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View my account settingsWe previously reported that osteoblasts at the curve apex in adolescent idiopathic scoliosis (AIS) exhibit a differential phenotype, compared to non-curve osteoblasts(1). However, the Hueter-Volkmann principle on vertebral body growth in spinal deformities (2) suggests this could be secondary to altered biomechanics. This study examined whether non-curve osteoblasts subjected to mechanical strain resemble the transcriptomic phenotype of curve apex osteoblasts.
Facet spinal tissue was collected perioperatively from three sites, (i) the concave and (ii) convex side at the curve apex and (iii) from outside the curve (non-curve) from six AIS female patients (age 13–18 years; NRES 19/WM/0083). Non-curve osteoblasts were subjected to strain using a 4-point bending device. Osteoblast phenotype was determined by RNA sequencing and bioinformatic pathway analysis.
RNAseq revealed that curve apex osteoblasts exhibited a differential transcriptome, with 1014 and 1301 differentially expressed genes (DEGs; p<0.05, fold-change >1.5) between convex/non-curve and concave/non-curve sites respectively. Non-curve osteoblasts subjected to strain showed increased protein expression of the mechanoresponsive biomarkers COX2 and C-Fos. Comparing unstimulated vs strain-induced non-curve osteoblasts, 423 DEGs were identified (p<0.05, fold-change >1.5). Of these DEGs, only 5% and 6% were common to the DEGs found at either side of the curve apex, compared to non-curve cells. Bioinformatic analysis of these strain-induced DEGs revealed a different array of canonical signalling pathways and cellular processes, to those significantly affected in cells at the curve apex.
Mechanical strain of AIS osteoblasts in vitro did not induce the differential transcriptomic phenotype of AIS osteoblasts at the curve apex.
A Core Outcome Set (COS) for treatment of adolescent idiopathic scoliosis (AIS) is essential to ensure that the most meaningful outcomes are evaluated and used consistently. Measuring the same outcomes ensures evidence from clinical trials and routine clinical practice of different treatments can be more easily compared and combined, therefore increasing the quality of the evidence base. The SPINE-COS-AYA project aims to develop a gold standard COS which can be used internationally in research and routine clinical practice to evaluate the treatment (surgical and bracing) of AIS.
In this qualitative study, the views of adolescents and young adults with AIS (10-25 years of age), their family members and healthcare professionals in a UK region were sought, via interviews, on treatment outcomes. Participants were purposively recruited from a variety of sources including NHS outpatient clinics and social media. Semi-structured interviews were analysed using thematic analysis.
Key findings will be presented, to include potential core outcome domains identified by the different subgroups.
The core outcome domains identified in this research programme will subsequently form part of an international consensus survey to agree a COS. In future, if the COS is used by healthcare staff and researchers, it will be easier for everyone, including patients and their families, to assess which treatment works best.
The lordosis distribution index (LDI) describes distribution of lumbar lordosis, measured as the % of lower lumbar lordosis (L4-S1) compared to global lordosis (L1-S1) with normal value 50–50%. Maldistributed LDI is associated with higher revision in short lumbar fusions, 4 vertebrae1. We hypothesise maldistributed LDI is also associated with mechanical failure in longer fusions.
Retrospective review of 29 consecutive ASD patients, aged 55+, undergoing long lumbar fusion, 4 levels, with >3-years follow-up. LDI, pelvic incidence (PI) and sagittal vertical axis (SVA) were measured on pre- and post-op whole spine standing X-rays (Fig A and B). Patients were categorized according to their pelvic incidence (PI) and postoperative LDI: Normal (LDI 50 80), Hypolordotic (LDI < 50), or Hyperlordotic (LDI > 80) and assessed for failure rate compared to normal LDI and PI <60.
Mean follow-up 4.5 years. 19 patients had mechanical failures including junctional failure and metalware fracture. PI >60o was associated with higher mechanical failure rates (Chi^2 p<0.05). Hypolordotic LDI was associated with 82% mechanical failure (Chi^2 p<0.001), Hyperlordotic 88% mechanical failure (Chi^2 p<0.001) and Normal 8% mechanical failure (Table 1).
Maldistributed LDI, whether Hyperlordotic or Hypolordotic, correlated with 10× greater mechanical failure rate compared to Normal LDI in long fusions. LDI is a useful measurement that should be considered, especially in high PI patients.
There is a need for non-radiographic, objective outcome measures for children with Adolescent Idiopathic Scoliosis (AIS). Standing balance and stability is altered in children with AIS. The Margin of Stability (MoS) has been used to compare gait stability in clinical populations. Our objective was to compare the MoS in anterior-posterior (MoSAP) and mediolateral (MoSML) directions in girls with AIS to Controls.
Girls with AIS and healthy girls walked at three speeds on an instrumented treadmill wearing retroreflective markers, surrounded by motion capture cameras. The MoSAP/ML was calculated at left and right heel strike. Data was processed in Visual 3D. A two-way ANOVA was used to compare MoSAP/ML between group, speed and the interaction between group and speed. Pearson's correlation coefficient was used to compare the MoS to Cobb angle. Statistical significance was accepted when
A priori power analysis suggested 12 participants per group. Three Cases and four Controls were recruited. Girls with AIS all had right-sided main thoracic curves (Lenke type 1a, 61.3° ± 10.0°). MoSAP was significantly bigger for Cases compared to Controls on the left (
Girls with Lenke type 1a AIS are more stable in the AP direction and less stable in the ML direction than Controls during treadmill walking. AP stability increases and ML stability decreases with increasing Cobb angle. This research suggests that the MoS could be used as an outcome measure for children with AIS. Continued work is required to increase the power of this study. Further work could consider these changes during walking overground, measuring an MoS or MoS-like measure using a wearable device, and in different curve types.
Thermal sensors have been used in bracing research as self-reported diaries are inaccurate. Little is known about new low-profile sensors, optimal location within a brace, locational thermal micro-climate and effect of brace lining. Our objective is to Determine an optimal temperature threshold for sensor-measured and true wear time agreement. Identify optimal sensor location. Assess all factors to determine the best sensor option for the Bracing AdoleScent Idiopathic Scoliosis (BASIS) multicentre RCT.
Seven Orthotimer and five iButton (DS1925L) sensors were synchronised to record temperature at five-minute intervals. Three healthy participants donned a rigid spinal brace, embedded with both sensors across four anatomical locations (abdomen/axilla/lateral-gluteal/sacral). Universal-coordinated-time wear protocols were performed in/out-doors. Intraclass correlation coefficient (ICC) assessed sensor-measured and true wear time agreement at thresholds 15–36oC.
Optimal thresholds, determined by largest ICC estimate: Orthotimer: Abdomen=26oC, axilla=27oC, lateral-gluteal=24.5oC, sacral=22.5oC. iButton: Abdomen=26oC, axilla=27oC, lateral-gluteal=23.5oC, sacral=23.5oC. Warm-up time and error at optimal thresholds increased for moulded sensors covered with 6mm lining.
Location: anterior abdominal wall. Excellent reliability and higher optimal thresholds, less likely to be exceeded by ambient temperature; not a pressure area. Sensor: iButton, longer battery life and larger memory than Orthotimer; allows recording at 10 min intervals for life of brace. Orthotimer only able to record every 30 mins, increasing error between true and measured wear time; Orthotimer needs 6-monthly data download. Threshold: 26oC is optimal threshold to balance warm-up and cool-down times for accurately measuring wear time. Sensor should not be covered by lining foam as this significantly prolongs warm-up time.
Children undergoing posterior spinal fusion (PSF) for neuromuscular and syndromic scoliosis were admitted to the paediatric intensive care (PIC) until about 6 years ago, at which time we created a new unit, a hospital floor-based spinal high-dependency unit-plus (SHDU-plus), in response to frequent bed-shortage cancellations. This study compares postoperative management on PIC with HDU-plus for these non-hospital floor suitable children with syndromic and neuromuscular scoliosis undergoing PSF.
Retrospective review of 100 consecutive children with syndromic and neuromuscular scoliosis undergoing PSF between June 2016 and January 2022. Inclusion criteria were: 1) diagnosis of syndromic or neuromuscular scoliosis, 2) underwent PSF, 3) not suitable for immediate postoperative hospital floor-based care. Exclusion criteria were children with significant cardio-respiratory co-morbidity requiring PIC postoperatively.
55 patients were managed postoperatively on PIC and 45 on SHDU-plus. No significant difference between groups was found with respect to age, weight, ASA grade, preoperative Cobb angles, operative duration, number of levels fused and estimated blood loss. 4 patients in the PIC group and 1 in the SHDU-plus group were readmitted back to PIC or HDU following step-down to the hospital floor. Average length of stay was 2 days on PIC and 1 day on SHDU-plus. Average total length of hospital stay was 16.5 days in the PIC group and 10.5 days in the HDU-plus group. 19 (35%) patients developed complications in the PIC group, compared to 18 (40%) in SHDU-plus. Mean specialist unit charge per day was less on SHDU-plus compared with PIC. There were no bed-shortage cancellations in the SHDU-plus group, compared to 11 in the PIC group.
For children with neuromuscular or syndromic scoliosis undergoing PSF and deemed not suitable for post-operative care on the hospital floor, creation of a SHDU-plus was associated with fewer readmissions back to PIC or HDU, shorter hospital stays, an equivalent complication rate, significant cost-saving and fewer cancellations. Level of Evidence: Therapeutic Level III.
The aim of this study is to clarify the implication of ciliary pathway on the onset of the spinal curvature that occurs in Adolescent Idiopathic Scoliosis (AIS) patients through functional studies of two genes: POC5 and TTLL11. Since the genetic implication for AIS is accepted, many association and candidate gene analysis revealed the implication of ciliary genes.
The characterisation of these two proteins was assessed by qPCR, WB and immunofluorescence in vitro using control cells and cells derived from AIS patients. The impact of genetic modification of these genes on the functionality of the proteins in vitro and in vivo was analysed in zebrafish model created by CRISPR/Cas9 using microCT and histologic analysis.
Our study revealed that mutant cells, for both gene, were less ciliated and the primary cilia was significantly shorter compared to control cells. We also observed a default in cilia glutamylation by immunofluorescence and Western Blot. Moreover, we observed in both zebrafish model, a 3D spine curvature similar to the spinal deformation in AIS. Interestingly, our preliminary results of immunohistology showed a retinal defect, especially at the cone cell layer level.
This study strongly supports the implication of the ciliary pathway in the onset of AIS and this is the first time that a mechanism is described for AIS. Indeed, we show that shorter cilia could be less sensitive to environmental factors due to lower glutamylation and result in altered signalling pathway. Identifying the biological mechanism involved is crucial for elucidating AIS pathogenesis.
Surgical site infections following spinal surgery profoundly influence continued treatment, significantly impacting psychological and economic dimensions and clinical outcomes. Its reported incidence varies up to 20%, with the highest incidence amongst neuromuscular scoliosis and metastatic cord compression patients.
We describe the first reported biphasic osteoconductive scaffold (Cerament G) with a logarithmic elution profile as a cumulative strategic treatment modality for adjacent spinal surgery infections.
All patients who developed surgical site infections following instrumented fusion (May 2021-December 2021) had their demographics (age, sex), type and number of procedures, isolated organism, antibiotics given, comorbidities, and WHO performance status analysed.
The infected wound was debrided to healthy planes, samples taken, and Cerament g applied.
Thirteen patients were treated for deep SSI following spinal instrumentation and fusion procedures with intraoperative Cerament G application. There were four males and nine females with an average age of 40 ranging between 12 and 87. Nine patients underwent initial surgery for spinal deformity, and four were treated for fractures as index procedure.
77% of infections were attributable to MSSA and Cutibacteriousm acnes; others included Klebsiella, Pseudomonas and Streptococcus and targeted with multimodal cumulative therapy. A WHO performance score improved in 11 patients. In addition, there was no wound leak, and infection was eradicated successfully in 12/13 with a single procedure.
This series shows the successful eradication of the infection and improved functional outcomes with Cerament G. However, the low numbers of patients in our series are an essential consideration for the broader applicability of this device.
Less invasive single-rod fusion technique may be indicated in the management of NMS to minimise operative time, blood loss and wound-related complications. This retrospective 12-year cohort study (2008–2020) aims to evaluate and compare the outcomes of this technique to the current standard dual rod technique to determine their safety and efficacy.
28 patients in the single rod group (Mean age = 16.4 [SD ±4.0]) and 30 in the double rod group (Mean age = 16.3 [SD±3.5]). Indications included a minimum 2 year follow period, detailed information on the type of implant and a complete pre- and post-operative imaging and medical records. Baseline demographics, comorbidities, and surgical characteristics were collected. Outcomes assessed included the immediate post-op and final follow up angles and general complications. All outcome analysis was performed using a regression approach.
Angles at final follow-up: lumbar (Difference ratio (DR)= 2.60 [95% CI 0.37 – 18.4], p=0.25), thoracic (DR= 1.08 [95% CI 0.19 – 6.28], p=0.92), thoracolumbar (major curve angle) (DR 1.35 [95% CI 0.60 – 3.06], p=0.46) and kyphosis (DR = 0.97 [0.66, 1.42] p=0.86). There was no statistically significant difference, between the two groups, for any of the above angle outcomes as well as for length of surgery, blood loss and complication outcomes.
Both single and double rod instrumentation achieves satisfactory and safe deformity correction which is maintained at final follow up. A larger scale study is warranted to further assess these techniques while also conducting a cost-benefit analysis between them.