Handgrip strength assessment at baseline in addition to bone parameters could potentially predict the risk of curve progression in adolescent idiopathic scoliosis

IntroductionAdolescent idiopathic scoliosis (AIS) is characterized by deranged bone and muscle qualities, which are important prognostic factors for curve progression. This retrospective case–control study aims to investigate whether the baseline muscle parameters, in addition to the bone parameters, could predict curve progression in AIS.MethodsThe study included a cohort of 126 female patients diagnosed with AIS who were between the ages of 12 and 14 years old at their initial clinical visit. These patients were longitudinally followed up every 6 months (average 4.08 years) until they reached skeletal maturity. The records of these patients were thoroughly reviewed as part of the study. The participants were categorized into two sub-groups: the progressive AIS group (increase in Cobb angle of ≥6°) and the stable AIS group (increase in Cobb angle <6°). Clinical and radiological assessments were conducted on each group.ResultsCobb angle increase of ≥6° was observed in 44 AIS patients (34.9%) prior to skeletal maturity. A progressive AIS was associated with decreased skeletal maturity and weight, lower trunk lean mass (5.7%, p = 0.027) and arm lean mass (8.9%, p < 0.050), weaker dominant handgrip strength (8.8%, p = 0.027), deranged cortical compartment [lower volumetric bone mineral density (vBMD) by 6.5%, p = 0.002], and lower bone mechanical properties [stiffness and estimated failure load lowered by 13.2% (p = 0.005) and 12.5% (p = 0.004)]. The best cut-off threshold of maximum dominant handgrip strength is 19.75 kg for distinguishing progressive AIS from stable AIS (75% sensitivity and 52.4% specificity, p = 0.011).DiscussionPatients with progressive AIS had poorer muscle and bone parameters than patients with stable AIS. The implementation of a cut-off threshold in the baseline dominant handgrip strength could potentially be used as an additional predictor, in addition to bone parameters, for identifying individuals with AIS who are at higher risk of experiencing curve progression

Global sagittal alignment after surgery of right thoracic idiopathic scoliosis in adolescents and adults with and without thoracic hypokyphosis

The study procedure was conducted in accordance to guidelines approved by the institutional clinical research ethics committee (CREC No. 2016.722) and the Declaration of Helsinki. Written informed consent was obtained from all subjects and their parents before participating in this study.AbstractThis study aimed to characterize global sagittal alignment in adolescent idiopathic scoliosis (AIS) with normal kyphosis (NTK, kyphosis > 10°) and with thoracic hypokyphosis (THK, kyphosis < 10°), before and after posterior spinal fusion, and compare them with asymptomatic controls. 27 AIS girls and young adults with right thoracic curves were included (seventeen with age ≤ 18 years, then age > 21). Biplanar radiographies were acquired at baseline, immediate post-operatively, 1-year and 2-year follow-up, and 3D reconstruction of the spine and pelvis was performed. NTK and THK showed different global sagittal alignment, as well as differences compared to controls. AIS with THK at baseline had higher SVA/SFD (2.0 ± 2.9 vs − 0.4 ± 1.9; P < 0.05) and OD-HA (0.2 ± 1.4° vs − 1.3 ± 1.6°; P < 0.05) than controls, indicating that THK had compensated balance with unusual forward leaning posture. Immediately post-operation, SVA/SFD remained high (1.3 ± 3.0) while OD-HA reversed (− 1.2 ± 1.7°), indicating that THK patients had found partially compensated balance. After 2-yeas, both SVA/SFD (− 1.3 ± 2.1) and OD-HA (− 1.4 ± 0.9°) were normalized. The changes in global sagittal alignment and mechanism of balance are different in AIS with or without THK. As the head plays a critical role on balance during immediate and delayed post-operation, OD-HA can be complementary parameter for assessing global balance during post-operative follow-up of AIS patients with THK.The investigation was fully supported by a grant from the General Research Funding of Hong Kong (Project no. 14206716) (W.C.W.C.), and a funding from the BiomecAM Chair Program on Musculoskeletal Modeling (with the support of Société Générale, Covea, Yves Cotrel Foundation, ParisTech Foundation and Proteor) (C.V.)

Genetic insight into the putative causal proteins and druggable targets of osteoporosis: a large-scale proteome-wide mendelian randomization study

Background: Osteoporosis is a major causative factor of the global burden of disease and disability, characterized by low bone mineral density (BMD) and high risks of fracture. We aimed to identify putative causal proteins and druggable targets of osteoporosis.Methods: This study utilized the largest GWAS summary statistics on plasma proteins and estimated heel BMD (eBMD) to identify causal proteins of osteoporosis by mendelian randomization (MR) analysis. Different GWAS datasets were used to validate the results. Multiple sensitivity analyses were conducted to evaluate the robustness of primary MR findings. We have also performed an enrichment analysis for the identified causal proteins and evaluated their druggability.Results: After Bonferroni correction, 67 proteins were identified to be causally associated with estimated BMD (eBMD) (p < 4 × 10−5). We further replicated 38 of the 67 proteins to be associated with total body BMD, lumbar spine BMD, femoral neck BMD as well as fractures, such as RSPO3, IDUA, SMOC2, and LRP4. The findings were supported by sensitivity analyses. Enrichment analysis identified multiple Gene Ontology items, including collagen-containing extracellular matrix (GO:0062023, p = 1.6 × 10−10), collagen binding (GO:0005518, p = 8.6 × 10−5), and extracellular matrix structural constituent (GO:0005201, p = 2.7 × 10−5).Conclusion: The study identified novel putative causal proteins for osteoporosis which may serve as potential early screening biomarkers and druggable targets. Furthermore, the role of plasma proteins involved in collagen binding and extracellular matrix in the development of osteoporosis was highlighted. Further studies are warranted to validate our findings and investigate the underlying mechanism

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Soft tissue release and osteotomies in the treatment of patients with spastic diplegic cerebral palsy

We aim to study the outcome of soft tissue releases by tendon elongations and osteotomies in fixed joint contractures by clinical examination and patient self-reported assessment on 20 patients (14 males and 6 females) with spastic diplegic cerebral palsy treated with single-event multilevel surgery (SEMLS) between 2000 and 2012. A questionnaire was used to collect information on problems encountered before and after surgery and decision on surgery. Comparing patients with Gross Motor Function Classification System class I/II, (N = 8), III (N = 8) and IV/V , patients of classes IV/V showed much slower mean recovery time than I/II group (14.00 vs. 4.38 months, p < 0.01). SEMLS in the treatment of patients with spastic diplegia had good mid-term results in most patients. The patients who had unfavourable outcomes are associated with mental retardation, general or local complications and previous selective dorsal rhizotomy surgery. Patient selection and good rehabilitations preoperation and postoperation provided the most favourable outcomes of SEMLS. 中 文 摘 要: 我們的目的是通過臨床檢查和患者自我報告，評估20例（男14例，女6例）痙攣型雙癱性腦癱患者在2000年至2012年之間進行單次多層手術治療（SEMLS），研究以肌腱延長和截骨術等軟組織鬆解治療固定關節攣縮弛的結果。使用問卷收集手術前後遇到的問題以及手術決定的信息。比較粗大運動功能分類系統運GMFCS I / II級（N = 8）、III（N = 8）和IV / V組患者的平均恢復時間比I / II組慢（14.00比4.38個月，p <0.01）。 SEMLS治療痙攣型雙癱性腦癱在大多數患者中有良好的中期療效。不良後果的患者與弱智、全身或局部並發症以及先前選擇性背側神經根切斷術相關。患者選擇、手術前後的良好康復提供了SEMLS最有利的結果。 Keywords: osteotomy, cerebral palsy, single-event multi-level surger

Twelve-year follow-up of a case of proximal femoral Unicameral Bone Cyst (UBC) treated by steroid injection using radiological and DXA scan data

This report is of a proximal femoral unicameral bone cyst in a patient presented at 3 years. Intra-lesional steroid injection was used to treat this large active lesion. The response to treatment was monitored with the use of dual-energy X-ray absorptiometry (DXA) scan as an indirect method of monitoring the activity of the bone cyst. The patient had developed stress fracture during the course of treatment which had remodelled fully after successful treatment with multiple injections; at 12-year follow-up, the patient reached skeletal maturity. The affected femur had remodelled back to normal radiological appearance without avascular necrosis. This has demonstrated that steroid injection is a safe and effective procedure to achieve regression of a large active bone cyst in the proximal femur. It is a minimal invasive procedure resulting in no scar. DXA scan is a useful method combining clinical assessment to monitor status of the bone cyst to allow timing of injection. 中文摘要: 本報告為3歲患者的股骨近端骨囊腫，以用病灶內類固醇注射來治療這個巨大的活性病灶。 使用雙能X射線吸收測定法 (DXA) 掃描作為間接方法監測骨囊腫活性對治療的反應。 患者在治療過程中出現了應力性骨折，經多次注射成功治療後已完全改型，隨訪12年，患者達到骨骼成熟。 受影響的股骨已經重新恢復正常的放射學外觀及沒有缺血性壞死。 這證明了類固醇注射是一種安全有效的方法，以實現股骨近端巨大活躍骨囊腫的消退。 這是微創手術，沒有疤痕。 DXA掃描結合臨床評估以監測骨囊腫狀態是有效的方法以允許注射時機。 Keywords: DXA, steroid injection, Unicameral Bone Cys

Towards in silico prognosis using big data

Clinical diagnosis and prognosis usually rely on few or even single measurements despite clinical big data being available. This limits the exploration of complex diseases such as adolescent idiopathic scoliosis (AIS) where the associated low bone mass remains unexplained. Observed low physical activity and increased RANKL/OPG, however, both indicate a mechanobiological cause. To deepen disease understanding, we propose an in silico prognosis approach using clinical big data, i.e. medical images, serum markers, questionnaires and live style data from mobile monitoring devices and explore the role of inadequate physical activity in a first AIS prototype. It employs a cellular automaton (CA) to represent the medical image, micro-finite element analysis to calculate loading, and a Boolean network to integrate the other biomarkers. Medical images of the distal tibia, physical activity scores, and vitamin D and PTH levels were integrated as measured clinically while the time development of bone density and RANKL/OPG was observed. Simulation of an AIS patient with normal physical activity and patient-specific vitamin D and PTH levels showed minor changes in bone density whereas the simulation of the same AIS patient but with reduced physical activity led to low density. Both showed unchanged RANKL/OPG and considerable cortical resorption. We conclude that our integrative in silico approach allows to account for a variety of clinical big data to study complex diseases