Transcriptome analysis of the diseased intervertebral disc tissue in patients with spinal tuberculosis.

OBJECTIVE: To investigate the differential expression genes (DEGs) in spinal tuberculosis using transcriptomics, with the aim of identifying novel therapeutic targets and prognostic indicators for the clinical management of spinal tuberculosis. METHODS: Patients who visited the Department of Orthopedics at the Second Hospital, Lanzhou University from January 2021 to May 2023 were enrolled. Based on the inclusion and exclusion criteria, there were 5 patients in the test group and 5 patients in the control group. Total RNA was extracted and paired-end sequencing was conducted on the sequencing platform. After processing the sequencing data with clean reads and annotating the reference genome, FPKM normalization and differential expression analysis were performed. The DEGs and long non-coding RNAs (LncRNAs) were analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. The cis-regulation of differentially expressed mRNAs (DE mRNAs) by LncRNAs was predicted and analyzed to establish a co-expression network. RESULTS: This study identified 2366 DEGs, with 974 genes significantly upregulated and 1392 genes significantly downregulated. The upregulated genes are associated with cytokine-cytokine receptor interactions, tuberculosis, and TNF-α signaling pathways, primarily enriched in biological processes such as immunity and inflammation. The downregulated genes are related to muscle development, contraction, fungal defense response, and collagen metabolism processes. Analysis of LncRNAs from bone tuberculosis RNA-seq data detected a total of 3652 LncRNAs, with 356 significantly upregulated and 184 significantly downregulated. Further analysis identified 311 significantly different LncRNAs that could cis-regulate 777 target genes, enriched in pathways such as muscle contraction, inflammatory response, and immune response, closely related to bone tuberculosis. There are 51 genes enriched in the immune response pathway regulated by cis-acting LncRNAs. LncRNAs that regulate immune response-related genes, such as upregulated RP11-451G4.2, RP11-701P16.5, AC079767.4, AC017002.1, LINC01094, CTA-384D8.35, and AC092484.1, as well as downregulated RP11-2C24.7, may serve as potential prognostic and therapeutic targets. CONCLUSION: The DE mRNAs and LncRNAs in spinal tuberculosis are both associated with immune regulatory pathways. These pathways promote or inhibit the tuberculosis infection and development at the mechanistic level and play an important role in the process of tuberculosis transferring to bone tissue.

Bacterial growth in patients with low back pain and Modic changes: protocol of a multicentre, case-control biopsy study.

INTRODUCTION: Bacterial infection and Modic changes (MCs) as causes of low back pain (LBP) are debated. Results diverged between two randomised controlled trials examining the effect of amoxicillin with and without clavulanic acid versus placebo on patients with chronic LBP (cLBP) and MCs. Previous biopsy studies have been criticised with regard to methods, few patients and controls, and insufficient measures to minimise perioperative contamination. In this study, we minimise contamination risk, include a control group and optimise statistical power. The main aim is to compare bacterial growth between patients with and without MCs. METHODS AND ANALYSIS: This multicentre, case-control study examines disc and vertebral body biopsies of patients with cLBP. Cases have MCs at the level of tissue sampling, controls do not. Previously operated patients are included as a subgroup. Tissue is sampled before antibiotic prophylaxis with separate instruments. We will apply microbiological methods and histology on biopsies, and predefine criteria for significant bacterial growth, possible contamination and no growth. Microbiologists, surgeons and pathologist are blinded to allocation of case or control. Primary analysis assesses significant growth in MC1 versus controls and MC2 versus controls separately. Bacterial disc growth in previously operated patients, patients with large MCs and growth from the vertebral body in the fusion group are all considered exploratory analyses. ETHICS AND DISSEMINATION: The Regional Committees for Medical and Health Research Ethics in Norway (REC South East, reference number 2015/697) has approved the study. Study participation requires written informed consent. The study is registered at ClinicalTrials.gov (NCT03406624). Results will be disseminated in peer-reviewed journals, scientific conferences and patient fora. TRIAL REGISTRATION NUMBER: NCT03406624.

Percutaneous Disc Biopsy versus Bone Biopsy for the Identification of Infectious Agents in Osteomyelitis/Discitis.

PURPOSE: To determine whether sampling of the disc or bone is more likely to yield positive tissue culture results in patients with vertebral discitis and osteomyelitis (VDO). MATERIALS AND METHODS: Retrospective review was performed of consecutive patients who underwent vertebral disc or vertebral body biopsy at a single institution between February 2019 and May 2023. Inclusion criteria were age ≥18 years, presumed VDO on spinal magnetic resonance (MR) imaging, absence of paraspinal abscess, and technically successful percutaneous biopsy with fluoroscopic guidance. The primary outcome was a positive biopsy culture result, and secondary outcomes included complications such as nerve injury and segmental artery injury. RESULTS: Sixty-six patients met the inclusion criteria; 36 patients (55%) underwent disc biopsy, and 30 patients (45%) underwent bone biopsy. Six patients required a repeat biopsy for an initially negative culture result. No significant demographic, laboratory, antibiotic administration, or pain medication use differences were observed between the 2 groups. Patients who underwent bone biopsy were more likely to have a history of intravenous drug use (26.7%) compared with patients who underwent disc biopsy (5.5%; P = .017). Positive tissue culture results were observed in 41% of patients who underwent disc biopsy and 15% of patients who underwent bone biopsy (P = .016). No vessel or nerve injuries were detected after procedure in either group. CONCLUSIONS: Percutaneous disc biopsy is more likely to yield a positive tissue culture result than vertebral body biopsy in patients with VDO.

New contributions on chronic low back pain: disc infection or contaminated cultures?

There is controversy about the likely infectious origin of chronic low back pain, because it has been suggested the possibility of a relationship with infection by Cutibacterium acnes (C. acnes). The aim of this study is to compare four methods to determine the presence of a likely infection caused by C. acnes in surgical disc samples. This work is a cross-sectional observational study in which there are included 23 patients with microdiscectomy indication. Disc samples were taken during surgery and analysis was done by culture, Sanger sequencing, next-generation sequencing (NGS), and real-time PCR (qPCR). Furthermore, clinical data collection was conducted, and it was analyzed the presence of the Modic-like changes on the magnetic resonance imaging. In 5 of the samples from among the 23 patients (21.7%), C. acnes was isolated by culture. However, in none of the samples could its genome be detected through Sanger sequencing, the less sensitive method. Only the qPCR and NGS were able to detect very few copies of the genome of this microorganism in all the samples, with no significant quantitative differences being observed between the patients in whom isolation of the microorganism by culture was evident or not. Furthermore, there were no significant relationships identified between the clinical variables, including Modic alterations and positive cultures. The most sensitive methods to the detect C. acnes were NGS and qPCR. The data obtained do not suggest association between the presence of C. acnes and the clinical process and support the hypothesis that C. acnes is found in these samples only because it is a contamination from the skin microbiome.

Discitis-osteomyelitis: optimizing results of percutaneous sampling.

Vertebral discitis-osteomyelitis is an infection of the spine that involves the intervertebral disc and the adjacent vertebral body but may also extend into the paraspinal and epidural soft tissues. If blood cultures and other culture data fail to identify a causative microorganism, percutaneous sampling is indicated to help guide targeted antimicrobial therapy. Despite limited supporting evidence, withholding antimicrobial therapy for up to 2 weeks is recommended to maximize microbiological yield, although literature supporting this recommendation is limited. During the procedure, technical factors that may improve yield include targeting of paraspinal fluid collections or soft tissue abnormalities for sampling, acquiring multiple core samples if possible, and use of larger gauge needles when available. Repeat sampling may be indicated if initial percutaneous biopsy is negative but should be performed no sooner than 72 h after the initial percutaneous biopsy to ensure adequate time for culture results to return.

Red Light-Mediated Photoredox Catalysis Triggers Nitric Oxide Release for Treatment of Cutibacterium Acne Induced Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) has been known as a highly prevalent and disabling disease, which is one of the main causes of low back pain and disability. Unfortunately, there is no effective cure to treat this formidable disease, and surgical interventions are typically applied. Herein, we report that the local administration of nitric oxide (NO)-releasing micellar nanoparticles can efficiently treat IVDD associated with Modic changes in a rat model established by infection with Cutibacterium acnes (C. acnes). By covalent incorporation of palladium(II) meso-tetraphenyltetrabenzoporphyrin photocatalyst and coumarin-based NO donors into the core of micellar nanoparticles, we demonstrate that the activation of the UV-absorbing coumarin-based NO donors can be achieved under red light irradiation via photoredox catalysis, although it remains a great challenge to implement photoredox catalysis reactions in biological conditions due to the complex microenvironments. Notably, the local delivery of NO can not only efficiently eradicate C. acnes pathogens but also inhibit the inflammatory response and osteoclast differentiation in the intervertebral disc tissues, exerting antibacterial, anti-inflammatory, and antiosteoclastogenesis effects. This work provides a feasible means to efficiently treat IVDD by the local administration of NO signaling molecules without resorting to a surgical approach.

Different responses of cervical intervertebral disc caused by low and high virulence bacterial infection: a comparative study in rats.

The aims of this study were to investigate the outcomes of low- and high-virulence bacterial cervical intervertebral discs (IVDs) infection and its association with cervical IVDs degeneration in rats. A total of 75 clean grade male rats were used to establish the corresponding animal models of low and high virulent bacterial cervical disc infection via an anterior cervical approach, with injection of Propionibacterium acnes (P. acnes) and Staphylococcus epidermidis (S. epidermidis) with a 29 G needle to cervical IVDs. Specimens were collected for evaluation of Blood routine (Blood-RT), histological staining, and gene expression assays after a magnetic resonance imaging (MRI) scan. There were no statistical differences in all groups in white blood cells (WBC) at 2 and 6 weeks postoperatively (P = 0.136). The highest percentage of neutrophils was found in the S. epidermidis group at 2 weeks postoperatively (P = 0.043). MRI and histology showed that at 6 weeks postoperatively, the puncture group and P. acnes group had similar disc degeneration. In the S. epidermidis group, the disc and subchondral bone structure had been destroyed and bony fusion had occurred after the discitis. The upregulation of pro-inflammatory factor expression had the strongest effect of S. epidermidis on the early stage, while the upregulation in the puncture and P. acnes groups was more persistent. P. acnes infection of the cervical IVDs can lead to degenerative changes, whereas S. epidermidis infection leads to the manifestation of septic discitis. The correlation between P. acnes infection and cervical IVDs degeneration found in clinical studies was confirmed.

Frequency and characteristics of bacterial and viral low-grade infections of the intervertebral discs: a prospective, observational study.

STUDY DESIGN: Monocentric, prospective, observational study. OBJECTIVE: The clinical relevance of bacterial colonization of intervertebral discs is controversial. This study aimed to determine a possible relationship between bacterial and viral colonization and low-grade infection of the discs. METHODS: We investigated 447 disc samples from 392 patients. Microbiological culture was used to examine the samples for bacterial growth, polymerase chain reaction (PCR) was used for detection of herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV), and histopathological analysis was used to detect signs of inflammation. The results were compared between subgroups organized according to gender, age, location of the samples, surgical approach, preoperative C-reactive protein (CRP), preoperative and 6 months postoperative Oswestry Disability Index (ODI) and Neck Disability Index (NDI), and Modic changes (MC) of the corresponding endplates. Also, we assessed the occurrence of postoperative infections within 6 months. RESULTS: Microbiological culture was positive in 38.78% of the analyzed intervertebral discs. Altogether, 180 bacteria were isolated. Coagulase-negative staphylococci (CONS) (23.41%) and Cutibacterium acnes (18.05%) were the most frequently detected microorganisms. None of HSV-1, HSV-2, or CMV were detected. Male patients (p = 0.00036) and cervical segments (p = 0.00001) showed higher rates of positive culture results. Ventral surgical approaches ( p < 0.001) and Type 2 MC (p = 0.0127) were significantly associated with a positive microbiological result ( p< 0.001). Neither pre- nor postoperative ODI and NDI are associated with positive culture results. In 4 (1.02%) patients, postoperative spondylodiscitis occurred. CONCLUSIONS: With 447 segments from 392 patients, we present one of the largest studies to date. While disc degeneration caused by HSV-1, HSV-2, and CMV seems unlikely, we found positive microbiological culture results in 38.78% of all discs. The role of local skin flora and sample contamination should be the focus of further investigations. LEVEL OF EVIDENCE: III. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ID: NCT04712487, https://www. CLINICALTRIALS: gov/ct2/show/study/NCT04712487 ).

The Effect of Cutibacterium acnes Infection on Nerve Penetration in the Annulus Fibrosus of Lumbar Intervertebral Discs via Suppressing Oxidative Stress.

Modic changes (MCs) and low back pain are highly correlated and an economic burden to the society. Previous studies have shown that Cutibacterium acnes (C. acnes) infection can lead to MCs. The purpose of this study was to clarify whether and how C. acnes contributes to oxidative stress and nerve growth that potentially leads to low back pain. Neurons from the hippocampus or dorsal root ganglion (DRG) of Sprague-Dawley (SD) rats were cocultured with annulus fibrosus cells (AFCs) with or without the presence of the C. acnes supernatant in vitro. Cell viability, neurite length, oxidative stress, and neuro-related gene expression were examined. Furthermore, samples from the patients with MCs and SD rat model of MCs were used to validate the nerve growth results. Neurons from both the hippocampus and DRG showed neurites when cocultured with AFCs in the environment with/without the C. acnes supernatant. The average neurite length was significantly longer when exposed to the C. acnes supernatant in the hippocampal neuron (217.1 ± 90.0 µm versus 150.1 ± 68.1 µm in the control group) and in the DRG neuron (229.1 ± 91.3 µm versus 149.2 ± 64.8 µm in the control group). Hippocampal neurons showed upregulated expression levels of NeuN, Map2, and Psd95, while upregulation was only seen in Tuj-1 in DRG neurons. Suppressed oxidative stress could be observed using axon growth symbols. Degenerated disc structures and abnormal bone remodelling were found in animal models and clinical samples of MCs, with astrocytes, microglia, and neurons in the disc. Therefore, C. acnes infection was found to cause back pain in the presence of MCs by promoting nerve penetration into the annulus fibrosus by suppressing oxidative stress.

Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen Cutibacterium acnes.

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1ß, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1ß, and other known IL-1ß-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1ß, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1ß and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.

Proteomic analysis reveals critical molecular mechanisms involved in the macrophage anti-spinal tuberculosis process.

Tuberculosis infection activates the autoimmune system. However, the role of host-pathogen interactions involved in Mycobacterium tuberculosis infection is unclear. In this study, we analyzed 6 spinal tuberculosis tissues and 6 herniated disc tissues by using liquid chromatography-tandem mass spectrometry coupled with tandem mass spectrometry, and immunohistochemical staining was performed for validating the results. We identified 42 differential immune-related proteins and 3 hub genes that are primarily localised in the tertiary granule and involved in biological processes such as cellular response to the presence of cadmium ions, regulation of ion transmembrane transport, transmembrane transport, and inflammatory responses. Genes encoding cytochrome B-245 beta chain (CYBB), matrix metallopeptidase 9 (MMP9), and C-X-C motif chemokine ligand 10 (CXCL10) were identified as the hub genes that exhibited anti-tuberculosis activity and were responsible for macrophage resistance against M. tuberculosis. In conclusion, CYBB, MMP9, and CXCL10 resist M. tuberculosis infection through chemotaxis and macrophage activation. Our results indicate that CYBB, MMP9, and CXCL10 could be considered as molecular targets for spinal tuberculosis treatment, which may significantly improve patients' quality of life and prognosis.

Predictive factors for positive disco-vertebral biopsy culture in pyogenic vertebral osteomyelitis, and impact of fluoroscopic versus scanographic guidance.

BACKGROUND: The aims of this study were to identify the predictive factors for microbiological diagnosis through disco-vertebral biopsy (DVB) in patients with pyogenic vertebral osteomyelitis (PVO) and negative blood cultures, and compare the performance of DVB under fluoroscopic versus scanographic guidance. METHODS: We performed a cohort study comparing positive and negative DVB among patients with PVO. All cases of PVO undergoing a DVB for microbiological diagnosis in our center were retrospectively reviewed. Infections due to Mycobacterium tuberculosis, infections on foreign device, and non-septic diseases were excluded. Anamnestic, clinical, biological, microbiological, as well as radiological data were collected from medical charts thanks to a standardized data set. RESULTS: A total of 111 patients were screened; 88 patients were included. Microbiological cultures were positive in 53/88 (60.2%) patients. A thickening of the paravertebral tissue ≥10 mm on magnetic resonance imaging (MRI) in axial MR scans was a predictive factor of DVB microbiological positivity (52.4% vs. 13.3%; p = 0.006; OR = 5.4). Overall, 51 DVB were performed under fluoroscopic guidance and 37 under scanographic guidance. Considering lumbar DVB, 25/36 (69.4%) of cases yielded positive results under fluoroscopic guidance versus 5/15 (33.3%) under scanographic guidance (p = 0.02; OR = 4.4). No adverse event linked to DVB was notified. CONCLUSION: Every patient with PVO and negative blood cultures should undergo a DVB. A thickening of the paravertebral tissue ≥10 mm on MRI is associated with a higher rate of positive DVB culture. A lumbar DVB under fluoroscopic guidance is more sensitive than under scanographic guidance to identify the micro-organism involved.

The role of Propionibacterium acnes in and Modic type 1 changes†:†A literature review.

Propionibacterium acnes (P. acnes) is part of the normal flora of human skin, oral cavity, intestinal tract and external ear canal. However, breach in the mucosa as well as ruptured annulus fibrosus provide favorable pathway for P. acnes to nucleus pulposus where it can proliferate under anaerobic condition. In past two decades many authors have identified P. acnes in routine culture of discs. There studies showed that almost 50% of discs cultured were positive for various organism, and in vast majority of culture positive disc, P. acnes was the primary organism isolated. However, there are few studies that refute the hypothesis that P. acnes has a role in pathogenesis of Modic type 1 changes. Identification of P. acnes in culture indicates the infective patho-mechanism in the pathogenesis of Modic type 1 changes, which may be ameable to antibiotic treatment. However, it is still difficult to identify which subset of these patients (patients with low back pain with type 1 Modic change) are infective in nature. Further investigation and more clinical trails will be required for clear identification of the infective subgroup among low back patient in general. J. Med. Invest. 67 : 21-26, February, 2020.

Percutaneous transforaminal endoscopic discectomy for the treatment of lateral recess stenosis secondary occurred the discal fungus infection.

BACKGROUND: This is a case of lateral recess stenosis secondary occurred the discal fungus infection treated with percutaneous transforaminal endoscopic discectomy (PTED). There has been no relevant reports before. CASE PRESENTATION: A 49-year-old patient who had taken itraconazole for 13 months for lateral recess stenosis secondary occurred the discal fungus infection complained of gradually worsening radiating pain and numbness in the back and inguinal and inner thigh region of right side. In order to relieve the radiating neuralgia and reduce the damage to spinal stability, the minimally invasive PTED was performed.The patient's prognosis was assessed using Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS). During the follow-up, the patient's ODI and VAS scores were decreased significantly. The radiating pain in the inguinal and inner thigh region of right side were significantly alleviated and the discomfort caused by lower back instability was improved by plaster vest. DISCUSSION AND CONCLUSION: PTED not only avoids further damage to the stability of the lumbar spine, but also effectively relieves the symptoms of leg neuroradialgia caused by lateral recess stenosis secondary occurred the discal fungus infection.

CT-guided discitis-osteomyelitis biopsies with negative microbiology: how many days should we wait before repeating the biopsy?

PURPOSE: To determine the number of days to positive CT-guided biopsy sample culture in patients with discitis-osteomyelitis. METHODS: Our study was IRB approved and HIPAA compliant. All CT-guided biopsies performed for acute discitis-osteomyelitis with positive microbiology between 2002 and 2018 were reviewed. Microbiological organism and days to positive biopsy were documented. Mean, median, skew, and standard deviation were calculated. The proportion of positive cultures that become positive after each day has elapsed was also calculated. RESULTS: There were 96 true positive cultures, with 64 (67%) male and 32 (33%) female, ages 57 ± 18 (range 19-87) years. Overall, including all culture results, the mean number of days to positive culture was 2.9 ± 3.5 days. The median number of days was 2, with a positive skew of 2.9. At days 1, 2, 3, 4, and 5, 48%, 68%, 78%, 85%, and 89%, respectively, of biopsy samples had a positive microbiology culture. CONCLUSION: Approximately three-quarters of discitis-osteomyelitis pathogens will be identified by biopsy sample culture by 3 days after CT-guided biopsy. This finding should be considered if planning for a repeat biopsy in the setting of a negative microbiology culture.

[Vertebral osteomyelitis in adults]. / Spondylodiscite chez l'adulte.

Back pain is a frequent reason for consultation. Although commonplace most of the time, back pain can sometimes be the only symptom of vertebral osteomyelitis, an infection that usually affects an intervertebral disc and the two adjacent vertebrae. Microbiology varies with the host's risk factors and local epidemiology. MRI is the preferred radiologic modality. Nevertheless, the definitive diagnosis is based on microbiological and histopathological elements. Antibiotic therapy alone may in some cases lead to cure, while in other cases the use of surgery is necessary. If it isn't diagnosed in time, vertebral osteomyelitis can have serious consequences. Thus, the physician must be familiar with the anamnestic, clinical and paraclinical elements that will bring him to actively look for this disease.

Les maux de dos sont un motif de consultation fréquent. Bien que souvent banals, ils peuvent parfois être le seul symptôme d'une spondylodiscite, une infection qui touche généralement un disque intervertébral et les deux vertèbres adjacentes. La microbiologie varie en fonction des facteurs de risque de l'hôte et de l'épidémiologie locale. L'IRM est la modalité radiologique de choix. Néanmoins, le diagnostic définitif repose sur des éléments microbiologiques et histopathologiques. Une antibiothérapie seule peut dans certains cas mener à la guérison, tandis que dans d'autres cas la chirurgie est nécessaire. Lorsqu'elle n'est pas diagnostiquée à temps, la spondylodiscite peut être lourde de conséquences. Le médecin doit ainsi connaître les éléments anamnestiques, cliniques et paracliniques devant le faire rechercher activement cette maladie.

Is the discopathy associated with Modic changes an infectious process? Results from a prospective monocenter study.

BACKGROUND: The local infectious origin and the putative role of Cutibacterium acnes (CA) of a particular subtype of discopathy (Modic 1) are still debated. PURPOSE: To establish the association of CA in intervertebral disc (IVD) and Modic 1 discopathy in patients with low back pain. METHODS: The prevalence of bacteria in IVD samples obtained by anterior approach in patient with chronic low back pain harboring Modic type 1, 2 or no Modic changes was compared to that measured in IVD samples obtained by posterior approach for sciatica. From 45 patients included in the study, 77 discs samples were obtained: 58 by anterior approach (32 Modic 1/2 changes, 26 without Modic change) and 19 by posterior approach. Conventional microbial cultures, universal 16S rRNA molecular detection and a CA specific PCR were performed. RESULTS: 12 /77 (15.6%) disc samples were culture positive. Among the 10 CA positive cultures, 5 out of 58 (8.6%) were identified from specimens obtained by anterior approach and 5/19 (26.3%) from posterior approach (p = 0.046). Moreover, the percentage of CA culture positive sample was statistically no different between the patient with or without Modic changes. The CA prevalence was lower through molecular, culture-free approaches: the universal 16S rRNA PCR was positive for 6 specimens, including one CA positive sample and the CA specific PCR was positive for one specimen obtained by posterior approach. CONCLUSIONS: In spine surgery the prevalence of CA in culture was significantly higher in IVD samples collected through a posterior approach compared to an anterior approach, suggesting a contamination process. This study did not support the CA related local infectious origin of Modic 1 discopathy.

The bacteria-positive proportion in the disc tissue samples from surgery: a systematic review and meta-analysis.

PURPOSE: The role of bacteria, especially Propionibacterium acnes (P. acnes), in human intervertebral disc diseases has raised attention in recent years. However, limited sample size of these studies and diverse bacteria-positive proportion made this topic still controversial. We aimed to review related articles and summarize the bacteria-positive proportion in these studies. METHODS: We searched the PubMed, Cochrane Library, Embase for related literature from January 2001 to May 2018, and the reference articles were also searched. The random effects or fixed effects meta-analysis was used to pool the overall positive proportion or odds ratio of these studies. RESULTS: We found 16 relevant articles and 2084 cases of the bacteria culture from surgery. Within the 16 included studies, 12 studies' results supported the infection in the discs. The pooled bacterial infection rate was 25.3%. The pooled P. acnes infection rate was 15.5%. The overall pooled P. acnes proportion in bacteria-positive discs was 56.4%. We also found that the presence of bacteria may contribute to the development of Modic change with the odds ratio as 1.27 (95% CI: 0.44-3.64), but this result is not significant due to heterogeneity, so further study is needed. CONCLUSION: The existence of bacteria in the intervertebral discs was proved by many studies. However, the variety in sample collecting and culture methods is still obvious and the positive rate also fluctuated within the studies. Standardized and reliable methods should be taken to promote the study in the future. These slides can be retrieved under Electronic Supplementary Material.

Latent infection of low-virulence anaerobic bacteria in degenerated lumbar intervertebral discs.

BACKGROUND: The existence of latent low-virulence anaerobic bacteria in degenerated intervertebral discs (IVDs) remains controversial. In this study, the prevalence of low-virulence anaerobic bacteria in degenerated IVDs was examined, and the correlation between bacterial infection and clinical symptoms was analysed. METHODS: Eighty patients with disc herniation who underwent discectomy were included in this study. Under a stringent protocol to ensure sterile conditions, 80 disc samples were intraoperatively retrieved and subjected to microbiological culture. Meanwhile, tissue samples from the surrounding muscle and ligaments were harvested and cultured as contamination markers. The severity of IVD degeneration and the prevalence of Modic changes (MCs) were assessed according to preoperative MRI analysis. RESULTS: Of the 80 cultured discs, 54 were sterile, and 26 showed the presence of bacteria: Propionibacterium acnes (21 cases) and coagulase-negative staphylococci (5 cases). MRI revealed that the presence of bacteria was significantly associated with MCs (P<0.001). However, there was no significant association between bacterial infection and the severity of IVD degeneration (P = 0.162). CONCLUSIONS: Our findings further validated the presence of low-virulence anaerobic bacteria in degenerated IVDs, and P. acnes was the most frequent bacterium. In addition, the latent infection of bacteria in IVDs was associated with Modic changes. Therefore, low-virulence anaerobic bacteria may play a crucial role in the pathophysiology of MCs and lumbar disc herniation.

Importance of Propionibacterium acnes hemolytic activity in human intervertebral discs: A microbiological study.

Most patients with chronic lower back pain (CLBP) exhibit degenerative disc disease. Disc specimens obtained during initial therapeutic discectomies are often infected/colonized with Propionibacterium acnes, a Gram-positive commensal of the human skin. Although pain associated with infection is typically ascribed to the body's inflammatory response, the Gram-positive bacterium Staphylococcus aureus was recently observed to directly activate nociceptors by secreting pore-forming α-hemolysins that disrupt neuronal cell membranes. The hemolytic activity of P. acnes in cultured disc specimens obtained during routine therapeutic discectomies was assessed through incubation on sheep-blood agar. The ß-hemolysis pattern displayed by P. acnes on sheep-blood agar was variable and phylogroup-dependent. Their molecular phylogroups were correlated with their hemolytic patterns. Our findings raise the possibility that pore-forming proteins contribute to the pathogenesis and/or symptomology of chronic P. acnes disc infections and CLBP, at least in a subset of cases.