SOX9 gene shows association with adolescent idiopathic scoliosis predisposition in Northwest Indians.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a common structural deformity of the spine affecting adolescent individuals globally. The disorder is polygenic and is accompanied by the association of various genetic loci. Genetic studies in Chinese and Japanese populations have shown the association of genetic variants of SOX9 with AIS curve severity. However, no genetic study evaluating the association of SRY-Box Transcription Factor 9 (SOX9) variants with AIS predisposition has been conducted in any Indian population. Thus, we aimed to investigate the association of the genetic variants of the SOX9 along with 0.88 Mb upstream region with AIS susceptibility in the population of Northwest India. METHODS: In total, 113 AIS cases and 500 non-AIS controls were recruited from the population of Northwest India in the study and screened for 155 genetic variants across the SOX9 gene and 0.88 Mb upstream region of the gene using Global Screening Array-24 v3.0 chip (Illumina). The statistical significance of the Bonferroni threshold was set at 0.000322. RESULT: The results showed the association of 11 newly identified variants; rs9302936, rs7210997, rs77736349, rs12940821, rs9302937, rs77447012, rs8071904, rs74898711, rs9900249, rs2430514, and rs1042667 with the AIS susceptibility in the studied population. Only one variant, rs2430514, was inversely associated with AIS in the population, while the ten variants were associated with the AIS risk. Moreover, 47 variants clustered in the gene desert region of the SOX9 gene were associated at a p-value ≤ 0.05. CONCLUSION: The present study is the first to demonstrate the association of SOX9 enhancer locus variants with AIS in any South Asian Indian population. The results are interesting as rs1042667, a 3' untranslated region (UTR) variant in the exon 3 and upstream variants of the SOX9 gene, were associated with AIS susceptibility in the Northwest Indian population. This provides evidence that the variants in the enhancer region of SOX9 might regulate its gene expression, thus leading to AIS pathology and might act as an important gene for AIS susceptibility.

A Prospective Multicenter ≥2 Years Clinical Study of the Active Apex Correction (APC) Technique in Early Onset Scoliosis (EOS) Patients.

STUDY DESIGN: prospective multicenter study. OBJECTIVES: Active apex correction (APC) is posterior tethering technique for correction of early onset scoliosis (EOS) via reverse modulation at the apex. Active apex correction has been increasingly used worldwide. This study aimed to assess short-term outcomes of multicenter study with ≥2 years of APC on spine length, curve correction, complications, unplanned surgeries, and proposed low crankshaft phenomena incidence. METHODS: Prospective multicenter study including 24 EOS patients treated by APC; involves inserting and compressing pedicle screws on convex side of apex proximal and distal to most wedged vertebra allowing apex modulation according to Hueter-Volkmann law. Excluded patients with <2 years follow-up whom APC was not primary surgery. RESULTS: Mean age 85.97 ± 32.43 months, 71% congenital scoliosis, mean follow-up 35.54 ± 12.36 months. At final follow-up, statistically significant improvement in Cobbs angle (∆ = 23.96%, P < .0001), spinal length T1-T12 (∆ = 12.83%, P < .0001), T1-L5 (∆ = 13.41%, P < .0001) but not in apical vertebral translation (AVT) albeit clinical improvement (∆ = 7.9%, P = .36) compared to preoperative measurements. Comparing immediate postoperative measurements to >2 years follow-up, statistically significant improvement in spinal length T1-T12 (∆ = 6.03%, P = .0002) and T1-L5 (∆ = 6.26%, P < .0001) but not in Cobbs angle (∆ = 4.93%, P = .3) or AVT (∆ = 14.77%, P = .25). 9 complications requiring 3 unplanned surgeries recorded in all patients including 2 broken rods, 2 adding-on and 4 screw dislodgement. CONCLUSION: Active apex correction is a novel technique that has been incorporated in several countries as treatment modality for EOS. Short-term outcomes are promising in terms of clinical improvement, complication rates and decreased need for multiple operations or unplanned surgeries.

Is the morphology of the apical pedicles influenced by apical rotation or the coronal curve magnitude in adolescent idiopathic scoliosis?: a radiographic assessment.

INTRODUCTION: Asymmetry in pedicle anatomy is most distinctly noted around the apex of the curve. The correlation of pedicle dysmorphia with apical vertebral rotation (AVR) and coronal Cobb angle (CCA) has not been studied. OBJECTIVE: To establish whether pedicle dysmorphism is linked to curve magnitude CCA and the AVR in adolescent idiopathic scoliosis (AIS). METHODOLOGY: Preoperative plain whole spine standing radiographs and non-contrast computed tomography (CT) scans of 25 AIS patients that were operated at a single centre from 2013 to 2019 were retrospectively reviewed by 3 independent co-investigators. CCA was noted on the standing radiograph, whereas the AVR was measured on the axial cuts of CT scan. Pedicle morphometric measurements were performed for apical and periapical pedicles. These included apical vertebra (when present), 2 vertebrae above (U1 and U2) and below (B1 and B2) the apex vertebra/disc. The pedicle morphometric measurements were performed on CT scans. We assessed the transverse pedicle diameter, transverse cancellous channel diameter, sagittal pedicle diameter, pedicle length and pedicle axis length. Correlation tests between various pedicle morphometric measurements, AVR and the curve magnitude (Cobb angle) was performed by the Pearson correlation test. RESULTS: The apex of the major curve was in the thoracic spine in 20 patients, thoracolumbar in three patients and in the lumbar spine in two patients. The mean Cobb angle was 61.5 ± 9.3° and the mean AVR was 28.4 ± 17.8°. A positive correlation was noted with the AVR for U1 concave pedicle length (r = 0.45, p = 0.03), pedicle axis length of the U2 concave pedicle (r = 0.6, p = 0.04), transverse pedicle diameter of the convex apical vertebrae (r = 0.82, p = 0.00009) and the convex apical transverse pedicle diameter (r = 0.80, p = 0.002). A negative correlation with the AVR was noted for U2 convex pedicle length (r = - 0.51, p = 0009), transverse cancellous channel diameter of the U2 concave pedicle (r = - 0.42, p = 0.04) and apical concave pedicle (r = - 0.78, p = 0.002) and the sagittal pedicle diameter for the convex pedicle of U2 (r = - 0.45, p = 0.03) and apex(r = - 0.59, p = 0.04). The Cobb angle did not show a significant correlation with any of the pedicle measurements at any of the levels on the convex and the concave sides. CONCLUSION: Pedicle asymmetry and dysmorphism demonstrate a morphometric association with the apical vertebral rotation than the curve magnitude. The pedicle length and the pedicle axis length increase on the concave apical and periapical region with increase in AVR. The transverse cancellous channel diameter significantly decreases on the concave apical region with the increase in AVR. The sagittal pedicle diameter decreases on the convex side with the increase in AVR.

SPINE20 recommendations 2023: One Earth, one family, one future WITHOUT spine DISABILITY.

Introduction: The purpose is to report on the fourth set of recommendations developed by SPINE20 to advocate for evidence-based spine care globally under the theme of "One Earth, One Family, One Future WITHOUT Spine DISABILITY". Research question: Not applicable. Material and methods: Recommendations were developed and refined through two modified Delphi processes with international, multi-professional panels. Results: Seven recommendations were delivered to the G20 countries calling them to:-establish, prioritize and implement accessible National Spine Care Programs to improve spine care and health outcomes.-eliminate structural barriers to accessing timely rehabilitation for spinal disorders to reduce poverty.-implement cost-effective, evidence-based practice for digital transformation in spine care, to deliver self-management and prevention, evaluate practice and measure outcomes.-monitor and reduce safety lapses in primary care including missed diagnoses of serious spine pathologies and risk factors for spinal disability and chronicity.-develop, implement and evaluate standardization processes for spine care delivery systems tailored to individual and population health needs.-ensure accessible and affordable quality care to persons with spine disorders, injuries and related disabilities throughout the lifespan.-promote and facilitate healthy lifestyle choices (including physical activity, nutrition, smoking cessation) to improve spine wellness and health. Discussion and conclusion: SPINE20 proposes that focusing on the recommendations would facilitate equitable access to health systems, affordable spine care delivered by a competent healthcare workforce, and education of persons with spine disorders, which will contribute to reducing spine disability, associated poverty, and increase productivity of the G20 nations.

Unmasking the great imitators-noninfectious conditions masquerading as spinal tuberculosis in a developing country: A single-center case series analysis.

Background: The diagnosis of spinal tuberculosis often relies on clinical, radiological, and laboratory findings, particularly in resource-constrained settings. However, numerous noninfectious conditions exhibit similar clinical and radiological features to spinal tuberculosis, leading to potential misdiagnosis in the absence of microbiological or histopathological confirmation. This study aims to present a case series from a developing country, highlighting noninfectious conditions that mimic spinal tuberculosis. Methods: A retrospective analysis was conducted on hospital records and imaging of patients diagnosed with spinal tuberculosis, lacking microbiological or histopathological evidence, and unresponsive to empirical antitubercular treatment. Patients displaying noninfectious conditions resembling spinal tuberculosis upon further investigation were included. Clinical and radiological findings of these patients were thoroughly analyzed. Results: Among a total of 23 patients observed over a 6-year period (2015-2020), various noninfectious conditions were identified as mimickers of spinal tuberculosis. These conditions included vertebral body haemangioma, ankylosing spondylitis (with or without Andersson lesion), rheumatoid pannus, osteoid osteoma, cystic hygroma, multiple myeloma, vertebral metastasis, malignant small round-cell tumor, pancreatic pseudocyst, esophageal duplication cyst, Modic changes in degenerative disc disease, Paget's disease, and psoas hematoma. Conclusion: Noninfectious spinal conditions can masquerade as spinal tuberculosis, underscoring the importance of obtaining a definitive tissue diagnosis before initiating antitubercular treatment. Particular attention should be given to features such as central lesions and the absence of soft tissue involvement in suspected cases of spinal tuberculosis, warranting a careful reconsideration of the diagnosis.

Impact of Bundled Intervention on Outcomes of Patients Undergoing Clean Orthopedic Surgeries With Hardware Implants: Small Prospective Randomized Controlled Trial.

Background: Prosthesis-related infections (PRIs) and surgical site infections (SSIs) remain one of the most devastating complications among patients undergoing clean orthopedic surgeries. Prevention strategies are critical to reduce infection rates in orthopedic surgeries. The current study aimed to determine the effectiveness of a set of evidence-based practices (bundled intervention) in reducing the incidence of PRIs and SSIs among patients undergoing clean orthopedic surgeries with hardware implants. Patients and Methods: A prospective, interventional randomized controlled trial was conducted for a period of three years. A total of 597 patients were enrolled, and depending on their Staphylococcus aureus carrier status were categorized into carrier group (n = 98) and non-carrier group (n = 499). Only carrier group patients were analyzed for effectiveness of bundled interventions, after being randomly assigned to two subgroups: interventional carrier group (ICG; n = 50) and non-interventional carrier group (NICG; n = 48). Results: Of the 597 patients, 98 (16.4%) were colonized with Staphylococcus aureus, among whom 9 (19.4%) had methicillin resistance. During follow-up, overall infection rate of 1.1% was observed (PRI, 0.3%; SSI, 0.8%). There was no case of PRI/SSI in the ICG. However, in the NICG, one patient developed SSI because of methicillin-resistant Staphylococcus aureus. An endogenous source of infection was demonstrated by pulsed field gel electrophoresis (PFGE). The SSI rate was higher in the NICG (p = 0.002). In the non-carrier group (n = 499), SSIs/PRIs occurred among 1.2% of the patients, because of organisms other than Staphylococcus aureus. Conclusions: Benefit of bundle intervention approach could be demonstrated. Further studies assessing the effectiveness of the individual components of the bundle can inform clinical practice greatly.

The Third Gender in a Third World Country: Major Concerns and the "AIIMS Initiative".

With a population dividend of around 1.3 billion, India is the largest democracy in the world that encompasses "unity in diversity". The kaleidoscope of the socio-cultural fabric comprises the transgender population too, which has a historical context dating back millennia and also plays a vital role as described in Hindu scriptures. The Indian transgender person's community shows a variety of gender identities and sexual orientations, which is unlikely from the West, forming a culturally unique gender group. In India, transgender persons were recognised as the 'third gender' in 2014. The third gender population of India is marginalised to a great extent in every sector. Often, transgender persons have been the subjects of sociology, psychology, and health issues. There was a dearth of data regarding their major health problems including bone health, which has not been reported in India and elsewhere before this study. Through a prospective cross-sectional study design, we aimed to determine the current health status of transgender persons with a special emphasis on bone health. Descriptive statistics were used for data analysis. The preliminary results of the study show poor bone health in the transgender population of India. The majority of transgender persons have low bone mineral density (BMD) at a much young age, even before the achievement of their peak bone mass. The health status of the transgender population in India is poor overall. Transgender persons have many impediments to optimal healthcare that requires holistic care. This study presents the current health challenges of the transgender population with a special emphasis on their bone health status as 'AIIMS initiative'. This study also shows transgender persons human rights needs to be explicitly discussed. The stakeholders of social policies require an urgent attention to unfold the major concerns encompassing transgender persons.

Augmenting the Angiogenic Profile and Functionality of Cord Blood Endothelial Colony-Forming Cells by Indirect Priming with Bone-Marrow-Derived Mesenchymal Stromal Cells.

Cellular therapy has shown promise as a strategy for the functional restoration of ischemic tissues through promoting vasculogenesis. Therapy with endothelial progenitor cells (EPCs) has shown encouraging results in preclinical studies, but the limited engraftment, inefficient migration, and poor survival of patrolling endothelial progenitor cells at the injured site hinder its clinical utilization. These limitations can, to some extent, be overcome by co-culturing EPCs with mesenchymal stem cells (MSCs). Studies on the improvement in functional capacity of late EPCs, also referred to as endothelial colony-forming cells (ECFCs), when cultured with MSCs have mostly focused on the angiogenic potential, although migration, adhesion, and proliferation potential also determine effective physiological vasculogenesis. Alteration in angiogenic proteins with co-culturing has also not been studied. We co-cultured ECFCs with MSCs via both direct and indirect means, and studied the impact of the resultant contact-mediated and paracrine-mediated impact of MSCs over ECFCs, respectively, on the functional aspects and the angiogenic protein signature of ECFCs. Both directly and indirectly primed ECFCs significantly restored the adhesion and vasculogenic potential of impaired ECFCs, whereas indirectly primed ECFCs showed better proliferation and migratory potential than directly primed ECFCs. Additionally, indirectly primed ECFCs, in their angiogenesis proteomic signature, showed alleviated inflammation, along with the balanced expression of various growth factors and regulators of angiogenesis.

Patient Positioning in Spine Surgery: What Spine Surgeons Should Know?

Spine surgery has advanced tremendously over the last decade. The number of spine surgeries performed each year has also been increasing constantly. Unfortunately, the reporting of position-related complications in spine surgery has also been steadily increasing. These complications not only result in significant morbidity for the patient but also raises the risk of litigation for the surgical and anesthetic teams. Fortunately, most position-related complications are avoidable with basic positioning knowledge. Hence, it is critical to be cautious and take all necessary precautions to avoid position-related complications. We discuss the various position-related complications associated with the prone position, which is the most commonly used position in spine surgery, in this narrative review. We also discuss the various methods for avoiding complications. Furthermore, we briefly discuss less commonly used positions in spine surgery, like the lateral and sitting positions.

Surgical Management of Paediatric Thoracolumbar Tuberculosis by a Combination of Anterior and Posterior Versus Posterior Only Approach: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic Review and Meta-analysis. OBJECTIVES: This systematic review and meta-analysis is aimed to assess effectiveness, safety, clinical, functional and radiological outcome of either combined anteroposterior or posterior-only approach in the surgical management of active tubercular disease of paediatric thoracolumbar spine. METHODS: A systematic literature search through PubMed, Scopus, Web of Science and Cochrane Library database was performed. Data extraction was undertaken following methodological quality assessment. RESULTS: 9 out of the 182 publications identified, were included for analysis. A total of 247 patients were analysed. Two amongst the 9 studies were retrospective comparative studies evaluating posterior approach with combined anteroposterior approach and were considered for comparative meta-analysis. Blood loss and duration of surgery was significantly higher in the anteroposterior group, as compared to the posterior-only group. There was no significant difference between the 2 groups in terms of post-operative kyphosis angles, final kyphosis angles, number of complications, functional outcome and spinal fusion time. However, all the included studies were non-randomised and retrospective. Only 2 of them had a control group with a high heterogeneity amongst these 2 studies. CONCLUSION: The inference from the studies included in this review suggests that equivalent results can be achieved with posterior-only approach for thoracolumbar tuberculosis in children as compared to anteroposterior approach, with much lower complexity, reduced blood loss and shorter surgical time. However, due to the high risk of bias and considerable heterogeneity among the studies included, we cannot conclude whether one approach is better than the other.

3D printing in spine care: A review of current applications.

3D printing (3DP) has been brought to medical use since the early part of this century- but it has been widely researched on and publicized only in the last few years. Amongst patients with spinal disorders, 3DP has been utilized in various facets of patient care. These include pre-operative aspects - such as patient education, resident training, pre-operative planning and simulations, intra-operative assistance in the form of customized jigs for pedicle screw insertion, patient specific interbody cages and vertebral body substitutes in complex malignancies and spinal infections. It has also been utilized in deformity surgeries and has opened new avenues in minimally invasive spine care. Guidelines have now been drafted by various organizations including the FDA with a prime focus on quality control measures applicable to this new technology. There has been a recent surge in publications supporting the use of 3DP in spinal disorders, reporting an improvement in various aspects of patient care. As the technology spreads out its wings further, more innovations and applications are expected to unfold in the coming years. Considering the rapid advances that 3DP has made, having a basic understanding of this technology is imperative for all spine surgeons. Despite promising preliminary results, there still exist a few pitfalls of the technology which have hindered the universal application of 3DP. Most importantly, there is a dearth of data related to long term outcomes supporting its clinical use. The prohibitive cost of 3D models, the specialized manpower it necessitates and the need for specific instrumentation are major deterrents to widespread use of this technology, particularly in small-scale healthcare setups. With further advancements in technology, the goal must be to make it more accurate and affordable to hospitals and patients so that the benefits of the technology can reach a wider patient population.

Protocol for Developing a Femur Osteotomy Model in Wistar Albino Rats.

Fracture healing is a physiological process resulting in the regeneration of bone defects by the coordinated action of osteoblasts and osteoclasts. Osteoanabolic drugs have the potential to augment the repair of fractures but have constraints like high costs or undesirable side effects. The bone healing potential of a drug can initially be determined by in vitro studies, but in vivo studies are needed for the final proof of concept. Our objective was to develop a femur osteotomy rodent model that could help researchers understand the development of callus formation following fracture of the shaft of the femur and that could help establish whether a potential drug has bone healing properties. Adult male Wistar albino rats were used after Institutional Animal Ethics Committee clearance. The rodents were anesthetized, and under aseptic conditions, complete transverse fractures at the middle one-third of the shafts of the femurs were created using open osteotomy. The fractures were reduced and internally fixed using intramedullary K-wires, and secondary fracture healing was allowed to take place. After surgery, intraperitoneal analgesics and antibiotics were given for 5 days. Sequential weekly x-rays assessed callus formation. The rats were sacrificed based on radiologically pre-determined time points, and the development of the fracture callus was analyzed radiologically and using immunohistochemistry.

Non-operative treatment for low back pain: A review of evidence and recommendations.

Background Low back pain (LBP) is a healthcare problem with high global prevalence, with non-operative management being the first line of treatment in the majority of patients. This literature review summarizes the current evidence for various modalities of non-operative treatment for LBP. Methods We did a literature search to elicit high-quality evidence for non-operative treatment modalities for LBP, including Cochrane Database reviews and systematic reviews or meta-analysis of randomized controlled trials. Only when these were not available for a particular treatment modality, other level 1 studies were included. The quality of evidence was categorized in accordance with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method-a globally adopted tool for grading the quality of evidence and making treatment recommendations. Results The treatment modalities that were reviewed included: general measures, medications/pharmacotherapy, exercises, electromagnetic therapies, alternative treatment modalities and interventional therapies. We found that high-quality evidence is lacking for most non-operative treatment modalities for LBP. The majority of interventions have small benefits or are similar to placebo. Conclusion The current evidence for non-operative treatment modalities for LBP is insufficient to draw conclusions or make recommendations to clinicians. High-quality trials are required before widespread use of any treatment modality. Considering that non-operative treatment is usually the first line of therapy for most patients with LBP, it deserves to be the focus of future research in spinal disorders.

Long-term implications of COVID-19 on bone health: pathophysiology and therapeutics.

BACKGROUND: SARS-CoV-2 is a highly infectious respiratory virus associated with coronavirus disease (COVID-19). Discoveries in the field revealed that inflammatory conditions exert a negative impact on bone metabolism; however, only limited studies reported the consequences of SARS-CoV-2 infection on skeletal homeostasis. Inflammatory immune cells (T helper-Th17 cells and macrophages) and their signature cytokines such as interleukin (IL)-6, IL-17, and tumor necrosis factor-alpha (TNF-α) are the major contributors to the cytokine storm observed in COVID-19 disease. Our group along with others has proven that an enhanced population of both inflammatory innate (Dendritic cells-DCs, macrophages, etc.) and adaptive (Th1, Th17, etc.) immune cells, along with their signature cytokines (IL-17, TNF-α, IFN-γ, IL-6, etc.), are associated with various inflammatory bone loss conditions. Moreover, several pieces of evidence suggest that SARS-CoV-2 infects various organs of the body via angiotensin-converting enzyme 2 (ACE2) receptors including bone cells (osteoblasts-OBs and osteoclasts-OCs). This evidence thus clearly highlights both the direct and indirect impact of SARS-CoV-2 on the physiological bone remodeling process. Moreover, data from the previous SARS-CoV outbreak in 2002-2004 revealed the long-term negative impact (decreased bone mineral density-BMDs) of these infections on bone health. METHODOLOGY: We used the keywords "immunopathogenesis of SARS-CoV-2," "SARS-CoV-2 and bone cells," "factors influencing bone health and COVID-19," "GUT microbiota," and "COVID-19 and Bone health" to integrate the topics for making this review article by searching the following electronic databases: PubMed, Google Scholar, and Scopus. CONCLUSION: Current evidence and reports indicate the direct relation between SARS-CoV-2 infection and bone health and thus warrant future research in this field. It would be imperative to assess the post-COVID-19 fracture risk of SARS-CoV-2-infected individuals by simultaneously monitoring them for bone metabolism/biochemical markers. Importantly, several emerging research suggest that dysbiosis of the gut microbiota-GM (established role in inflammatory bone loss conditions) is further involved in the severity of COVID-19 disease. In the present review, we thus also highlight the importance of dietary interventions including probiotics (modulating dysbiotic GM) as an adjunct therapeutic alternative in the treatment and management of long-term consequences of COVID-19 on bone health.

Enhanced recovery after surgery (ERAS) protocol in spine surgery.

Enhanced recovery after surgery (ERAS) protocols are a set of interventions which are carried out in the preoperative and perioperative period. They are aimed to decrease the harmful effects of surgery on the body and help the patient recover better post-surgery. The effectiveness of ERAS has been well established in various other surgical specialities. Earlier spine surgery was thought to be very complex for application of ERAS protocols. However, this has changed over the last decade with (ERAS) protocols gaining widespread popularity in spine surgery. Initial studies involving ERAS in spine surgery were limited to lumbar spine. However, over the years the horizon of ERAS has expanded to include anterior cervical surgeries, spine deformity, spinal tumors and spine surgery in the elderly. ERAS has been shown to reduce the length of hospital stay, overall hospital costs, opioid consumption in perioperative and postoperative period and to lower complication rates in spine surgery. In this narrative review, we discuss various aspects of ERAS in spine surgery including the benefits of ERAS in spine surgery, the various components of preoperative, intraoperative and postoperative measures of ERAS protocol.