Progenitor-like cells contributing to cellular heterogeneity in the nucleus pulposus are lost in intervertebral disc degeneration.

The nucleus pulposus (NP) in the intervertebral disc (IVD) arises from embryonic notochord. Loss of notochordal-like cells in humans correlates with onset of IVD degeneration, suggesting that they are critical for healthy NP homeostasis and function. Comparative transcriptomic analyses identified expression of progenitor-associated genes (GREM1, KRT18, and TAGLN) in the young mouse and non-degenerated human NP, with TAGLN expression reducing with aging. Lineage tracing using Tagln-CreERt2 mice identified peripherally located proliferative NP (PeriNP) cells in developing and postnatal NP that provide a continuous supply of cells to the entire NP. PeriNP cells were diminished in aged mice and absent in puncture-induced degenerated discs. Single-cell transcriptomes of postnatal Tagln-CreERt2 IVD cells indicate enrichment for TGF-ß signaling in Tagln descendant NP sub-populations. Notochord-specific removal of TGF-ß/BMP mediator Smad4 results in loss of Tagln+ cells and abnormal NP morphologies. We propose Tagln+ PeriNP cells are potential progenitors crucial for NP homeostasis.

Nusinersen Initiation After Onset of Weakness Does Not Prevent Progression of Hip Instability.

BACKGROUND: We report changes in the natural history of hip instability with nusinersen treatment among patients with spinal muscular atrophy (SMA) type II after onset of weakness, historically wheelchair-bound but now potentially ambulatory in the era of disease-modifying therapy. METHODS: Patients with genetically confirmed diagnoses of SMA type II who received intrathecal nusinersen from January 1, 2018, to June 30, 2022, were screened for inclusion. Patients with less than 6 months of follow-up, or prior hip surgeries were excluded. Primary clinical outcome measures included scores from Hammersmith motor functional scale expanded (HMFSE), revised upper limb module (RULM), 6-minute walk test (6MWT), and ambulatory status. Radiographic outcomes, including Reimer migration index, the presence of scoliosis, and pelvic obliquity, were also assessed. Secondary outcomes involved comparisons with a historical cohort of SMA type II patients treated at our institution who never received nusinersen. RESULTS: Twenty hips from 5 boys and 5 girls were included in the analysis, with a mean follow-up of 3 years and 8 months. The median age at time of nusinersen initiation was 6.8 years old, ranging between 2.5 and 10.3 years. All patients developed lower limb motor weakness before nusinersen initiation. After treatment with nusinersen, 1 previously stable hip (5%) developed subluxation, 15 hips (75%) remain subluxated, 3 hips (15%) remain dislocated, and 1 hip (5%) remained stable, with a statistically significant difference between the pretreatment and posttreatment groups (P<0.01). Six patients (60%) were ambulatory at latest follow-up. Six patients (60%) had improved ambulatory ability; 2 had static ambulatory ability (20%); and 2 had deterioration in their walking ability. The median HFMSE score improved from 18.5 (range 0 to 46) to 22 (range 0 to 49) (P=0.813), whereas the median RULM score improved from 17 (range 2 to 28) to 21.5 (range 5 to 37), which was statistically significant (P=0.007). CONCLUSIONS: Hip instability persists despite treatment with nusinersen among patients with SMA type II who received nusinersen after onset of lower limb weakness. LEVEL OF EVIDENCE: Therapeutic Level IV.

Suppression of apoptosis impairs phalangeal joint formation in the pathogenesis of brachydactyly type A1.

Apoptosis occurs during development when a separation of tissues is needed. Synovial joint formation is initiated at the presumptive site (interzone) within a cartilage anlagen, with changes in cellular differentiation leading to cavitation and tissue separation. Apoptosis has been detected in phalangeal joints during development, but its role and regulation have not been defined. Here, we use a mouse model of brachydactyly type A1 (BDA1) with an IhhE95K mutation, to show that a missing middle phalangeal bone is due to the failure of the developing joint to cavitate, associated with reduced apoptosis, and a joint is not formed. We showed an intricate relationship between IHH and interacting partners, CDON and GAS1, in the interzone that regulates apoptosis. We propose a model in which CDON/GAS1 may act as dependence receptors in this context. Normally, the IHH level is low at the center of the interzone, enabling the "ligand-free" CDON/GAS1 to activate cell death for cavitation. In BDA1, a high concentration of IHH suppresses apoptosis. Our findings provided new insights into the role of IHH and CDON in joint formation, with relevance to hedgehog signaling in developmental biology and diseases.

Elasticity and cross-sectional thickness of paraspinal muscles in progressive adolescent idiopathic scoliosis.

Objectives: (1) Compare the cross-sectional thickness (CST) and shear wave speed (SWS) of paraspinal muscles (PSM) in adolescent idiopathic scoliosis (AIS) with and without curve progression; (2) investigate the relationship between CST/SWS and radiographic characteristics in AIS with curve progression; (3) compare the CST/SWS between AIS and non-scoliosis controls. Methods: This cross-sectional study analyzed the CST and SWS of PSM in 48 AIS with mild to moderate curvature and 24 non-scoliosis participants. Participants with scoliosis greater than 45° of Cobb angles were excluded. The Change of Cobb angles within the last 6-months was retrieved to allocate AIS into progression and non-progression groups. The SWS and CST of multifidus; longissimus and iliocostalis of the major curve were measured using B-mode ultrasound image with an elastography mode. Discrepancies of the SWS (SWS-ratio: SWS on the convex side divided by SWS on the concave side) and CST (CST-ratio: CST on the convex side divided by CST on the concave side) at the upper/lower end and apical vertebrae were studied. Results: A higher SWS at the apical vertebrae on the concave side of the major curve (multifidus: 3.9 ± 1.0 m/s vs. 3.1 ± 0.6 m/s; p < 0.01, longissimus: 3.3 ± 1.0 m/s vs. 3.0 ± 0.9 m/s; p < 0.01, iliocostalis: 2.8 ± 1.0 m/s vs. 2.5 ± 0.8 m/s; p < 0.01) was observed in AIS with curve progression. A lower SWS-ratio at apical vertebrae was detected with a greater vertebral rotation in participants with curve progression (multifidus [grade II]: 0.7 ± 0.1 vs. grade I: 0.9 ± 0.2; p = 0.03, longissimus [grade II]: 0.8 ± 0.2 vs. grade I: 1.1 ± 0.2; p < 0.01). CST was not different among the progressive, non-progressive AIS and non-scoliosis controls. Conclusions: Increased SWS of PSM without change of CST was observed on the concave side of the major curve in participants with progressive AIS.

Virtual reality-based surgical planning simulator for tumorous resection in FreeForm Modeling: an illustrative case of clinical teaching.

The importance of virtual reality (VR) has been emphasized by many medical studies, yet it has been relatively under-applied to surgical operation. This study characterized how VR has been applied in clinical education and evaluated its tutorial utility by designing a surgical model of tumorous resection as a simulator for preoperative planning and medical tutorial. A 36-year-old male patient with a femoral tumor who was admitted to the Affiliated Jiangmen Traditional Chinese Medicine Hospital was randomly selected and scanned by computed tomography (CT). The data in digital imaging and communications in medicine (*.DICOM) format were imported into Mimics to reconstruct a femoral model, and were generated to the format of *.stl executing in the computer-aided design (CAD) software SenSable FreeForm Modeling (SFM). A bony tumor was simulated by adding clay to the femur, the procedure of tumorous resection was virtually performed with a toolkit called Phantom, and its bony defect was filled with virtual cement. A 3D workspace was created to enable the individual multimodality manipulation, and a virtual operation of tumorous excision was successfully carried out with indefinitely repeated running. The precise delineation of surgical margins was shown to be achieved with expert proficiency and inexperienced hands among 43 of 50 participants. This simulative educator presented an imitation of high definition, those trained by VR models achieved a higher success rate of 86% than the rate of 74% achieved by those trained by conventional methods. This tumorous resection was repeatably handled by SFM, including the establishment of surgical strategy, whereby participants felt that respondent force feedback was beneficial to surgical teaching programs, enabling engagement of learning experiences by immersive events which mimic real-world circumstances to reinforce didactic and clinical concepts.

Scoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patients.

BACKGROUND: Scoliosis is widely prevalent among osteogenesis imperfecta (OI) patients, and is progressive with age. However, factors affecting scoliosis in OI are not well known. METHODS: We retrospectively retrieved longitudinal radiographic and clinical records of consecutive OI patients seeking treatments at our hospital from 2014 to 2022, graded their pre-operative spinal conditions into four outcome groups, estimated their progression rates, and descriptively and inferentially analyzed the genetic and non-genetic factors that may affect the outcomes and progression rates. RESULTS: In all, 290 OI patients met the inclusion criteria, where 221 had genetic records. Of these 221, about 2/3 had mutations in COL1A1 or COL1A2, followed by mutations in WNT1 (9.0%), IFITM5 (9.0%) and other OI risk genes. With an average age of 12.0 years (interquartile range [IQR] 6.9-16.1), 70.7% of the cohort had scoliosis (Cobb angle > 10°), including 106 (36.5%) mild (10°-25°), 40 (13.8%) moderate (25°-50°), and 59 (20.3%) severe (> 50°) scoliosis patients. Patients with either COL1A1 and COL1A2 were strongly biased toward having mild or no scoliosis, whereas patients with mutations in IFITM5, WNT1 and other recessive genes were more evenly distributed among the four outcome grades. Lower-limb discrepancy, bone mineral density (BMD) and age of first drug used were all significantly correlated with severity outcomes. Using multivariate logistic regression, we estimated that each year older adds an odds ratio of 1.13 (95% confidence interval [CI] 1.07-1.2) in progression into advanced stages of scoliosis. We estimated a cohort-wide progression rate of 2.7 degrees per year (95% CI 2.4-3.0). Early-onset patients experienced fast progressions during both infantile and adolescent stages. Twenty-five of the 59 (42.8%) patients with severe scoliosis underwent spinal surgeries, enjoying an average Cobb angle reduction of 33° (IQR 23-40) postoperatively. CONCLUSION: The severity and progression of scoliosis in osteogenesis imperfecta were affected by genetic factors including genotypes and mutation types, and non-genetic factors including age and BMD. As compared with COL1A1, mutations in COL1A2 were less damaging while those on IFITM5 and other recessive genes conferred damaging effects. Progression rates were the fastest in the adolescent adult age-group.

Electromyographic Discrepancy in Paravertebral Muscle Activity Predicts Early Curve Progression of Untreated Adolescent Idiopathic Scoliosis.

STUDY DESIGN: This study adopted a prospective cohort study design. PURPOSE: This study aimed to examine electromyogram (EMG) discrepancy in paravertebral muscle activity and scoliosis progression, determine how vertebral morphology and EMG discrepancy evolve during scoliosis progression, and identify differences in EMG activity between individuals with and without adolescent idiopathic scoliosis (AIS). OVERVIEW OF LITERATURE: Higher EMG activity is observed in the convex side of scoliotic curves, but not in populations without scoliosis, suggesting that higher EMG activity is a causative factor for curve progression. METHODS: In this study, 267 matched pairs of AIS and controls were recruited. The participants underwent EMG measurements at their first presentation and did not receive any treatment for 6 months at which point they underwent EMG and radiographs. Early curve progression was defined as >5° in Cobb angle at 6 months. The root mean square of the EMG (rms-EMG) signal was recorded with the participants in sitting and back extension. The rms-EMG ratio at the upper end vertebrae, apical vertebrae (AV), and lower end vertebrae (LEV) of the major curve was calculated. RESULTS: The rms-EMG ratio in the scoliosis cohort was high compared with that in the controls (sitting: 1.2±0.3 vs. 1.0±0.1, p<0.01; back extension: 1.1±0.2 vs. 1.0±0.1, p<0.01). An AV rms-EMG ratio in back extension, with a cutoff threshold of ≥1.5 in the major thoracic curve and ≥1.3 in the major lumbar curve, was a risk factor for early curve progression after 6 months without treatment (odds ratio, 4.1; 95% confidence interval, 2.8-5.9; p<0.01). Increases in side deviation (SD) (distance between the AV and the central sacral line) were related to a higher rms-EMG ratio in LEV of the major thoracic curve (baseline: rs=0.2, p=0.03; 6 months: rs=0.3, p<0.01). CONCLUSIONS: An EMG discrepancy was detected in the scoliosis cohort, which was related to increases in SD in the major thoracic curve. The AV rms-EMG ratio in back extension was correlated with curve progression after 6 months of no treatment.

Virtual operation for hip joint replacement implemented by Sensable_FreeForm_Modelling: A surgical drill.

OBJECTIVE: To design a virtual operation of joint replacement for surgical drills using a haptic device, SenSable_FreeForm_Modelling (SFM), to enhance surgeons' efficiency and enable "Virtual tutorial without reality" for interns. METHOD: A patient with hip joint osteoarthritis is randomly selected to perform Total Hip Replacement (THR). The hip images were input into Mimics in the format of *.dicom after CT scan and then exported to SFM using the stereolithographic (*.stl) format. A surgical toolkit can be created virtually with Computer Aided Design software such as Pro-E or Ghost SDK and a visual drill scenario of THR directed by a force-respondent stick, namely Phantom. RESULT: 3D models of the hip joint were rebuilt illustrating clearly that the geometrical shapes of the surgical equipment created are similar to real instruments, and the THR operation is emulated distinctly in novelty. CONCLUSION: In obedience to an ancient maxim, so called 'genuine knowledge originated from practice', this simulative operation offers hands-on experience for students in the orthopaedics field with remarkable effects, contributing not only teaching cases for medical courses but also a planning basis for physical surgery.

Assessment of reliability and validity of a handheld surface spine scanner for measuring trunk rotation in adolescent idiopathic scoliosis.

PURPOSE: To assess the reliability and validity of a handheld scanner (SpineScan3D) for trunk rotation measurement in adolescent idiopathic scoliosis (AIS) subjects, as compared with Scoliometer. METHODS: This was a cross-sectional study with AIS subjects recruited. Biplanar spine radiographs were performed using an EOS imaging system with coronal Cobb angle (CCA) determined. The angle of trunk rotation (ATR) was measured using Scoliometer. SpineScan3D was employed to assess the axial rotation of subjects' back at forward bending, recorded as surface tilt angle (STA). Intra- and inter-examiner repeats were conducted to evaluate the reliability of SpineScan3D. RESULTS: 97 AIS patients were recruited. Intra- and inter-examiner reliability of STA measures were good to excellent in major thoracic and lumbar curves (p < 0.001). A strong correlation was found between STA and ATR measures in both curve types (p < 0.001) with a standard error of the ATR estimate of between 1 and 2 degrees from linear regression models (R squared: 0.8-0.9, p < 0.001). A similar correlation with CCA was found for STA and ATR measures (r: 0.5-0.6, p < 0.002), which also demonstrated a similar sensitivity (72%-74%) and specificity (62%-77%) for diagnosing moderate to severe curves. CONCLUSION: SpineScan3D is a handheld surface scanner with a potential of wide applications in subjects with AIS. The current study indicated that SpineScan3D is reliable and valid for measuring trunk rotation in AIS subjects, comparable to Scoliometer. Further studies are planned to investigate its measurements in coronal and sagittal planes and the potential of this device as a screening and monitoring tool. TRIAL REGISTRATION NUMBER (DATE OF REGISTRATION): HKUCTR-2288 (06 Dec 2017). LEVEL OF EVIDENCE: Level III.

Absence of TRIC-B from type XIV Osteogenesis Imperfecta osteoblasts alters cell adhesion and mitochondrial function - A multi-omics study.

Osteogenesis Imperfecta (OI) is a heritable collagen-related bone dysplasia characterized by bone fractures, growth deficiency and skeletal deformity. Type XIV OI is a recessive OI form caused by null mutations in TMEM38B, which encodes the ER membrane intracellular cation channel TRIC-B. Previously, we showed that absence of TMEM38B alters calcium flux in the ER of OI patient osteoblasts and fibroblasts, which further disrupts collagen synthesis and secretion. How the absence of TMEM38B affects osteoblast function is still poorly understood. Here we further investigated the role of TMEM38B in human osteoblast differentiation and mineralization. TMEM38B-null osteoblasts showed altered expression of osteoblast marker genes and decreased mineralization. RNA-Seq analysis revealed that cell-cell adhesion was one of the most downregulated pathways in TMEM38B-null osteoblasts, with further validation by real-time PCR and Western blot. Gap and tight junction proteins were also decreased by TRIC-B absence, both in patient osteoblasts and in calvarial osteoblasts of Tmem38b-null mice. Disrupted cell adhesion decreased mutant cell proliferation and cell cycle progression. An important novel finding was that TMEM38B-null osteoblasts had elongated mitochondria with altered fusion and fission markers, MFN2 and DRP1. In addition, TMEM38B-null osteoblasts exhibited a significant increase in superoxide production in mitochondria, further supporting mitochondrial dysfunction. Together these results emphasize the novel role of TMEM38B/TRIC-B in osteoblast differentiation, affecting cell-cell adhesion processes, gap and tight junction, proliferation, cell cycle, and mitochondrial function.

Application of silver nanoparticles for improving motor recovery after spinal cord injury via reduction of pro-inflammatory M1 macrophages.

Silver nanoparticles (AgNPs) possess anti-inflammatory activities and have been widely deployed for promoting tissue repair. Here we explored the efficacy of AgNPs on functional recovery after spinal cord injury (SCI). Our data indicated that, in a SCI rat model, local AgNPs delivery could significantly recover locomotor function and exert neuroprotection through reducing of pro-inflammatory M1 survival. Furthermore, in comparison with Raw 264.7-derived M0 and M2, a higher level of AgNPs uptake and more pronounced cytotoxicity were detected in M1. RNA-seq analysis revealed the apoptotic genes in M1 were upregulated by AgNPs, whereas in M0 and M2, pro-apoptotic genes were downregulated and PI3k-Akt pathway signaling pathway was upregulated. Moreover, AgNPs treatment preferentially reduced cell viability of human monocyte-derived M1 comparing to M2, supporting its effect on M1 in human. Overall, our findings reveal AgNPs could suppress M1 activity and imply its therapeutic potential in promoting post-SCI motor recovery.

Can anterior vertebral body tethering provide superior range of motion outcomes compared to posterior spinal fusion in adolescent idiopathic scoliosis? A systematic review.

PURPOSE: Anterior vertebral body tethering (AVBT) was introduced as a fusionless alternative to treating adolescent idiopathic scoliosis (AIS) while preserving range of motion (ROM). This is the first systematic review to compare the ROM outcomes between AVBT and PSF in treating AIS. METHODS: We conducted a comprehensive search on PubMed, EMBASE, MEDLINE, and Cochrane Library. Inclusion criteria were patients with AIS treated with AVBT or PSF or both, and clearly defined ROM outcomes; exclusion criteria were scoliosis other than AIS, biomechanical or cadaveric studies, non-English publications, case reports, conference summaries, unpublished literature, commentaries, and reviews. Primary outcome was ROM. Secondary outcomes included Cobb angle correction, quality of life (QOL), complications, and muscle strength and endurance. RESULTS: Twelve studies were included in this review. We found moderate evidence to support that AVBT results in superior ROM outcomes than PSF while achieving comparable Cobb angle correction with low evidence. The comparison of QOL outcomes between AVBT and PSF remained inconclusive. In addition to the complications noted conventionally in PSF, AVBT could result in over-correction and distal adding-on. We also found very low evidence to support that AIS patients treated with AVBT have superior muscle strength and endurance when compared to those treated with PSF. CONCLUSIONS: AVBT provides better preservation of ROM and muscle strength postoperatively when compared with PSF, while achieving comparable curve correction. Future studies should explore the spinal growth trajectory to determine the window of opportunity for AVBT in AIS.

Fibro-Gel: An All-Aqueous Hydrogel Consisting of Microfibers with Tunable Release Profile and its Application in Wound Healing.

Injectable hydrogels are valuable tools in tissue engineering and regenerative medicine due to their unique advantages of injectability with minimal invasiveness and usability for irregularly shaped sites. However, it remains challenging to achieve scalable manufacturing together with matching physicochemical properties and on-demand drug release for a high level of control over biophysical and biomedical cues to direct endogenous cells. Here, the use of an injectable fibro-gel is demonstrated, a water-filled network of entangled hydrogel microfibers, whose physicochemical properties and drug release profiles can be tailored to overcome these shortcomings. This fibro-gel exhibits favorable in vitro biocompatibility and the capability to aid vascularization. The potential use of the fibro-gel for advancing tissue regeneration is explored with a mice excision skin model. Preliminary in vivo tests indicate that the fibro-gel promotes wound healing and new healthy tissue regeneration at a faster rate than a commercial gel. Moreover, it is demonstrated that the release of distinct drugs at different rates can further accelerate wound healing with higher efficiency, by using a two-layer fibro-gel model. The combination of injectability and tailorable properties of this fibro-gel offers a promising approach in biomedical fields such as therapeutic delivery, medical dressings, and 3D tissue scaffolds for tissue engineering.

Clinical features and molecular characterization of Chinese patients with FKBP10 variants.

BACKGROUND: Osteogenesis imperfecta (OI) is a group of rare skeletal dysplasia. Long bone deformity and scoliosis are often associated with progressively deforming types of OI. FKBP65 (encoded by FKBP10, OMIM *607063) plays a crucial role in the processing of type I procollagen. Autosomal recessive variants in FKBP10 result in type XI osteogenesis imperfecta. METHODS: Patients diagnosed with OI were recruited for a genetic test. RT-PCR and Sanger sequencing were applied to confirm the splicing defect in FKBP10 mRNA with the splice-site variant. The bone structure was characterized by Goldner's trichrome staining. Bioinformatic analyses of bulk RNA sequencing data were performed to examine the effect of the FKBP10 variant on gene expression. RESULTS: Here we reported three children from a consanguineous family harboured a homozygous splice-site variant (c.918-3C > G) in FKBP10 intron and developed long bone deformity and early onset of scoliosis. We also observed frequent long bone fractures and spinal deformity in another 3 OI patients with different FKBP10 variants. The homozygous splicing variant identified in the fifth intron of FKBP10 (c.918-3C > G) led to abnormal RNA processing and loss of FKBP65 protein and consequently resulted in aberrant collagen alignment and porous bone morphology. Analysis of transcriptomic data indicated that genes involved in protein processing and osteoblast differentiation were significantly affected in the patient-derived osteoblasts. CONCLUSION: Our study characterized the clinical features of OI patients with FKBP10 variants and revealed the pathogenesis of the c.918-3C > G variant. The molecular analyses helped to gain insight into the deleterious effects of FKBP10 variants on collagen processing and osteoblast differentiation.

Retrospective analyses of clinical features in 28 Chinese patients with type V osteogenesis imperfecta: new perspectives in an old issue.

Type V osteogenesis imperfecta (OI) is a form of OI characterized by radial head dislocation (RHD), calcification of interosseous membrane (CIM), and hyperplastic callus (HPC). In this study, we characterized the clinical features of 28 type V OI patients. We presented that dysfunctions of elbow, hip joint, and abnormal epiphyseal growth plate were associated with ectopic calcification and summarized the history of HPC progression and treatment. INTRODUCTION: The current study aims to systematically characterize the skeletal phenotypes of patients with type V OI and suggested possible surgical solutions. METHODS: A total of 28 patients were admitted for inpatient care at The Hong Kong University-Shenzhen Hospital diagnosed with type V OI (either clinically diagnosed or genetically confirmed with the IFITM5 c.-14C > T mutation). RESULTS: Prevalence of type V radiological features was comparable to previous literatures (RHD, 100%; CIM, 100%; HPC, 44%; and scoliosis, 50%). Novel skeletal phenotypes were presented including extension of coronoid process, acetabular labrum, acetabular protrusion, spontaneous autofusion of the hip, bulbous epiphysis, and popcorn calcification. Significant increase in BMD was observed in patients with bisphosphonate treatment. Twenty-five percent (3/12) of patients with preoperative use of indomethacin developed HPC postoperatively, and HPCs were absorbed in 2 young patients 2 years later. CONCLUSION: This retrospective study summarized the clinical features and highlighted the abnormalities in elbow, hip joint, and growth plate in type V OI patients. Our study contributed to a more comprehensive clinical spectrum of type V OI. We also characterized the natural progression of HPC formation and resorption in patients in different ages. The use of bisphosphonate treatment is effective in improving bone mineral density in type V OI patients, and whether indomethacin can reduce incidence of HPC formation deserves further investigation.

Percutaneous endoscopic lumbar discectomy in lumbar disc herniation with posterior ring apophysis fracture: A case report in a 15-year-old child.

RATIONALE: Lumbar disc herniation (LDH) with posterior ring apophysis fracture (PRAF) is rather rare in children, and in all age-stratified LDH patients, the incidence of RAF was 5.3% to 7.5%. Interestingly, the incidence of LDH with RAF in children (15%-32%) is several times higher than in adults, the mis-diagnosis of which may lead to delayed treatment. PATIENT CONCERNS: Here, we report a 15-year-old schoolboy who suffered from sudden low back pain and radiating pain in both lower limbs after sport activities. Symptoms persisted after 3 months of conservative treatment. Computer radiography and magnetic resonance imaging indicated central disc herniation with PRAF at L4-5. DIAGNOSIS: LDH with PRAF. INTERVENTIONS: The herniated disc and epiphyseal fragments were successfully excised by the percutaneous endoscopic lumbar discectomy minimal-invasive technique. OUTCOMES: Surgery was successful. Symptoms were immediately relieved postoperatively with a wound of only about 7.0 mm. Discharged on the next day. No perioperative complications occurred. Moreover, the imaging and clinical outcomes were also more satisfactory during the post-operative 15 months outpatient follow-up. LESSONS: Pediatric LDH with PRAF is extremely uncommon, and there is a lack of training among physicians for such cases, which may lead to delayed diagnosis and treatment. Once a diagnosis for LDH with PRAF is established, percutaneous endoscopic lumbar discectomy is a safe and effective minimally invasive treatment to be considered, and we hope that this technique can provide more assistance in the future.

SSVEP-Based Brain Computer Interface Controlled Soft Robotic Glove for Post-Stroke Hand Function Rehabilitation.

Soft robotic glove with brain computer interfaces (BCI) control has been used for post-stroke hand function rehabilitation. Motor imagery (MI) based BCI with robotic aided devices has been demonstrated as an effective neural rehabilitation tool to improve post-stroke hand function. It is necessary for a user of MI-BCI to receive a long time training, while the user usually suffers unsuccessful and unsatisfying results in the beginning. To propose another non-invasive BCI paradigm rather than MI-BCI, steady-state visually evoked potentials (SSVEP) based BCI was proposed as user intension detection to trigger the soft robotic glove for post-stroke hand function rehabilitation. Thirty post-stroke patients with impaired hand function were randomly and equally divided into three groups to receive conventional, robotic, and BCI-robotic therapy in this randomized control trial (RCT). Clinical assessment of Fugl-Meyer Motor Assessment of Upper Limb (FMA-UL), Wolf Motor Function Test (WMFT) and Modified Ashworth Scale (MAS) were performed at pre-training, post-training and three months follow-up. In comparing to other groups, The BCI-robotic group showed significant improvement after training in FMA full score (10.05 ± 8.03, p = 0.001), FMA shoulder/elbow (6.2 ± 5.94, p = 0.0004) and FMA wrist/hand (4.3 ± 2.83, p = 0.007), and WMFT (5.1 ± 5.53, p = 0.037). The improvement of FMA was significantly correlated with BCI accuracy (r = 0.714, p = 0.032). Recovery of hand function after rehabilitation of SSVEP-BCI controlled soft robotic glove showed better result than solely robotic glove rehabilitation, equivalent efficacy as results from previous reported MI-BCI robotic hand rehabilitation. It proved the feasibility of SSVEP-BCI controlled soft robotic glove in post-stroke hand function rehabilitation.

Patient-reported outcomes in a Chinese cohort of osteogenesis imperfecta unveil psycho-physical stratifications associated with clinical manifestations.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare congenital disorder of the skeletal system, inflicting debilitating physical and psychological distress on patients and caregivers. Over the decades, much effort has been channeled towards understanding molecular mechanisms and developing new treatments. It has recently become more apparent that patient-reported outcome measurements (PROM) during treatment, healing and rehabilitation are helpful in facilitating smoother communication, refining intervention strategies and achieving higher quality of life. To date, systematic analyses of PROM in OI patients remain scarce. RESULTS: Here, utilizing a PROM Information System, we report a cross-sectional and longitudinal study in a southern Chinese cohort of 90 OI patients, covering both the child and adult age-groups. In the child group where both self and parental surveys were obtained, we identified two clusters of comparable sizes showing different outlooks in physical mobility and emotional experiences. One cluster (Cluster 1) is more negative about themselves than the other (Cluster 2). A concordance of 84.7% between self and parental assessments was recorded, suggesting the stability and validity of PROM-based stratification. Clinical subtyping, deformity, leg length discrepancy, and limited joint mobility were significantly associated with this stratification, with Cluster 1 showing higher percentages of severe phenotypes than Cluster 2. Since OI is a genetic disorder, we performed genetic testing on 72 of the 90 patients, but found no obvious association between genotypes and the PROM stratification. Analyses of longitudinal data suggested that patients tended to stay in the same psychological state, in both clusters. Adult patients also showed a continuous spectrum of self-evaluation that matches their clinical manifestations. CONCLUSION: By systematically analyzing patient-reported outcomes, our study demonstrated the link between the sociopsychological wellbeing of OI patients, and their clinical manifestations, which may serve as the basis for evaluating clinical interventions and help achieve better patient-centric medical practices. The lack of genotype-PROM association may be due to the diverse mutational spectrum in OI, which warrants further investigation when a larger sample size is available.

The Relationship Between Compliance of Physiotherapeutic Scoliosis Specific Exercises and Curve Regression With Mild to Moderate Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective Case-control Study. OBJECTIVES: To determine the requisite exercise compliance (EC) of physiotherapeutic scoliosis-specific exercise (PSSE) for achieving curve regression; to analyze whether the apical translation (AT), apical wedging (AW), and apical rotation (AR) of the major curve improve with regression effect. METHODS: Between 2019 and 2021, a total of 763 patients undertook a 6-month PSSE treatment. This resulted 426 compliable and 302 uncompliable patients remained available for analysis. For compliable patients, 213 with curve regression and 213 age-/sex-matched with curve stabilization/deterioration at the 6-month, were eligible for regression analysis to detect the relationship between EC and regression effect at the 6-month; receiver operating characteristic (ROC) curve analysis and Youden's index were applied to identify the threshold of EC leading to curve regression at the 6-month. The AT, AW, and AR of the major curve were compared before and after 6-month PSSE to investigate the radiographic parameters that improved with regression effect. RESULTS: EC was correlated with regression effect (odds ratio: 19.9, 95% confidence interval: 11.3-35.0, P < .001) and the cutoff threshold of EC was 4.4 h/week for 6 months to realize such an effect. AT was improved by 47.6% with curve regression, in which 152 cases remained curve regression and no case progressed into the operative threshold at the 1.5- to 2-year. CONCLUSIONS: A 6-month PSSE protocol of 4.4 hours per week was potentially leading to curve regression in treating mild to moderate scoliosis. An improvement in AT of the major curve was observed with the regression effect.

Comprehensive risk assessments and anesthetic management for children with osteogenesis imperfecta: A retrospective review of 252 orthopedic procedures over 5 years.

BACKGROUND: Major anesthetic risks arise in orthopedic surgeries for children with osteogenesis imperfecta, a rare genetically inherited condition presenting diverse skeletal issues. AIM: We aimed to investigate anesthetic risks, including difficult airway, hypo- and hyperthermia, blood loss, and pain, in connection with patient, anesthetic, and surgical factors. METHODS: Both descriptive and inferential statistics were employed to study the anesthetic risks and their predictors. Data of 252 surgeries for 132 Chinese osteogenesis imperfecta patients aged 18 or below were retrieved from the authors' hospital between 2015 and 2019. RESULTS: Two thirds of the cohort were Sillence type IV patients, with types I, III, and V accounting for 7.6%, 14.4%, and 11.4%, respectively. Video and direct laryngoscopy were used. No case of difficult airway was identified. Due to a careful management strategy, intraoperative temperature varied on average between -0.38°C and +0.89°C from the initial temperature. Fifty-two and 18 cases of hyper- and hypothermia were encountered, respectively. The use of sevoflurane for maintenance resulted in a mean increase of +0.24°C [95% CI 0.05 ~ 0.42] in the maximum temperature. Massive blood losses (>20% of estimated total blood volume) were observed in 18.3% of the cases. Neither intraoperative temperature changes nor blood loss was found to be related to Sillence classification. Regional anesthesia techniques were applied to 72.6% of the cases. Ultrasound guidance was used per the judgment of anesthesiologists or when in case of difficult landmarks. The incidence of difficult regional anesthesia was low (4 out of 252). For postoperative analgesia, 154 neuraxial blocks (including 77 caudal and 77 lumbar epidural) and 29 peripheral nerve blocks were performed. CONCLUSION: Anesthesia for children with osteogenesis imperfecta undergoing complex orthopedic procedures was challenging. Proper anesthesia planning was essential for both intraoperative management and postoperative analgesia. Age, surgical duration, and use of sevoflurane for maintenance impacted the intraoperative temperature most, and massive blood loss was not uncommon. The risks for airway or regional anesthesia difficulties were low. Pain scores could be controlled to be ≤3 via multiple techniques.