A novel rat model of vertebral inflammation-induced intervertebral disc degeneration mediated by activating cGAS/STING molecular pathway.

In this study, we describe a new rat model of vertebral inflammation-induced caudal intervertebral disc degeneration (VI-IVDD), in which IVD structure was not damaged and controllable segment and speed degeneration was achieved. VI-IVDD model was obtained by placing lipopolysaccharide (LPS) in the caudal vertebral bodies of rats. Rat experimental groups were set as follows: normal control group, group with a hole drilled in the middle of vertebral body and not filled with LPS (Blank group), group with a hole drilled in the middle of vertebral body and filled with LPS (Mid group), and group with hole drilled in the vertebral body in proximity of IVD and filled with LPS (NIVD group). Radiological results of VI-IVDD rats showed a significant reduction in the intervertebral space height and decrease in MRI T2 signal intensity. Histological stainings also revealed that the more the nucleus pulposus and endplate degenerated, the more the annulus fibrosus structure appeared disorganized. Immunohistochemistry analysis demonstrated that the expression of Aggrecan and collagen-II decreased, whereas that of MMP-3 increased in Mid and NIVD groups. Abundant local production of pro-inflammatory cytokines was detected together with increased infiltration of M1 macrophages in Mid and NIVD groups. Apoptosis ratio remarkably enhanced in Mid and NIVD groups. Interestingly, we found a strong activation of the cyclic GMP-AMP synthase /stimulator of interferon gene signalling pathway, which is strictly related to inflammatory and degenerative diseases. In this study, we generated a new, reliable and reproducible IVDD rat model, in which controllable segment and speed degeneration was achieved.

Identifying risk groups of infectious spondylitis in patients with end-stage renal disease under hemodialysis: a propensity score-matched case-control study.

BACKGROUND: Patients with end-stage renal disease (ESRD) under hemodialysis (HD) are at greater risks of infectious spondylitis (IS), but there is no reliable predictor that facilitate early detection of this relatively rare and insidious disease. METHODS: A retrospective review of the medical records from patients with ESRD under HD over a 12-year period was performed at a tertiary teaching hospital, and those with a first-time diagnosis of IS were identified. A 1:4 propensity score-matched case-control study was carried out, and baseline characteristics, underlying diseases, and laboratory data were compared between the study group and the control group, one month before the date of diagnosis or the index date respectively. RESULTS: A total of 16 patients with IS were compared with 64 controls. After adjustment, recent access operation (odds ratio [OR], 13.27; 95% confidence interval [CI], 3.53 to 49.91; p <  0.001), degenerative spinal disease (OR, 12.87; 95% CI, 1.89 to 87.41; p = 0.009), HD through a tunneled cuffed catheter (OR, 6.75; 95% CI, 1.74 to 26.14; p = 0.006), low serum levels of hemoglobin, albumin, as well as high levels of red blood cell volume distribution width (RDW), alkaline phosphatase (ALP), and high sensitivity C-reactive protein were significant predictors for a IS diagnosis one month later. Receiver operating characteristic curves for hemoglobin, RDW, ALP, and albumin all showed good discrimination. The further multivariate models identified both high serum ALP levels and low serum RDW levels following a recent access intervention in patients with relatively short HD vintages may be indicative of the development of IS. CONCLUSION: Patients under HD with relatively short HD vintages showing either elevated ALP levels or low RDW levels following a recent access intervention should prompt clinical awareness about IS for timely diagnosis.

Bacille Calmette-Guérin (BCG) spondylitis with adjacent mycotic aortic aneurysm after intravesical BCG therapy: a case report and literature review.

BACKGROUND: Although intravesical bacille Calmette-Guérin (BCG) therapy is accepted as an effective treatment for bladder cancer, serious complications may occur in rare cases. To date, only 4 cases have been reported in which the patient developed a combination of mycotic aortic aneurysm and BCG spondylitis. Accurate diagnosis of BCG spondylitis is important because it is an iatrogenic disease, and its treatment is different from usual tuberculous spondylitis. However, distinguishing BCG spondylitis from usual tuberculous spondylitis is very difficult and takes a long time. In this study, we were able to suspect BCG spondylitis at an early stage from the result of the interferon-gamma release assay (IGRA). CASE PRESENTATION: We encountered a case of BCG spondylitis with adjacent mycotic aortic aneurysm after intravesical BCG therapy in a 76-year-old man. We performed a 2-stage operation to obtain spine stabilization and replace the aneurysm with a synthetic graft. We started multidrug therapy with antituberculosis medication, excluding pyrazinamide, because the patient's history of BCG therapy, negative IGRA, and positive of tuberculosis-polymerase chain reaction (Tb-PCR) suggested that the pathogenic bacteria of the spondylitis was BCG. Eventually the bacterial strain was identified as BCG by PCR-based genomic deletion analysis. CONCLUSIONS: BCG infection should be considered in patients who have been treated with BCG therapy, even if the treatment was performed several months to several years previously. In the case of a patient with a history of BCG therapy, a positive Tb-PCR result and negative IGRA result probably suggest BCG infections, if the possibility of false-negative IGRA result can be excluded.

Increased and normalized uptake of 18F-FDG in a case of bone periprosthetic infection treated by antibiotics.

We report the case of a 69 years old man with left hip prosthesis, who presented clinical, biochemical and imaging signs of periprosthetic infection treated with linezolid, an antibacterial agent of the oxazolidinone class. Two weeks after this treatment, a fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan showed increased uptake in the skeleton and also increased uptake in several focal areas in the spine and near the prosthesis and the surgical wound on the left gluteus medius. Bone marrow biopsy was negative; meanwhile the antibiotic therapy, after four weeks of treatment was stopped due to red blood cells and platelets toxicity. Six weeks later, the patient developed high fever again and in order to revaluate the periprosthetic inflammation, he was resubmitted to 18F-FDG PET/CT which showed normal 18F-FDG uptake in the whole skeleton, including the prosthesis and the subcutaneous wound. Some focal areas of increased uptake in the lumbar spine were still detected. In the next 4 weeks the patient was under a "watch and wait" follow-up in a steady state. IN CONCLUSION: In the case we report, since we found no otnt focal areas in the lumbar spine where due to age-related bone deformities including some Schmorl's nodes. The inflammation in the bone prosthesis and the subcutaneous wound responded almost totally to the antibiotic treatment we applied.

Whole-body Vibration at Thoracic Resonance Induces Sustained Pain and Widespread Cervical Neuroinflammation in the Rat.

BACKGROUND: Whole-body vibration (WBV) is associated with back and neck pain in military personnel and civilians. However, the role of vibration frequency and the physiological mechanisms involved in pain symptoms are unknown. QUESTIONS/PURPOSES: This study asked the following questions: (1) What is the resonance frequency of the rat spine for WBV along the spinal axis, and how does frequency of WBV alter the extent of spinal compression/extension? (2) Does a single WBV exposure at resonance induce pain that is sustained? (3) Does WBV at resonance alter the protein kinase C epsilon (PKCε) response in the dorsal root ganglia (DRG)? (4) Does WBV at resonance alter expression of calcitonin gene-related peptide (CGRP) in the spinal dorsal horn? (5) Does WBV at resonance alter the spinal neuroimmune responses that regulate pain? METHODS: Resonance of the rat (410 ± 34 g, n = 9) was measured by imposing WBV at frequencies from 3 to 15 Hz. Separate groups (317 ± 20 g, n = 10/treatment) underwent WBV at resonance (8 Hz) or at a nonresonant frequency (15 Hz). Behavioral sensitivity was assessed throughout to measure pain, and PKCε in the DRG was quantified as well as spinal CGRP, glial activation, and cytokine levels at Day 14. RESULTS: Accelerometer-based thoracic transmissibility peaks at 8 Hz (1.86 ± 0.19) and 9 Hz (1.95 ± 0.19, mean difference [MD] 0.290 ± 0.266, p < 0.03), whereas the video-based thoracic transmissibility peaks at 8 Hz (1.90 ± 0.27), 9 Hz (2.07 ± 0.20), and 10 Hz (1.80 ± 0.25, MD 0.359 ± 0.284, p < 0.01). WBV at 8 Hz produces more cervical extension (0.745 ± 0.582 mm, MD 0.242 ± 0.214, p < 0.03) and compression (0.870 ± 0.676 mm, MD 0.326 ± 0.261, p < 0.02) than 15 Hz (extension, 0.503 ± 0.279 mm; compression, 0.544 ± 0.400 mm). Pain is longer lasting (through Day 14) and more robust (p < 0.01) after WBV at the resonant frequency (8 Hz) compared with 15 Hz WBV. PKCε in the nociceptors of the DRG increases according to the severity of WBV with greatest increases after 8 Hz WBV (p < 0.03). However, spinal CGRP, cytokines, and glial activation are only evident after painful WBV at resonance. CONCLUSIONS: WBV at resonance produces long-lasting pain and widespread activation of a host of nociceptive and neuroimmune responses as compared with WBV at a nonresonance condition. Based on this work, future investigations into the temporal and regional neuroimmune response to resonant WBV in both genders would be useful. CLINICAL RELEVANCE: Although WBV is a major issue affecting the military population, there is little insight about its mechanisms of injury and pain. The neuroimmune responses produced by WBV are similar to other pain states, suggesting that pain from WBV may be mediated by similar mechanisms as other neuropathic pain conditions. This mechanistic insight suggests WBV-induced injury and pain may be tempered by antiinflammatory intervention.

Occult radiological sacroiliac abnormalities in patients with inflammatory bowel disease who do not present signs or symptoms of axial spondylitis.

OBJECTIVES: To investigate radiological sacroiliac abnormalities in IBD patients without musculoskeletal symptoms and to determine the clinical and familiar differences between IBD patients with and without radiologic sacroiliac joint (SIJ) abnormalities. Subsequently, the patients with x-ray alterations were followed for 3 years in order to assess the onset of chronic inflammatory back pain (IBP). METHODS: 81 patients (55 Crohn-CD- and 26 ulcerative rettocolitis-UC) with remittent and low active IBD, from a tertiary referral centre of Gastroenterology Unit, were studied using SIJ x-rays. Differences in IBD clinical variables (activity and duration of CD and UC, extra-intestinal involvement, treatment with surgery and not, ESR and CRP levels), familiarity (for psoriasis, IBD, spondyloarthritis, coeliac syndrome), between patients with SIJ x-ray findings and without were investigated. Patients with radiological sacroiliac joint abnormalities were followed up clinically for 3 years and the onset of symptoms of chronic (higher than 3 consecutive months) IBP was investigated. RESULTS: 22/81 patients (27.1%) showed radiological SIJ abnormalities at baseline: isolated sclerosis in 17/22 (77.3%) and localised erosions in 12/22 (54.5%). Radiological SIJ involvement did not correlate with IBD clinical and familial variables. All patients were HLA B27 negative. At 3 years, 4/22 patients (18.1%) presented chronic IBP symptoms with bone oedema at MRI. CONCLUSIONS: In IBD, occult radiological SIJ alterations might precede the onset of axial symptoms but, in the absence of clinical signs, it is not possible to identify some IBD features or familiar predisposition that might be more frequent when SIJ abnormalities are involved. Clinical follow-up might be useful in these patients for a diagnosis of axial spondyloarthritis onset.

[Pneumorrhachis, spondylitis and meningitis secondary to emphysematous cystitis. Report of one case]. / Pneumorraquis, espondilitis y meningitis secundarios a cistitis enfisematosa.

We report a 57-year-old woman who presented with low back pain, fever and impairment of consciousness. The patient was admitted to the intensive care unit in Glasgow 8, with neck stiffness, peritoneal irritation, leukocytosis, hyperglycemia requiring insulin and a urine test suspecting an infection. Brain CT was unremarkable, while CT of the abdomen and pelvis evidenced emphysematous cystitis, retropneumoperitoneum and pneumorrhachis. Blood, urine and cerebrospinal fluid cultures were positive to Escherichia coli. She was treated with ceftriaxone, ciprofloxacin and amikacin during one month followed by ciprofloxacin until completing 100 days. The air in the spinal canal and bladder decreased. However she suffered several infectious complications such as multiple paravertebral, epidural and psoas abscesses, L5-S1 spondylitis and a L3 fracture. As an inflammatory complication she developed a bulbar infarction and tetraparesis. She had a good clinical response with medical treatment, partial improvement of the paresis and reduction of epidural abscesses.

[Septic arthritis and spondylitis].

Septic arthritis and spondylitis in elderly adult are uncommon disease. But symptoms and signs of septic arthritis and spondylitis are an important medical emergency, with high mortality and morbidity. Delayed or inadequate treatment can result in irreversible joint destruction and neurological condition. Early diagnoses as well as prompt and effective treatment are essential for avoiding severe outcomes. In spite of advances in diagnostic imaging techniques, the incidence of septic arthritis and spondylitis appears to have been increased. The aging of the population, the widespread use of immunosuppressant therapies, including systemic corticosteroids, cytokines and anticytokines, and growing resistance to conventional antibiotics seem to be the major cause.

[A case of lung disease and spondylitis due to Mycobacterium intracellulare in a immunocompetent patient].

A 73-year-old immunocompetent woman was diagnosed with pulmonary nontuberculous mycobacterial (NTM) infection and followed up without treatment. She developed lumbago and consulted a physician. Spinal magnetic resonance imaging (MRI) indicated pyogenic spondylitis and she was admitted to the orthopedics department at our hospital 4 months after developing lumbago. Spinal MRI on admission revealed spondylitis in L5/S1 and thus antibiotic agents were administered. However, the antibiotics were ineffective and she underwent surgery. Mycobacterium avium complex (MAC) was identified from cultures of surgical specimens, and the histopathological findings revealed epithelioid cell granuloma with necrosis. Spondylitis due to MAC was diagnosed and the patient was administered with rifampicin, ethambutol, clarithromycin and streptomycin. She was discharged on hospital day 113 with a good outcome. Recently, the number of spondylitis due to NTM infection in immunocompetent patients have been increasing. We should take it into consideration that not only bacteria and Mycobacterium tuberculosis but also NTM infection can cause infectious spondylitis.

[Case of pyogenic spondylitis and epidural abscess after chemoradiotherapy for hypopharyngeal cancer].

Osteomyelitis is one of the most severe late complications of radiation therapy. The condition can arise from osteoradionecrosis and can be fatal if it occurrs in vertebrae. A 71-year-old woman, who had undergone chemoradiotherapy for hypopharyngeal cancer 6 months previously, presented with severe neck pain. An MRI examination revealed pyogenic spondylitis and an epidural abscess of the neck. Neurological disturbance in the extremities developed despite the administration of antibiotics for 5 days. Drainage and a laminectomy were performed to control the infection and to relieve spinal cord compression. The patient had no postoperative complications at 15 months after surgery. Previous case reports of osteomyelitis and epidural abscess following radiation therapy for head and neck cancer with surgical treatment tended to have a good clinical course. Severe neck pain and a limitation in the range of motion of the neck are considered to be serious clinical features of osteomyelitis. Since infection in the necrotic mucosa leads to pyogenic spondylitis, a repeated cultivation survey of the mucosa is nessesary for adequate antibiotics therapy. For osteomyelitis and epidural abscess following radiation therapy, immediate specific surgical treatment of the involved region is strongly suggested if antibiotics are not effective or spinal cord compression develops.

Capacitive coupling reduces instrumentation-related infection in rabbit spines: a pilot study.

BACKGROUND: Postoperative spine infections cause considerable morbidity. Patients are subjected to long-term antibiotic regimens and may require further surgery. Delivery of electric current through instrumentation can detach biofilm, allowing better antibiotic penetration and assisting in eradicating infection. QUESTION/PURPOSES: We asked (1) whether capacitive coupling treatment in combination with a single dose of antibiotics would reduce infection rates when compared with antibiotics alone in a rabbit spine infection model, (2) whether it would decrease the overall bacterial burden, and (3) whether there was a time-dependent response based on days treated with capacitive coupling. METHODS: Thirty rabbits were subjected to a well-established spine infection model with a single dose of intravenously administered systemic ceftriaxone (20 mg/kg of body weight) prophylaxis. Two noncontiguous rods were implanted inside dead space defects at L3 and L6 challenged with 10(6) colony-forming units of Staphylococcus aureus. Rabbits were randomly treated with a capacitive coupling or control device. Instrumentation and soft tissue bacterial growth were assessed after 7 days. RESULTS: Sites treated with capacitive coupling showed a decrease in the incidence of positive culture: 36% versus 81% in the control group. We observed no difference in the soft tissue's infectious burden. Overall bacterial load was not decreased with capacitive coupling. CONCLUSIONS: Capacitive coupling in conjunction with antibiotics reduced the instrumentation-related infection rate compared with antibiotics alone. CLINICAL RELEVANCE: Capacitive coupling noninvasively delivers an alternating current that may detach biofilm from instrumentation. Treatment of infection may be successful without removal of instrumentation, allowing for improved stability and overall decreased morbidity.

Vertebral body osteolysis following the use of bone morphogenetic protein in spinal surgery: a mimicker of infection.

This report describes the imaging findings in three patients who developed lumbar spine osteolysis after posterior spinal fusion using rhBMP-2. These cases demonstrate the variable course of osteolysis, as well as the importance of recognizing its radiological appearances to prevent confusion with infection following spinal fusion.

Pyogenic Spondylitis Caused by Staphylococcus schleiferi in a Patient with Crohn's Disease.

Staphylococcus schleiferi has rarely been reported to cause pyogenic spondylitis. A 42-year-old man had been treated for Crohn's disease with immunosuppressive agents and home parenteral nutrition via a central vein (CV) port. The patient was admitted to our hospital, presenting with neck pain and a fever. A neurological examination showed slight weakness in his left-hand muscles, and he was diagnosed with pyogenic spondylitis of C6 and C7 vertebral bodies due to catheter-related blood stream infection caused by S. schleiferi. An early diagnosis by magnetic resonance imaging, CV port removal and antibiotic therapy targeting S. schleiferi improved his symptoms.

Psoriatic arthritis: update on pathophysiology, assessment and management.

Psoriatic arthritis (PsA) is classified as a spondyloarthropathy and characterised by synovitis, enthesitis, dactylitis and spondylitis usually manifesting as skin and nail psoriasis. Our understanding about the PsA disease state, its genetics, pathophysiology and comorbidities, as well as the ability to assess and treat the disease, has advanced as a result of significant collaborative efforts by rheumatologists and dermatologists in the development of classification criteria, outcome measures to assess the various clinical domains, and treatment trials with agents also used for diseases such as rheumatoid arthritis (RA) and psoriasis. Biological agents, especially the antitumour necrosis factors, have demonstrated significant efficacy and reasonable safety in all clinical domains of the disease, resulting in amelioration of clinical symptoms, inhibition of structural damage and improvement of function and quality of life. Although there is considerable overlap with RA, there are some differences in pathophysiology and approach to assessment and management that are important to consider. This paper reviews these subjects, with an emphasis on recent data.

The effectiveness of a biologic agent on axial manifestations of psoriatic arthritis. A twelve months observational study in a group of patients treated with etanercept.

OBJECTIVES: To investigate the effectiveness of etanercept on axial manifestations of a group of patients with established psoriatic arthritis (PsA). METHODS: This was a multicentre observational study. PsA was classified based on the CASPAR criteria. Inclusion criteria were refractory PsA with axial manifestations and suitability for anti TNF-α therapy. Effectiveness was defined according to the ASAS response criteria (BASDAI: 50% relative or absolute change of 20mm and expert opinion in favour of continuation), and on the improvements of BASFI, anthropometric measures, PASI, ESR and CRP at 12 months. PASI 50 and 75 were also assessed, as well as the ACR20 and ACR50 response criteria for patients with peripheral arthritis. Comparisons between baseline and after 12-month treatment were done using the Wilcoxon signed rank test for the end-points considered. RESULTS: The study included 32 patients (25/7 M/F; median age 51yrs; 25th-75th percentiles: 34.5-58.7; median disease duration 14.5 yrs; 25th-75th percentiles: 9.2-17.00). Effectiveness of etanercept was observed in 72% of patients for the BASDAI (p<0.001), in 68% for the BASFI (p<0.001), in 76% for ESR (p<0.001) and in 68% of patients for CRP (p<0.01). The PASI improved in 72% of patients treated (p<0.0001), while PASI 50 and PASI 75 was reached in 81% and 55% of patients, respectively. ACR 20 and 50 was reached in 78 and 56% of patients with peripheral involvement respectively. CONCLUSIONS: The present study has shown that etanercept is effective on axial manifestations of established PsA, confirming the positive effects of anti TNF-α therapy on clinical manifestations of the disease.

Pyogenic Spondylitis in Multidisciplinary Therapies of Gynecologic Malignancies: Three Cases Reports.

Both during and after cancer treatment, pyogenic spondylitis is an uncommon but serious complication. Because pyogenic spondylitis is often recognized as a complication of a distant process causing bacteremia, it initially may be misdiagnosed the primary infection such as urinary tract infection. Consequently, a considerable delay in diagnosis frequently occurs. In addition, estrogen deprivation caused by cancer treatments including RT/CCRT, CT and surgical therapy promotes changes of the immune system. We report two cases of pyogenic spondylitis in a patient with vaginal cancer that occurred delay of the diagnosis, and in a patient with endometrial cancer that had chronic steroid use, and one case of suppurative osteomyelitis in a patient with vulvar cancer that had diabetes mellitus with obesity. Gynecologic oncologists must consider the diagnosis of pyogenic spondylitis based on clinical symptoms such as localized lumbago and medical history. Estrogen deprivation, repeated cancer treatment, diabetes mellitus with obesity, immunosuppression by chronic steroid use are risk factors of pyogenic spondylitis. To prevent delay in diagnosis of pyogenic spondylitis, it is necessary that we must have careful management and follow-up considering all of information such as clinical features and medical history on patients during and after treating for gynecologic malignancies.

Analysis of the Curative Effect of Posterior Approach on Lumbar Brucellar Spondylitis with Abscess through Magnetic Resonance Imaging under Improved Watershed Algorithm.

To explore the performance of improved watershed algorithm in processing magnetic resonance imaging (MRI) images and the effect of the processed images on the treatment of lumbar brucellar spondylitis (BS) with abscess by the posterior approach, the watershed algorithm was improved by adding constraints such as noise reduction and regional area attribute. 50 patients with abscessed lumbar disc herniation admitted to the hospital from January 2018 to January 2019 were selected, and all of them were examined by MRI. They were rolled into two groups in random. The treatment group (n = 25) accepted surgery with the aid of MRI images processed by the improved watershed algorithm, and the control group (Ctrl group) (n = 25) accepted surgery with the aid of unprocessed MRI images. The improved watershed algorithm can accurately segment the spine, and the segmentation results were relatively excellent. In contrast with the unprocessed MRI image, that processed by the improved watershed algorithm had a positive effect on the operation. In contrast with the Ctrl group, the visual analogue scale pain score (VAS), oxygen desaturation index (ODI), erythrocyte sedimentation rate (ESR), and high sensitivity C-reactive protein (CRP) were obviously lower (p < 0.05). The improved watershed algorithm proposed performs better in MRI image processing and can effectively enhance the resolution of MRI images. At the same time, the posterior approach has a good effect in the treatment of lumbar BS with abscess and is worthy of clinical promotion.

[Spinal infections: typical and atypical imaging features]. / Infections rachidiennes: aspects typiques et atypiques.

While the imaging features of established spondylodiscitis are well known, other presentations may be misleading. The purpose of this article is to review the typical imaging features of spondylodiscitis as well as some more atypical and unusual imaging features (early spondylodiscitis, sceptic spondylitis, septic arthritis of facet joints, primary epidural abscess, unusual germs, neonate).