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Background: Multiple osteochondroma (MO), an autosomal dominant genetic disease, is caused by heterozygous mutations in the EXT1 and EXT2 genes. Approximately 80% of pathogenic mutations are nonsense/missense mutations, small indels, and splicing mutations. Splicing mutations, particularly at the 3′ and 5′ splice sites, disrupt normal mRNA processing and cause exon skipping or aberrant splicing, ultimately resulting in protein truncation and loss of function. Methods: Polymerase chain reaction (PCR) and Sanger sequencing were applied to detect subtle mutations in a Chinese family with MO, the pathogenicity of a splicing variant was predicted by bioinformatics and further verified using a minigene splicing assay. Results: A novel and heterozygous splicing mutation, c.626 + 2_626 + 5delTAGG, was identified in the EXT2 gene of the proband and the father by PCR and Sanger sequencing, whereas the unaffected mother and brother had wild-type alleles at the same site. Bioinformatics predicted that the 5′ splicing site of exon 3 in the EXT2 gene was destroyed due to this mutation. A hybrid minigene splicing assay (HMSA) indicated that the mutation disturbed the normal splicing of the EXT2 gene mRNA and led to a deletion of 79 bp at the 5′ end of exon 3, which resulted in aberrant splicing of exon 3 and introduced an earlier stop codon in the EXT2 gene. Conclusion: A novel splicing mutation was identified that produced the MO phenotype through aberrant splicing in a Chinese family. This observation, expands our knowledge of the spectrum of molecular pathogenic mechanisms leading to aberrant mRNA splicing. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the correlation between avascular necrosis (AVN) and the amount (severity) and direction (translation and angulation) of initial displacement of pediatric femoral neck fractures.Methods: We retrospectively reviewed 108 pediatric patients (mean age 10.3 ± 4.1 years) with femoral neck fractures. The amount of initial translation (T) and angulation (A) was measured on anteroposterior (AP; TAP% and AAP) and lateral (TL% and AL) radiographs. The direction of translation was determined on AP (medial or lateral) and lateral radiographs (anterior or posterior). Furthermore, the presence of a comminuted medial cortex on the AP pelvis radiograph was also recorded. Logistic regression analysis, receiver operating characteristic (ROC) curve analysis, student's t tests, and chi-square tests were used to evaluate the correlation between AVN and the severity and direction of displacement.Results: Twenty-eight out of 108 hips (25.9%) developed AVN of the femoral head. Logistical regression analysis indicated that TAP%, TL%, AAP, and AL were risk factors for AVN (P < 0.05). The analysis of ROC curves found that TAP% over 37.4% and TL% over 29% were the cut-off values for an increased incidence of AVN; similarly, AAP over 8° and AL over 18.6° were the cut-off values for an increased incidence of AVN. The amount of initial translation is a better predictor of AVN than angulation is; fractures with posterior translation (P = 0.002) and/or medial comminution had a significantly higher incidence of AVN (P = 0.005). The mean diagnostic accuracy of translation (74-75%) was significantly higher than that of angulation (65-66%).Conclusions: Displacement severity and direction are important radiological parameters to be assessed in children with femoral neck fractures. Initial translation better predicts AVN than angulation does. Posterior translation and medial comminution are associated with an increased risk of AVN. [ABSTRACT FROM AUTHOR]

Purpose: Long-term nonunion of the lateral humeral condyle (LHC) can result in progressive cubitus valgus, elbow pain, instability, and delayed ulnar nerve palsy. Various techniques have been proposed for correction, each with its own advantages and disadvantages. The purpose of this study was to introduce a lateral open wedge osteotomy (LOWO) procedure combined with in situ osteosynthesis of nonunited LHC for the treatment of long-term LHC nonunion with cubitus valgus deformity., Methods: We evaluated 18 pediatric patients who had a cubitus valgus deformity greater than 10 degrees after nonunion of the LHC for more than 2 years. The LHC was fixed in situ with 1 or 2 cancellous screws, and the LOWO was fixed with a locking plate. All patients underwent clinical and radiologic evaluation, and the pre- and postoperative carrying angle (CA), range of motion (ROM), and Mayo elbow performance score (MEPS) were analyzed., Results: Eighteen patients, with a mean age of 9.9 ± 3.9 years, underwent treatment for LHC nonunion and cubitus valgus deformity after a mean interval of 61.6 ± 24.1 months from the initial injury. The mean follow-up period was 57.6 ± 22.8 months. Union of the LHC and LOWO was achieved in all patients. The mean CA decreased significantly from 31.6 ± 4.8 degrees before surgery to 10.4 ± 2.2 degrees after surgery (P<0.001). Surgery did not decrease elbow range of motion (P=0.202). The mean MEPS increased significantly from a preoperative value of 55 ± 4.9 to a postoperative value of 91.1 ± 5.6 (P<0.001). No significant complications were observed., Conclusions: LOWO combined with in situ fixation of nonunited LHC is an effective approach for treating long-term LHC nonunion associated with cubitus valgus deformity., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To investigate the risk factors for unsuccessful radial head reduction (RHR) in children with chronic Monteggia fractures (CMFs) treated surgically., Methods: A total of 209 children (mean age 6.84 years (SD 2.87)), who underwent surgical treatment for CMFs between March 2015 and March 2023 at six institutions, were retrospectively reviewed. Assessed risk factors included age, sex, laterality, dislocation direction and distance, preoperative proximal radial metaphysis width, time from injury to surgery, reduction method, annular ligament reconstruction, radiocapitellar joint fixation, ulnar osteotomy, site of ulnar osteotomy, preoperative and postoperative ulnar angulation, ulnar fixation method, progressive ulnar distraction, and postoperative cast immobilization. Independent-samples t -test, chi-squared test, and logistic regression analysis were used to identify the risk factors associated with unsuccessful RHR., Results: Redislocation occurred during surgery in 48 patients (23%), and during follow-up in 44 (21.1%). The mean follow-up of patients with successful RHR was 13.25 months (6 to 78). According to the univariable analysis, time from injury to surgery (p = 0.002) and preoperative dislocation distance (p = 0.042) were identified as potential risk factors for unsuccessful RHR. However, only time from injury to surgery (p = 0.007) was confirmed as a risk factor by logistic regression analysis. Receiver operating characteristic curve analysis and chi-squared test confirmed that a time from injury to surgery greater than 1.75 months increased the rate of unsuccessful RHR above the cutoff (p = 0.002)., Conclusion: Time from injury to surgery is the primary independent risk factor for unsuccessful RHR in surgically treated children with CMFs, particularly in those with a time from injury to surgery of more than 1.75 months. No other factors were found to influence the incidence of unsuccessful RHR. Surgical reduction of paediatric CMFs should be performed within the first two months of injury whenever possible., Competing Interests: The authors confirm that they have no conflict of interest to declare., (© 2024 Wang et al.)

Background: The incidence of aggravation or occurrence of avascular necrosis (AVN) following hardware removal in surgically treated pediatric femoral neck fractures who achieved radiologic consolidation is unknown. This study aimed to investigate the risk factors for this complication., Methods: Seventy-one pediatric (mean age: 9.8±3.9 y) were retrospectively analyzed. Risk factors (age, sex, laterality, severity of initial displacement, type of fracture, time from trauma to reduction, reduction and fixation method, quality of reduction, time required to achieve radiologic union, duration of hardware retention, presence of AVN before hardware removal and follow-up time) were recorded. The severity of AVN was assessed based on radiographs with Ratliff's classification., Results: Following hardware removal, the aggravation/occurrence of AVN was detected in 11 hips (15.5%). Among the 5 hips (7%) with aggravation of AVN, 1 (1.4%) with type II AVN and 3 (4.2%) with type III AVN exhibited aggravation of type I AVN, while the remaining hip (1.4%; type I) showed enlargement of the involved AVN area. Six hips (8.5%) developed AVN following hardware removal: 2 (2.8%) were classified as type I and 4 (5.6%) as type III. Receiver operating characteristic curve analysis indicated that hardware retention >7 months after union is associated with a decreased rate of aggravation or occurrence of AVN of the femoral neck or head following hardware removal., Conclusions: The incidence of aggravation or occurrence of AVN following hardware removal in surgically treated pediatric femoral neck fractures is 15.5%; hardware retention >7 months after radiologic union may reduce the risk of aggravation or occurrence of AVN of the femoral neck or head postimplant removal., Level of Evidence: Level III., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

MicroRNA (miR)-335-5P has the ability to regulate chondrogenic differentiation and promote chondrogenesis in mouse mesenchymal stem cells. It is also abnormally elevated in human osteoarthritic chondrocytes. However, the biological function of miR-335-5P in osteoarthritis (OA) is not well understood. The present study investigated the mechanism of miR-335-5P in the pathogenesis of OA. To investigate the effect of miR-335-5P on the pathogenesis of OA in vitro , a miR-335-5P mimic and inhibitor were transfected into chondrocytes. Cell Counting kit-8 assay and flow cytometry were used to observe the effects of miR-335-5P on chondrocyte apoptosis and the expression of cartilage-specific genes, such as aggrecan, collagen II, matrix metalloproteinase 13 and collagen X, were detected by reverse transcription-quantitative PCR and western blot analysis. Moreover, the current study assessed whether HMG-box transcription factor 1 (HBP1) is a novel target of miR-335-5P with dual luciferase reporter assays. Finally, a rescue experiment was used to prove the regulation between miR-335-5P and HBP1. The results revealed that HBP1 was a novel target of miR-335-5P, and that miR-335-5P mediated the apoptosis of chondrocytes and changes in cartilage-specific genes via targeting HBP1. Overall, the present study revealed that miR-335-5P mediated the development of OA by targeting the HBP1 gene and promoting chondrocyte apoptosis. These data suggested that miR-335-5P may be used to develop novel early-stage diagnostic and therapeutic strategies for OA., (Copyright: © Lu et al.)

This study evaluated the outcomes of distal tibia metaphyseal fractures (DTMFs) managed surgically and compared the outcomes of patients with and without associated fibula fracture fixation. Thirty-two consecutive patients (14 males; mean age at the time of injury: 7.8 years) with closed displaced DTMFs, with (22 patients; group A) or without associated fibula fractures fixation (10 patients; group B), were included. Besides standard radiographic measurements, the following static and dynamic pedobarographic parameters were evaluated: foot total static plantar pressure percentage (PP%), static plantar pressure percentage of the forefoot (PP%) and of the rear foot (PP%), landing sequence of the metatarsals during contact with the ground (MT), and impulse percentage of the metatarsal heads (MT%) and the medial and lateral heel (MH% and LH%). All patients were followed for at least 2 years (range: 2-4.5 years). Functional outcomes were excellent to good in all but two patients (93.8%) at the last follow-up visit using the Johner-Wruths criteria'. Radiographic measurements, PP%, PP%, PP%, MT%, MH% and LH% were not significantly different between two groups as well as between injured and uninjured side of patients within the same group (P > 0.05). Abnormal MT sequence was found in 40.9% of group A (9/22) and in 40% of group B patients (4/10) (P > 0.05). Stabilization of associated fibula fractures did not significantly impact the clinical, radiographic and pedobarographic outcomes of the children with displaced DTMFs who were surgically treated. Level of evidence: Level III.

The Pavlik harness and the Tübingen hip flexion splint (Tübingen hip flexion splint) are two effective options for the early management of patients younger than 6 months of age with developmental dysplasia of the hip (DDH). The main objective of this study was to evaluate the clinical and radiological outcomes of patients younger than 6 months of age with type IIb to IV DDH managed by Pavlik harness or Tübingen hip flexion splint. The Pavlik harness and Tübingen hip flexion splint groups were comparable regarding the affected side (P = 0.09), Graf grade (P = 0.635), and age at initial treatment (P = 0.77). Overall, failure rates were 12 and 33% in Pavlik harness (4/33 hips) and Tübingen hip flexion splint groups (14/43 hips), respectively (P = 0.038). No cases of avascular necrosis (AVN) were found in either group. In the Tübingen hip flexion splint group, the failure rate was significantly higher in bilateral cases (66.6%; P = 0.004), in severe forms (Graf grade IV hips; P ≤ 0.0001), and in patients with lower age at initial treatment (67.7 ± 39.3 days; P = 0.005). The average follow-up time was 30.35 ± 3.58 months (range: 24-36). At the last follow-up visit, no statistically significant differences were found between the Pavlik harness and Tübingen hip flexion splint groups regarding the acetabular index (t = 0.632; P = 0.53) or center-edge angle (Z = -0.303; P = 0.762). Our study showed that both the brace treatments for DDH in children younger than 6 months of age were effective and well tolerated. However, Tübingen hip flexion splint should not be used in patients with severe forms of DDH (Graf grade IV hips).

Background & Objectives: Obesity, hyperlipidaemia and hypercholesterolaemia are known risk factors in the pathogenesis of hypertension. Squalene has been shown to reduce serum cholesterol and triglycerides in dogs although its therapeutic use in high BP and obese patients has not been established. This study evaluates the effect of feeding high doses of squalene on plasma leptin, glucose, testosterone, blood pressure (BP) and body fat in rats., Methods: Wistar rats (male, 22 days old) were randomly divided into two groups receiving either regular control diet or a squalene-containing diet. After feeding squalene for 4 wk, 10 rats each from the squalene and control groups were sacrificed and blood samples were collected for measurement of leptin, cholesterol, triglycerides and testosterone. Blood pressure was monitored weekly., Results: Following squalene feeding, BP and body weight gain were lower in the squalene group. BP was significantly lower from 47 days of age in squalene fed group compared to controls. The levels of plasma leptin, glucose, cholesterol and triglycerides were significantly lower in squalene fed rats than those from the control group at 51 and 75 days of age. However, testicular weights (only 75 days) and testosterone levels were significantly higher in rats from the squalene group than those from the control group at days 51 and 75., Interpretation & Conclusion: Our results suggested that squalene may counteract the increase in body fat, BP and levels of plasma leptin, glucose, cholesterol and triglycerides. These effects of squalene may be further explored as a likely new approach for clinical management of high BP and obesity.