Meta-analysis of pre-clinical studies of early decompression in acute spinal cord injury:a battle of time and pressure

The use of early decompression in the management of acute spinal cord injury (SCI) remains contentious despite many pre-clinical studies demonstrating benefits and a small number of supportive clinical studies. Although the pre-clinical literature favours the concept of early decompression, translation is hindered by uncertainties regarding overall treatment efficacy and timing of decompression.We performed meta-analysis to examine the pre-clinical literature on acute decompression of the injured spinal cord. Three databases were utilised; PubMed, ISI Web of Science and Embase. Our inclusion criteria consisted of (i) the reporting of efficacy of decompression at various time intervals (ii) number of animals and (iii) the mean outcome and variance in each group. Random effects meta-analysis was used and the impact of study design characteristics assessed with meta-regression.Overall, decompression improved behavioural outcome by 35.1% (95%CI 27.4-42.8; I(2)=94%, p<0.001). Measures to minimise bias were not routinely reported with blinding associated with a smaller but still significant benefit. Publication bias likely also contributed to an overestimation of efficacy. Meta-regression demonstrated a number of factors affecting outcome, notably compressive pressure and duration (adjusted r(2)=0.204, p<0.002), with increased pressure and longer durations of compression associated with smaller treatment effects. Plotting the compressive pressure against the duration of compression resulting in paraplegia in individual studies revealed a power law relationship; high compressive forces quickly resulted in paraplegia, while low compressive forces accompanying canal narrowing resulted in paresis over many hours.These data suggest early decompression improves neurobehavioural deficits in animal models of SCI. Although much of the literature had limited internal validity, benefit was maintained across high quality studies. The close relationship of compressive pressure to the rate of development of severe neurological injury suggests that pressure local to the site of injury might be a useful parameter determining the urgency of decompression

Translational considerations in injectable cell-based therapeutics for neurological applications: concepts, progress and challenges

Significant progress has been made during the past decade towards the clinical adoption of cell-based therapeutics. However, existing cell-delivery approaches have shown limited success, with numerous studies showing fewer than 5% of injected cells persisting at the site of injection within days of transplantation. Although consideration is being increasingly given to clinical trial design, little emphasis has been given to tools and protocols used to administer cells. The different behaviours of various cell types, dosing accuracy, precise delivery, and cell retention and viability post-injection are some of the obstacles facing clinical translation. For efficient injectable cell transplantation, accurate characterisation of cellular health post-injection and the development of standardised administration protocols are required. This review provides an overview of the challenges facing effective delivery of cell therapies, examines key studies that have been carried out to investigate injectable cell delivery, and outlines opportunities for translating these findings into more effective cell-therapy interventions

Adolescent idiopathic scoliosis: current perspectives

Firoz MiyanjiBritish Columbia Children&#39;s Hospital, Vancouver, BC, CanadaAbstract: Adolescent idiopathic scoliosis (AIS) remains a common and potentially severe musculoskeletal disorder. Although its etiology is largely unknown, ongoing research endeavors continue to improve our understanding of its potential origin and its natural history. Advances in understanding its true three-dimensional nature have sought to improve classification and management strategies. This review will attempt to highlight and give an overview of the current concepts in adolescent idiopathic scoliosis.Keywords: AIS, current, natural history, management strategie

Minimally invasive surgery for adolescent idiopathic scoliosis: correction of deformity and peri-operative morbidity in 70 consecutive patients.

The aim of this study was to report a retrospective, consecutive series of patients with adolescent idiopathic scoliosis (AIS) who were treated with posterior minimally invasive surgery (MIS) with a mean follow-up of two years (sd 1.4; 0.9 to 0 3.7). Our objectives were to measure the correction of the deformity and record the peri-operative morbidity. Special attention was paid to the operating time (ORT), estimated blood loss (EBL), length of stay (LOS) and further complications. We prospectively collected the data of 70 consecutive patients with AIS treated with MIS using three incisions and a muscle-splitting approach by a single surgeon between June 2013 and February 2016 and these were retrospectively reviewed. There were eight male and 62 female patients with a mean age of 15 years (sd 4.5 ) with a mean body mass index of 19.8 kg/m2 (sd 5.4). The curves were classified according to Lenke; 40 curves were type 1, 15 were type 2, three were type 3, two were type 4, eight were type 5 and two were type 6. The mean primary Cobb angle was corrected from 58.9° (sd 12.6°) pre-operatively to 17.7° (sd 10.2°) post-operatively with a mean correction of 69% (sd 20%, p &lt; 0.001). The mean kyphosis at T5 to T12 increased from 24.2° (sd 12.2°) pre-operatively to 30.1° (sd 9.6°, p &lt; 0.001) post-operatively. Peri-operative (30 days) complications occurred in three patients(4.2%): one subcutaneous haematoma, one deep venous thrombosis and one pulmonary complication. Five additional complications occurred in five patients (7.1%): one superficial wound infection, one suture granuloma and three delayed deep surgical site infections. The mean ORT was 337.1 mins (sd 121.3); the mean EBL was 345.7 ml (sd 175.1) and the mean LOS was 4.6 days (sd 0.8). The use of MIS for patients with AIS results in a significant correction of spinal deformity in both the frontal and sagittal planes, with a low EBL and a short LOS. The rate of peri-operative complications compares well with that following a routine open technique. The longer term safety and benefit of MIS in these patients needs to be evaluated with further follow-up of a larger cohort of patients. Cite this article: Bone Joint J 2017;99-B:1651-7