Variation in thoracic inlet measurements and its correlation with pulmonary dysfunction in kyphoscoliotic deformities: a prospective case-control study.

BACKGROUND: Pulmonary dysfunction in thoracic kyphoscoliosis has been correlated with chest wall distortion, uneven trunk growth and restrictive pattern. The study aims to analyse the variation in thoracic inlet measurements on pulmonary dysfunction with varying curve magnitude and thoracic cage parameters. METHODS: In a non-randomised, prospective case-control study, 80 consecutive patients with thoracic kyphoscoliosis were divided into 3 groups based on Cobb angle: Group 1 (31-50), Group 2 (51-80) and Group 3 (> 80). Thoracic inlet measurement was calculated by thoracic inlet index (TI) on MRI at the sternal level. Pulmonary function and thoracic cage parameters [hemi thorax height, rib-apex distance, AP chest diameter at sternal level and transverse thoracic diameter] were documented. TI values were compared with 20 age-matched asymptomatic controls. Multivariate correlation and regression analysis were performed to investigate the correlations. RESULTS: The mean age of the study cohort was 14.1 ± 4.4 years, including Group 1 (6 patients), Group 2 (55 patients) and Group 3 (19 patients) versus 12.9 ± 2.2 years in controls. The mean TI was 2.8 ± 0.56 in Group 1, 3.7 ± 0.9 in Group 2 and 4.0 ± 1.12 in Group 3 versus 2.6 ± 0.43 in controls. Pulmonary dysfunction was severe with TI > 7.1 (p < 0.001) in Group 3 patients with thoracic hypokyphosis. Multivariate regression for thoracic parameters and TI > 5.6 showed significant correlation of pulmonary dysfunction in Group 2 and 3 curves with apex between T1 and T4, whereas transverse thoracic diameter, rib-apex distance and hemi thorax height were weakly associated. CONCLUSION: Thoracic inlet index (TI), a neglected pre-operative variable associated with pulmonary dysfunction in thoracic kyphoscoliosis, can be evaluated on MRI without an additional cost and radiation.

A Validated Score for Evaluating Spinal Instability to Assess Surgical Candidacy in Active Spinal Tuberculosis-An Evidence Based Approach and Multinational Expert Consensus Study.

STUDY DESIGN: Modified Delphi Consensus and Observational Study. OBJECTIVE: Instability in spinal tuberculosis (STB) leads to disabling spinal deformity and neurodeficit. Identifying and estimating instability remains subjective, mainly based on experience. This study aims to develop an objective scoring system to determine instability in STB. MATERIALS AND METHODS: The study included 4 phases. (1) A panel of 10 experienced spine surgeons developed a questionnaire based on literature. (2) 68 spine surgeons from 12 countries opined on the importance of each factor in a survey. Five factors deemed important by >70% of participants were further analyzed (3) 60 representative cases of STB were analyzed for instability. A preliminary scoring system was developed, a threshold score for determining instability was derived, and (4) Results were validated. RESULTS: All the 5 factors ("Spine at risk" signs, severity of vertebral body loss, Cervicothoracic/Thoracolumbar junction involvement, age ≤15, and kyphotic deformity ≥30°) considered important by >70% of participants were associated with instability and included in scoring: age ≤15 years (P-value, 0.05), cervicothoracic/thoracolumbar junction involvement (P-value, 0.028), sagittal deformity angle ratio (DAR) ≥ 15° (P-value, <.001), vertebral body loss-segmental ratio ≥.5 (P-value, <.001), and presence of spine at risk signs (P-value, <.001). A total score of ≥3/09 indicated definite instability with good sensitivity (77%) and excellent specificity (100%). Repeatability assessment showed a good agreement (.9625), and Cohen's kappa coefficient was strong (.809). CONCLUSION: A simple objective scoring system for predicting instability in STB has been developed using 5 main factors; young age, junctional involvement, severity of the deformity, vertebral body loss, and presence of spine at risk signs.

Novel Biomarkers of Health and Degeneration in Human Intervertebral Discs: In-depth Proteomic Analysis of Collagen Framework of Fetal, Healthy, Scoliotic, Degenerate, and Herniated Discs.

STUDY DESIGN: Profiling proteins expressed in the nucleus pulposus (NP) of intervertebral discs (IVDs) in five different biological states. PURPOSE: To evaluate the molecular complexity of the collagen (COL) framework and its role in the health and disease of human IVDs. OVERVIEW OF LITERATURE: Changes in COL composition have been linked to degenerative disk disease (DDD). Despite the fact that humans have 28 different types of COLs, most of the literature focuses solely on COL-1 and COL-2. This study used high-end proteomic technology to examine the entire COL composition of the human IVD across fetal (developmental-FD), normal (healthy-ND), scoliotic (early degeneration-SD), herniated (degenerate-DH), and degenerated (DD) disk phenotypes. METHODS: Forty NP tissues were snap-frozen in liquid nitrogen (-196°C) immediately before being subjected to proteomic and bioinformatic analyses from five different disk phenotypes (eight each). RESULTS: Tandem mass spectrometric analysis revealed a total of 1,050 proteins in FDs, 1,809 in ND, 1,487 in SD, 1,859 in DH, and 1,538 in the DD group. Of 28 major collagens reported in the human body, this study identified 24 different collagens with 34 subtypes in NP. Fibril-forming collagens (COL-1, 2, and 11A1) and fibril-associated collagens with interrupted triple helices (COL-9A1, 12A1, and 14A1) were abundantly expressed in FDs, representing their role in the development of NP. Multiplexin (COL-15), a hybrid proteoglycan-collagen molecule, was discovered only in FDs. Degeneration was associated with COL2A1 downregulation and COL-10A1 upregulation. CONCLUSIONS: COL10 was discovered to be a new biomarker for disk degeneration. Besides COL-1 and 2, other important COLs (6, 9, 11, 12, 14, 15) with anabolic potential and abundant expression in the fetal phenotype could be investigated for tissue engineering and novel DDD therapy.

Are Modic changes 'Primary infective endplatitis'?-insights from multimodal imaging of non-specific low back pain patients and development of a radiological 'Endplate infection probability score'.

PURPOSE: To probe the pathophysiological basis of Modic change (MC) by multimodal imaging rather than by MRI alone. METHODS: Nineteen radiological signs found in mild infections and traumatic endplate fractures were identified by MRI and CT, and by elimination, three signs unique to infection and trauma were distilled. By ranking the Z score, radiological 'Endplate Infection Probability Score' (EIPS) was developed. The score's ability to differentiate infection and traumatic endplate changes (EPC) was validated in a fresh set of 15 patients each, with documented infection and trauma. The EIPS, ESR, CRP, and Numeric Pain Rating Scale (NRS) were then compared between 115 patients with and 80 patients without MC. RESULTS: The EIPS had a confidence of 66.4%, 83% and, 100% for scores of 4, 5 and, 6, respectively, for end plate changes suggesting infection. The mean EIPS was 4.85 ± 1.94 in patients with Modic changes compared to - 0.66 ± 0.49 in patients without Modic changes (p < 0.001). Seventy-eight (67.64%) patients with MC had a score of 6, indicating high infection possibility. There was a difference in the NRS (p < 0.01), ESR (p = 0.05), CRP (p < 0.01), and type of pain (p < 0.01) between patients with and without MC. CONCLUSION: Multimodal imaging showed many radiological signs not easily seen in MRI alone and thus missed in Modic classification. There were distinct radiological differences between EPCs of trauma and infection which allowed the development of an EIPS. The scores showed that 67.64% of our study patients with Modic changes had EPCs resembling infection rather than trauma suggesting the possibility of an infective aetiology and allowing us to propose an alternate theory of 'Primary Endplatitis'.

Can Scoliotic Discs Be Controls for Molecular Studies in Intervertebral Disc Research? Insights From Proteomics.

STUDY DESIGN: Proteomic analysis of human intervertebral discs. OBJECTIVES: To compare the characters of scoliotic discs and discs from magnetic resonance imaging (MRI)-normal voluntary organ donors controls used in disc research employing proteomics and establish "true controls" that can be utilized for future intervertebral disc (IVD) research. METHODS: Eight MRI-normal discs from 8 brain-dead voluntary organ donors (ND) and 8 scoliotic discs (SD) from 3 patients who underwent anterior surgery for adolescent idiopathic scoliosis were subjected to tandem mass spectrometry, and further analysis was performed. RESULTS: Mass spectrometry identified a total of 235 proteins in ND and 438 proteins in the SD group. Proteins involved in extracellular matrix integrity (Versican, keratins KRT6A, KRT14, KRT5, and KRT 13A1, A-kinase anchor protein 13, coagulation factor XIII A chain, proteoglycan 4) and proteins involved in transcription and DNA repair (Von Willebrand factor A domain-containing 3B, eukaryotic initiation factor 2B, histone H4, leukocyte cell-derived chemotaxin 2) were found to be downregulated in SD. Inflammatory proteins (C3, C1S), and oxidative stress response proteins (peroxiredoxin-2,6, catalase, myeloperoxidase, apolipoprotein E) were found to be upregulated in SD. These changes were reflected at the pathway level also. CONCLUSION: Findings of our study confirm that scoliotic discs have an abundance of inflammatory, oxidative stress response proteins, which are either absent or downregulated in the ND group indicating that scoliotic discs are not pathologically inert. Furthermore, this study has established MRI-normal discs from voluntary organ donors as the "true" control for molecular studies in IVD research.

Influence of endplate avulsion and Modic changes on the inflammation profile of herniated discs: a proteomic and bioinformatic approach.

PURPOSE: The aim of this observational radiographic and proteomic study is to explore the influence of both Modic change (MC) and endplate avulsion (EPA) on the inflammation profile of herniated discs using a proteomic and bioinformatics approach. METHODS: Fifteen nucleus pulposus (NP) harvested from surgery underwent LC-MS/MC analysis, the proteome was subsequently scanned for inflammatory pathways using a bioinformatics approach. All proteins that were identified in inflammatory pathways and Gene Ontology and present in > 7 samples were integrated in a multiple regression analysis with MC and EPA as predictors. Significant proteins were imputed in an interaction and pathway analysis. RESULTS: Compared to annulus fibrosus tear (AFT), six proteins were significantly altered in EPA: catalase, Fibrinogen beta chain, protein disulfide-isomerase, pigment epithelium-derived factor, osteoprotegerin and lower expression of antithrombin-III, all of which corresponded to an upregulation of pathways involved in coagulation and detoxification of reactive oxygen species (ROS). Moreover, the presence of MC resulted in a significant alteration of nine proteins compared to patients without MC. Patients with MC showed a significantly higher expression of clusterin and lumican, and lower expression of catalase, complement factor B, Fibrinogen beta chain, protein disulfide-isomerase, periostin, Alpha-1-antitrypsin and pigment epithelium-derived factor. Together these altered protein expressions resulted in a downregulation of pathways involved in detoxification of ROS, complement system and immune system. Results were verified by Immunohistochemistry with CD68 cell counts. CONCLUSION: Both EPA and MC status significantly influence disc inflammation. The beneficial inflammatory signature of EPA illustrates that endplate pathology does not necessarily have to worsen the outcome, but the pathological inflammatory state is dependent on the presence of MC.

Modic changes are associated with activation of intense inflammatory and host defense response pathways - molecular insights from proteomic analysis of human intervertebral discs.

BACKGROUND CONTEXT: Patients with modic changes (MC) form a distinct clinical subset with reports of higher intensity of pain, poor clinical and surgical outcomes and higher incidence of recurrence. MC also is an independent risk factor for increased post-operative surgical site infection. PURPOSE: This study aimed to investigate the biological changes at molecular level, in discs with MCs. We also aim to identify biological biomarkers and potential targets for molecular therapy. STUDY DESIGN: Experimental analysis MATERIALS AND METHODS: Nucleus pulposus (NP) from 24 patients undergoing microdiscectomy for disc herniation [14 discs with MC and 10 without modic changes (NMC)] were procured. The overall expression of proteins, biological processes, protein-protein and metabolite interactions were analysed and compared. Host defense response proteins (HDRPs) and immunological pathways activated in patients with MC were documented and analysed. RESULTS: Label-free proteomic approach with stringent filters revealed a total of 208 proteins in MC and 193 in NMC groups. 45 proteins were specific to MC; 30 to NMC and 163 common to both. Downregulated proteins in MC belonged to components of extracellular matrix such as collagens (COL- 6A1, 6A2, 6A3, 11A1, 12A1, and 20A1), and proteoglycans (versican (VCAN), and biglycan (BGN)). Inflammatory molecules [plasminogen (PLG), angiogenin (ANG), fibroblast growth factor-binding protein 2 (FGFBP2), tetranectin (CLEC3B), cartilage acidic protein 1(CRTAC1), kininogen (KNG-1), chitinase-3-like protein 2 (CHI3L2), and ferritin (FTL) were expressed only in the MC group. The significantly altered pathways in MC included Fc Fragment of IgG Receptor IIIa (FCGR3A)-mediated phagocytosis, regulation of Toll-like receptors (TLR) by endogenous ligand, neutrophil and platelet degranulation. 50 HDRPs were identified in the study, 14 of which were specific to MC and included acute phase reactants, antimicrobial peptides, complement cascade proteins, inflammatory molecule and stress response proteins. Metabolite-protein interaction analysis revealed a significant interaction between 19 proteins, specifically involving ubiquitin mediating proteasome degradative pathway and an association with the metabolite-glutamic acid in the MC group. Accumulation of glutamic acid in MC discs was confirmed by quantitative amino acid analysis using High-performance liquid chromatography. CONCLUSION: Our study confirms that MC represents an intense inflammatory status and activation of host defense response and immunological pathways. Downstream effects leading to ubiquitin mediated proteasomal degradation of ECM proteins and the resulting metabolites such as glutamic acid could cause excessive pain and needs further investigation. CLINICAL SIGNIFICANCE: We have documented the expression of inflammatory molecules, immune mechanisms and host defense response proteins which throw molecular insights into the pathological mechanisms of MC. Further, ubiquitin mediated proteasomal degradation and accumulation of glutamate in discs with MC might serve as targets for molecular therapy.

Lumbar Disc Herniation and Preoperative Modic Changes: A Prospective Analysis of the Clinical Outcomes After Microdiscectomy.

STUDY DESIGN: Prospective comparative cohort study. OBJECTIVES: The study aims to elucidate the relationship between Modic endplate changes and clinical outcomes after a lumbar microdiscectomy. METHODS: Consecutive patients undergoing microdiscectomy for lumbar disc herniation (LDH) were prospectively studied. Pre-operative clinical and radiological parameters were recorded. The pain was assessed by Numeric pain rating scale (NPRS), and functional assessment by Oswestry Disability Index (ODI). Minimal clinically important difference (MCID) in outcome was calculated for both the groups. Complications related to surgery were studied. Follow-up was done at 6 weeks, 3 months, 6 months and 1 year. Mac Nab criteria were used to assess patient satisfaction at 1 year. RESULTS: Out of 309 patients, 86 had Modic changes, and 223 had no Modic changes. Both groups had similar back pain (p-value: 0.07) and functional scores (p-value: 0.85) pre-operatively. Postoperatively patients with Modic changes had poorer back pain and ODI scores in the third month, sixth month and 1 year (p-value: 0.001). However, MCID between the groups were not significant (p-value: 0.18 for back pain and 0.58 for ODI scores). Mac Nab criteria at 1 year were worse in Modic patients (p-value: 0.001). No difference was noted among Modic types in the pre-operative and postoperative pain and functional outcomes. Four patients in Modic group (4.7%) and one patient in the non-Modic group (0.5%) developed postoperative discitis (p-value: 0.009). CONCLUSIONS: Preoperative Modic changes in lumbar disc herniation is associated with less favorable back pain, functional scores and patient satisfaction in patients undergoing microdiscectomy.

Profiling extra cellular matrix associated proteome of human fetal nucleus pulposus in search for regenerative targets.

Degeneration of the intervertebral disc is associated with a decrease in extra-cellular matrix (ECM) content due to an imbalance in anabolic and catabolic signaling. Our previous study profiled the core matrisome of fetal NP's and identified various proteins with anabolic potential for regenerative therapies. This study aims to complement those results by exploring ECM regulators, associated proteins and secreted factors of the fetal nucleus pulposus (NP). Proteomic data of 9 fetal, 7 healthy adults (age 22-79), and 11 degenerated NP's was analyzed. Based on the selection criteria, a total of 45 proteins were identified, of which 14 were uniquely expressed or upregulated in fetus compared to adult NP's. Pathway analysis with these proteins revealed a significant upregulation of one pathway and two biological processes, in which 12 proteins were involved. Prolyl 4 hydroxylase (P4HA) 1 and 2, Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) 1, and Heat shock protein 47 (SERPINH1) were involved in 'collagen biosynthesis' pathway. In addition, PLOD 1, SERPINH1, Annexin A1 and A4, CD109 and Galectin 3 (LGALS3) were all involved in biological process of 'tissue development'. Furthermore Annexin A1, A4 and A5, LGALS-3 and SERPINF1 were featured in 'negative regulation of cell death'. In conclusion, additionally to core ECM proteome, this study reveals ECM regulators and ECM affiliated proteins of interest to study for regenerative therapies, and their potential should be validated in future mechanistic experiments.

Uncovering molecular targets for regenerative therapy in degenerative disc disease: do small leucine-rich proteoglycans hold the key?

BACKGROUND CONTEXT: Small leucine-rich proteoglycans (SLRPs) play an essential role in extracellular matrix (ECM) organization and function. Recently, dysregulation of SLRPs has been implicated in degenerative disc disease (DDD). An in-depth analysis using high-throughput proteomic sequencing might provide valuable information on their implications in health and disease. PURPOSE: To utilize proteomics for analyzing the expression of SLRPs in fetal, healthy adult, and degenerated discs, to identify possible molecular targets to halt or reverse the degenerative process. STUDY DESIGN: Experimental analysis. METHODS: Proteomic signatures of 8 magnetic resonance imaging (MRI) normal lumbar discs (ND) [harvested from brain dead alive organ donors] were compared to 8 fetal disc samples (FD) [harvested from fetal spines devoid of congenital anomalies following spontaneous or medical termination of pregnancy] and 8 degenerate discs (DD) [collected from patients undergoing fusion surgery]. The various functional pathways along with the differential expression of SLRPs and the associated changes in collagens, large proteoglycans (LLRPs), matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) have been analyzed further using bioinformatics. This project was self-funded by the Ganga Orthopedic Research and Education Foundation. RESULTS: ESI-LC-MS/MS analysis revealed a total of 1,029 proteins in FD, 1,785 proteins in ND, and 1,775 proteins in DD. Fetal disc proteins were engaged mainly in ribosomal pathways (indicating active proliferation and regenerative potential). The healthy adult discs (ND) primarily participated in ECM maintenance and basic metabolic pathways, whereas the unique proteins of DD group were involved in inflammatory (Complement and coagulation cascades, Systemic Lupus Erythematosus and Leukocyte transendothelial migration) pathways and infective (Staphylococcus aureus infection, Prion diseases, Amoebiasis, Pertussis, and Legionellosis) channels which favor the recent concepts of inflammaging and subclinical infection as causes of DDD. Analysis of SLRPs revealed the upregulation of Biglycan in FDs and downregulation of Lumican, Decorin, Prolargin, and Chondroadherin in the DD group. The universal decrease in the abundance of SLRPs in the DD group was associated with an increase in MMPs and a reduction in TIMPs, collagen and LLRP content. CONCLUSIONS: Our study documents the influence of SLRPs in the maintenance of disc health and also the need for future research in using them for disc regeneration. CLINICAL SIGNIFICANCE: The various SLRPs that we identified are all known to have a beneficial influence on ECM integrity and a negative effect on the degenerative process at different stages in the evolution of degeneration. Biglycan, which is abundantly present in a fetus, may be suitable for regenerative therapy, and the other SLRPs like Lumican, Prolargin, Decorin, and Chondroadherin may serve the same purpose and/or as biomarkers.

Drug-resistant spinal tuberculosis - Current concepts, challenges, and controversies.

The alarming global increase in drug-resistant strains plagues the global fight to end tuberculosis (TB), especially in developing countries. The often reported poor treatment outcomes, sequelae, and lack of best practice guidelines in drug-resistant spinal TB poses a significant challenge in its efficient management. While multi-drug chemotherapy is still the primary modality of treatment, surgical intervention is essential in specific scenarios. With limited data on management and outcomes in drug-resistant spinal TB, there is no consensus on the appropriate therapy regarding the number and duration of drugs and therapeutic endpoints of this conundrum. In this light of limited evidence, we have performed a systematic computerized search using the Cochrane Database of Systematic Reviews, Scopus, Embase, Web of Science, and PubMed databases and studies published over the past 30 years on drug-resistance in spinal TB have been analyzed. This systematic review aims to review the current epidemiology, clinical features, updates in clinical diagnostics and chemotherapy, surgical management, and outcomes in drug-resistant spinal TB. We also consolidate potential areas of action and emphasize the need for research and large scale trials in the management of drug-resistant spinal TB.

Part 1: profiling extra cellular matrix core proteome of human fetal nucleus pulposus in search for regenerative targets.

Intervertebral disc degeneration is accompanied by a loss of Extra-cellular matrix (ECM) due to an imbalance in anabolic and catabolic pathways. Identifying ECM proteins with anabolic and/or regenerative potential could be the key to developing regenerative therapies. Since human fetal discs grow and develop rapidly, studying these discs may provide valuable insights on proteins with regenerative potential. This study compares core matrisome of 9 fetal and 7 healthy adult (age 22-79) nucleus pulposus (NP), using a proteomic and bioinformatic approach. Of the 33 upregulated proteins in fetus NP's, 20 of which were involved in ECM assembly pathways: fibromodulin, biglycan, heparan sulfate proteoglycan 2, chondroitin sulfate proteoglycan 4, procollagen C-endopeptidase enhancer and Collagen-type 1a1, 1a2, 6a1, 6a3, 11a1, 11a2, 12a1, 14a1 and 15a1. Moreover, 10 of the upregulated proteins were involved in growth pathways 'PI3L-Akt signaling' and 'regulation of insulin like growth factor transport and uptake.' Thrombospondin 1,3 and 4, tenascin C, matrilin-3, and collagen- type 1a1, 1a2, 6a1, 6a3 and 9a1. Additionally, matrillin-2 and 'Collagen triple helix repeat containing 1' were identified as possible regenerative proteins due to their involvement in 'Regeneration' and 'tissue development' respectively. In conclusion, the consistency of human fetal NP's differs greatly from that of healthy adults. In view of these outcomes, the core matrisome of human fetal discs contains an abundant number of proteins that could potentially show regenerative properties, and their potential should be explored in future machinal experiments.

Proteomic Signatures of Healthy Intervertebral Discs From Organ Donors: A Comparison With Previous Studies on Discs From Scoliosis, Animals, and Trauma.

OBJECTIVE: To catalog and characterize the proteome of normal human intervertebral disc (IVD). METHODS: Nine magnetic resonance imaging (MRI) normal IVDs were harvested from 9 different brain dead yet alive voluntary organ donors and were subjected to electrospray ionization-liquid chromatography tandem mass spectrometry (ESI-LC-MS/MS) acquisition. RESULTS: A total of 1,116 proteins were identified. Functional enrichment analysis tool DAVID ver. 6.8 categorized: extracellular proteins (38%), intracellular (31%), protein-containing complex (13%), organelle (9%), membrane proteins (6%), supramolecular complex (2%), and 1% in the cell junction. Molecular function revealed: binding activity (42%), catalytic activity (31%), regulatory activity (14%), and structural activity (7%). Molecular transducer, transporter, and transcription regulator activity together contributed to 6%. A comparison of the proteins obtained from this study to others in the literature showed a wide variation in content with only 3% of bovine, 5% of murine, 54% of human scoliotic discs, and 10.2% of discs adjacent to lumbar burst fractures common to our study of organ donors. Between proteins reported in scoliosis and lumbar fracture patients, only 13.51% were common, further signifying the contrast amongst the various MRI normal IVD samples. CONCLUSION: The proteome of "healthy" human IVDs has been defined, and our results show that proteomic data on IVDs obtained from scoliosis, fracture patients, and cadavers lack normal physiological conditions and should not be used as biological controls despite normal MRI findings. This questions the validity of previous studies that have used such discs as controls for analyzing the pathomechanisms of disc degeneration.

Human intervertebral discs harbour a unique microbiome and dysbiosis determines health and disease.

BACKGROUND: To document the role of sub-clinical infections in disc disorders and investigate the existence of microbiome in intervertebral discs (IVD). METHODS: Genomic DNA from 24 lumbar IVDs [8-MRI normal discs (ND) from brain dead yet alive organ donors, 8-disc herniation (DH), 8-disc degeneration (DD)] was subjected to 16SrRNA sequencing for profiling the diversity of human disc microbiome in health and disease. The disc microbiome was further compared to established human gut and skin microbiomes. RESULTS: All healthy MRI normal discs from brain dead yet alive organ donors also had a rich bacterial presence. A total of 424 different species (355-ND, 346-DD, and 322-DH) were detected, with 42.75% OTUs being classified at kingdom level, 44% at the phylum level, 22.62% at genus level, and 5.5% at species level. Varying biodiversity and abundance between healthy and diseased discs were documented with protective bacteria being abundant in normal discs, and putative pathogens abundant in DD and DH. Propionibacterium acnes had a similar but lower abundance to other pathogens in all three groups ND (3.07%), DD (3.88%), DH (1.56%). Fifty-eight bacteria were common between gut and IVD microbiomes, 29 between skin and IVD microbiomes, and six common to gut/skin/IVD. CONCLUSION: Our study challenges the hitherto concept of sterility in healthy IVD and documented a microbiome even in MRI normal healthy discs. The varying abundance of bacteria between ND, DD, and DH documents 'dysbiosis' as a possible etiology of DD. Many known pathogens were identified in greater abundance than Propionibacterium acnes, and there was evidence for the presence of the gut/skin/spine microbiome axis.

Delayed presentation of urinoma mimicking spondylodiscitis secondary to ureteric injury following carrot stick fracture in ankylosing spondylitis.

INTRODUCTION: Ureteric injuries are rarely associated with spinal trauma with an incidence of less than 1%. Missed injuries can lead to urinoma collection, urosepsis and even death. MATERIALS AND METHODS: A 75-year-old man presented 1 month following fall with high-grade fever and severe back pain mimicking spondylodiscitis clinically. Plain radiograph showed features of ankylosing spondylitis with a suspicious trans-discal injury at L3-L4. Hyper-intense fluid within L3/L4 disk space communicating to a large psoas collection measuring 13 × 6 cms mimicking spondylodiscitis with abscess formation was observed in magnetic resonance imaging (MRI). MRI with contrast enhancement demonstrated a leak through left ureter into the psoas muscle raising suspicion of a ureteric injury. Plain computerized tomography revealed a three-column fracture at L4, and a ureteric leak into the psoas collection with proximal hydronephrosis was seen after contrast administration, establishing the presence of a ureteric fistula resulting in urinoma. RESULTS: Following initial symptomatic improvement after ureteric stenting, the patient succumbed to urosepsis at 3 months. CONCLUSION: We report for the first time a post-traumatic urinoma secondary to ureteric injury clinically mimicking spondylodiscitis. Clinicians need to be aware of the possibility of ureteric injury in hyperextension lumbar fractures occurring in ankylosing spondylitis and treat them early to avoid urological complications.

Motion-Preserving Navigated Primary Internal Fixation of Unstable C1 Fractures.

STUDY DESIGN: Prospective observational study. PURPOSE: To assess the safety, efficacy, and benefits of computed tomography (CT)-guided C1 fracture fixation. OVERVIEW OF LITERATURE: The surgical management of unstable C1 injuries by occipitocervical and atlantoaxial (AA) fusion compromises motion and function. Monosegmental C1 osteosynthesis negates these drawbacks and provides excellent functional outcomes. METHODS: The patients were positioned in a prone position, and cranial traction was applied using Mayfield tongs to restore the C0-C2 height and obtain a reduction in the displaced fracture fragments. An intraoperative, CT-based navigation system was used to enable the optimal placement of C1 screws. A transverse rod was then placed connecting the two screws, and controlled compression was applied across the fixation. The patients were prospectively evaluated in terms of their clinical, functional, and radiological outcomes, with a minimal follow-up of 2 years. RESULTS: A total of 10 screws were placed in five patients, with a mean follow-up of 40.8 months. The mean duration of surgery was 77±13.96 minutes, and the average blood loss was 84.4±8.04 mL. The mean combined lateral mass dislocation at presentation was 14.6±1.34 mm and following surgery, it was 5.2±1.64 mm, with a correction of 9.4±2.3 mm (p <0.001). The follow-up CT showed excellent placement of screws and sound healing. There were no complications and instances of AA instability. The clinical range of movement at 2 years in degrees was as follows: rotation to the right (73.6°±9.09°), rotation to the left (71.6°±5.59°), flexion (35.4°±4.5°), extension (43.8°±8.19°), and lateral bending on the right (28.4°±10.45°) and left (24.8°±11.77°). Significant improvement was observed in the functional Neck Disability Index from 78±4.4 to 1.6±1.6. All patients returned to their occupation within 3 months. CONCLUSIONS: Successful C1 reduction and fixation allows a motion-preserving option in unstable atlas fractures. CT navigation permits accurate and adequate monosegmental fixation with excellent clinical and radiological outcomes, and all patients in this study returned to their preoperative functional status.

Proteomic Signature of Nucleus Pulposus in Fetal Intervertebral Disc.

STUDY DESIGN: Profiling proteins expressed in the nucleus pulposus of fetal intervertebral disc (IVD). PURPOSE: To evaluate the molecular complexity of fetal IVDs not exposed to mechanical, traumatic, inflammatory, or infective insults to generate improved knowledge on disc homeostasis. OVERVIEW OF LITERATURE: Low back pain is the most common musculoskeletal disorder, causing a significant reduction in the quality of life, and degenerative disc disorders mainly contribute to the increasing socioeconomic burden. Despite extensive research, the causative pathomechanisms behind degenerative disc disorders are poorly understood. Precise molecular studies on the intricate biological processes involved in maintaining normal disc homeostasis are needed. METHODS: IVDs of nine fetal specimens obtained from medical abortions were used to dissect out the annulus fibrosus and nucleus pulposus under sterile operating conditions. Dissected tissues were transferred to sterile Cryovials and snap frozen in liquid nitrogen before transporting to the research laboratory for protein extraction and further liquid chromatography tandem mass spectrometry (LC-MS/ MS) analysis. Collected data were further analyzed using Gene Functional Classification Tool in DAVID and STRING databases. RESULTS: A total of 1,316 proteins were identified through LC-MS/MS analysis of nine fetal IVD tissues. Approximately 247 proteins present in at least four fetal discs were subjected to further bioinformatic analysis. The following 10 clusters of proteins were identified: collagens, ribosomal proteins, small leucine-rich proteins, matrilin and thrombospondin, annexins, protein disulfide isomerase family proteins and peroxiredoxins, tubulins, histones, hemoglobin, and prolyl 4-hydroxylase family proteins. CONCLUSIONS: This study provides fundamental information on the proteome networks involved in the growth and development of healthy fetal discs in humans. Systematic cataloging of proteins involved in various structural and regulatory processes has been performed. Proteins expressed most abundantly (collagen type XIV alpha 1 chain, biglycan, matrilin 1, and thrombospondin 1) in their respective clusters also elucidate the possibility of utilizing these proteins for potential regenerative therapies.

Inflammaging determines health and disease in lumbar discs-evidence from differing proteomic signatures of healthy, aging, and degenerating discs.

BACKGROUND CONTEXT: The true understanding of aging and disc degeneration (DD) is still elusive. MRI has not helped our attempts to understand the health and disease status of the discs as it reflects mainly the end morphologic changes and not the changes at a molecular level. Understanding degeneration at a molecular level through proteomics might allow differentiation from normal aging and also aid in the development of biomarkers for early diagnosis and preventive therapies. PURPOSE: To utilize proteomics to understand the molecular basis of healthy, aging, and degenerating discs and conclusively differentiate normal aging and degeneration. STUDY DESIGN: Proteomic analysis of human intervertebral disc samples. METHODS: L4-L5 disc samples from three groups were acquired and subjected to proteomic analysis. Samples from individuals aged in the second, third, and fourth decades were used to represent young healthy discs (Group A). Those from MRI normal donors aged in the fifth, sixth, and seventh decades represented normal aging (Group B). Five degenerated discs obtained from patients at surgery represented degeneration (Group C). The entire proteome map and alteration in protein expressions were further analyzed using bioinformatics analysis. This was a self-funded project. RESULTS: There were 84 common proteins. Specific proteins numbered 225 in A, 315 in B, and 283 in C. By gene ontology biological process identification, Group A predominated with extracellular matrix organization, cytoskeletal structural and normal metabolic proteins. Group B differed in having additional basal expression of immune response, complement inhibitors, and senescence proteins. Group C was different, with upregulation of proteins associated with oxidative stress response, positive regulators of apoptosis, innate immune response, complement activation and defense response to gram positive bacteria indicating ongoing inflammaging. CONCLUSIONS: Our study documented diverse proteome signatures between the young, aging and degenerating discs. Inflammaging was the main differentiator between normal biological aging and DD. CLINICAL SIGNIFICANCE: Multiple inflammatory molecules unique to DD were identified, allowing the possibility of developing specific biomarkers for early diagnosis and thereby provide evidence-based metrics for preventive measures rather than surgical intervention and also to monitor progress of the disease.

Spinal Tuberculosis: Current Concepts.

STUDY DESIGN: Review article. OBJECTIVES: A review of literature on the epidemiology, diagnosis, and management of spinal tuberculosis (TB). METHODS: A systematic computerized literature search was performed using Cochrane Database of Systematic Reviews, EMBASE, and PubMed. Studies published over the past 10 years were analyzed. The searches were performed using Medical Subject Headings terms, and the subheadings used were "spinal tuberculosis," "diagnosis," "epidemiology," "etiology," "management," "surgery," and "therapy." RESULTS: Tissue diagnosis remains the only foolproof investigation to confirm diagnosis. Magnetic resonance imaging and Gene Xpert help in early detection and treatment of spinal TB. Uncomplicated spinal TB has good response to appropriately dosed multimodal ambulant chemotherapy. Surgery is warranted only in cases of neurological complications, incapacitating deformity, and instability. CONCLUSIONS: The incidence of atypical clinicoradiological presentations of spinal TB is on the rise. Improper dosing, inadequate duration of treatment, and inappropriate selection of candidates for chemotherapy has not only resulted in the resurgence of TB but also led to the most dreadful consequence of multidrug resistant strains. In addition, global migration phenomenon has resulted in worldwide spread of spinal TB. The current consensus is to diagnose and treat spinal TB early, prevent complications, promote early mobilization, and restore the patient to his or her earlier functional status.