Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.

Core planar cell polarity genes VANGL1 and VANGL2 in predisposition to congenital vertebral malformations.

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.

"Am I different?" Coping and mental health among teenagers with adolescent idiopathic scoliosis: A qualitative study.

PURPOSE: To explore the stressors, coping strategies, and mental health of adolescents diagnosed with idiopathic scoliosis. DESIGN AND METHODS: This study adopted a descriptive qualitative study design. Twelve participants were recruited from a local non-government organization in Hong Kong. Semi-structured interviews were conducted to collect data. Verbatim transcriptions of interviews were coded and analyzed using thematic analysis. The guideline of the Consolidated Criteria for Reporting Qualitative Studies was used to report the findings. RESULTS: Five themes were identified: "Disease- and treatment-induced changes and stressors", "Cognitive assessment and personal perceptions", "Behavioral and emotional coping strategies", "Social interactions and social support", and "Deteriorating or thriving in psychological development and well-being". CONCLUSIONS: Adolescents with idiopathic scoliosis experienced a variety of physical and psychological stressors. It is imperative to prioritize efforts to promote adaptive coping and activate social support systems to achieve better outcomes in this population. PRACTICAL IMPLICATIONS: Healthcare providers should aim to comprehend the experiences of adolescents with idiopathic scoliosis for improved clinical interactions and holistic care. Future research should prioritize coping-based interventions, to enhance adaptive coping behaviors and the well-being of this population.

Can the proximal humeral ossification system (PHOS) effectively guide brace weaning in patients with adolescent idiopathic scoliosis?

PURPOSE: The proximal humeral epiphyses can be conveniently viewed in routine spine radiographs. This study aimed to investigate whether the proximal humeral epiphyseal ossification system (PHOS) can be used to determine the timing of brace weaning in adolescent idiopathic scoliosis (AIS), as assessed by the rate of curve progression after brace weaning. METHODS: A total of 107 patients with AIS who had weaned brace-wear at Risser Stage ≥  4, no bodily growth and post-menarche ≥  2 years between 7/2014 and 2/2016 were studied. Increase in major curve Cobb angle > 5° between weaning and 2-year follow-up was considered curve progression. Skeletal maturity was assessed using the PHOS, distal radius and ulna (DRU) classification, Risser and Sanders staging. Curve progression rate per maturity grading at weaning was examined. RESULTS: After brace-wear weaning, 12.1% of the patients experienced curve progression. Curve progression rate for weaning at PHOS Stage 5 was 0% for curves < 40°, and 20.0% for curves ≥ 40°. No curve progression occurred when weaning at PHOS Stage 5 with radius grade of 10 for curves ≥ 40°. Factors associated with curve progression were: Months post-menarche (p = 0.021), weaning Cobb angle (p = 0.002), curves < 40° versus ≥ 40° (p = 0.009), radius (p = 0.006) and ulna (p = 0.025) grades, and Sanders stages (p = 0.025), but not PHOS stages (p = 0.454). CONCLUSION: PHOS can be a useful maturity indicator for brace-wear weaning in AIS, with PHOS Stage 5 having no post-weaning curve progression in curves < 40°. For large curves ≥ 40°, PHOS Stage 5 is also effective in indicating the timing of weaning together with radius grade ≥ 10.

Patient and surgical predictors of 3D correction in posterior spinal fusion: a systematic review.

BACKGROUND: Restoration of three-dimensional (3D) alignment is critical in correcting patients with adolescent idiopathic scoliosis using posterior spinal fusion (PSF). However, current studies mostly rely on 2D radiographs, resulting in inaccurate assessment of surgical correction and underlying predictive factors. While 3D reconstruction of biplanar radiographs is a reliable and accurate tool for quantifying spinal deformity, no study has reviewed the current literature on its use in evaluating surgical prognosis. PURPOSE: To summarize the current evidence on patient and surgical factors affecting sagittal alignment and curve correction after PSF based on 3D parameters derived from reconstruction of biplanar radiographs. METHODS: A comprehensive search was conducted by three independent investigators on Medline, PubMed, Web of Science, and Cochrane Library to obtain all published information on predictors of postoperative alignment and correction after PSF. Search items included "adolescent idiopathic scoliosis," "stereoradiography," "three-dimensional," "surgical," and "correction." The inclusion and exclusion criteria were carefully defined to include clinical studies. Risk of bias was assessed with the Quality in Prognostic Studies tool, and level of evidence for each predictor was rated with the Grading of Recommendations, Assessment, Development, and Evaluations approach. 989 publications were identified, with 444 unique articles subjected to full-text screening. Ultimately, 41 articles were included. RESULTS: Strong predictors of better curve correction included preoperative normokyphosis (TK > 15°), a corresponding rod contour, intraoperative vertebral rotation and translation, and upper and lower instrumented vertebrae selected based on sagittal and axial inflection points. For example, for Lenke 1 patients with junctional vertebrae above L1, fusion to NV-1 (1 level above the neutral vertebra) achieved optimal curve correction while preserving motion segments. Pre-op coronal Cobb angle and axial rotation, distal junctional kyphosis, pelvic incidence, sacral slope, and type of instrument were identified as predictors with moderate evidence. For Lenke 1C patients, > 50% LIV rotation was found to increase spontaneous lumbar curve correction. Pre-op thoracolumbar apical translation and lumbar lordosis, Ponte osteotomies, and rod material were found to be predictors with low evidence. CONCLUSIONS: Rod contouring and UIV/LIV selection should be based on preoperative 3D TK in order to achieve normal postoperative alignment. Specifically, Lenke 1 patients with high-lying rotations should be fused distally at NV-1, while hypokyphotic patients with large lumbar curves and truncal shift should be fused at NV to improve lumbar alignment. Lenke 1C curves should be corrected using > 50% LIV rotation counterclockwise to the lumbar rotation. Further investigation should compare surgical correction between pedicle-screw and hybrid constructs using matched cohorts. DJK and overbending rods are potential predictors of postoperative alignment.

Impact of mental health components on the development of back pain in young adults with adolescent idiopathic scoliosis.

BACKGROUND: Back pain occurs commonly in adults and is multifactorial in nature. This study aimed to assess the prevalence and intensity of back pain during young adulthood in subjects with adolescent idiopathic scoliosis (AIS), as well as factors that may be associated with its prognosis. METHODS: Subjects with AIS aged 20-39 treated conservatively were included in this study. Patient-reported outcome measures in adulthood involved episodes of back pain, and scales of self-image, depression, anxiety, and stress. Additionally, pain, self-image, and mental health scores were retrieved at the first clinic consultation. Occurrence of back pain was defined as a numeric pain rating scale ≥ 6. RESULTS: 101 participants were enrolled. The prevalence of back pain in the lifetime, past 12 months, past 6 months, past 1 month, past 7 days, and past 24 h were 37%, 35%, 31%, 27%, 23%, and 20%, respectively. Male, self-image, and depression were significant associated factors for the development of back pain at all time points. Furthermore, the analyses of the initial presentation of participants have shown that participants with back pain in adulthood were characterised by poor self-image and mental health during their adolescence. CONCLUSION: The present study addressed the natural history of back pain in young adults with conservatively treated AIS. Psychological makeup has been shown to constitute the development of back pain and is strongly hinted as an early sign of having back pain in adulthood among subjects with AIS.

Is impaired lung function related to spinal deformities in patients with adolescent idiopathic scoliosis? A systematic review and meta-analysis-SOSORT 2019 award paper.

PURPOSE: Some teenagers with adolescent idiopathic scoliosis (AIS) display compromised lung function. However, the evidence regarding the relations between pulmonary impairments and various spinal deformity parameters in these patients remains unclear, which affects clinical management. This systematic review and meta-analysis aimed to summarize the associations between various lung function parameters and radiographic features in teenagers with AIS. METHODS: A search of PubMed, Embase, PEDro, SPORTDiscus, CINAHL, Cochrane Library, and PsycINFO (from inception to March 14, 2022) without language restriction. Original studies reporting the associations between lung function and spinal deformity in patients with AIS were selected. Independent reviewers extracted data and evaluated the methodological quality of the included studies according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pearson correlation and 95% confidence intervals were calculated using random-effects meta-analysis. RESULTS: Twenty-seven studies involving 3162 participants were included. Limited-quality evidence supported that several spinal parameters were significantly related to lung function parameters (e.g., absolute value and percent of the predicted forced vital capacity (FVC; %FVC), forced expiratory volume in one second (FEV1; %FEV1), and total lung capacity (TLC; %TLC)) in AIS patients. Specifically, meta-analyses showed that main thoracic Cobb angles in the coronal plane were significantly and negatively related to FVC (r = - 0.245), %FVC (r = - 0.302), FEV1 (r = - 0.232), %FEV1 (r = - 0.348), FEV1/FVC ratio (r = - 0.166), TLC (r = - 0.302), %TLC (r = - 0.183), and percent predicted vital capacity (r = - 0.272) (p < 0.001). Similarly, thoracic apical vertebral rotation was negatively associated with %FVC (r = - 0.215) and %TLC (r = - 0.126) (p < 0.05). Conversely, thoracic kyphosis angles were positively related to %FVC (r = 0.180) and %FEV1 (r = 0.193) (p < 0.05). CONCLUSION: Larger thoracic Cobb angles, greater apical vertebral rotation angle, or hypokyphosis were significantly associated with greater pulmonary impairments in patients with AIS, although the evidence was limited. From a clinical perspective, the results highlight the importance of minimizing the three-dimensional spinal deformity in preserving lung function in these patients. More research is warranted to confirm these results.

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.

Clinical effectiveness of reduction and fusion versus in situ fusion in the management of degenerative lumbar spondylolisthesis: a systematic review and meta-analysis.

PURPOSE: To compare the clinical effectiveness of reduction and fusion with in situ fusion in the management of patients with degenerative lumbar spondylolisthesis (DLS). METHODS: The systematic review was conducted following the PRISMA guidelines. Relevant studies were identified from PubMed, Embase, Scopus, Cochrane Library, ClinicalTrials.gov, and Google Scholar. The inclusion criteria were: (1) comparative studies of reduction and fusion versus in situ fusion for DLS patients, (2) outcomes reported as VAS/NRS, ODI, JOA score, operating time, blood loss, complication rate, fusion rate, or reoperation rate, (3) randomized controlled trials and observational studies published in English from the inception of the databases to January 2023. The exclusion criteria included: (1) reviews, case series, case reports, letters, and conference reports, (2) in vitro biomechanical studies and computational modeling studies, (3) no report on study outcomes. The risk of bias 2 (RoB2) tool and the Newcastle-Ottawa scale was conducted to assess the risk of bias of RCTs and observational studies, respectively. RESULTS: Five studies with a total of 704 patients were included (375 reduction and fusion, 329 in situ fusion). Operating time was significantly longer in the reduction and fusion group compared to in situ fusion group (weighted mean difference 7.20; 95% confidence interval 0.19, 14.21; P = 0.04). No additional significant intergroup differences were noted in terms of other outcomes analyzed. CONCLUSION: While the reduction and fusion group demonstrated a statistically longer operating time compared to the in situ fusion group, the clinical significance of this difference was minimal. The findings suggest no substantial superiority of lumbar fusion with reduction over without reduction for the management of DLS.

A solitary osteolytic lesion with pathological fracture in the cervical spine - a case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder. The treatment options vary depending on how many organs are involved and how extensive the disease is. In this report, a case of LCH with isolated 6th cervical vertebra (C6) collapse was presented. This case was treated with anterior corpectomy and instrumented fusion, followed by local radiotherapy (RT), with a good clinical outcome up to postoperative six months. CASE PRESENTATION: This was a 47-year-old female patient with a complaint of neck pain and bilateral shoulder pain for two months before consultation. She was initially treated with analgesics, but the pain was persistent. Further radiological evaluations revealed an osteolytic lesion within the C6 vertebral body with a pathological fracture. Magnetic resonance imaging (MRI) with contrast of the cervical spine revealed diffused hypointense signal changes on the T1-weighted images and hyperintense signal changes on the T2-weighted images in the C6 vertebral body, with significant contrast-enhanced infiltration signals. Furthermore, in positron emission tomography-computed tomography (PET-CT), focal hypermetabolism and abnormal uptake signals were seen only in the C6 vertebral body. The patient underwent an anterior cervical corpectomy with instrumented fusion. The histopathological results confirmed the diagnosis of LCH. The patient reported significant pain relief on postoperative day one. Moreover, she was treated by local RT at postoperative one month. Good clinical outcomes were achieved in the form of no pain and recovery in neck mobility up to postoperative six months. No evidence of recurrence was observed at the final follow-up. CONCLUSIONS: This case report describes a treatment option for a solitary C6 collapse with LCH managed by anterior corpectomy and instrumented fusion, followed by local RT, with a good clinical outcome at postoperative six months. More studies are needed to elucidate whether such a treatment strategy is superior to surgery or RT alone.

Enhancing end of life care on general internal medical wards: the 3 Wishes Project.

BACKGROUND: Initially developed in the intensive care unit (ICU) at St. Joseph's Healthcare Hamilton (SJHH) the 3 Wishes Project (3WP) provides personalized, compassionate care to dying patients and their families. The objective of this study was to develop and evaluate 3WP expansion strategies for patients cared for on General Internal Medicine (GIM) wards in our hospital. METHODS: From January 2020-November 2021, we developed a phased, multicomponent approach for program expansion. We enrolled patients on the GIM wards who had a high probability of dying in hospital, then elicited, implemented, and documented wishes for them or their families. Data were analyzed descriptively. RESULTS: From March 2020 to November 2020, we implemented staff education and engagement activities, created an Expansion Coordinator position, held strategic consultations, and offered enabling resources. From March 2020 to November 2021, we enrolled 62 patients and elicited 281 wishes (median [1st, 3rd quartiles] 4 [4, 5] wishes/patient). The most common wish categories were personalizing the environment (67 wishes, 24%), rituals and spiritual support (42 wishes, 15%), and facilitating connections (39 wishes, 14%). The median [1st, 3rd] cost/patient was $0 [0, $10.00] (range $0 to $86); 91% of wishes incurred no cost to the program. CONCLUSIONS: The formal expansion of the 3WP on GIM wards has been successful despite COVID-19 pandemic disruptions. While there is still work ahead, these data suggest that implementing the 3WP on the GIM wards is feasible and affordable. Increased engagement of the clinical team during the pandemic suggests that it is positively received.

Psychosocial interventions for teenagers with adolescent idiopathic scoliosis: A systematic literature review.

OBJECTIVES: Psychosocial interventions can improve teenagers' self-esteem, mental health and bracing compliance. There is a need to compile available evidence of psychosocial care in adolescent idiopathic scoliosis. This systematic review aimed to identify and evaluate the effects of existing interventional studies of psychosocial care for the adolescent idiopathic scoliosis population. METHODS: A comprehensive search of relevant literature published from the inception to March 2023 was conducted using nine databases. A google scholar search was performed on 1 July 2023, to update the searching results. Two reviewers independently assessed the methodological quality and extracted details of the included studies. Given the heterogeneity of the selected articles, the findings were synthesized narratively without conducting a meta-analysis. RESULTS: Four randomized controlled trials reported in six articles involving 385 teenagers were included. The interventions appeared acceptable with high recruitment rates and low dropout rates reported. Psychosocial interventions had shown significant positive effects on postoperative pain, engagement in daily and social activities as well as brace use, coping abilities and anxiety. CONCLUSION: Psychosocial interventions are generally feasible and acceptable among the adolescent idiopathic scoliosis population and have produced positive effects on a variety of physical and psychosocial outcomes. Study findings need to be interpreted with caution due to the limited number of available articles and the methodological concerns of the reviewed articles. PRACTICAL IMPLICATIONS: Well-designed clinical trials are warranted in people from cultural backgrounds to develop and implement effective psychosocial interventions for teenagers with adolescent idiopathic scoliosis, not only for those at the post-surgery stage but also for those receiving conservative treatment.

Learning-based fully automated prediction of lumbar disc degeneration progression with specified clinical parameters and preliminary validation.

BACKGROUND: Lumbar disc degeneration (LDD) may be related to aging, biomechanical and genetic factors. Despite the extensive work on understanding its etiology, there is currently no automated tool for accurate prediction of its progression. PURPOSE: We aim to establish a novel deep learning-based pipeline to predict the progression of LDD-related findings using lumbar MRIs. MATERIALS AND METHODS: We utilized our dataset with MRIs acquired from 1,343 individual participants (taken at the baseline and the 5-year follow-up timepoint), and progression assessments (the Schneiderman score, disc bulging, and Pfirrmann grading) that were labelled by spine specialists with over ten years clinical experience. Our new pipeline was realized by integrating the MRI-SegFlow and the Visual Geometry Group-Medium (VGG-M) for automated disc region detection and LDD progression prediction correspondingly. The LDD progression was quantified by comparing the Schneiderman score, disc bulging and Pfirrmann grading at the baseline and at follow-up. A fivefold cross-validation was conducted to assess the predictive performance of the new pipeline. RESULTS: Our pipeline achieved very good performances on the LDD progression prediction, with high progression prediction accuracy of the Schneiderman score (Accuracy: 90.2 ± 0.9%), disc bulging (Accuracy: 90.4% ± 1.1%), and Pfirrmann grading (Accuracy: 89.9% ± 2.1%). CONCLUSION: This is the first attempt of using deep learning to predict LDD progression on a large dataset with 5-year follow-up. Requiring no human interference, our pipeline can potentially achieve similar predictive performances in new settings with minimal efforts.

Reliability of a three-dimensional spinal proprioception assessment for patients with adolescent idiopathic scoliosis.

PURPOSE: Although it is evident that some patients with adolescent idiopathic scoliosis (AIS) have proprioceptive deficit in peripheral joints, knowledge on the proprioceptive function of the deformed spine is limited. Nonetheless, spinal proprioception in AIS may be affected three-dimensionally, prior studies only focussed on evaluating peripheral proprioception in single plane. Therefore, this study aimed to develop a novel spinal proprioception assessment using three-dimensional motion analysis in patients with AIS. METHODS: Participants were included if they had a primary diagnosis of AIS who did not receive or failed conservative treatments. Three trunk repositioning tests involving flexion-extension, lateral-flexion, and axial-rotation were conducted. A three-dimensional kinematics of the trunk was used as the outcome measures. The proprioceptive acuity was quantified by the repositioning error. The intra-examiner and test-retest reliability were analysed by the intraclass correlation coefficient (ICC). RESULTS: Fifty-nine patients with AIS were recruited. Regarding the trunk flexion-extension test, the single measure ICC showed moderate reliability (0.46) and the average measures ICC demonstrated good reliability (0.72). As for the trunk lateral-flexion test, the reliability of single measure and average measures ICC was moderate (0.44) and good (0.70) reliability, respectively. For the trunk axial-rotation test, the single measure ICC indicated fair reliability (0.32), while the average measures ICC showed moderate reliability (0.59). CONCLUSION: This is the first study to evaluate the reliability of novel three-dimensional spinal proprioception assessments in patients with AIS. The trunk flexion-extension repositioning test may be preferable clinical test given its highest reliability.

Poor Bone Quality, Multilevel Surgery, and Narrow and Tall Cages Are Associated with Intraoperative Endplate Injuries and Late-onset Cage Subsidence in Lateral Lumbar Interbody Fusion: A Systematic Review.

BACKGROUND: A major complication of lateral lumbar interbody fusion (LLIF) is cage subsidence, which may lead to clinical problems, including loss of disc height correction, altered spinal alignment, recurrent pain, and vertebral body fracture. A thorough review of the current knowledge about the risk factors for the two types of cage subsidence after LLIF-intraoperative endplate injury and late-onset cage subsidence-could bring attention to well-established risk factors for clinical consideration while identifying any incompletely characterized factors that require further research to clarify. QUESTIONS/PURPOSES: We performed a systematic review to answer the following questions: (1) Are bone quality and surrogates for bone quality, such as patient age and sex, associated with an increased likelihood of cage subsidence? (2) Are implant-related factors associated with an increased likelihood of cage subsidence? METHODS: Two independent reviewers comprehensively searched Medline, Embase, Cochrane Library, PubMed, and Web of Science from 1997 to 2020 to identify all potential risk factors for cage subsidence after LLIF. Discrepancies were settled through discussion during full-text screening. Search terms included "lateral" AND "interbody fusion" AND "subsidence" OR "settling" OR "endplate injury" OR "endplate violation" WITHOUT "cervical" OR "transforaminal" OR "biomechanical." Eligible studies were retrospective or prospective comparative studies, randomized controlled trials, and case series with sample sizes of 10 patients or more reporting risk factors for cage subsidence or endplate injury after LLIF. Studies that involved cervical interbody fusions and biomechanical and cadaveric experiments were excluded. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the studies' quality of evidence. The initial database review found 400 articles. Thirty-four articles with moderate- to very-low-quality evidence met the inclusion criteria for analysis. A total of 3233 patients (58% [1860] of whom were female) were included in this review. Two types of cage subsidence were reviewed: late-onset cage subsidence, which occurs gradually postoperatively, and intraoperative endplate injury, which is derived from iatrogenic endplate violation during endplate preparation or cage insertion. Among 20 studies with moderate quality of evidence according to the GRADE criteria, eight studies reported risk factors for cage subsidence related to bone mineral density and its surrogates and 12 studies focused on risk factors regarding implant factors, including cage dimension, cage material, construct length, and supplementary instrumentation. RESULTS: Patients with a dual x-ray absorptiometry T-score of -1.0 or less, age older than 65 years, and female sex were considered to have a high risk of both types of cage subsidence. Regarding cage size, cage width ≥ 22 mm helped to avoid late-onset cage subsidence, and cage height ≤ 11 mm was recommended by some studies to avoid intraoperative endplate injuries. Studies recommended that multilevel LLIF should be conducted with extra caution because of a high risk of losing the effect of indirect decompression. Studies found that standalone LLIF might be sufficient for patients without osteoporosis or obesity, and supplementary instrumentation should be considered to maintain the postoperative disc height and prevent subsidence progression in patients with multiple risk factors. The effect of the bone graft, cage material, endplate condition, and supplementary instrumentation on cage subsidence remained vague or controversial. CONCLUSION: Patients with poor bone density, patients who are older than 65 years, and female patients should be counseled about their high risk of developing cage subsidence. Surgeons should avoid narrow cages when performing LLIF to minimize the risk of late-onset cage subsidence, while being cautious of an aggressive attempt to restore disc height with a tall cage as it may lead to intraoperative endplate injury. For multilevel constructs, direct decompression approaches, such as posterior and transforaminal LIF, should be considered before LLIF, since the effect of indirect decompression may be difficult to maintain in multilevel LLIF because of high risks of cage subsidence. The effect of the cage material and supplementary instrumentation require stronger evidence from prospectively designed studies with larger sample size that randomly assign patients to polyetheretherketone (PEEK) or titanium cages and different fixation types. Future research on intraoperative endplate injuries should focus on the specific timing of when endplate violation occurs with the help of intraoperative imaging so that attempts can be made to minimize its occurrence. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Contribution of coronal vertebral and IVD wedging to Cobb angle changes in adolescent idiopathic scoliosis during growth.

STUDY DESIGN: Prospective study BACKGROUND: Vertebral and intervertebral disc (IVD) wedging are often seen in patients with adolescent idiopathic scoliosis (AIS). However, the relationship between wedging and curve progression, and the change of wedging before bracing to final weaning is unknown. The aim of this study was to investigate the pattern and sequence of vertebral and IVD wedging development, and to determine the relationship between the change of wedging and curve progression in AIS during growth. METHODS: This was a prospective study of 32 AIS females with right-sided thoracic curves and/or left-sided lumbar curves who completed brace treatment. They were classified into progression and non-progression groups. Vertebral and IVD wedging were calculated for each spinal segment. The wedging pattern was first identified and then used to determine the sequence of wedging development. Percentage change in the sum of wedging during growth was calculated and compared. RESULTS: The sum of vertebral wedging for both groups was 2.4° to 8.7° more than that of IVD wedging in the thoracic spine but 8.7° to 17.7° less in the lumbar spine. Out of the 20 curves assessed, 5 thoracic curves and 1 lumbar curve developed vertebral wedging before IVD wedging, and 3 thoracic curves and 4 lumbar curves had the opposite pattern. The progression group had larger increases in sum of vertebral (40%) and IVD (28.6%) wedging as compared to the non-progression group (both 16.7%). A significant difference in wedging between the first and the latest visits was found in the progression group only (p < 0.05). CONCLUSION: Pattern and sequence of vertebral and IVD wedging were related to the location of the curve rather than the presence of curve progression. Progressed curves were associated with increased wedging during growth. LEVEL OF EVIDENCE: II.

Predictive factors for successful non-operative treatment and achieving MCID improvement in health-related quality of life in adult spinal deformity.

BACKGROUND: Adult spinal deformity is a spectrum of degenerative spinal diseases with increasing prevalence and healthcare burden worldwide. Identification of patients who are more likely to improve through conservative management may reduce cost and potentially prevent surgery and its associated costs and complications. This study aims to identify predictive factors for MCID in improvement of ODI and SRS-22r questionnaires in patients with adult spinal deformity treated with conservative treatment. METHODS: A prospective, observational cohort study of 46 patients was conducted at a spine specialist clinic. Inclusion criteria were 30-80 years of age, diagnosis of neglected adolescent idiopathic scoliosis, de-novo scoliosis, degenerative spondylolisthesis, and sagittal plane deformities (thoracic hypokyphosis, lumbar hypolordosis), presenting with mechanical back pain with or without radicular leg pain. All patients received conservative management including medication and physiotherapy. Radiological and clinical parameters were measured at baseline and at 1-year follow-up. Primary outcomes were ODI and SRS-22r scores. Secondary outcomes were EQ-5D-5L scores and requiring spine surgery during conservative treatment. Predictors for MCID improvement in ODI and SRS-22r were identified using multivariate regressions and receiver operating characteristic (ROC) analyses. RESULTS: At baseline, patients who reached MCID in ODI and/or SRS-22r showed less comorbidities (diabetes mellitus, hypertension, ischemic heart disease, osteoarthritis, cancer), smaller range of lateral spinal flexion, larger trunk shift, larger pelvic incidence, a higher EQ-5D-5L anxiety/depression dimension score, a lower SRS-22r total score, and presence of spondylolisthesis. Lateral flexion range < 25 degrees, trunk shift > 14 mm, pelvic incidence > 50 degrees, EQ-5D-5L anxiety/depression dimension score > 1, and SRS-22r total score < 3.5 were the cut-off values generated by ROC analysis. CONCLUSIONS: Both radiological and clinical predictive factors for MCID improvement in health-related quality of life were identified. Future research should identify subgroups of patients who are responsive to specific conservative treatment modalities, so as to provide information for personalized medicine. LEVEL OF EVIDENCE: II.

Longitudinal comparison of direct medical cost, radiological and health-related quality of life treatment outcomes between traditional growing rods and magnetically controlled growing rods from preoperative to maturity.

BACKGROUND: Magnetically controlled growing rods (MCGR) have replaced traditional growing rods (TGR) in the past decade, however, a comparison of their direct costs and treatment outcomes based on real longitudinal data is lacking. This study aims to compare the direct cost and treatment outcomes between TGR and MCGR, whilst incorporating complications, reoperations and changes in health-related quality of life (HRQoL) throughout the entire treatment course. METHODS: Patients with early onset scoliosis (EOS) who underwent initial growing rod surgery between 2003 and 2016 at a tertiary scoliosis clinic were studied with longitudinal data. Accumulated direct medical costs were calculated based on the unit cost of surgeries of each TGR and MCGR, costs incurred for any rod exchange or remedial surgery for post-operative complication. Treatment outcomes were evaluated via: Patient's HRQoL using SRS-22r questionnaire, and radiological parameters (including major curve correction, spine length gains, spinal balance) throughout the treatment until maturity. RESULTS: A total of 27 EOS patients (16 MCGR, 11 TGR) were studied. Total direct cost of index surgery for MCGR was HKD$223,108 versus lower cost of HKD$135,184 for TGR (p < 0.001). At 2-3 years post-index surgery, accumulative total direct medical cost of MCGR and TGR became most comparable (TGR:MCGR ratio = 1.010) and had reached neutrality between the two groups since. Radiological parameters had no intergroup differences at maturity. For HRQoL, TGR group had shown the trend of less pain (domain score mean difference: 0.53, p = 0.024) post-index surgery and better self-appearance (domain score mean difference: 1.08, p = 0.017) before fusion. Higher satisfaction with treatment (domain score mean difference: 0.76, p = 0.029) was demonstrated by TGR patients at fusion/maturity. MCGR had negative (rs = -0.693) versus TGR's positive (rs = 0.989) correlations (p < 0.05) of cost and SRS-22r total scores at 2-3 years post-index surgery. CONCLUSIONS: From index surgery to maturity, TGR demonstrated better satisfaction with treatment by patients and comparable overall HRQoL with MCGR during the treatment course, as MCGR did not show apparent benefit despite less surgeries and cost neutrality between the two groups at 2-3 years post-index surgery.

A pilot study on the validity and psychometric properties of the electronic EQ-5D-5L in routine clinical practice.

BACKGROUND: Electronic measurement of health-related quality of life (HRQOL) may facilitate timely and regular assessments in routine clinical practice. This study evaluated the validity and psychometric properties of an electronic version of the EQ-5D-5L (e-EQ-5D-5L) in Chinese patients with chronic knee and/or back problems. METHODS: 151 Chinese subjects completed an electronic version of the Chinese (Hong Kong) EQ-5D-5L when they attended a primary care or orthopedics specialist out-patient clinic in Hong Kong. They also completed the Chinese Western Ontario and McMaster University Osteoarthritis Index (WOMAC), a Pain Rating Scale, and a structured questionnaire on socio-demographics, co-morbidities and health service utilization. 32 subjects repeated the e-EQ-5D-5L two weeks after the baseline. 102 subjects completed e-EQ-5D-5L and 99 completed the Global Rating on Change Scale at three-month clinic follow up. Construct validity was assessed by the association of EQ-5D-5L scores with external criterion of WOMAC scores. We tested mean differences of WOMAC scores between adjacent response levels of the EQ-5D-5L dimensions by one-way ANOVA, test-retest reliability by intra-class correlation, sensitivity by known group comparisons and responsiveness by changes in EQ-5D-5L scores over 3 months. RESULTS: There was an association between EQ-5D-5L and WOMAC scores. Mean WOMAC scores increased with the increase in adjacent response levels of EQ-5D-5L dimensions. Test-retest intraclass correlation coefficient (ICC) of EQ-5D-5L utility and EQ-VAS scores were 0.76 and 0.83, respectively, indicating good reliability. There were significant differences in the proportions reporting limitations in the EQ-5D-5L dimensions, the utility and VAS scores between the mild and severe pain groups (utility = 0.28, p = 0.001; VAS = 11.46, p < 0.001), and between primary care and specialist out-patient clinic patients (utility = 0.15, p = 0.001; VAS = 10.21, p < 0.001), supporting sensitivity. Among those reporting 'better' global health at three-months, their EQ-5D-5L utility and EQ-VAS scores were significantly increased from baseline (utility = 0.18, p < 0.001; VAS = 10.75, p = 0.005). CONCLUSIONS: The electronic version of the EQ-5D-5L is valid, reliable, sensitive and responsive in the measurement of HRQOL in Chinese patients with chronic knee or back pain in routine clinical practice.