Characteristics of terminal hemimelia: What is the difference between terminal hemimelia and classic fibular hemimelia?

Purpose: Fibular hemimelia has denoted a spectrum of postaxial longitudinal deficiency with fibular aplasia/hypoplasia; the term "terminal hemimelia" is reserved for patients with postaxial longitudinal deficiency having a normal fibula. We aimed to delineate the characteristics of terminal hemimelia. Methods: In total, 30 patients with postaxial longitudinal deficiency who had a normal or hypoplastic fibula and visited our institution between 1992 and 2022 were reviewed. Patients were divided into terminal hemimelia and classic fibular hemimelia groups, and their demographic characteristics and clinical and radiographic findings were compared. Results: Femoral shortening, knee valgus, and tibial spine hypoplasia were less common in terminal hemimelia (n = 13) than in classic fibular hemimelia (n = 17) (p = 0.03, p < 0.001, and p = 0.003, respectively). None of the patients in the terminal hemimelia group exhibited knee instability, whereas 12% of patients with classic fibular hemimelia did. Ball-and-socket ankle and absence of lateral rays were commonly observed in both groups. However, tarsal coalition was observed less frequently in terminal hemimelia (p = 0.004). All terminal hemimelia patients exhibited a painless plantigrade foot without ankle instability. Despite limb-length discrepancy at maturity averaging 40.4 mm for terminal hemimelia and 67.0 mm for classic fibular hemimelia (p < 0.001), patients with terminal hemimelia, except for one, exhibited > 20 mm of limb-length discrepancy. However, 46% of them underwent limb-length equalization procedures, mostly single-stage tibial lengthening, at a mean age of 11.2 years. Conclusion: Terminal hemimelia may present with a milder phenotype than classic fibular hemimelia. It mainly overlaps with the symptoms of fibular hemimelia below the ankle joint and manifests as limb-length discrepancy. However, a considerable number of patients with terminal hemimelia required limb-length equalization procedures, for example single-stage tibial lengthening. Level of evidence: level IV.

Use of lateral-exit crossed-pin fixation for pediatric supracondylar humeral fractures: a retrospective case series.

Surgeons have been reluctant to perform crossed-pin fixation for displaced pediatric supracondylar humeral (SCH) fractures because it carries a risk of iatrogenic ulnar nerve injury. This study aimed to introduce lateral-exit crossed-pin fixation for displaced pediatric SCH fractures and to evaluate its clinical and radiological outcomes, with a particular focus on iatrogenic ulnar nerve injuries. Children who underwent lateral-exit crossed-pin fixation for displaced SCH fractures between 2010 and 2015 were retrospectively reviewed. Lateral-exit crossed-pin fixation involved the introduction of a medial pin from the medial epicondyle, as in the conventional method, followed by pulling the pin through the lateral skin until the distal and medial aspects of the pin were just under the cortex of the medial epicondyle. The time to union and loss of fixation were assessed. Flynn's clinical criteria (cosmetic and functional factors) and complications including iatrogenic ulnar nerve injury were investigated. A total of 81 children with displaced SCH fractures were treated with lateral-exit crossed-pin fixation. All but one patient achieved union with good alignment, with an average time to union of 7.9 weeks (3.9-10.3 weeks). Only one patient exhibited cubitus varus deformity associated with loss of reduction. All patients recovered to almost their full range of motion. No case of iatrogenic ulnar nerve injury developed; however, iatrogenic radial nerve injury developed in one patient. Lateral-exit crossed-pin fixation provides sufficient stability with a lower risk of iatrogenic ulnar nerve injury in children with displaced SCH fractures. This method is an acceptable technique for crossed-pin fixation.

Incidence and Clinical Characteristics of Slipped Capital Femoral Epiphysis in Patients with Endocrinopathy: A Population-Based Cohort Study.

BACKGROUND: Endocrinopathy is a risk factor for slipped capital femoral epiphysis (SCFE). We aimed to determine (1) the incidence of endocrinopathy-associated SCFE compared with that of non-endocrinopathy-associated SCFE, (2) whether the incidence of SCFE increases with the number of deficient hormones, and (3) the clinical characteristics of endocrinopathy-associated SCFE. METHODS: We conducted a population-based cohort study using a nationwide database in South Korea. All new diagnoses of endocrinopathy or SCFE between 2002 and 2019 in children born between 2002 and 2005 were identified. The incidence of SCFE was calculated for each type of endocrinopathy. The trend of the incidence of SCFE relative to the number of deficient hormones was analyzed. The male:female ratio was compared between endocrinopathy-associated SCFE and non-endocrinopathy-associated SCFE. For endocrinopathy-associated SCFE, the time between the diagnoses of SCFE and endocrinopathy was evaluated. RESULTS: The incidence of SCFE was higher in children with endocrinopathy than in those without endocrinopathy (37.1/100,000 versus 9.0/100,000 children) (relative risk, 4.1 [95% confidence interval, 2.8-6.1]). Among various endocrinopathies, growth hormone deficiency showed the highest incidence of SCFE (583.8/100,000 children). The Cochran-Armitage test showed a linear trend, with an increased number of deficient hormones being associated with a higher incidence of SCFE (p < 0.001). Male sex was dominant in the non-endocrinopathy-associated SCFE group (73%; 117 of 161), whereas female sex was dominant in the endocrinopathy-associated SCFE group (53%; 16 of 30) (p = 0.009). Twenty-two of the 30 cases of endocrinopathy-associated SCFE were diagnosed after the diagnosis of endocrinopathy, with a median time of 3.6 years between the diagnoses. Six (27%) of these 22 children developed SCFE >5 years after the diagnosis of endocrinopathy. CONCLUSIONS: The incidence of SCFE was approximately 4 times higher in children with endocrinopathy than in those without endocrinopathy. The risk of SCFE increased with an increased number of deficient hormones. Long-term monitoring of SCFE occurrence in children with endocrinopathies is strongly recommended. LEVEL OF EVIDENCE: Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Operative Versus Nonoperative Management of Pediatric Proximal Humerus Fractures: A Meta-Analysis and Systematic Review.

Background: Proximal humerus fractures account for 2% of all pediatric fractures. A nonoperative approach is the treatment of choice for most of these fractures; however, debates continue regarding the treatment of displaced fractures, especially in adolescents. In this study, we aimed to examine demographic data and treatment strategies for proximal humerus fractures in the pediatric population by conducting a meta-analysis. Additionally, we investigated the preferred surgical technique for operative treatment. Methods: A systematic online search of databases, including Embase, Medline, PubMed, and Cochrane Library, was conducted to identify studies that matched our search criteria. Data collection was completed on May 1, 2022. Age, sex, degree of angulation, Neer-Horwitz classification, Salter-Harris classification, treatment method (operative vs. nonoperative), and instrument used for internal fixation were classified and documented. Effect size analysis was performed using odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs), based on data types. Results: Eight studies met our inclusion criteria. Overall, 33% of the patients (n = 195) underwent operative treatment, whereas 67% of them (n = 392) received nonoperative treatment. Among the demographic risk factors, severely displaced fracture type (OR, 10.00; 95% CI, 1.56-64.22; p = 0.020) and older age (WMD, 3.26; 95% CI, 2.29-4.23; p < 0.001) were significantly associated with operative treatment. There was no significant difference in the preference for percutaneous pinning or intramedullary nailing, the most frequently employed surgical techniques (OR, 5.09; 95% CI, 0.65-39.58; p = 0.120). Conclusions: The operative treatment rate in pediatric proximal humerus fractures was 33%, which increased to 60% in severely displaced fractures (Neer-Horwitz grade III/IV). Severely displaced fractures and older age significantly contributed to the establishment of a treatment strategy for operative treatment. The choice of surgical technique may seem to be based on the anatomical location of the fracture rather than the surgeon's preference.

Long-term Outcomes of Posterior Multilevel Crack Osteotomy: Revisional Surgery for Scoliosis With a Fusion Mass.

OBJECTIVE: Osteotomies are required for the mobilization of spinal segments in patients with revisional scoliosis surgery with a fusion mass; however, only a few techniques have shown efficacy and safety, and their mid- and long-term outcomes remain unelucidated. This study aimed to analyze long-term outcomes of the posterior multilevel crack osteotomy (PMCO) technique for revisional surgery for scoliosis with a fusion mass. METHODS: Data from 18 patients who underwent revisional scoliosis surgery using PMCO between 2009 and 2015 and had more than 5-year follow-up were retrospectively reviewed. The Cobb angle and coronal and sagittal balance parameters were examined preoperatively, postoperatively, and during the final follow-up. Perioperative parameters and complications were also assessed. RESULTS: Preoperative and postoperative Cobb angles were 60.5° and 29.9°, respectively (p < 0.001); this improvement was maintained until the final follow-up (33.4°, p = 0.058). The difference in preoperative and postoperative coronal balance was statistically significant (15.9 mm and 9.2 mm, respectively; p < 0.001); this was maintained until the final follow-up (p = 0.071). There was no change in sagittal balance parameters over the 3 measurement periods. Only 1 patient showed PMCO-related motor weakness, but he spontaneously recovered 3 months after postsurgery. Pseudarthrosis was not observed during the follow-up period. CONCLUSION: Incomplete osteotomy using PMCO provided satisfactory deformity correction without severe complications during revisional surgery for scoliosis with a fusion mass. It may be a less invasive procedure that maintains cortical continuity, preserves soft tissues, and provides sufficient mobility for the correction of spinal segments.

When to Combine Acetabular Osteotomy in Patients With Proximal Femoral Deformity Causing Residual Hip Dysplasia/Subluxation After Reduction of Developmental Dysplasia of the Hip.

BACKGROUND: After the successful reduction of developmental dysplasia of the hip, residual hip dysplasia may persist and lead to early osteoarthritis. Femoral and/or acetabular osteotomy has been used to address this problem. The purpose of this study is to determine the indication of femoral versus combined femoral-acetabular osteotomy in the management of residual hip dysplasia. METHODS: Fifty-five patients with unilateral dislocated-type dysplasia of the hip, who had residual hip dysplasia after reduction, underwent femoral osteotomy with or without acetabular osteotomy before 8 years of age, and were followed for more than 2 years and over 8 years of age, were the subjects of this retrospective study. Twenty-eight patients underwent femoral osteotomy only at a median age of 34 months (group F), and 27 underwent combined femoral-Dega osteotomy at a median age of 49 months (group C). Seventeen patients in group F and 4 in group C had an additional osteotomy due to persistent hip dysplasia. Acetabular index (AI), lateral center-edge angle, and center-head distance difference were measured on serial radiographs. The z-value of AI (Z AI ) was calculated. At the latest follow-up, patients in group F with Severin I/II who did not have an additional osteotomy were considered satisfactory, and patients with Severin III/IV or those who had an additional osteotomy were considered unsatisfactory. Preoperative variables were tested for the difference between satisfactory and unsatisfactory cases. Receiver operating characteristic analysis was performed to delineate a cutoff value of a significant parameter dividing the outcome. RESULTS: AI and Z AI before index osteotomy were significant parameters predicting a satisfactory outcome in group F. Receiver operating characteristic analysis returned a cutoff value of Z AI 2.6 (Area Under the Curve=0.86, P =0.001). Eight of 12 cases (66.7%) with Z AI <2.6 in group F achieved a satisfactory outcome, whereas only 2 of 14 cases with Z AI ≥2.6 in group F did ( P =0.02). CONCLUSION: Z AI 2.6 may serve as a threshold to combine acetabular osteotomy with femoral osteotomy in the management of residual hip dysplasia before 8 years of age. LEVEL OF EVIDENCE: Therapeutic III.

Pseudo-Protrusio Acetabular Deformity in Osteogenesis Imperfecta Patients.

BACKGROUND: Osteogenesis imperfecta (OI) can develop a protrusio acetabuli deformity. However, the authors observed a pseudo-protrusio-type acetabular deformity (PPAD) on 3-dimensional computed tomography (3D-CT). Hence, we systematically reviewed 3D-CT and pelvis radiographs of OI patients and report the incidence and patterns of acetabular deformity in OI patients and the associated radiographic signs. METHODS: The study included 590 hips of 295 OI patients, who were older than 5 years, and did not have a pelvic fracture. The incidence of a deformed acetabulum (center-edge angle >40 degrees) and its correlation with disease severity were investigated. In 40 hips for which 3D-CT was available, 3-dimensional morphology of the acetabular deformity was analyzed to delineate PPAD. On plain radiographs, PPAD-related signs were determined, focusing on the contour of ilioischial line, iliopectineal line, acetabular line, and their relationship. These radiographic signs were also evaluated in the remaining hips with deformed acetabula that did not have 3D-CT. RESULTS: One hundred twenty-three hips of 590 hips (21%) showed deformed acetabula. The incidence of deformed acetabula was significantly associated with disease severity (P<0.001). Three-dimensional analysis showed that 10 hips had protrusio acetabuli, whereas 17 had PPAD, which showed that the hemipelvis was crumpled, the acetabular roof was rotated upwardly and medially, and the hip center migrated superiorly, uncovering the anterior femoral head. Among the PPAD-related signs, superomedial bulging of the iliopectineal line was the most predictive radiographic sign (73% sensitivity and 100% specificity). This sign was also observed in almost one third of deformed acetabula of those investigated only with plain radiographs. CONCLUSIONS: This study showed that acetabular deformity is common in OI patients and is associated with disease severity. A substantial number of hips showed PPAD, which may not cause femoroacetabular impingement but result in anterior uncovering of the hip joint. Superomedial bulging of the iliopectineal line suggests this pattern of acetabular deformity. LEVEL OF EVIDENCE: Lever IV-prognostic studies.

Inter-limb difference of mechanical work in limb length discrepancy.

BACKGROUND: Limb length discrepancy (LLD) is common and is associated with musculoskeletal disorders. Selection of adaptation strategies, the side more susceptible to complications, and the relationships between LLD magnitude and musculoskeletal complications are unclear. To elucidate these ambiguities, studies on gait parameters in LLD have been conducted. However, studies on inter-limb difference of mechanical work in LLD are rare. RESEARCH QUESTION: To investigate whether inter-limb differences in mechanical work in LLD and the relationship between LLD magnitude and mechanical work performed by each lower limb are significant. METHODS: Thirty-seven participants with LLD and without neuromuscular disorders disturbing normal gait were included. Three-dimensional motion analysis was conducted to obtain data on mechanical work, including joint work and the individual limb method (ILM) work. Mechanical work performed by the longer and shorter limbs was compared using paired t-test. Relationships between LLD and mechanical work were investigated using correlation and multiple regression analyses in both limbs. Eighteen participants had LLD > 20 mm, large group (LG), and 19 had LLD < 20 mm, small group (SG). Data exploration was conducted for the effect of LLD severity (LG vs. SG) on mechanical work. RESULTS: LLD showed significant inter-limb difference of mechanical work and negative correlations with positive and negative ILM work performed by the shorter limb. The shorter limb in SG performed significantly larger positive ILM work than the longer limb, whereas the longer limb in LG performed significantly larger negative ILM work than the shorter limb. SIGNIFICANCE: LLD showed inter-limb difference of ILM work and different adaptation strategies between LG and SG. These differences attribute to the decrease in ILM work performed by the shorter limb with the increase in LLD. Mechanical work including ILM work should be included in future studies to prevent complications and development of treatment methods for LLD.

Enhanced tendon restoration effects of anti-inflammatory, lactoferrin-immobilized, heparin-polymeric nanoparticles in an Achilles tendinitis rat model.

Gradual wear and tear can cause a local inflammatory response in tendons. The trauma and inflammatory reaction eventually impair the biomechanical properties of the tendon. In this study, we prepared lactoferrin-immobilized, heparin-anchored, poly(lactic-co-glycolic acid) nanoparticles (LF/Hep-PLGA NPs) and evaluated their in vitro anti-inflammatory effects on interleukin-1ß (IL-1ß)-treated tenocytes and in vivo tendon healing effects in a rat model of Achilles tendinitis. Long-term LF-deliverable NPs (LF/Hep-PLGA NPs) remarkably decreased mRNA levels of pro-inflammatory factors [cyclooxygenase-2 (COX-2), IL-1ß, matrix metalloproteinase-3 (MMP-3), MMP-13, IL-6, and tumor necrosis factor-α (TNF-α)] and increased mRNA levels of anti-inflammatory cytokines (IL-4 and IL-10) in both IL-1ß-treated tenocytes and the Achilles tendons of a collagenase-induced Achilles tendinitis rat model. Interestingly, anti-inflammatory LF/Hep-PLGA NPs greatly enhanced collagen content, mRNA levels of tenogenic markers [collagen type I (COL1A1), decorin (DCN), tenascin-C (TNC)], and biomechanical properties such as tendon stiffness and tensile strength. These results suggest that anti-inflammatory LF/Hep-PLGA NPs are effective at restoring tendons in Achilles tendinitis.

Therapeutic Efficacy of Intratendinous Delivery of Dexamethasone Using Porous Microspheres for Amelioration of Inflammation and Tendon Degeneration on Achilles Tendinitis in Rats.

Achilles tendinitis caused by overuse, aging, or gradual wear induces pain, swelling, and stiffness of Achilles tendon and leads to tendon rupture. This study was performed to investigate the suppression of inflammation responses in interleukin-1ß- (IL-1ß-) stimulated tenocytes in vitro and the suppression of the progression of Achilles tendinitis-induced rat models in vivo using dexamethasone-containing porous microspheres (DEX/PMSs) for a sustained intratendinous DEX delivery. DEX from DEX/PMSs showed the sustained release of DEX. Treatment of IL-1ß-stimulated tenocytes with DEX/PMSs suppressed the mRNA levels for COX-2, IL-1ß, IL-6, and TNF-α. The intratendinous injection of DEX/PMSs into Achilles tendinitis rats both decreased the mRNA levels for these cytokines and increased mRNA levels for anti-inflammatory cytokines IL-4 and IL-10 in tendon tissues. Furthermore, DEX/PMSs effectively prevented tendon degeneration by enhancing the collagen content and biomechanical properties. Our findings suggest that DEX/PMSs show great potential as a sustained intratendinous delivery system for ameliorating inflammation responses as well as tendon degeneration in Achilles tendinitis.

In Vivo Response of Growth Plate to Biodegradable Mg-Ca-Zn Alloys Depending on the Surface Modification.

Because Mg-Ca-Zn alloys are biodegradable and obviate secondary implant removal, they are especially beneficial for pediatric patients. We examined the degradation performance of Mg-Ca-Zn alloys depending on the surface modification and investigated the in vivo effects on the growth plate in a skeletally immature rabbit model. Either plasma electrolyte oxidation (PEO)-coated (n = 18) or non-coated (n = 18) Mg-Ca-Zn alloy was inserted at the distal femoral physis. We measured the degradation performance and femoral segment lengths using micro-CT. In addition, we analyzed the histomorphometric and histopathologic characteristics of the growth plate. Although there were no acute, chronic inflammatory reactions in either group, they differed significantly in the tissue reactions to their degradation performance and physeal responses. Compared to non-coated alloys, PEO-coated alloys degraded significantly slowly with diminished hydrogen gas formation. Depending on the degradation rate, large bone bridge formation and premature physeal arrest occurred primarily in the non-coated group, whereas only a small-sized bone bridge formed in the PEO-coated group. This difference ultimately led to significant shortening of the femoral segment in the non-coated group. This study suggests that optimal degradation could be achieved with PEO-coated Mg-Ca-Zn alloys, making them promising and safe biodegradable materials with no growth plate damage.

Novel loss-of-function variants of TRAPPC2 manifesting X-linked spondyloepiphyseal dysplasia tarda: report of two cases.

BACKGROUND: X-linked spondyloepiphyseal dysplasia tarda (SEDT-XL) is a skeletal disorder characterized by defective structures of vertebral bodies and/or of epiphyses of the long bones, resulting in moderately short stature and early joint degeneration. TRAPPC2 gene, which is important for collagen secretion, has been reported as causative for SEDT-XL. CASE PRESENTATION: Here, we report two variants of TRAPPC2 gene of SEDT-XL patients, a missense variant of start codon, c.1A > T, and a deletion variant, c.40delG. To understand molecular consequence of the variants, we establish an in vitro gene expression assay system and demonstrate that both mutated genes are transcribed, but are not properly translated, indicative of the pathogenic nature of those TRAPPC2 variants. CONCLUSIONS: In the current study, we provide additional experimental data showing that loss-of-function TRAPPC2 variants are probably causative for SEDT-XL phenotype. These findings further contribute to the understanding the clinical picture related to TRAPPC2 gene.

Low-intensity pulsed ultrasound enhances callus consolidation in distraction osteogenesis of the tibia by the technique of lengthening over the nail procedure.

BACKGROUND: Low-intensity pulsed ultrasound (LIPUS) has been widely accepted in promoting the fracture healing process. However, there have been limited clinical trials focused on the efficacy of LIPUS during distraction osteogenesis (DO) by the technique of lengthening over the nail procedure. The purpose of the current study was to evaluate the efficacy of LIPUS during DO. METHODS: We retrospectively evaluated 30 patients (60 segments) who underwent simultaneous bilateral tibial lengthening over the nail. The patients were grouped into the LIPUS group and the control group based on LIPUS stimulation. The two patient groups were compared for demographic data (sex, age at operation, preoperative height, BMI, and smoking history), qualitative assessments of the callus (callus shape and type), external fixation index, and four cortical healing indexes. RESULTS: Fifteen patients (30 segments) were classified as the LIPUS group, and another 15 patients (30 segments) were classified as the control group. No significant differences were found in the assessed demographic data between the groups. LIPUS stimulated a more cylindrical, more homogenous, and denser type of callus formation at the end of the distraction phase. The two groups exhibited equivalent outcomes in terms of external fixation index (p = 0.579). However, significant differences were found in healing indexes of the anterior and medial cortices (p <  0.001 and p = 0.002, respectively). The healing indexes of those cortices in the LIPUS group (mean of 36.6 days/cm and 32.5 days/cm, respectively) reflected their significantly faster healing compared to the control group (mean HI of 57.5 days/cm and 44.2 days/cm, respectively). There were no LIPUS-related complications. CONCLUSIONS: LIPUS is a noninvasive and effective adjuvant therapy to enhance callus maturation during DO. It enhances callus consolidation and may have a positive effect on the appropriate callus shape and type.

Nonoperative versus operative treatment for displaced midshaft clavicle fractures in adolescents: a comparative study.

We aimed to compare the outcomes and complications of nonoperative and operative treatment for displaced midshaft clavicle fractures in adolescents. Radiological and functional evaluations and complications for 23 patients with nonoperative treatment were compared with those for 18 patients with operative treatment. No nonunion developed in either group. No significant intergroup differences were observed for occurrence of delayed union or time to union (P=0.851 and 0.887, respectively). Both groups showed excellent functional outcomes on the basis of Disabilities of the Arm, Shoulder and Hand scores and Constant Shoulder Scores. Shoulder abduction strength and range of motion were also well restored in both treatment groups. However, recovery of shoulder range of motion was significantly faster in the operative group (mean: 5.3 weeks; range: 4.0-7.0 weeks) than in the nonoperative group (mean: 9.9 weeks; range: 8.0-19.0 weeks) (P<0.001). There were no patients in either treatment group who needed revisional surgery to address complications with functional deficits. Both nonoperative and operative treatments yielded excellent outcomes, without severe complications. On the basis of our results, nonoperative treatment is recommended as a primary treatment option for displaced midshaft clavicle fractures in adolescents. However, operative treatment can be considered in selected patients who require early functional recovery or have a high activity level.

Sustained hip flexion contracture after femoral lengthening in patients with achondroplasia.

BACKGROUND: Hip flexion contracture often occurs after femoral lengthening in patients with achondroplasia, but few studies have investigated its development in these patients. The purpose of this study was to analyze sustained hip flexion contracture in achondroplasia patients who underwent femoral lengthening and to identify contributing factors. METHODS: This study included 34 patients with achondroplasia who underwent femoral lengthening (mean age at operation, 11.1 years). Sustained hip flexion was defined as flexion contracture lasting > 6 months postoperatively despite physiotherapy. Demographic data, spinopelvic parameters (pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, and sagittal vertical axis), and quantitative assessments of femoral lengthening were investigated. The associations among these factors and the development of sustained hip flexion contracture were assessed. RESULTS: Sustained hip flexion contracture developed in 13 (38%) of 34 achondroplasia patients after femoral lengthening. Eight (62%) of these 13 patients concomitantly exhibited limitation of knee flexion. Excessive femoral lengthening (odds ratio [OR], 1.450; 95% confidence interval [CI], 1.064 to 1.975; p = 0.019) and forward sagittal vertical axis tilt (OR, 1.062; 95% CI, 1.001 to 1.127; p = 0.047) contributed to sustained hip flexion contracture. CONCLUSIONS: Sustained hip flexion contracture frequently occurs after femoral lengthening in achondroplasia patients. Both excessive femoral lengthening and preoperative forward SVA tilt may contribute to the development of sustained hip flexion contracture in these patients.

Exploring the In Vivo Anti-Inflammatory Actions of Simvastatin-Loaded Porous Microspheres on Inflamed Tenocytes in a Collagenase-Induced Animal Model of Achilles Tendinitis.

Tendon rupture induces an inflammatory response characterized by release of pro-inflammatory cytokines and impaired tendon performance. This study sought to investigate the therapeutic effects of simvastatin-loaded porous microspheres (SIM/PMSs) on inflamed tenocytes in vitro and collagenase-induced Achilles tendinitis in vivo. The treatment of SIM/PMSs in lipopolysaccharide (LPS)-treated tenocytes reduced the mRNA expressions of pro-inflammatory cytokines (Matrix metalloproteinase-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)). In addition, the local injection of SIM/PMSs into the tendons of collagenase-induced Achilles tendinitis rat models suppressed pro-inflammatory cytokines (MMP-3, COX-2, IL-6, TNF-α, and MMP-13). This local treatment also upregulated anti-inflammatory cytokines (IL-4, IL-10, and IL-13). Furthermore, treatment with SIM/PMSs also improved the alignment of collagen fibrils and effectively prevented collagen disruption in a dose-dependent manner. Therefore, SIM/PMSs treatment resulted in an incremental increase in the collagen content, stiffness, and tensile strength in tendons. This study suggests that SIM/PMSs have great potential for tendon healing and restoration in Achilles tendinitis.

Slipped capital femoral epiphysis in children younger than 10 years old: clinical characteristics and efficacy of physeal-sparing procedures.

We aimed to investigate the clinical characteristics of slipped capital femoral epiphysis (SCFE) in patients aged less than 10 years and identify the efficacy of physeal-sparing procedures in this age group. Demographic data of 18 SCFE patients aged less than 10 years were compared with those of 71 older patients to investigate the clinical characteristics. The efficacy of physeal-sparing procedures (n=5) was investigated compared with that of in-situ screw fixation (n=13). Obese children were noticeably more common among SCFE patients aged less than 10 years (P=0.034). The slip angle improved significantly more in the physeal-sparing subgroups (P=0.038) without the occurrence of further slippage. Moreover, physeal-sparing procedures allow persistent growth of the proximal femoral physis. However, most of the patients in the physeal-sparing subgroup needed additional surgeries when the proximal femoral physis outgrew the implant. Obesity may be associated more with early-onset SCFE (onset<10 years). Physeal-sparing procedures are safe and effective in preventing leg-length discrepancy and allowing the remodeling of the deformed proximal femur in this age group.

Femoral overgrowth in children with congenital pseudarthrosis of the Tibia.

BACKGROUND: Having observed a tendency towards femoral overgrowth (FO) of the affected limb in children with atrophic-type congenital pseudarthrosis of the tibia (CPT), we aimed to identify the incidence of, contributors to, and patterns of FO among such children. METHODS: We retrospectively evaluated 55 children with CPT, 22 with prepseudarthrosis and 33 with atrophic-type CPT from 1989 to 2012. FO was defined as an affected femoral segment ≥10 mm longer than the contralateral segment. We investigated FO incidences in prepseudarthrosis versus atrophic-type CPT. Sex, laterality, coexistence of neurofibromatosis type 1, development of frank pseudarthrosis, extent of tibial shortening, shortening in foot height, deformity severity, distraction osteogenesis (DO) treatment, refracture, increased femoral neck-shaft angle, tibiofemoral angle, and ankle valgus angle were investigated to identify potential contributors to FO. Patterns of FO were also determined. RESULTS: At initial presentation, 11 patients exhibited a mean of 13 mm (10-23) of FO. However, the nature of FO changed over time during the follow-up period (mean, 10.8 years; range, 4.3-19.3). At the last follow-up, 14 patients presented with a mean of 12 mm (10-18) of FO. With the exception of one patient, all patients with FO presented with atrophic-type CPT. Frank pseudarthrosis, DO treatment, and increased femoral neck-shaft angle were significantly associated with FO (p = 0.016, p = 0.001, and p = 0.005, respectively). Diverse patterns of FO were observed. CONCLUSIONS: FO of the affected limb is frequently encountered in patients with atrophic-type CPT. A compensatory response to frank pseudarthrosis, DO treatment, and neurofibromatosis may play a role in the diverse patterns of FO.

Acromesomelic dysplasia, type maroteaux caused by novel loss-of-function mutations of the NPR2 gene: Three case reports.

The C-type natriuretic peptide (CNP)-natriuretic peptide receptor 2 (NPR2) signaling pathway plays an important role in chondrocyte development. Homozygous loss-of-function mutations of the NPR2 gene cause acromesomelic dysplasia, type Maroteaux (AMDM). The aim of this study was to identify and characterize NPR2 loss-of-function mutations in patients with AMDM. The NPR2 gene was sequenced in three Korean patients with AMDM and functional analysis of the mutated proteins was performed in vitro. Five novel NPR2 mutations were found in the three patients: two compound heterozygous mutations [c.1231T>C (Tyr411His) and c.2761C>T (Arg921X) in Patient 1 and c.1663A>T (Lys555X) and c.1711-1G>C (M571VfsX12) in Patient 3] and a homozygous mutation [c.2762G>A (Arg921Gln) in Patient 2]. Serum NT-proCNP concentration was significantly increased in each patient compared to control subjects. Cells transfected with the expression vector of each mutant except those found in Patient 3 showed a negligible or a markedly low cGMP response after treatment with CNP. HA-tagged wild-type (wt) and HA-mutant NPR2 were expressed at comparable levels: there were two bands of ∼130 and ∼120 kDa in wt and Arg921Gln, a single ∼120 kDa band in Tyr411His, and a single ∼110 kDa in the nonsense mutant. With respect to subcellular localization, Arg921Gln as well as wt-NPR2 reached the cell surface, whereas Tyr411His and Arg921X mutants did not. The Tyr411His and Arg921X NPR2 proteins were co-localized with an endoplasmic reticulum (ER) marker and failed to traffic from the ER to the Golgi apparatus. These results are consistent with deglycosylation experiments. Tyr411His and Arg921X NPR2 are complete loss-of-function mutations, whereas Arg921Gln behaves as a receptor for CNP with limited function.