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Neutrophils migrate into inflamed tissue, engage in phagocytosis, and clear pathogens or apoptotic cells. These processes require well-coordinated events involving the actin cytoskeleton. We describe a child with severe neutropenia and episodes of soft tissue infections and pneumonia. Bone marrow examination showed granulocytic hypoplasia with dysplasia. Whole-exome sequencing revealed a de novo heterozygous missense mutation in LCP1, which encodes the F-actin–binding protein Lymphocyte Cytosolic Protein 1. To determine its pathophysiological significance, we stably transduced cells with doxycycline-inducible wild-type LCP1 and LCP1 I232F lentiviral constructs. We observed dysplastic granulocytic 32D cells expressing LCP1 I232F cells. These cells showed decreased proliferation without a block in differentiation. In addition, expression of LCP1 I232F resulted in a cell cycle arrest at the G2/M phase, but it did not lead to increased levels of genes involved in apoptosis or the unfolded protein response. Both 32D and HeLa cells expressing mutant LCP1 displayed impaired cell motility and invasiveness. Flow cytometry showed increased F-actin. However, mutant LCP1-expressing 32D cells exhibited normal oxidative burst upon stimulation. Confocal imaging and subcellular fractionation revealed diffuse intracellular localization of LCP1, but only the mutant form was found in the nucleus. We conclude that LCP1 is a new gene involved in granulopoiesis, and the missense variant LCP1 I232F leads to neutropenia and granulocytic dysplasia with aberrant actin dynamics. Our work supports a model of neutropenia due to aberrant actin regulation.

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.

To compare the clinical, radiological and functional outcomes of three-column osteotomy (3CO) by a single-stage posterior approach in patients with isolated congenital angular kyphosis (CK) and healed post-tubercular kyphosis (PTK).The hospital records of 30 patients with isolated congenital kyphosis (Group CK) and 51 patients with healed post-tubercular kyphosis (Group PTK), operated at a single centre utilizing a 3CO by a single-stage posterior-only approach, were retrospectively analysed. The two groups were compared with respect to selected demographic variables with clinical, radiological and functional outcome measures at a minimum follow-up of 24 months.Patients in Group CK (median: 13 years, range: 4-30 years) presented earlier than those in Group PTK (median: 16 years, range: 6-45 years). The apex of the deformity was most often located in the thoracic spine in Group PTK, and in the thoracolumbar or lumbar spine in Group CK. The mean operative time (198.2 ± 31.5 min v/s 174.4 ± 34.5; p = 0.01) and estimated blood loss (859.6 ± 312.2 ml v/s 720.8 ± 187.3; p = 0.04) were significantly higher in Group PTK. While the local kyphosis angle was significantly corrected with surgery in both groups, the correction was significantly better in Group CK-this group also had significantly better overall functional (SRS-22r) scores at a follow-up of 24 months (p 0.05). The overall complication rate (29.4% v/s 23.3%) and neurological complication rate (9.8% v/s 6.6%) were higher in Group PTK. Permanent neurological deterioration occurred in one patient in each group.Patients with PTK have significantly higher age of presentation, higher operative time and higher complication rate as compared to CK. However, good functional outcomes and kyphosis angle correction can be achieved in both the groups with posterior-only three-column osteotomies.

Aims The aims of this study were to determine the diagnostic yield of image-guided biopsy in providing a final diagnosis in patients with suspected infectious spondylodiscitis, to report the diagnostic accuracy of various microbiological tests and histological examinations in these patients, and to report the epidemiology of infectious spondylodiscitis from a country where tuberculosis (TB) is endemic, including the incidence of drug-resistant TB. Methods A total of 284 patients with clinically and radiologically suspected infectious spondylodiscitis were prospectively recruited into the study. Image-guided biopsy of the vertebral lesion was performed and specimens were sent for various microbiological tests and histological examinations. The final diagnosis was determined using a composite reference standard based on clinical, radiological, serological, microbiological, and histological findings. The overall diagnostic yield of the biopsy, and that for each test, was calculated in light of the final diagnosis. Results The final diagnosis was tuberculous spondylodiscitis in 250 patients (88%) and pyogenic spondylodiscitis in 22 (7.8%). Six (2.1%) had a noninfectious condition-mimicking infectious spondylodiscitis, and six (2.1%) had no definite diagnosis and improved without specific treatment. The diagnosis was made by image-guided biopsy in 152 patients (56%) with infectious spondylodiscitis. Biopsy was contributory in identifying 132/250 patients (53%) with tuberculous spondylodiscitis, and 20/22 patients (91%) with pyogenic spondylodiscitis. Histological examination was the most sensitive diagnostic modality, followed by Xpert MTB/RIF assay. Conclusion Image-guided biopsy has a reasonably high diagnostic yield in patients with suspected infectious spondylodiscitis. A combination of histological examination, Xpert MTB/RIF assay, bacterial culture, and sensitivity provides high diagnostic accuracy in a country in which TB is endemic. Cite this article: Bone Joint J 2022;104-B(1):120–126.

EOS is a new tool in the armamemtarium of orthopedicians. Its ability to give a standing 3 dimesnionla image of the spine, has made it an indespenisble tool, specially for spine surgeons. Scoliosis is a 3 dimesnional deformity with multiple compensatory mechanisms being applied at the level of the pelvis and lower limbs as well as in spine. Operating on such patients needs thorough understanding of the 3D anatomy. EOS, provides this along with its low radiation dose, quick scan time and ability to repeat test multiple times if needed. The uses of this modality is on the rise, and as awareness and accessibility to EOS increases, so will the diversity of uses of this tool. Spine surgeons need to understand and use EOS for planning of their surgeries more compared to orther specializations of orthopaedics. EOS is truly a game-changer for spine imaging.

BACKGROUND: The expression pattern of micro-RNAs (miRNA) has been implicated in the pathomechanism of various bone disorders, and has a role in differentiation of osteoblasts and osteoclasts. The purpose of the study was to investigate the differential miRNA profiles of osteoporotic hip fractures compared to young patients with hip fractures. METHODS: Blood samples from ten osteoporosis patients and ten young, healthy patients, presenting with acute hip fractures were collected and subjected to an initial miRNA profiling to detect those miRNAs with significant variations between the two groups based on polymerase chain reactions performed in duplicate. A real-time quantitative polymerase chain reaction-based analysis was then performed for validation of specific miRNAs that were significantly different between the two groups. RESULTS: A total of 182 miRNAs were analyzed. Thirty-nine of them showed significant differences between the two groups in the initial miRNA profiling. The validation results suggested that five miRNAs related to bone metabolism had significantly different expression among the osteoporotic hip fracture group compared to the young, healthy group: miR-23b-3p and miR-140-3p were up-regulated; miR-21-5p, miR-122-5p and miR-125b-5p were down-regulated. CONCLUSIONS: Differential expression of selected miRNAs in patients with osteoporotic hip fracture suggests a possible role of miRNAs as potential biomarkers in prevention or timely prediction of osteoporotic fractures in the elderly. Further research is required to elucidate the mechanism of their involvement in osteoporosis. LEVEL OF EVIDENCE: Not applicable.

Purpose The purpose of this paper is to establish a methodology for the design and development of patient-specific elbow implant with an elastic modulus close to that of the human bone. One of the most preferred implant material is titanium alloy which is about 8 to 9 times higher in strength than that of the human bone and is the closest than other metallic biomedical materials. Design/methodology/approach The methodology begins with the design of the implant from patient-specific computed tomography information and incorporates the manufacturing of the implant via a novel rapid prototyping assisted microwave sintering process. Findings The elastic modulus and the flexural strength of the implant were observed to be comparable to that of human elbow bones. The fatigue test depicts that the implant survives the one million cycles under physiological loading conditions. Other mechanical properties such as impact energy absorption, hardness and life cycle tests were also evaluated. The implant surface promotes human cell growth and adhesion and does not cause any adverse or undesired effects i.e. no cytotoxicity. Practical implications Stress shielding, and therefore, aseptic loosening of the implant shall be avoided. In the event of any trauma post-implantation, the implant would not hurt the patient. Originality/value The present study describes a methodology for the first time to be able to obtain the strength required for the medical implant without sacrificing the fatigue life requirement.

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.

Variant rs11190870 is located 7.5 kb downstream of LBX1 gene and several studies have implicated its association with Adolescent Idiopathic Scoliosis (AIS) in different populations. However, any genetic study is altogether lacking in South-Asian Indian (SAI) populations. We have recently reported lower incidence of AIS in SAI populations. Based on it, a case-control association study was designed to carry out replication of variant rs11190870 in a SAI population. In the study, 95 AIS cases and 282 non-AIS controls from Northwest India were screened and the variant was found to be following Hardy Weinberg equilibrium but did not show significant association (p = 0.66) with AIS. Interestingly, differences in frequency distribution as well as Linkage Disequilibrium (LD) of the variant were observed in SAI populations than other populations in 1000 Genomes phase 3 data. The findings hint at genetic heterogeneity to AIS susceptibility in SAI populations, warranting further studies.

To describe clinical, radiological and functional outcomes of patients with post-tubercular healed kyphosis operated by posterior-only three-column osteotomy. The hospital records of 47 patients from a single center, operated for healed, post-tubercular kyphosis were retrospectively analyzed. Deformity correction in all patients was done utilizing a three-column osteotomy by a single-stage, posterior-only approach. Radiological parameters (local kyphosis angle; KA, thoracic kyphosis; TK, lumbar lordosis; LL, pelvic tilt; PT, sacral slope; SS, C7 sagittal vertical axis; C7 SVA, pelvic incidence minus lumbar lordosis; PI-LL), functional scores and clinical details of complications were recorded. The median age of the study population was 16 years (6–45). The apex of deformity was in thoracic, thoracolumbar and lumbar spine in 22, 19 and 6 cases, respectively. The mean operative time was 197.2 ± 30.5 min and the mean operative blood loss was 701 ± 312 ml. KA (preoperative: 68.2° ± 26.9° v/s postoperative: 29.6° ± 20.3°; p value

Background: Abnormal anatomy is a contributory factor to wrong-level surgery. Variations in the number of vertebrae in populations from different races and geographical regions have been described. A ∼10% prevalence of variations in number of thoracic and lumbar vertebrae in adolescent idiopathic scoliosis (AIS) patients has been previously reported. The objectives of present study were (i) to find out the prevalence of variations in the number of thoracic and lumbar vertebrae and the presence of lumbosacral transitional vertebrae (LSTV) in Indian AIS patients and (ii) to correlate these variations with gender and type of curve. Methods: Hospital records and imaging of 198 AIS patients were reviewed retrospectively. A standardized numbering strategy was used to identify the number of thoracic vertebrae, number of lumbar vertebrae, and presence of LSTV. Patients9 gender and curve type were correlated with the presence of an abnormal number of thoracic or lumbar vertebrae. Radiology reports and operation notes were reviewed to find out instances when the radiologist or surgeon had identified an abnormal number of vertebrae. Results: Forty patients (20.2%) with abnormally numbered thoracic or lumbar vertebrae were identified. Twenty patients (10.1%) had abnormally numbered thoracic vertebrae, and 33 patients (16.7%) had abnormally numbered lumbar vertebrae. The prevalence of LSTV was 18.2%. Presence of variations did not correlate with gender or curve type. Radiology reports identified 2/40 patients with variations, whereas operation notes showed 4/40 patients had been correctly identified to have abnormally numbered vertebrae. Conclusions: There is high prevalence of variation in the number of thoracic or lumbar vertebrae in AIS patients, with most of those missed being identified by radiologists or surgeons. The patient9s preoperative imaging must be scrutinized to identify these patients and take the variation into account to avoid wrong selection of fusion levels. Level of Evidence: 3. Clinical Relevance: Text. The study raises awareness about possibility of wrong selection in fusion levels due to anatomical variations in surgery for AIS.

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.

A seizure is defined as transient change in neurological functioning which is characterised by hypersynchronous discharges of neurons in the brain regions whereas epilepsy is defined as a syndrome consisting of various recurrent seizures and it is associated with the psychological and neuropathological effects. Early recognition and management of psychiatric disorders in patients with epilepsy is extremely important, because it improves the quality of life and aids in better seizure control. Newer antiepileptics with less interaction with psychotropics and less behavioural manifestations should be used for management of epilepsy; and psychotropics having low potential for lowering seizure threshold are generally preferred. A holistic approach to assess psychiatric comorbidity and judicious use of medicine can help in comprehensive patient care planning and reduced health burden. How to cite this article:Sharma S, Kumar P, Seth S, Garg B, Raut N, Kukreti P. Psychiatric Aspects of Epilepsy. J Adv Res Psychol Psychother 2020; 3(3&4): 15-20. DOI: https://doi.org/10.24321/2581.5822.202009

BACKGROUND: Accurate prediction of operative duration is necessary for efficient operating room scheduling, minimizing cancellations, shortening waitlists, better risk stratification, and effective preoperative counseling. Prolonged operative duration is also associated with negative patient outcomes. Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) is typically a lengthy surgical procedure with variable operative duration. The purpose of this study is to identify patient-, procedure-, and surgeon-specific variables that influence the operative duration in PSF for AIS and determine its impact on early postoperative outcomes. METHODS: Hospital records of 150 AIS patients who underwent PSF at a single center were retrospectively reviewed. Various patient-, procedure-, and surgeon-specific variables—deemed to be possibly affecting the operative duration—were analyzed. A multivariate regression model was used to identify independent predictors of operative duration. The association between operative duration and early postoperative outcome measures was determined. RESULTS: The final model obtained from the multivariate regression analysis included the following factors: experience of the chief surgeon (β = −0.36), Cobb angle of the major structural curve (β = 0.35), number of screws inserted (β = 0.28), coronal deformity angular ratio (β = 0.20), and apical vertebral rotation (β = −0.21 to 0.03). The model could explain 44% of the variability in the operative duration (R (2) = 0.44). The operative duration had a significant correlation with estimated blood loss, need for perioperative blood transfusion, and length of hospital stay. CONCLUSIONS: A set of variables that predict the variability in operative duration during PSF for AIS was identified, with the experience of the chief surgeon and the severity of the curve being the strongest predictors. CLINICAL RELEVANCE: The results of this study emphasize the need for each hospital and surgical team to identify predictors of operative duration in their setup in order to better anticipate prolonged operative duration. LEVEL OF EVIDENCE: 3.

LBX1 is a developmental gene involved in skeletal muscle development and somatosensory functioning and proven to be an important gene involved in Adolescent Idiopathic Scoliosis (AIS) etiology. Variant rs11190870 is located 7.5 kb downstream of LBX1 gene and is part of haplotype that is reported to provide risk for AIS. Several studies, including various Genome Wide Association, replication and meta-analyses studies have implicated its association with AIS in different populations. However, any such study is altogether lacking in South-Asian Indian populations. In this first genetic association study for AIS from the region, we tried to replicate association of variant rs11190870 in 95 AIS cases and 282 healthy non-AIS controls from Northwest India. The genotyping was carried out on a Realtime PCR using TaqMan allele discrimination assay and the variant was found to be following Hardy Weinberg equilibrium. The statistical analyses of the genotyping data did not show significant association (p=0.66) of variant rs11190870 with AIS in the population of Northwest India. The results are interesting findings in a population that has never been studied before for AIS susceptibility. However, the findings can be attributed to under power study thus, need evaluation in a large sample set from the population. Interestingly, frequency distribution of the variant in Indian control population datasets was found to be different than other global populations. Linkage Disequilibrium (LD) differences in the genomic region were also observed in these populations while analysing 1000Genomes phase 3 data. It hints at existence of either haplotypic differences in LBX1 locus in South-Asian Indian populations with respect to other populations or genetic heterogeneity in AIS susceptibility. This lays a foundation for genome wide association study (GWAS) in Indian populations cohort, for better understanding of AIS, a task we are pursuing.

Depression in pregnancy affects nearly one in five women in low- and middle-income countries and is associated with adverse obstetric and neonatal outcome. Burden of morbidity is high, but specialized mental health resources are meager. Effective low intensity psychosocial interventions hold promise to fill the treatment gap for maternal depression. In this paper, we aim to describe the process of development of a stepped care model incorporating screening, providing brief intervention, and referral pathways developed for managing depression in pregnancy in antenatal care health facilities in India.Using complex intervention development and evaluation method of Medical Research Council, United Kingdom, we searched evidence-based strategies from preexisting manuals, conducted formative research for need assessment and stakeholder engagement, and developed the intervention following an expert review panel. We conducted pilot testing to assess the feasibility and acceptability of intervention supplemented by three focused group discussions.Manual review identified psychoeducation, empathetic listening, behavior activation, and supportive counseling as important elements. Need assessment revealed huge gap in perinatal mental health knowledge. Nearly 92% of total 272 perinatal women had poor awareness and 35%-70% of total 62 health-care providers had poor knowledge. In qualitative interview, women reported depressive symptoms as a normal part of pregnancy and had poor help seeking, behavior symptoms of depression were more prominent. A stepped care algorithm was developed for screening all expectant mothers in each trimester for depression using Patient Health Questionnaire-9 (PHQ-9). Women with PHQ-9 score19 or reporting self-harm ideation were urgently referred to psychiatrist. Women with PHQ-9 score 5-19 were given brief intervention for depression in pregnancy intervention by antenatal nurse. The intervention developed consists of three sessions of psychoeducation, relaxation exercise, and mental health promotion, each lasting 20 min and at gap of 2 weeks each. Service providers and mothers reported good acceptability of psychosocial intervention and reported satisfaction with content and delivery of intervention.Low intensity brief psychosocial interventions can be adapted for implementation if relevant stakeholders are engaged at each step right from development of such as screening, intervention pathway to delivery, and effectiveness study.

An insight into musculoskeletal disorders through advancements in next-generation sequencing (NGS) promises to maximize benefits and improve outcomes through improved genetic diagnosis.The primary use of whole exome sequencing (WES) for musculoskeletal disorders is to identify functionally relevant variants.The current evidence has shown the superiority of NGS over conventional genotyping for identifying novel and rare genetic variants in patients with musculoskeletal disorders, due to its high throughput and low cost.Genes identified in patients with scoliosis, osteoporosis, osteoarthritis, and osteogenesis imperfecta using NGS technologies are listed for further reference.

‘Awake spinal fusion’ is a novel approach to spine surgery that combines modern anaesthetic and surgical technique resulting in improved patient satisfaction and overall outcomes. Along with techniques of regional anaesthesia, minimally invasive or endoscopic surgical techniques are used to minimize surgical dissection and blood loss. Although, it is a relatively new concept with limited supporting evidence till date, it may prove to be highly effective in reducing post-operative hospital stays, in-hospital complications and cost of surgery while at the same time expediting recovery and rehabilitation. The current review focuses on techniques, advantages, limitations and the available evidence on awake spinal fusion.

Posterior vertebral column resection (PVCR) has several advantages over a combined anterior-posterior procedure for management of severe, rigid spinal deformities. The technique, described by Suk et al., has a high complication rate. Modifications of the technique which can reduce this complication rate might make this challenging procedure safer.To report the results of PVCR in severe, rigid spinal deformity; to describe a modified technique for PVCR and compare its results with the conventional technique.Retrospective cohort.A total of 38 patients who underwent PVCR for severe, rigid spinal deformities.Mean correction of deformity (sagittal and/or coronal), estimated blood loss, operation time, neurological and non-neurological complications, patient-reported outcome score (SRS-22r).Thirty-eight patients underwent PVCR for severe, rigid spinal deformities. These patients had a deformity in excess of 90° and a flexibility index20%. Twenty-one of 38 patients (Group 1) underwent PVCR by the technique reported by Suk et al.; 17 patients (Group 2) underwent a modified PVCR technique. Our technique involves retaining the posterior elements until the other steps of PVCR are completed, which prevents ventral settling and allows for less handling of an already tight spinal cord. The results and complications were compared between the two groups.The mean operating time was 251 minutes and the mean blood loss was 1,251 mL. Mean coronal correction of 50% and a mean sagittal correction of 52.4% were achieved. Intraoperative loss of motor evoked potentials was seen in eight patients while there were two instances of permanent postoperative deficit, both occurring with the conventional PVCR technique. The average operating time, mean correction and blood loss did not differ between the two techniques. There was, however, a reduction in the occurrence of neurological complications with the authors' modified technique.Our retrospective study with a small cohort suggests that the authors' modified technique of PVCR, wherein the posterior elements are preserved until just prior to attempting to correct the deformity, may be safer in terms of neurological complications when compared with the conventional technique. However, larger studies are warranted to conclusively establish this.

EOS® imaging is a proprietary imaging technology that was launched in 2007. Based on a gaseous particle detector with a multi-wire proportional chamber, it offers several advantages over other imaging modalities: low dose of radiation, ability to create 3D reconstructions, ability to conduct whole body imaging, high reproducibility in measuring various parameters of alignment and faster imaging time. EOS® imaging is slowly gaining widespread acceptance as its applications in various disorders continue to evolve. It has been found to be particularly useful and has opened up new avenues of research in the field of spinal deformities. This narrative review seeks to provide an overview of the proprietary technology behind EOS® imaging, compare it to existing imaging modalities, summarize its current applications in various spinal disorders and outline its limitations.

Colon cancer cells can migrate and metastasize by undergoing epithelial-to-mesenchymal transition (EMT). Mesenchymal stem cells (MSCs) are non-cancerous, multipotent adult stem cells, which can also migrate. In this study, we wanted to compare the biological, physical, and functional properties of these migratory cells. HT-29 and HCT-116, two human colon carcinoma cell lines, represent less aggressive and more aggressive cancer cells, respectively. MSCs were isolated from human bone marrow. After confirming the identity of all the cell types, they were evaluated for E-cadherin, β1-integrin, Vimentin, ZEB-1, β-catenin, and 18S rRNA using Q-PCR. MMP-2 and MMP-9 activity were evaluated using gelatin zymography. Functional tests like wound healing assay, migration assay, and invasion assay were also done. Biomechanical properties like cell stiffness and non-specific adhesion (between indenter probe and cell membrane) were evaluated through nanoindentation using atomic force microscopy (AFM). Expression of EMT and stem cell markers showed typical expression patterns for HT-29, HCT-116, and MSCs. Functional tests showed that MSCs migrated faster than malignant cells. MMP-2 and MMP-9 activity reinforced this behavior. Interestingly, the migration/invasion capacity of MSCs was comparable to aggressive HCT-116, and more than HT-29. MSCs also showed the maximum cell stiffness and non-specific cell-probe adhesions, followed by HCT116 and HT29 cells. Our findings indicate that the migratory properties of MSCs is comparable or even greater than that of cancer cells and despite their high migration potential, they also have the maximum stiffness.

Study Design: Multicenter validation study.Purpose: To evaluate the inter-rater reliability of Rajasekaran’s kyphosis classification through a multicenter validation study.Overview of Literature: The classification of kyphosis, developed by Rajasekaran, incorporates factors related to curve characteristics, including column deficiency, disc mobility, curve magnitude, and osteotomy requirements. Although the classification offers significant benefits in determining prognosis and management decisions, it has not been subjected to multicenter validation.Methods: A total of 30 sets of images, including plain radiographs, computed tomography scans, and magnetic resonance imaging scans, were randomly selected from our hospital patient database. All patients had undergone deformity correction surgery for kyphosis. Twelve spine surgeons from the Asia-Pacific region (six different countries) independently evaluated and classified the deformity types and proposed their surgical recommendations. This information was then compared with standard deformity classification and surgical recommendations.Results: The kappa coefficients for the classification were as follows: 0.88 for type 1A, 0.78 for type 1B, 0.50 for type 2B, 0.40 for type 3A, 0.63 for type 3B, and 0.86 for type 3C deformities. The overall kappa coefficient for the classification was 0.68. Regarding the repeatability of osteotomy recommendations, kappa values were the highest for Ponte’s (Schwab type 2) osteotomy (kappa 0.8). Kappa values for other osteotomy recommendations were 0.52 for pedicle subtraction/disc-bone osteotomy (Schwab type 3/4), 0.42 for vertebral column resection (VCR, type 5), and 0.30 for multilevel VCRs (type 6).Conclusions: Excellent accuracy was found for types 1A, 1B, and 3C deformities (ends of spectrum). There was more variation among surgeons in differentiating between one-column (types 2A and 2B) and two-column (types 3A and 3B) deficiencies, as surgeons often failed to recognize the radiological signs of posterior column failure. This failure to identify column deficiencies can potentially alter kyphosis management. There was excellent consensus among surgeons in the recommendation of type 2 osteotomy; however, some variation was observed in their choice for other osteotomies.

Trans-scaphoid perilunate dislocations are complex injuries; usually occur as a result of high-energy trauma and are frequently missed. Chronic trans-scaphoid perilunate dislocation is often difficult to manage and delayed presentation leads to poor functional outcomes. Various treatment modalities have been described which range from open reduction and internal fixation, staged reduction, proximal row carpectomy and wrist arthrodesis.

To investigate whether intraoperative neuromonitoring (IONM) may be avoided in growing rod lengthening procedures in early onset scoliosis (EOS). A total of 636 primary growing rod surgeries and lengthening procedures were performed in 112 patients with EOS. Traditional growing rods (TGR) or magnetically controlled growing rods (MCGR) were implanted and subsequent lengthening procedures were done at stipulated intervals. Combined multi-modality IONM was used in all index surgeries—but was only used in lengthening procedures in patients with existing spinal cord abnormality or a history of neurosurgical procedure for the same, patients with prior history of a neuromonitoring alert in their index surgery and when lengthening was accompanied by an implant exchange/revision. All the remaining growing rod lengthening procedures were carried out without IONM. Hospital records and operation notes were retrospectively reviewed with focus on details of neurological events/complications. In 112 primary growing rod applications (TGR = 96, MCGR = 16) and 524 lengthening procedures (TGR = 444, MCGR = 80), intraoperative neuromonitoring ‘alerts’ were encountered in 6/112 index surgeries and temporary postoperative neurological deficits were seen in 2/112 index surgeries. No intraoperative neuromonitoring event or postoperative neurological complication was encountered in 524 lengthening procedures—irrespective of whether they were carried out along with implant exchange, or in patients with spinal cord abnormality or prior neuromonitoring event during index surgery. While IONM should be used in primary growing rod application surgeries, its use may be avoided in lengthening and implant exchange procedures in a resource-limited setting. Level 3.

Study Design: Prospective, comparative.Purpose: To compare the histopathological and electron microscopic changes in the ligamentum flavum (LF) between degenerative lumbar canal stenosis (LCS) and lumbar disk herniation (LDH).Overview of Literature: The LF has been implicated as a key structure in the pathogenesis of LCS. With aging, the LF undergoes morphological changes–a decrease in the elastic component and an increase in the collagen component, in addition to other focal changes. By comparing the histopathological and electron microscopic picture of the LF in elderly patients with LCS with that in young patients with LDH, the role of this ligament in the pathogenesis of LCS may be clarified.Methods: Forty patients were prospectively recruited and divided into two groups: group 1 included 20 patients with degenerative LCS aged >55 years and group 2 included patients with LDH aged

Case series. To describe a novel surgical strategy for severe, rigid post-tubercular cervical kyphosis with treatment outcomes in two patients. Spinal tuberculosis is a common cause of kyphotic deformity in the developing world with 3–5% of non-operatively managed patients ending up with kyphosis exceeding 60°. Ventral, dorsal and combined approaches have been described for cervical kyphosis, but there is no established surgical strategy for severe, rigid post-tubercular cervical kyphosis. We operated on two girls with severe, rigid cervical kyphosis with preoperative kyphosis measuring 98° and 62°. Our surgical strategy included a three-step approach in the same sitting—(1) An anterior approach to osteotomize the fused vertebral body mass, decompress the spinal cord ventrally and place a temporary cage to stabilize the spine, (2) A posterior approach to osteotomize the fused facets and decompress the cord dorsally. With the completion of the osteotomy, a combination of pedicle screws and lateral mass screws was used to correct the deformity via an anterior opening, posterior closing type of osteotomy. This was followed by, (3) An anterior approach to replace the corpectomy cage with a larger one supplemented with an anterior cervical plate. Our 540° approach achieved a substantial improvement in each of the clinical and radiological parameters we measured, viz. C2–C7 lordosis angle, C2–C7 sagittal vertical axis, neck tilt and Neck Disability Index. For severe, rigid post-tubercular cervical spine kyphosis, a three-step, anterior–posterior–anterior procedure can be used for achieving acceptable correction, improving symptoms and avoiding further progression. IV.

Study Design: Retrospective cohort. Objective: ( a) To compare the recommendations of Lenke and Peking Union Medical College (PUMC) classifications in choosing distal fusion levels in Lenke 1 adolescent idiopathic scoliosis (AIS) curves and ( b) to analyze whether the variability in distal fusion levels influences treatment outcomes. Methods: Hospital records of Lenke 1 AIS patients operated for single stage, posterior-only deformity correction were analyzed. Distal fusion levels recommended by Lenke and PUMC classifications were calculated and were compared with the actual distal fusion levels. The study population was divided based on whether the actual distal fusion levels were in agreement, shorter or longer than those recommended by Lenke classification. Subgroup analysis of Lenke 1C curves was done. The groups were compared with regard to the following outcome measures: Cobb angle correction, postoperative sagittal vertical axis, postoperative C7 offset, and Scoliosis Research Society–22r (SRS-22r) score at 24 months. Results: The distal fusion levels recommended by the 2 classifications were in agreement in 92 of 104 cases. In all the cases with disparity, Lenke classification recommended shorter fusions than the PUMC classification. No statistically significant difference was observed in the outcome measures—whether the actual distal fusion levels were in agreement, shorter, or longer than those recommended by the Lenke classification or whether or not the recommendations for selective fusion of any of these classifications were adhered to. Conclusion: Lenke classification can save fusion levels without compromising on treatment outcomes when compared with PUMC classification. Variability in choice of distal fusion levels is not clinically significant at 24-month follow-up.

Pedicle screw instrumentation is currently the “gold standard” in scoliosis surgery. However, placement of pedicle screws in thoracic spine is considered challenging. Previous studies have described morphometric changes in the pedicle when a larger screw is inserted, with pedicle expansion preceding screw cutout and pedicle fracture. We report an unusual case of neurological deficit due to cord compression by an expanded pedicle following pedicle screw insertion on the concave side of the apical vertebra in a 14-year-old patient with Lenke Type 3C(-) adolescent idiopathic scoliosis. Identification of the expanded pedicle as the cause of neurological symptoms, prompt action, and deferring the corrective surgery while accepting less correction helped us in negotiating the problem without causing permanent neurological deficit. Pedicle expansion in an immature spine can cause neurological complications. The screw diameter at the apical vertebrae on the concave side should be carefully selected.

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.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.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.

Current advancements in spine surgery have led to a recent interest in regional anesthesia for spine surgery. Spinal anesthesia, epidural anesthesia, and their combination are commonly used modalities for regional anesthesia in spine surgeries. The successful use of regional anesthesia has led to the emergence of several new concepts such as awake spinal fusion and outpatient spinal surgery. Regarding analgesic techniques, several new modalities have been described recently such as erector spinae and thoracolumbar interfascial plane blocks. These regional analgesic modalities are aimed at decreasing perioperative pain and enhancing early recovery in patients undergoing spine surgery. This narrative review focuses on the techniques, indications and contraindications, benefits, and complications of regional anesthesia in the context of spine surgery.

Aims To describe the clinical, radiological, and functional outcomes in patients with isolated congenital thoracolumbar kyphosis who were treated with three-column osteotomy by posterior-only approach. Methods Hospital records of 27 patients with isolated congenital thoracolumbar kyphosis undergoing surgery at a single centre were retrospectively analyzed. All patients underwent deformity correction which involved a three-column osteotomy by single-stage posterior-only approach. Radiological parameters (local kyphosis angle (KA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), sacral slope (SS), C7 sagittal vertical axis (C7 SVA), T1 slope, and pelvic incidence minus lumbar lordosis (PI-LL)), functional scores, and clinical details of complications were recorded. Results The mean age of the study population was 13.9 years (SD 6.4). The apex of deformity was in thoracic, thoracolumbar, and lumbar spine in five, 14, and eight patients, respectively. The mean operating time was 178.4 minutes (SD 38.5) and the mean operative blood loss was 701.8 ml (SD 194.4). KA (preoperative mean 70.8° (SD 21.6°) vs final follow-up mean 24.7° (SD 18.9°); p < 0.001) and TK (preoperative mean -1.48° (SD 41.23°) vs final follow-up mean 24.28° (SD 17.29°); p = 0.005) underwent a significant change with surgery. Mean Scoliosis Research Society (SRS-22r) score improved after surgical correction (preoperative mean 3.24 (SD 0.37) vs final follow-up mean 4.28 (SD 0.47); p < 0.001) with maximum improvement in self-image and mental health domains. The overall complication rate was 26%, including two neurological and five non-neurological complications. Permanent neurological deficit was noted in one patient. Conclusion Deformity correction employing three-column osteotomies by a single-stage posterior-only approach is safe and effective in treating isolated congenital thoracolumbar kyphosis. Cite this article: Bone Joint J 2021;103-B(7):1309–1316.

Background Lumbar radicular pain (LRP) results from inflammation and irritation of lumbar spinal nerves and the dorsal root ganglion (DRG). Methods Our study is a prospective, triple-blind, randomized, activecontrol trial (CTRI/2016/02/006666) comparing transforaminal epidural local anesthetic (LA) injection and pulsed radiofrequency treatment of DRG in patients with chronic LRP. Patients with LRP after failed conservative management for >3 months received selective diagnostic nerve root block with 1 mL 2% lidocaine. Fifty patients showing positive responses were divided into groups of 25 each. The LA group received transforaminal epidural injection of 1 mL 0.5% bupivacaine. The lumbar pulsed radiofrequency (LPRF) group received transforaminal epidural injection of 1 mL 0.5% bupivacaine with 3 cycles of pulsed radiofrequency of the DRG for 180 seconds RESULTS: Both groups were compared by observing pain intensity on a 0- to 100-point VAS and improvement in functional status by the Oswestry Disability Index (ODI version 2.0) at 2 weeks and 1, 2, 3, and 6 months. All baseline variables were comparable between the 2 groups. Statistically significant reduction in both outcomes was seen in the LPRF group compared to the LA group from 2 weeks to 6 months. One hundred percent of patients in the LPRF group had a ≥20- point decrease in VAS and significant percentage reduction in ODI at all time intervals up to 6 months, whereas it was seen in 80% and 28% of patients in the LA group at 3 and 6 months, respectively. No complications were seen in any patients CONCLUSION: Pulsed radiofrequency of the DRG applied for longer duration results in long-term pain relief and improvement in the functional quality of life in patients with chronic LRP.

Minimal access surgery has revolutionized most surgical disciplines and spine surgery is no exception. Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) was devised to reduce the approach-related morbidity of open TLIF and has flourished in the last decade. With expanding indications, standardization of technique and equipment, publication of more studies on its results and complications being brought to light – an update of the existing knowledge on MI-TLIF is imminent. We provide a review of the indications, technique, results and complications of MI-TLIF while also highlighting its variations and utility in special situations.

Osteoporosis and fragility fractures have become a major healthcare challenge globally in the recent years. However, this problem has only recently been accorded its due importance in developing countries such as India. India is a model case study for the management of osteoporosis and fragility fractures in a resource-limited setting, as it harbors a large geriatric population and has the highest prevalence of osteopenia globally. It is imperative to identify the myriad factors contributing to poor bone health and understand the many hurdles encountered to tackle this healthcare problem in a developing country. Innovative methods for managing fragility fractures are commonly seen. Collaborative multidisciplinary care and structured, evidence-based management has finally found its place in India with the establishment of a regional fragility fracture network. This chapter outlines the current status of management of fragility fractures in India by focusing on the disease burden, hurdles, innovative treatment methods, and the challenges lying ahead.

Multiple myeloma (MM) is a hematological malignancy marked by uncontrolled proliferation and accumulation of plasma cells in bone marrow. Despite presence of numerous diagnostic markers for MM, their invasive and non-specific nature demands identification of some effective biomarker. Small non-coding RNAs, i.e., microRNAs being secreted out in circulation could depict the change in homeostasis. Earlier, we reported diagnostic potential of a proteoglycan, Versican (VCAN) in MM, hence, VCAN linked cell-free microRNAs have been explored to study their diagnostic involvement in MM. Biopsy proven MM patients and controls were recruited. The relative microRNA expression of VCAN linked microRNAs (miR-143, miR-144, miR-199, and miR-203) along with levels of VCAN have been investigated in bone marrow supernatant fluid (BMSF) and blood serum and their correlation were done with clinico-pathological parameters. The diagnostic potential was assessed using ROC curve. Relative microRNA expression of all microRNAs was found significantly lower in MM patients in both BMSF and serum while VCAN levels were substantially higher in patients. VCAN levels showed positive trend while microRNAs expression showed negative trend with severity of disease. miR-203 showed significant correlation with myeloma-associated parameters and also showed optimum sensitivity and specificity for diagnosis of MM in serum. Downregulation of cell-free microRNAs illustrates their importance in MM. The negative trend of microRNAs with disease progression suggests their diagnostic significance. Correlation of miR-203 with myeloma clinical parameters along with optimum sensitivity and specificity affirms its non-invasive diagnostic potential in MM which could further be validated in larger patient cohort.

Background Context Spinal deformities are very challenging to treat and have a great risk of neurologic complications because of hardware placement during corrective surgery. Various techniques have been introduced to ensure safe and accurate placement of pedicle screws. Patient-specific screw guides with predrawn and prevalidated trajectory seem to be an attractive option. Purpose We have focused on developing three-dimensional (3D) printing technique for complex spinal deformities in India. This study also aimed to compare the placement of pedicle screw with 3D printing and freehand technique. Study Design/Settings This is a retrospective comparative clinical study in an academic institutional setting. Patient Sample A total of 20 patients were enrolled during the study: 10 were operated on with the help of 3D printing (Group 1) and 10 were operated on with freehand technique (Group 2). Group 1 included six patients with congenital scoliosis, three patients with adolescent idiopathic scoliosis (AIS), and one patient with post-tubercular kyphosis, and Group 2 included five patients with congenital scoliosis, four patients with AIS, and one patient with post-tubercular kyphosis. Outcome Measures Primary outcomes were measured in terms of screw violation, and secondary outcomes were measured in terms of surgical time, blood loss, radiation exposure (number of shoots required), and complications. Materials and Methods MIMICS Base v18.0 software was used for 3D reconstruction from computed tomography scan images of all the patients. 3-Matic software was used to create a drill guide. A 3D printer from Stratasys Mojo with ABS P430 model material cartilage (a thermoplastic material) was used for the printing of the vertebra model and jigs. A two-sample test of proportion was used to compare correctly and wrongly placed pedicle screws with 3D printing and freehand technique. t Test with equal variance was used for operating surgical time and blood loss. Results No superior or inferior screw violation was observed in any of our patients in either group. We found a significant difference (p=.03) between the two groups regarding perfect screw placement in favor of 3D printing. There were 13 Grade 2 medial perforations in the freehand group and 3 in the 3D printing group. There was no Grade 3 medial perforation in either group. Six Grade 2 lateral perforations in the freehand group and seven in the 3D printing group were observed. Three Grade 3 lateral perforations in the freehand group and two in 3D printing group were observed. Analysis showed a statistically significant (p=.005) medial violation in the freehand group. Surgical time was significantly less (p=.03) in the 3D printing group compared with the freehand group. Mean blood loss was higher in the freehand group but was not statistically significant (p=.3) in the 3D printing group. Fluoroscopic shots required were less in number in the 3D printing group compared with the freehand group. There was no neurologic deficit in any of the patients in the two groups. Conclusions In our study, focusing on spinal deformities with statistically significant higher rates of accurate screw positioning and higher numbers of inserted screws with 3D printing was possible because of enhanced safety, particularly at apical levels. As such, spinal deformities are difficult to treat worldwide. In India, these deformities are often neglected and present at a very late and a much more deformed state when their treatment becomes even more challenging. Developing these patient-specific drill templates will enable an average spine surgeon to treat these patients with much ease and safety.

Insulin resistance has been associated with depressive symptoms and depressive syndrome. Studies have attempted to assess the relationship between metabolic syndrome and depression and more specifically insulin resistance and depression. Studies have also been carried out to assess the direction of this relationship. This brief review is purported to present and discuss the currently available literature evidence about relationship of insulin resistance with depression and the treatment implications of this relationship. The presence of insulin resistance in an individual is positively associated with increased depressive symptoms and the presence of depressive symptoms is found to be associated with insulin resistance. However, a causal relationship could not be established. Prospective study designs can help to enhance our knowledge in finding a causal relationship. Intervention studies that will further help in treatment decisions are required.

Background: Bacterial adherence and biofilm formation on the surface of biomaterials can often lead to implant-related infections, which may vary depending on the species of microorganisms, type of biomaterial used, and physical characteristics of implant surfaces. However, there are limited studies specifically comparing biofilm formation between commonly used metallic orthopaedic implant materials and different bacterial strains. This in vitro study is to evaluate the ability of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa to adhere to and to form biofilms on the surface of five orthopaedic biomaterials, viz., cobalt and chromium, highly cross-linked polyethylene, stainless steel, trabecular metal, and titanium alloy. Materials and Methods: Bacterial adherence and bacterial biofilm-formation assays were performed by culturing S. aureus ATCC 29213, S. epidermidis ATCC 35984, E. coli ATCC 35218, K. pneumoniae ATCC 700603, and P. aeruginosa ATCC 27853 for 48 h on five different biomaterials. Quantitative bacterial adherence and biofilm formation were analyzed with a scanning electron microscope. Results: The highest level of adherence was observed on highly cross-linked polyethylene, followed by titanium, stainless steel, and trabecular metal, with the lowest occurring on the cobalt-chromium alloy. Among the bacterial strains tested, the ability for high adherence was observed with S. epidermidis and K. pneumoniae followed by P. aeruginosa and E. coli, whereas S. aureus showed the least adherence. Conclusion: Cobalt-chromium was observed to have the lowest proclivity towards bacterial adherence compared to the other biomaterials tested. However, bacterial adhesion occurred with all the materials. Hence, it is necessary to further evaluate newer biomaterials that are resistant to bacterial adherence.