffness variations through a well-established analytical model during the healing period.

This study compared muscle strength and foot pressure among patients with metatarsalgia, patients with plantar fasciitis, and healthy controls. A total of 31 patients with foot pain (14 metatarsalgia and 17 plantar fasciitis) and 29 healthy controls participated in the study. The strengths of the plantar flexor and hip muscles were measured using isokinetic and handheld dynamometers, respectively. Foot pressure parameters, including the pressure-time integral (PTI) and foot arch index (AI), were assessed using pedobarography. Compared with the healthy control group, plantar flexor strength was significantly reduced in the affected feet of the metatarsalgia and plantar fasciitis groups (F = 0.083, all p < 0.001); however, hip strength was significantly decreased only in the affected feet of the metatarsalgia group (F = 20.900, p < 0.001). Plantar flexor (p < 0.001) and hip (p = 0.004) strength were significantly lower in the metatarsalgia group than in the plantar fasciitis group. The PTI was lower in the forefeet of the affected feet in the metatarsalgia (p < 0.001) and plantar fasciitis (p = 0.004) groups. Foot AI (p < 0.001) was significantly reduced only in the metatarsalgia group. These results suggest the need to consider the evaluation of muscle strength and foot pressure in both feet for the diagnosis and treatment of foot pain., (© 2024. The Author(s).)

Background and Objectives : Soft tissue sarcomas represent a heterogeneous group of malignant mesenchymal tissues. Despite their low prevalence, soft tissue sarcomas present clinical challenges for orthopedic surgeons owing to their aggressive nature, and perioperative wound infections. However, the low prevalence of soft tissue sarcomas has hindered the availability of large-scale studies. This study aimed to analyze wound infections after wide resection in patients with soft tissue sarcomas by employing big data analytics from the Hub of the Health Insurance Review and Assessment Service (HIRA). Materials and Methods : Patients who underwent wide excision of soft tissue sarcomas between 2010 and 2021 were included. Data were collected from the HIRA database of approximately 50 million individuals' information in the Republic of Korea. The data collected included demographic information, diagnoses, prescribed medications, and surgical procedures. Random forest has been used to analyze the major associated determinants. A total of 10,906 observations with complete data were divided into training and validation sets in an 80:20 ratio (8773 vs. 2193 cases). Random forest permutation importance was employed to identify the major predictors of infection and Shapley Additive Explanations (SHAP) values were derived to analyze the directions of associations with predictors. Results : A total of 10,969 patients who underwent wide excision of soft tissue sarcomas were included. Among the study population, 886 (8.08%) patients had post-operative infections requiring surgery. The overall transfusion rate for wide excision was 20.67% (2267 patients). Risk factors among the comorbidities of each patient with wound infection were analyzed and dependence plots of individual features were visualized. The transfusion dependence plot reveals a distinctive pattern, with SHAP values displaying a negative trend for individuals without blood transfusions and a positive trend for those who received blood transfusions, emphasizing the substantial impact of blood transfusions on the likelihood of wound infection. Conclusions : Using the machine learning random forest model and the SHAP values, the perioperative transfusion, male sex, old age, and low SES were important features of wound infection in soft-tissue sarcoma patients.

This study reports the effect of the not-calcining process on the bioresorption and biomineralization of hydroxyapatite through in vitro dissolution assessment. The prepared calcined hydroxyapatite (c-HAp) and uncalcined hydroxyapatite (unc-HAp) have a particle size of 2 μm and 13 μm, surface areas of 4.47 m 2 /g and 108.08 m 2 /g, and a Ca/P ratio of 1.66 and 1.52, respectively. In vitro dissolution assessments of c-HAp and unc-HAp were performed for 20 days at 37 °C in a citric acid buffer according to ISO 10993-14. During the dissolution, the c-HAp and unc-HAp confirmed an increase in weight, and the calcium and phosphorous ions were rapidly released. The calcium ions released from c-HAp formed rod-shaped particles with a longer and thinner morphology, while in unc-HAp, they appeared thicker and shorter. In the ICP-OES results, the concentrations of calcium elements were initially increased and then decreased by this formation. The rod-shaped particles identified as calcium citrate (Ca-citrate) through the XRD pattern. The calcium content of Ca-citrate particles from unc-HAp was higher than that from c-HAp. The unc-HAp demonstrated non-toxic properties in a cytotoxicity evaluation. Therefore, due to its higher bioresorption and biomineralization, unc-HAp exhibits enhanced biocompatibility compared to c-HAp.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo + self-assembly composed of azobenzene derivatives (Azo + ) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis -Azo + -mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of "closely nanospaced" ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo , including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo + molecules and loaded molecules. Conversely, visible light induces trans -Azo + formation that facilitates cation-π interactions, thereby deflating self-assembly with "closely nanospaced" ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of "distantly nanospaced" ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Obesity has been increasing in many regions of the world, including Europe, USA, and Korea. To manage obesity, we should consider it as a disease and apply therapeutic methods for its treatment. Molecular and therapeutic approaches for obesity management involve regulating biomolecules such as DNA, RNA, and protein in adipose-derived stem cells to prevent to be fat cells. Multiple factors are believed to play a role in fat differentiation, with one of the most effective factor is Ca 2+ . We recently reported that the electromagnetic perceptive gene (EPG) regulated intracellular Ca 2+ levels under various electromagnetic fields. This study aimed to investigate whether EPG could serve as a therapeutic method against obesity. We confirmed that EPG serves as a modulator of Ca 2+ levels in primary adipose cells, thereby regulating several genes such as CasR, PPARγ, GLU4, GAPDH during the adipogenesis. In addition, this study also identified EPG-mediated regulation of myogenesis that myocyte transcription factors (CasR, MyoG, MyoD, Myomaker) were changed in C2C12 cells and satellite cells. In vivo experiments carried out in this study confirmed that total weight/ fat/fat accumulation were decreased and lean mass was increased by EPG with magnetic field depending on age of mice. The EPG could serve as a potent therapeutic agent against obesity., (© 2023. The Author(s).)

Background: This study aimed to evaluate the annual trends of transfusion rates and utilization of blood management agents in total knee arthroplasty (TKA) based on the operation type and to analyze the risk factors of transfusion after TKA., Methods: Using the Korean National Insurance claims database of 797,106 primary and revision TKAs between January 2008 and October 2019, data on the patients' characteristics, comorbidities, utilization of transfusion, and blood management agents were collected. The patients were categorized into three groups based on the operation type: primary, revision, and simultaneous bilateral TKA. The transfusion rate and utilization of blood management agents (intraoperative tranexamic acid [TXA] and preoperative iron supplements) were compared, and the risk factors for transfusion were evaluated., Results: After excluding the inaccurate data, 730,554 arthroplasties (636,292 primary, 10,540 revision, and 41,861 simultaneous bilateral TKAs) were identified. The transfusion rates of primary, revision, and simultaneous bilateral TKAs in 2019 were 64.0%, 67.7%, and 68.9%, respectively, which were significantly decreased compared with 83.2%, 88.0%, and 92.5% in 2008, respectively ( p < 0.001). Conversely, the utilization of intraoperative TXA and preoperative iron supplements was significantly increased from 4.6% and 13.8%, respectively, in 2008 to 52.4% and 27.0%, respectively, in 2019 ( p < 0.001). The utilization of intraoperative TXA and preoperative iron supplements significantly lowered the risk of transfusion after TKA (odds ratio [OR], 0.20; p < 0.001 and OR, 0.71; p < 0.001)., Conclusions: The transfusion rate after TKA decreased gradually from 83.5% to 64.5% between 2008 and 2019 in South Korea corresponding with the increased utilization of blood management agents. Therefore, consistent attention to patient blood management should be emphasized to reduce the transfusion rate after TKA., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2023 by The Korean Orthopaedic Association.)

Background: Osteosarcoma is the most common secondary malignancy among survivors of retinoblastoma. Most previous reports on secondary malignancy of retinoblastoma included all types of secondary malignancies without a focus on osteosarcoma, owing to its rarity. In addition, there are few studies suggesting tools for regular surveillance for early detection., Questions/purposes: (1) What are the radiologic and clinical characteristics of secondary osteosarcoma after retinoblastoma? (2) What is the clinical survivorship? (3) Is a radionuclide bone scan a reasonable imaging modality for early detection in patients with retinoblastoma?, Methods: Between February 2000 and December 2019, we treated 540 patients for retinoblastoma. Twelve patients (six male, six female) subsequently developed an osteosarcoma in the extremities; two of these patients had two sites of osteosarcoma (10 femurs, four tibiae) . A Technetium-99m bone scan image was examined annually in all patients for regular surveillance after the treatment of retinoblastoma as per our hospital's policy. All patients were treated with the same strategy as that used for primary conventional osteosarcoma, namely neoadjuvant chemotherapy, wide excision, and adjuvant chemotherapy. The median follow-up period was 12 years (range 8 to 21 years). The median age at the time of diagnosis of osteosarcoma was 9 years (range 5 to 15 years), and the median interval from retinoblastoma diagnosis to osteosarcoma diagnosis was 8 years (range 5 to 15 years). Radiologic characteristics were assessed with plain radiographs and MRI, while clinical characteristics were assessed through a retrospective review of medical records. For clinical survivorship, we evaluated overall survival, local recurrence-free survival, and metastasis-free survival. We reviewed the results of bone scans and clinical symptoms at the time of diagnosis for osteosarcoma after retinoblastoma., Results: In nine of 14 patients, the tumor had a diaphyseal center, and five of the tumors were located at the metaphysis. The femur was the most common site (n = 10), followed by the tibia (n = 4). The median tumor size was 9 cm (range 5 to 13 cm). There was no local recurrence after surgical resection of the osteosarcoma, and the 5-year overall survival rate after the diagnosis of osteosarcoma was 86% (95% CI 68% to 100%). In all 14 tumors, the Technetium bone scan showed increased uptake in the lesions. Ten of 14 tumors were examined in clinic because of patient complaints of pain in the affected limb. Four patients showed no clinical symptoms detected by abnormal uptake on bone scan., Conclusion: For unclear reasons, secondary osteosarcomas in patients who were alive after the treatment of retinoblastoma had a slight predilection for the diaphysis of the long bone compared with patients with spontaneous osteosarcoma in other reports. The clinical survivorship of osteosarcoma as a secondary malignancy after retinoblastoma may not be inferior to that of conventional osteosarcoma. Close follow-up with at least yearly clinical assessment and bone scans or other imaging modalities appears to be helpful in detecting secondary osteosarcoma after the treatment of patients with retinoblastoma. Larger multi-institutional studies will be needed to substantiate these observations.Level of Evidenc e Level IV, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

This study reports the preparation of silica-coated and nano-fructosome encapsulated Candida antarctica lipase B particles (CalB@NF@SiO 2 ) and a demonstration of their enzymatic hydrolysis and acylation. CalB@NF@SiO 2 particles were prepared as a function of TEOS concentration (3-100 mM). Their mean particle size was 185 nm by TEM. Enzymatic hydrolysis was performed to compare catalytic efficiencies of CalB@NF and CalB@NF@SiO 2 . The catalytic constants (K m , V max , and K cat ) of CalB@NF and CalB@NF@SiO 2 were calculated using the Michaelis-Menten equation and Lineweaver-Burk plot. Optimal stability of CalB@NF@SiO 2 was found at pH 8 and a temperature of 35 °C. Moreover, CalB@NF@SiO 2 particles were reused for seven cycles to evaluate their reusability. In addition, enzymatic synthesis of benzyl benzoate was demonstrated via an acylation reaction with benzoic anhydride. The efficiency of CalB@NF@SiO 2 for converting benzoic anhydride to benzyl benzoate by the acylation reaction was 97%, indicating that benzoic anhydride was almost completely converted to benzyl benzoate. Consequently, CalB@NF@SiO 2 particles are better than CalB@NF particles for enzymatic synthesis. In addition, they are reusable with high stability at optimal pH and temperature.

Extracorporeal shockwave therapy (ESWT) can induce wound healing by increasing tissue microcirculation. However, studies on the effect of ESWT on enhancing tissue microcirculation in diabetic foot ulcer (DFU), particularly on when the microcirculation increases after ESWT application, are still lacking. Therefore, we aimed to examine the effectiveness of ESWT in promoting microcirculation in DFU patients in a time-dependent manner. We included 50 feet of 25 patients with type 2 diabetes mellitus and Wagner grade I to II DFU in this study. The affected feet were used as the ESWT group and the unaffected contralateral feet were used as the control group. ESWT was performed in 3 sessions per week for a total of 3 weeks. Transcutaneous partial oxygen pressure (TcPO2) was used to evaluate the tissue microcirculation. The TcPO2 level (>43 mm Hg) in the ESWT group was recovered by the 2nd week of treatment, and statistical significance (P < .05) was demonstrated at the same time. From the 2nd week of ESWT, a significant increase in TcPO2 was observed in Wagner grade I and II DFU. These findings imply that the ESWT may improve microcirculation in patients with Wagner grades I to II DFU. However, this impact requires at least 2 weeks or more than 6 sessions. For better comparison, further studies with larger clinical groups and extended period are needed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abnormal foot posture and poor muscle performance are potential causes of plantar fasciitis (PF). However, no study has compared the differences between lower extremity muscle performance and foot pressure in patients who have PF with and without abnormal foot postures. This study aimed to compare the differences in lower extremity muscle performance, such as in the hip, quadriceps, hamstring, and plantar flexor, and foot pressure in patients who have PF with and without flat foot postures. Seventy patients with plantar heel pain were enrolled (37 flat feet and 33 without flat feet). The hip muscle strength was measured using a handheld digital dynamometer. The strength and reaction time of the quadriceps, hamstring, and plantar flexor muscles were evaluated using an isokinetic device. Foot pressure parameters were assessed using pedobarography. The strength of the plantar flexor muscles was significantly lower ( p = 0.008), while the reaction time of the plantar flexor muscles was significantly faster ( p = 0.007) for the involved feet of PF patients with flat feet than in those without flat feet. This study confirmed the differences in muscle performance between patients who have PF with different foot postures. Therefore, clinicians and therapists should plan treatment considering the differences in these characteristics for the management of these patients.

Dynamic manipulation of supramolecular self-assembled structures is achieved irreversibly or under non-physiological conditions, thereby limiting their biomedical, environmental, and catalysis applicability. In this study, microgels composed of azobenzene derivatives stacked via π-cation and π-π interactions are developed that are electrostatically stabilized with Arg-Gly-Asp (RGD)-bearing anionic polymers. Lateral swelling of RGD-bearing microgels occurs via cis-azobenzene formation mediated by near-infrared-light-upconverted ultraviolet light, which disrupts intermolecular interactions on the visible-light-absorbing upconversion-nanoparticle-coated materials. Real-time imaging and molecular dynamics simulations demonstrate the deswelling of RGD-bearing microgels via visible-light-mediated trans-azobenzene formation. Near-infrared light can induce in situ swelling of RGD-bearing microgels to increase RGD availability and trigger release of loaded interleukin-4, which facilitates the adhesion structure assembly linked with pro-regenerative polarization of host macrophages. In contrast, visible light can induce deswelling of RGD-bearing microgels to decrease RGD availability that suppresses macrophage adhesion that yields pro-inflammatory polarization. These microgels exhibit high stability and non-toxicity. Versatile use of ligands and protein delivery can offer cytocompatible and photoswitchable manipulability of diverse host cells., (© 2022 Wiley-VCH GmbH.)

We thank Dr. Sadettin Ciftci for his comment on the key point issues in measuring the alpha and beta angle with Graf method. We appreciated his feedback [...].

Cell adhesion occurs when integrin recognizes and binds to Arg-Gly-Asp (RGD) ligands present in fibronectin. In this work, submolecular ligand size and spacing are tuned via template-mediated in situ growth of nanoparticles for dynamic macrophage modulation. To tune liganded gold nanoparticle (GNP) size and spacing from 3 to 20 nm, in situ localized assemblies of GNP arrays on nanomagnetite templates are engineered. 3 nm-spaced ligands stimulate the binding of integrin, which mediates macrophage-adhesion-assisted pro-regenerative polarization as compared to 20 nm-spaced ligands, which can be dynamically anchored to the substrate for stabilizing integrin binding and facilitating dynamic macrophage adhesion. Increasing the ligand size from 7 to 20 nm only slightly promotes macrophage adhesion, not observed with 13 nm-sized ligands. Increasing the ligand spacing from 3 to 17 nm significantly hinders macrophage adhesion that induces inflammatory polarization. Submolecular tuning of ligand spacing can dominantly modulate host macrophages., (© 2022 Wiley-VCH GmbH.)

An effective wound management strategy needs accurate assessment of wound status throughout the whole healing process. This can be achieved by examining molecular biomarkers including proteins, DNAs, and RNAs. However, existing methods for quantifying these biomarkers such as immunohistochemistry and quantitative polymerase chain reaction are usually laborious, resource-intensive, and disruptive. This article reports the development and utilization of mRNA nanosensors (i.e., NanoFlare) that are topically applied on cutaneous wounds to reveal the healing status through targeted and semi-quantitative examination of the mRNA biomarkers in skin cells. In 2D and 3D in vitro models, the efficacy and efficiency of these nanosensors are demonstrated in revealing the dynamic changes of mRNA biomarkers for different stages of wound development. In mouse models, this platform permits the tracking and identification of wound healing stages and a normal and diabetic wound healing process by wound healing index in real time., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The receptor-ligand interactions in cells are dynamically regulated by modulation of the ligand accessibility. In this study, we utilize size-tunable magnetic nanoparticle aggregates ordered at both nanometer and atomic scales. We flexibly anchor magnetic nanoparticle aggregates of tunable sizes over the cell-adhesive RGD ligand (Arg-Gly-Asp)-active material surface while maintaining the density of dispersed ligands accessible to macrophages at constant. Lowering the accessible ligand dispersity by increasing the aggregate size at constant accessible ligand density facilitates the binding of integrin receptors to the accessible ligands, which promotes the adhesion of macrophages. In high ligand dispersity, distant magnetic manipulation to lift the aggregates (which increases ligand accessibility) stimulates the binding of integrin receptors to the accessible ligands available under the aggregates to augment macrophage adhesion-mediated pro-healing polarization both in vitro and in vivo. In low ligand dispersity, distant control to drop the aggregates (which decreases ligand accessibility) repels integrin receptors away from the aggregates, thereby suppressing integrin receptor-ligand binding and macrophage adhesion, which promotes inflammatory polarization. Here, we present "accessible ligand dispersity" as a novel fundamental parameter that regulates receptor-ligand binding, which can be reversibly manipulated by increasing and decreasing the ligand accessibility. Limitless tuning of nanoparticle aggregate dimensions and morphology can offer further insight into the regulation of receptor-ligand binding in host cells.

The modified Broström procedure (MBP) is an initial treatment for symptomatic chronic ankle instability (CAI) patients. This study aimed to compare the proprioception and neuromuscular control ability of both affected and unaffected ankles at the time of return to sports after MBP for patients with scores of normal controls. 75 individuals (40 who underwent MBP, 35 normal controls) participated. The dynamic balance test scores were significantly higher in the affected ankle of the patients than in the controls (1.5 ± 0.6° vs. 1.1 ± 0.4°, p < 0.003). The time to peak torque for dorsiflexion (60.8 ± 13.9 ms vs. 52.2 ± 17.5 ms, p < 0.022) and eversion (68.9 ± 19.1 ms vs. 59.3 ± 21.1 ms, p < 0.043) was significantly delayed in the affected ankle of the patients than in the controls. The dynamic balance test and time to peak torque in CAI patients remained significantly reduced at the time of return-to-sport after MBP. Clinicians and therapists should be aware of potential deficits in proprioception and neuromuscular control when determining the timing of return to sports after MBP., (© 2022. The Author(s).)

Abstract: In the pubertal period, bone age advances rapidly in conjunction with growth spurts. Precise bone-age assessments in this period are important, but results from the hand and elbow can be different. We aimed to compare the bone age between the hand and elbow around puberty onset and to elucidate the chronological age confirming puberty onset according to elbow-based bone age.A total of 211 peripubertal subjects (127 boys and 84 girls) who underwent hand and elbow radiographs within 2 months was enrolled. Two radiologists and a pediatric orthopedic surgeon assessed bone age. Hand bone age was graded using the Greulich-Pyle (GP) method, and elbow bone age was determined using the Sauvegrain method. The correlation of 2 methods was evaluated by Demining regression analysis, and the mean absolute difference (MAD) with chronological age was compared between pre-pubertal and pubertal subjects. Receiver-operating characteristic curve analysis was performed to determine the chronological age confirming puberty onset.There was a statistically significant difference in bone age revealed by the GP and Sauvegrain methods in the pubertal group. In the pubertal group, the MAD was 1.26 ± 0.90 years with the GP method and 0.61 ± 0.47 years with the Sauvegrain method in boys (P < .001), while in girls, the MAD was 0.84 ± 0.60 years and 0.53 ± 0.36 years with the same 2 methods (P = .033). The chronological age for confirming puberty onset using the elbow was 12.2 years in boys and 10.3 years in girls.The bone ages of hand and elbow were different at puberty, and the elbow was a more reliable location for bone-age assessment at puberty. Puberty onset according to elbow occurred slightly earlier than expected., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

In native microenvironment, diverse physical barriers exist to dynamically modulate stem cell recruitment and differentiation for tissue repair. In this study, nanoassembly-based magnetic screens of various sizes are utilized, and they are elastically tethered over an RGD ligand (cell-adhesive motif)-presenting material surface to generate various nanogaps between the screens and the RGDs without modulating the RGD density. Large screens exhibiting low RGD distribution stimulate integrin clustering to facilitate focal adhesion, mechanotransduction, and differentiation of stem cells, which are not observed with small screens. Magnetic downward pulling of the large screens decreases the nanogaps, which dynamically suppress the focal adhesion, mechanotransduction, and differentiation of stem cells. Conversely, magnetic upward pulling of the small screens increases the nanogaps, which dynamically activates focal adhesion, mechanotransduction, and differentiation of stem cells. This regulation mechanism is also shown to be effective in the microenvironment in vivo. Further diversifying the geometries of the physical screens can further enable diverse modalities of multifaceted and safe unscreening of the distributed RGDs to unravel and modulate stem cell differentiation for tissue repair., (© 2021 Wiley-VCH GmbH.)

Abstract: This study aimed to describe the shape of the limbus arthroscopically and via arthrogram and magnetic resonance imaging (MRI), and to determine whether it prevents concentric reduction of the femoral head in developmental dysplasia of the hip (DDH).Twelve patients (mean age, 10.2 months; range, 3-31 months) who underwent arthroscopic-assisted reduction for DDH were retrospectively reviewed. Limbus shapes were captured on arthrogram before reduction, after closed reduction, and after arthroscopic-assisted reduction and categorized according to the Miyake classification.On arthrogram, the superior limbus was blocked in 2 hips, inverted in 2, intermediate in 5, and everted in 3 after attempted closed reduction. After arthroscopic-assisted reduction, the limbus was everted in 7 hips and normal in 5. On arthroscopy, in all cases, the limbus appeared as a whitish, cartilage-like ring with a variably blunted edge before reduction, without inversion or eversion. On postoperative MRI, 10 of 12 superior limbi showed hypertrophy or globular compression by the femoral head with intermediate or mixed MRI signal intensities and blunted edges. The remaining 2 hips had hypertrophied superior limbi with sharp edges. On transverse plane MRI, the posterior limbus of all hips showed sharp margins with low MRI signal intensity. Residual subluxation was observed in 7 of the 12 hips with interposition of the anteroinferior limbus.The appearance of the limbus varied according to the femoral head position, and it was neither inverted nor everted. Interposed anteroinferior limbi with residual subluxation suggest impeded concentric reduction in DDH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Bone age is considered an indicator for the diagnosis of precocious or delayed puberty and a predictor of adult height. We aimed to evaluate the performance of a deep neural network model in assessing rapidly advancing bone age during puberty using elbow radiographs., Methods: In all, 4437 anteroposterior and lateral pairs of elbow radiographs were obtained from pubertal individuals from two institutions to implement and validate a deep neural network model. The reference standard bone age was established by five trained researchers using the Sauvegrain method, a scoring system based on the shapes of the lateral condyle, trochlea, olecranon apophysis, and proximal radial epiphysis. A test set (n = 141) was obtained from an external institution. The differences between the assessment of the model and that of reviewers were compared., Results: The mean absolute difference (MAD) in bone age estimation between the model and reviewers was 0.15 years on internal validation. In the test set, the MAD between the model and the five experts ranged from 0.19 to 0.30 years. Compared with the reference standard, the MAD was 0.22 years. Interobserver agreement was excellent among reviewers (ICC: 0.99) and between the model and the reviewers (ICC: 0.98). In the subpart analysis, the olecranon apophysis exhibited the highest accuracy (74.5%), followed by the trochlea (73.7%), lateral condyle (73.7%), and radial epiphysis (63.1%)., Conclusions: Assessment of rapidly advancing bone age during puberty on elbow radiographs using our deep neural network model was similar to that of experts., Key Points: • Bone age during puberty is particularly important for patients with scoliosis or limb-length discrepancy to determine the phase of the disease, which influences the timing and method of surgery. • The commonly used hand radiographs-based methods have limitations in assessing bone age during puberty due to the less prominent morphological changes of the hand and wrist bones in this period. • A deep neural network model trained with elbow radiographs exhibited similar performance to human experts on estimating rapidly advancing bone age during puberty., (© 2021. European Society of Radiology.)

In neonates, timely detection of septic arthritis of the hip can be challenging. Joint aspiration can be a useful diagnostic procedure, but scanty fluid in a septic joint has been reported, leading false-negative results. This study aimed to investigate clinical course of neonates with septic arthritis of the hip despite initial negative findings on joint aspiration. The neonates who surgically treated for septic arthritis of the hip between 2003 and 2013 for septic arthritis of the hip despite initial negative joint aspiration were retrospectively reviewed. Clinical presentations, MRI, intraoperative findings, functional and radiographic outcomes were evaluated. Six neonates were included with a mean follow-up of 12 years (range 5-15 years). All patients showed negative results on joint aspirations performed with ultrasound guidance or fluoroscopy. The mean duration between the onset of symptoms and initial surgery was 15.2 days (range 4-25 days). Four patients (67%) had extracapsular abscesses that were connected to perforated joint capsules on MRI. Intraoperatively, all patients were found to have hip joint instability with a ruptured capsule. Five (83%) patients experienced a complicated recovery. Four patients required reconstructive hip surgery, or further procedures to correct leg length discrepancy. Neonates with false-negative aspiration typically had a delay in appropriate surgical treatment. These cases suggest that the absence of aspirable fluid contents in the hip joint does not rule out septic arthritis in neonates. Our findings highlight the importance of considering spontaneous hip joint capsular perforation as the cause of extra-articular drainage of pus and instability., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

We aimed to analyze the differences in static (including conventional and modified [single-leg heel-raise balance]) and dynamic postural stability and muscle endurance between patients with chronic ankle instability (CAI) and healthy controls, and to determine the reliability and usefulness of the single-leg heel-raise balance test in patients with CAI. In total, 26 patients with CAI and 26 healthy controls were enrolled. Postural stability was assessed using a postural stabilometry system. Muscle endurance was measured in dorsiflexion and plantarflexion using an isokinetic device. Modified static postural stability (P < 0.001) and dynamic postural stability (P < 0.001) were significantly poorer in the affected ankles of patients with CAI than in the controls. Plantarflexion endurance was significantly lower in the affected ankles of the patients with CAI than in the controls (P = 0.023). Modified static postural stability significantly correlated with plantarflexion endurance in both groups (CAI group: r = - 0.470, P = 0.015; healthy controls group: r = - 0.413, P = 0.036). Plantarflexion endurance was a significant risk factor for modified static postural stability in both the CAI group (R 2  = 0.221, P = 0.015) and healthy controls (R 2  = 0.170, P = 0.036). Given the reliability of the modified static postural stability test, clinicians and therapists should consider using it to assess improvements in postural stability and muscle endurance in patients with CAI before and after rehabilitation., (© 2021. The Author(s).)

This study aimed to compare the mean ankle dorsiflexion range between individuals with and without plantar fasciitis using passive ankle dorsiflexion with consistent pressure, and to identify the prevalence of an isolated gastrocnemius and gastrocnemius soleus complex contracture in 2 groups. 91 participants were prospectively classified into the plantar fasciitis group (45 subjects) and the control group (46 subjects). Ankle dorsiflexion was measured with the knee extended and with the knee flexed 90° using a standard orthopedic goniometer while a consistent force of 2 kg was applied under the plantar surface of the forefoot using a custom-made scale. Intraclass correlation coefficients (ICC) were calculated to determine the interobserver and intraobserver reliability of the current ankle dorsiflexion measurement. The current ankle dorsiflexion measurement revealed excellent interobserver and intraobserver reliability. The mean ankle dorsiflexion in the knee extended was -9.6° ± 8.1° and -11.2° ± 8.2° in the study and control groups, respectively (p = .353). The mean ankle dorsiflexion in the knee flexed was 7.8° ± 6.5° and 5.1° ± 7.4° in the study and control groups, respectively (p = .068). In the study and control groups, 68.9% and 65.2%, respectively, had an isolated gastrocnemius contracture and 24.4% and 30.4%, respectively, had a gastrocnemius-soleus complex contracture (p = .768). The present study demonstrated that there were no significant differences in passive ankle dorsiflexion and in the prevalence of an isolated gastrocnemius or gastrocnemius soleus complex contracture between individuals with and without plantar fasciitis., (Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

The effect of deer antler extract on muscle differentiation and muscle atrophy were evaluated to minimize muscle loss following aging. Various deer antler extracts (HWE, hot water extract of deer antler; FE, HWE of fermented deer antler; ET, enzyme-assisted extract of deer antler; UE, extract prepared by ultrasonication of deer antler) were evaluated for their effect on muscle differentiation and inhibition of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR)-induced muscle atrophy in C2C12 cells. Morphological changes according to the effect of antler extracts on muscle differentiation were confirmed by Jenner-Giemsa staining. In addition, the expression levels of genes related to muscle differentiation and atrophy were confirmed through qRT-PCR. In the presence of antler extracts, the length and thickness of myotubes and myogenin differentiation 1 (MyoD1) and myogenic factor 5 (Myf5) gene expression were increased compared to those in the control group (CON). Gene expression of AMP-activated protein kinase (AMPK), MyoD1, and myogenin, along with the muscle atrophy factors muscle RING finger-1 (MuRF-1) and forkhead box O3a (FoxO3a) upon addition of deer antler extracts to muscle-atrophied C2C12 cells was determined by qRT-PCR after treatment with AICAR. The expression of MuRF-1 and FoxO3a decreased in the groups treated with antler extracts compared to that in the group treated with AICAR alone. In addition, gene expression of MyoD1 and myogenin in the muscle atrophy cell model was significantly increased compared that into the CON. Therefore, our findings indicate that antler extract can increase the expression of MyoD1, Myf5 and myogenin, inhibit muscle atrophy, and promote muscle differentiation., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Hip joint ultrasonographic (US) imaging is the golden standard for developmental dysplasia of the hip (DDH) screening. However, the effectiveness of this technique is subject to interoperator and intraobserver variability. Thus, a multi-detection deep learning artificial intelligence (AI)-based computer-aided diagnosis (CAD) system was developed and evaluated. The deep learning model used a two-stage training process to segment the four key anatomical structures and extract their respective key points. In addition, the check angle of the ilium body balancing level was set to evaluate the system's cognitive ability. Hence, only images with visible key anatomical points and a check angle within ±5° were used in the analysis. Of the original 921 images, 320 (34.7%) were deemed appropriate for screening by both the system and human observer. Moderate agreement (80.9%) was seen in the check angles of the appropriate group (Cohen's κ = 0.525). Similarly, there was excellent agreement in the intraclass correlation coefficient (ICC) value between the measurers of the alpha angle (ICC = 0.764) and a good agreement in beta angle (ICC = 0.743). The developed system performed similarly to experienced medical experts; thus, it could further aid the effectiveness and speed of DDH diagnosis.

Rationale: Localized chondrosarcoma of the scapula has a favorable long-term survival outcome. Therefore, recovery of shoulder function after surgery is important in middle-aged patients. Currently, three-dimensional (3-D) printing implants can be applied for personalized limb salvage surgery., Patient Concerns: A 41-year-old woman with a palpable scapular area presented with shoulder pain for 3 months, which was aggravated during shoulder exercise., Diagnoses: Chondrosarcoma at left scapular (Malawer S1, Enniking II B, and grade II chondrosarcoma)., Interventions: Wide excision for a localized chondrosarcoma at the infrascapular lesion was performed and the resected muscles around the scapula were repaired with a 3-D printed segmental scapula prosthesis for recovery of shoulder function., Outcomes: The affected shoulder achieved satisfactory function after operation using the 3-D printed segmental scapula prosthesis at 1 year 6 months after the operation., Lessons: The 3-D printed segmental scapula prosthesis is a useful method for shoulder functional recovery in patients with scapula chondrosarcoma., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The impact of surgical margin status on the survival of patients with extremity soft tissue sarcoma (STS) remains to be clearly defined. The evidence regarding the impact of surgical margins on survival is limited by retrospective single-institution cohort studies. We conducted a systematic review and meta-analysis to examine the impact of surgical margin status on patient survival in extremity STS., Methods: A literature search in the PubMed, EMBASE, and Cochrane Controlled Trials Register electronic databases, and a manual search of reference lists of original studies was performed. The following text words and/or Medical Subject Heading terms were searched: (neoplasm) or/and (sarcoma) and/or (connective tissue) and/or (soft tissue) and/or (extremity) and/or (extremity) and/or (surgical margin)., Results: Six selected studies that reported a total of 2917 cases of extremity STS were published between 1994 and 2013. All the eligible studies were observational cohort studies, and the sample size ranged from 95 to 1261 patients. A meta-analysis of 6 studies showed that a positive surgical margin predicted poor 5-year OS in a random-effects model (summary hazard ratio, 1.56; 95% confidence interval, 1.12-2.17). Moderate heterogeneity was observed among the studies (P < .075; heterogeneity, 45.6%)., Conclusions: This meta-analysis supports the hypothesis that adequate surgical margins are associated with improved survival in extremity STS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Mitochondrial dysfunction contributes to neurodegenerative diseases and developmental disorders such as Fragile X syndrome (FXS). The cross-talk between mitochondria and extracellular vesicles (EVs) suggests that EVs may transfer mitochondrial components as intermediators for intracellular communication under physiological and pathological conditions. In the present study, the ability of EVs to transfer mitochondrial components and their role in mitochondrial dysfunction in astrocytes were examined in the brains of Fmr1 knockout (KO) mice, a model of FXS. The amounts of mitochondrial transcription factor NRF-1, ATP synthases ATP5A and ATPB, and the mitochondrial membrane protein VDAC1 in EVs were reduced in cerebral cortex samples and astrocytes from Fmr1 KO mice. These reductions correspond to decreased mitochondrial biogenesis and transcriptional activities in Fmr1 KO brain, along with decreased mitochondrial membrane potential (MMP) with abnormal localization of vimentin intermediate filament (VIF) in Fmr1 KO astrocytes. Our results suggest that mitochondrial dysfunction in astrocytes is associated with the pathogenesis of FXS and can be monitored by depletion of components in EVs. These findings may improve the ability to diagnose developmental diseases associated with mitochondrial dysfunction, such as FXS and autism spectrum disorders (ASD).

Background: Infant hip screening for early detection of developmental dysplasia of the hip (DDH) is essential as early detection can enable less invasive treatments and achieve better long-term results. A previous meta-analysis assessed about 10,000 infants per group, which is insufficient for evaluating the effect of different infant hip screening strategies on early detection and treatment of DDH. Therefore, we conducted a systematic review and meta-analysis using both randomized controlled trials and cohort studies to determine the effects of universal hip ultrasonography screening (UHUS) and selective hip ultrasonography screening (SHUS) on the incidence of late-diagnosed DDH., Methods: A literature search of PubMed, EMBASE, and Cochrane databases was performed. The summary odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed-effects models., Results: Meta-analysis of five studies that met the eligibility criteria revealed a significant difference in late-diagnosed DDH (OR 0.44, 95% CI 0.23-0.83) between infants screened using UHUS (n = 29,070) and those screened using SHUS (n = 30,442) in a fixed-effects model without heterogeneity among studies. In the subgroup analysis, meta-analysis of the randomized controlled trials showed no significant difference in late-diagnosed DDH (OR 0.52, 95% CI 0.20-1.39) between infants screened using UHUS (n = 11,453) and those screened using SHUS (n = 12,077) in a fixed-effects model with low heterogeneity among studies (I = 0.9%). However, meta-analysis of the cohort studies showed a significant difference in late-diagnosed DDH (OR 0.38, 95% CI 0.17-0.89) between infants screened using UHUS (n = 17,617) and those screened using SHUS (n = 18,345) in a fixed-effects model with low heterogeneity among studies. Sensitivity analysis revealed that the impact of each study on the summary results was not significant. There was no publication bias in our meta-analysis., Conclusions: Our meta-analysis suggests that a statistically significant decrease in the incidence of late-diagnosed DDH is possible when UHUS is adopted compared with SHUS. Our study provides information about the effects of different infant hip screening strategies on the incidence of late-diagnosed DDH, which can help decide upon which strategy to apply.

Background: Muscle weakness is an important etiological factor in plantar fasciitis (PF), but available data on the role of the quadriceps, hamstring, and gastrocnemius (GCM) muscles are limited. The aim of this study was to compare the strength and reaction time of the quadriceps, hamstring, and GCM muscles and foot pressure between patients with PF and normal controls., Methods: A total of 21 PF patients and 21 normal controls were enrolled. Muscle strength was measured by the peak torque per body weight (Nmkg - 1  × 100). Muscle reaction time was evaluated by the acceleration time (AT, milliseconds). Foot pressure and posture were assessed by pedobarography [valgus/varus index (VV index), %]., Results: The strength of the quadriceps was significantly lower in the affected ankles of the PF group than in the control group (p = 0.005). The AT of the quadriceps and hamstring muscles was significantly increased in the affected ankles of the PF group than in the control group (quadriceps: p = 0.012, hamstring: p = 0.001), while the AT of the GCM muscle was significantly decreased (p = 0.009) and significantly correlated negatively with quadriceps muscle strength (r = -.598, p = 0.004) and AT (r = -.472, p = 0.031). Forefoot (p = 0.001) and hindfoot (p = 0.000) pressure were significantly greater, with the VV index showing hindfoot valgus, in the affected ankles in the PF group compared to the control group (p = 0.039)., Conclusions: This study demonstrated weakness and delayed reaction time of the quadriceps and hamstring muscles, with a rapid reaction time of the GCM muscle, in patients with PF., Clinical Relevance: Clinicians and therapists should assess the function of the quadriceps and hamstring muscles when planning the management of PF patients without muscle tightness.

Bacterial infection and infection-induced immune response have been a life-threatening risk for patients having orthopedic implant surgeries. Conventional biomaterials are vulnerable to biocontamination, which causes bacterial invasion in wounded areas, leading to postoperative infection. Therefore, development of anti-infection and immune-evasive coating for orthopedic implants is urgently needed. Here, we developed an advanced surface modification technique for orthopedic implants termed lubricated orthopedic implant surface (LOIS), which was inspired by slippery surface of Nepenthes pitcher plant. LOIS presents a long-lasting, extreme liquid repellency against diverse liquids and biosubstances including cells, proteins, calcium, and bacteria. In addition, we confirmed mechanical durability against scratches and fixation force by simulating inevitable damages during surgical procedure ex vivo. The antibiofouling and anti-infection capability of LOIS were thoroughly investigated using an osteomyelitis femoral fracture model of rabbits. We envision that the LOIS with antibiofouling properties and mechanical durability is a step forward in infection-free orthopedic surgeries., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Allogeneic red blood cell transfusion (ABT) is 1 of the poor prognostic factors for morbidity and mortality in patients with hip fracture, particularly among elderly patients. This study aimed to investigate the risk factors for ABT and 1-year mortality in elderly patients undergoing surgery for femoral neck fracture.A total of 225 elderly patients who underwent femoral neck fracture surgery between May 2013 and November 2015 at a tertiary medical center were retrospectively recruited. Medical records were analyzed.The median patient age was 80 years and 28.4% were men. A total of 113 patients received ABT (50.2%). Multivariate logistic regression analysis showed that female sex (odds ratio [OR] 2.606, 95% confidence interval [CI] 1.283-5.295, P = .008), malignancy (OR 5.098, 95% CI 1.725-15.061, P = .003), chronic kidney disease stage ≥ 3 (OR 3.258, 95% CI 1.603-6.622, P = .001), and anemia (hemoglobin < 12 g/dL) (OR 4.684, 95% CI 2.230-9.837, P < .001) were significantly associated with ABT. The 1-year mortality rate after surgery was 15.1%. Male sex (OR 2.477, 95% CI 1.101-5.575, P = .028), ABT (OR 2.367, 95% CI 1.036-5.410, P = .041), and intensive care unit admission (OR 5.564, 95% CI 1.457-21.249, P = .012) were significantly associated with 1-year mortality.In this study, underlying comorbidities such as chronic kidney disease and malignancy were associated with ABT. Furthermore, ABT was a significant independent risk factor for 1-year mortality. These findings suggest that underlying comorbidities and the need for ABT should be considered in the risk assessment of elderly patients with femoral neck fracture to improve the outcomes after surgery.

Aims: For paediatric and adolescent patients with growth potential, preservation of the physiological joint by transepiphyseal resection (TER) of the femur confers definite advantages over arthroplasty procedures. We hypothesized that the extent of the tumour and changes in its extent after neoadjuvant chemotherapy are essential factors in the selection of this procedure, and can be assessed with MRI. The oncological and functional outcomes of the procedure were reviewed to confirm its safety and efficacy., Methods: We retrospectively reviewed 16 patients (seven male and nine female, mean age 12.2 years (7 to 16)) with osteosarcoma of the knee who had been treated by TER. We evaluated the MRI scans before and after neoadjuvant chemotherapy for all patients to assess the extent of the disease and the response to treatment., Results: The mean follow-up period was 64.3 months (25 to 148) after surgery and no patients were lost to follow-up. On MRI evaluation, 13 tumours were near but not in contact with the physes and three tumours were partially in contact with the physes before neoadjuvant chemotherapy. Bone oedema in the epiphysis was observed in eight patients. After neoadjuvant chemotherapy, bone oedema in the epiphysis disappeared in all patients. In total, 11 tumours were not in contact and five tumours were in partial contact with the physes. The postoperative pathological margin was negative in all patients. At the last follow-up, 12 patients were continuously disease-free and three had no evidence of disease. One patient died due to the disease. Functionally, the patients with retained allograft or recycled autograft had a mean knee range of flexion of 126° (90° to 150°). The mean Musculoskeletal Tumor Society functional score was 27.6 (23 to 30)., Conclusion: TER is an effective limb-salvage technique for treating malignant metaphyseal bone tumours in paediatric and young osteosarcoma patients with open physes when a good response to chemotherapy and no progression of the tumour to the epiphysis have been confirmed by MRI. Cite this article: Bone Joint J 2020;102-B(6):772-778.

Purpose: To investigate the long-term outcome of stent angioplasty for symptomatic severe intracranial artery stenosis., Method: In this study 95 consecutive patients with intracranial atherosclerotic stenosis (>70%) underwent stent angioplasty using Wingspan stents. The primary endpoints were stroke or death within 30 days of the procedure and subsequent stroke attributed to the stented vessel. Disabling stroke was defined as stroke with a modified Rankin scale > 3. Secondary endpoints included transient ischemic attacks, contralateral stroke, nonstroke death, and other events. Patients underwent prestent balloon dilation with or without poststent balloon dilation, close restenosis follow-up, and selective retreatment, as required., Result: The mean follow-up duration was 34.9 ± 23.3 months. Primary endpoint events occurred in 23% of the patients. The median infarction volume was 2.6 ml, and 11 (68%) of 16 infarctions were <5 ml in volume. Disabling stroke occurred in 3% of patients. The primary endpoint rates were 17.9% within 30 days and 2.1% from 30 days to 1 year. Secondary endpoint events occurred in 27.3% of the patients. Mean stenosis was reduced from 76.8 ± 6.1% to 7.5 ± 13.4%. Of 80 patients who underwent angiographic follow-up, 11 (14%) experienced restenosis (≥50%) and 7 (9%) exhibited restenosis-related symptoms of transient ischemic attack. The rate of symptomatic restenosis was significantly higher in patients who underwent prestent balloon dilation alone than in patients who underwent prestent and poststent balloon dilation (p = 0.016)., Conclusion: The postprocedural stroke rate was similar to that observed in the SAMMPRIS study. Symptomatic restenosis may be reduced by poststent dilation, close angiographic follow-up, and retreatment.

Purpose: To compare muscle strength, muscle endurance, and postural stability in both the affected and unaffected ankles between patients with chronic ankle instability (CAI) who underwent conservative treatment and those who underwent the modified Broström procedure (MBP)., Methods: A total of 67 patients (37, conservative treatment; 30, MBP) participated. Muscle strength and muscle endurance were measured using an isokinetic device, and postural stability was tested using a postural stabilometry system. We used the independent t test for continuous variables with a normal distribution and Fisher's exact test for categorical variables., Results: There was no difference in the muscle strengths of the affected and unaffected ankles between the groups. The muscle endurance of plantarflexion and inversion muscles was significantly lower in the affected ankles of the conservative treatment group than in those of the MBP group (plantarflexion: 209 ± 103.1 vs. 318 ± 162.2, p = 0.001; inversion: 93 ± 58.7 vs. 154 ± 65.9, p < 0.001). Static postural stability testing showed no significant differences between the affected and unaffected ankles of the two groups. In the dynamic postural stability test, the overall, anterior-posterior, and medial-lateral stability indices were all significantly higher in the affected ankles of the conservative treatment group than in those of the MBP group (p < 0.001, p = 0.004, p = 0.004, respectively), with no differences observed in the unaffected ankles., Conclusion: The MBP may significantly improve muscle endurance and dynamic postural stability in CAI patients in whom conservative treatment has failed. Therefore, clinicians should consider using MBP instead of conservative treatment when patients show severe muscle weakness or dynamic postural instability., Level of Evidence: Case-control study, Level III.

Purpose: To compare proprioception, postural stability, and neuromuscular control between patients with mechanical laxity and recurrent ankle sprain., Methods: Among 86 patients with ankle instability, 45 patients had mechanical laxity (mean age 27.2 ± 7.0 years) and 41 had recurrent ankle sprain (mean age 25.1 ± 9.2 years). Both the affected and unaffected ankles of each patient were evaluated. Proprioception and neuromuscular control tests were conducted using an isokinetic machine, and postural stability was tested using a postural stabilometry system., Results: Proprioception was not significantly different between the unaffected or affected ankles of the mechanical laxity group compared with those of the recurrent ankle sprain group (n.s). Static and dynamic postural stability and neuromuscular control were similar in the affected ankles between the two groups (n.s). However, postural stability (static, overall: p = 0.009, anterior-posterior: p = 0.028, medial-lateral: p = 0.022; dynamic, overall: p = 0.012, anterior-posterior: p = 0.004, medial-lateral: p = 0.001) and neuromuscular control (inversion: p = 0.031, eversion: p = 0.039, dorsiflexion: p = 0.029, plantarflexion: p = 0.035) were significantly decreased in the unaffected ankles of the recurrent ankle sprain group compared with those of the mechanical laxity group., Conclusion: The unaffected ankles of the recurrent ankle sprain group showed significant decreases in both postural stability and neuromuscular control compared with the mechanical laxity group. Clinicians and therapists should consider unaffected ankle rehabilitation in patients with recurrent ankle sprain to prevent future sprain events., Level of Evidence: Case-control study, III.

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by cognitive impairment, progressive neurodegeneration, and amyloid-β (Aβ) lesion. In the neuronal death and disease progression, inflammation is known to play an important role. Our previous study on acute-phase protein serum amyloid A1 (SAA1) overexpressed mice showed that the liver-derived SAA1 accumulated in the brain by crossing the brain blood barrier (BBB) and trigger the depressive-like behavior on mouse. Since SAA1 involved in immune responses in other diseases, we focused on the possibility that SAA1 may exacerbate the neuronal inflammation related to Alzheimer's disease. A APP/SAA overexpressed double transgenic mouse was generated using amyloid precursor protein overexpressed (APP)-c105 mice and SAA1 overexpressed mice to examine the function of SAA1 in Aβ abundant condition. Comparisons between APP and APP/SAA1 transgenic mice showed that SAA1 exacerbated amyloid aggregation and glial activation; which lead to the memory decline. Behavior tests also supported this result. Overall, overexpression of SAA1 intensified the neuronal inflammation in amyloid abundant condition and causes the greater memory decline compared to APP mice, which only expresses Aβ 1-42.

Case: A 10-year-old boy presented with chronic ulnohumeral subluxation 6 months after an open reduction of a Milch type II lateral condyle fracture subluxation performed at another hospital. The patient had persistent elbow pain and limited range of motion (ROM) between 20° and 50°. After the open reduction for chronic ulnohumeral subluxation and corrective osteotomy for articular surface reconstruction, he had an uneventful recovery with improved ROM of the affected elbow and no pain., Conclusions: Intra-articular corrective osteotomy for articular surface reconstruction may be feasible to improve mobility and relieve pain in pediatric patients with lateral condylar malunion and elbow subluxation.

Allogeneic blood transfusions (ABTs) are common in patients with cancer. The present study investigated the safety of a restrictive ABT strategy in patients with extremity sarcomas.Patients who underwent operations for extremity bone sarcomas between May 2008 and November 2018 were retrospectively reviewed. Clinical outcomes based on hemoglobin concentrations, postoperative infections, and hospital stay were compared between 20 patients who received liberal ABT (control group) and 19 patients who received restrictive ABT (restrictive group). The rates of distant metastasis and death were compared between the groups.The mean number of ABTs was 3.6 ± 3.8 units in the control group and 0.33 ± 0.74 units in the restrictive group (P < .001). Only 3 of 19 patients received transfusions (2 red cell packs each). The hemoglobin levels tended to fall during the first 3 postoperative days but seemed to stabilize within the first postoperative week in both groups. Postoperative surgical site infections only occurred in the patients who received ABTs regardless of the group. The rates of distant metastasis and death were higher in the control group than in the restrictive group (25.0% vs 15.7% and 10.0% vs 0%, respectively), but the differences were not significant.A restrictive ABT strategy may be safely performed in patients with extremity bone sarcomas depending on the intraoperative status and specific characteristics of each patient.

Purpose: To examine the efficacy, safety, and clinical outcomes of distraction osteogenesis through the physis (PDO) or through subphyseal osteotomy (SPDO) in patients with atrophic-type congenital pseudarthrosis of tibia with proximal tibial dysplasia., Methods: To validate the efficacy and safety of PDO and SPDO, radiographic and clinical parameters were compared between 5 patients who underwent proximal tibial metaphyseal or metadiaphyseal lengthening as a control (group 1) and 7 patients who underwent PDO or SPDO (group 2). Postoperative complication was also compared between the groups., Results: A significant difference in terms of healing index (group 1, 83.3±24.7 d/cm; group 2, 35.0±11.1 d/cm; P=0.001) and percentage increase (11.0%±3.7% vs. 23.1%±10.5%, P=0.034) was observed between the 2 groups. According to the Paley classification, group 1 included 1 "problems" case and 3 "obstacles" cases, whereas group 2 included 2 "problems" cases and 1 "obstacles" case. According to the Lascombes classification, group 1 included 2 grade IIIb cases and 3 grade IV cases, whereas group 2 included 6 grade I cases and 1 grade IIa case. Severe complications were significantly higher in group 1 compared with the group 2 (P=0.007)., Conclusions: This study demonstrated that PDO or SPDO can be effectively and safely performed for tibial lengthening in atrophic-type congenital pseudarthrosis of tibia patients with proximal tibial dysplasia., Level of Evidence: Level III.

Introduction: A pulled elbow is a common cause of acute elbow pain that is generally managed by a reduction maneuver without radiographic examination. However, children with atypical presentation with no history of abrupt longitudinal traction should undergo elbow imaging. This study aimed to investigate plain radiography findings and determine the usefulness of ultrasonography (US) in atypical pulled elbow., Materials and Methods: We retrospectively reviewed the medical records and images of 37 (22 males) consecutive patients with pulled elbow who presented with an atypical history or failed reduction between April 2015 and September 2018. Mean age at presentation was 4.34 years (range, 1.25-9.5 years). Of the 37 elbows, 20 were left elbows. The injury mechanism, incidence of the posterior fat pad sign on plain radiographs, and characteristic US findings, pre- and post- reduction, were investigated., Results: The original mechanisms of injury included slipping (n = 14), rolling over the arm (n = 7), vague history (n = 6), falling down (n = 6), abrupt longitudinal traction (n = 2), and direct injury (n = 2). On plain radiographs, six of the 37 elbows (16%) showed the posterior fat pad sign. Before the reduction, an entrapped supinator, a pathognomonic sign of pulled elbow, was identified on US in all cases. After reduction, the characteristic US findings showed a disentangled and swollen supinator (100%) and restored annular ligament (100%) in all successful cases. Although a click was not felt in three cases, the reductions were considered successful because the annular ligament was restored on US with free elbow motion., Conclusion: Pulled elbow may be caused by atypical mechanisms of injury, such as slipping and rolling over the arm. Clinicians should be aware of the possibility of the posterior fat pad sign on plain radiographs of pulled elbow to prevent unnecessary immobilization. In such circumstances, US is a useful method for detecting an entrapped supinator and confirming adequate reduction via restoration of the annular ligament in children with atypical pulled elbow., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Serum amyloid A (SAA) is an acute phase protein with pro-inflammatory cytokine-like properties. Recent studies have revealed that SAA promoted interleukin-17 (IL-17) production by various cells, including γδ T cells. γδ T cells are innate immune cells and express Toll-like receptor 2 (TLR2) on their surface, which is one of the SAA receptors. In this study, we investigated the relationship between γδ T cells and SAA1 through TLR2, by using hepatic SAA1-overexpressing transgenic (TG) mice. By injecting CU-CPT22, which is a TLR2 inhibitor, into the mice, we confirmed that SAA1 induced IL-17 in γδ T cells through TLR2. In vitro studies have confirmed that SAA1 increased IL-17 secretion in γδ T cells in combination with IL-23. We also observed a thickened epidermis layer and granulocyte penetration into the skin similar to the pathology of psoriasis in TG mice. In addition, strongly expressed SAA1 and penetration of γδ T cells in the skin of TG mice were detected. The exacerbation of psoriasis is associated with an increase in IL-17 levels. Therefore, these symptoms were induced by IL-17-producing γδ T cells increased by SAA1. Our study confirmed that SAA1 was a prominent protein that increased IL-17 levels through TLR2 in γδ T cells, confirming the possibility that SAA1 may exacerbate inflammatory diseases through γδ T cells., (© 2019 The Foundation for the Scandinavian Journal of Immunology.)

Rationale: Plantar fasciitis is a common cause of foot pain presenting with morning stiffness and plantar area pain. This case study is to optimize the management in patient with plantar fasciitis accompanied by apparent high-arch foot., Patient Concerns: A 55-year-old women presented with plantar fasciitis accompanied by apparent high-arch foot. The pain presents for the heel and pelvic areas with long-distance walking., Diagnoses: She was diagnosed with plantar fasciitis accompanied by apparent high-arch foot for physical examination and plain radiographs. In muscle performance and dynamic postural stability tests, indicated the muscle weakness and postural instability., Interventions: The patient was treated with manual therapy such as joint and soft tissue mobilization interventions including plantar fascia and gastrocnemius stretching, but the heel and pelvic pain were aggravated during long-distance walking. After hip strengthening exercises, the heel and pelvic pain significantly improved., Outcomes: The 3-month follow-up revealed that the heel and pelvic pain did not occur in the long-distance walking, and there was no pain and discomfort at one year follow-up., Lessons: To optimize the management in patient with plantar fasciitis accompanied by apparent high-arch deformity, clinicians should try to identify the hip abductor muscles weakness, and therapists should consider incorporating hip strengthening exercises.

Purpose: This systematic review aimed to compare radiographic correction, clinical outcomes, complications, and re-operations between lateral column lengthening (LCL) and arthroereisis (AR) for treating symptomatic flatfoot in children., Methods: We conducted a comprehensive search on MEDLINE, EMBASE, and Cochrane Library databases. Literature search, data extraction, and quality assessment were conducted by two independent reviewers. The outcomes analyzed included radiographic parameters, clinical scores, satisfaction, complications, and re-operations., Results: Twenty-one and 13 studies were included in the LCL and AR groups, respectively. The change in anteroposterior talo-first metatarsal angle was greater in the LCL (9.5° to 21.7°) than in the AR group (10.6° to 12.8°). The change in calcaneal pitch was greater in the LCL (2.1° to 26.53°) than in the AR group (- 1.3° to 3.23°). Improvements in the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score were greater in the LCL (27.7 to 39.1) than in the AR group (17 to 22). The percentage of satisfaction was similar between the LCL (68% to 89%) and AR (78.5% to 96.4%) groups. The complication rate was higher in the LCL (0% to 86.9%) than in the AR group (3.5% to 45%). The most common complications were calcaneocuboid subluxation and persistent pain in the LCL and AR groups, respectively. The re-operation rate was similar between the LCL (0% to 27.3%) and AR (0% to 36.4%) groups., Conclusions: The LCL group has achieved more radiographic corrections and more improvements in the AOFAS score than the AR group. Complications were more common in the LCL group than in the AR group, and the re-operation rates were similar between the two groups.