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1.
Br J Neurosurg ; 37(2): 177-181, 2023 Apr.
Article in English | MEDLINE | ID: mdl-34904496

ABSTRACT

Spondylodiscitis is a common referral to spinal on call services. Identification of the causative organism is vital in order to dictate the appropriate antibiotic treatment. In this context, the surgical and interventional radiology team is often asked to perform a diagnostic biopsy. The aim of the present study was to assess whether the sampling location affects the diagnostic yield. Our results suggest that the overall positive diagnostic yield was 35%. When disc material was included in the sample the diagnostic yield significantly improved to 47%. Bone sampling alone had a positive yield of 15%. Age, pre-biopsy CRP, pre-biopsy use of antibiotics did not seem to affect the likelihood of obtaining a positive yield. These results suggests that when performing image guided biopsies for suspected cases of spondylodiscitis the inclusion of disc material is important.


Subject(s)
Discitis , Intervertebral Disc , Humans , Discitis/diagnostic imaging , Discitis/surgery , Tomography, X-Ray Computed/methods , Retrospective Studies , Intervertebral Disc/diagnostic imaging , Intervertebral Disc/surgery , Intervertebral Disc/pathology , Image-Guided Biopsy/methods , Anti-Bacterial Agents/therapeutic use
2.
Rheumatology (Oxford) ; 60(5): 2461-2466, 2021 05 14.
Article in English | MEDLINE | ID: mdl-33253386

ABSTRACT

OBJECTIVES: Dupilumab blocks the IL-4 receptor (IL-4R) and thus signalling of the 'Th2' cytokines IL-4 and IL-13. It has a license to treat atopic eczema and was recently linked to emergent enthesitis and psoriasis. We investigated the cellular and functional basis for how IL-4/IL-13 regulates the IL-23-IL-17 axis in entheseal stromal, myeloid and lymphocyte cells. METHODS: Immunohistochemistry was performed on healthy enthesis samples from patients undergoing elective spinal surgery to investigate entheseal tissue IL-4R expression and cytokine expression by intracellular flow cytometry for IL-4 and IL-13. Digested human enthesis samples were stimulated with lipopolysaccharide (LPS) for IL-23 induction, either alone or with IL-4 or IL-13. Enthesis fibroblasts were stimulated with TNF and IL-17 with and without IL-4 or IL-13 to assess the effect on CCL20 secretion. Synovial fluid samples from PsA patients were also analysed by ELISA for levels of IL-4 and IL-13. RESULTS: The IL-4/IL-13 receptor was present in both the peri-entheseal bone and enthesis soft tissue, and entheseal-derived T cells produced basal levels of IL-4, but not IL-13. Both IL-4 and IL-13 attenuated LPS-induced entheseal IL-23 production. IL-4 also downregulated secretion of TNF/IL-17A-induced CCL20 from entheseal fibroblasts. Both IL-13 and IL-4 were also detectable in the synovial fluid of PsA patients. We also noted a seronegative inflammatory oligoarthritis whilst under dupilumab therapy. CONCLUSION: Our findings suggest a previously unknown protective role for IL-4/IL-13 in entheseal induction of the IL-23-IL-17 axis. These findings point towards a novel explanation for IL-13 pathway single nucleotide polymorphisms in PsA and also a molecular explanation for why anti-IL-4/IL-13 therapy may induce musculoskeletal entheseal pathology as recently reported.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Eczema/drug therapy , Enthesopathy/chemically induced , Interleukin-13/metabolism , Interleukin-23/metabolism , Interleukin-4/metabolism , Eczema/metabolism , Enthesopathy/metabolism , Humans , Receptors, Interleukin-13/metabolism , Receptors, Interleukin-4/metabolism , Synovial Fluid/metabolism
3.
Ann Rheum Dis ; 79(8): 1044-1054, 2020 08.
Article in English | MEDLINE | ID: mdl-32404344

ABSTRACT

BACKGROUND: The human enthesis conventional T cells are poorly characterised. OBJECTIVES: To study the biology of the conventional T cells in human enthesis. METHODS: CD4+ and CD8+ T cells were investigated in 25 enthesis samples using immunofluorescence, cytometrically, bulk RNAseq and quantitative real-time PCR following anti-CD3/CD28 bead stimulation to determine interleukin (IL)-17A and tumour necrosis factor (TNF) levels. T-cell receptor (TCR) repertoires were characterised and a search for putative T-cell reactivity was carried out using TCR3 database. The impact of pharmacological antagonism with retinoic acid receptor-related orphan nuclear receptor gamma t inhibitor (RORγti), methotrexate and phosphodiesterase type 4 inhibitor (PDE4i) was investigated. RESULTS: Immunofluorescence and cytometry suggested entheseal resident CD4+ and CD8+ T cells with a resident memory phenotype (CD69+/CD45RA-) and tissue residency gene transcripts (higher NR4A1/AhR and lower KLF2/T-bet transcripts). Both CD4+ and CD8+ T cells showed increased expression of immunomodulatory genes including IL-10 and TGF-ß compared with peripheral blood T cells with entheseal CD8+ T cells having higher CD103, CD49a and lower SIPR1 transcript that matched CD4+ T cells. Following stimulation, CD4+ T cells produced more TNF than CD8+ T cells and IL-17A was produced exclusively by CD4+ T cells. RNAseq suggested both Cytomegalovirus and influenza A virus entheseal resident T-cell clonotype reactivity. TNF and IL-17A production from CD4+ T cells was effectively inhibited by PDE4i, while RORγti only reduced IL-17A secretion. CONCLUSIONS: Healthy human entheseal CD4+ and CD8+ T cells exhibit regulatory characteristics and are predicted to exhibit antiviral reactivity with CD8+ T cells expressing higher levels of transcripts suggestive of tissue residency. Inducible IL-17A and TNF production can be robustly inhibited in vitro.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Ligaments, Articular/immunology , T-Lymphocytes, Regulatory/immunology , Tendons/immunology , Adult , CD4-Positive T-Lymphocytes/immunology , Female , Humans , Interleukin-17/immunology , Male , Middle Aged , Tumor Necrosis Factor-alpha/immunology
4.
Ann Rheum Dis ; 78(11): 1559-1565, 2019 11.
Article in English | MEDLINE | ID: mdl-31530557

ABSTRACT

OBJECTIVES: Murine models of interleukin (IL)-23-driven spondyloarthritis (SpA) have demonstrated entheseal accumulation of γδT-cells which were responsible for the majority of local IL-17A production. However, IL-23 blockers are ineffective in axial inflammation in man. This study investigated γδT-cell subsets in the normal human enthesis to explore the biology of the IL-23/17 axis. METHODS: Human spinous processes entheseal soft tissue (EST) and peri-entheseal bone (PEB) were harvested during elective orthopaedic procedures. Entheseal γδT-cells were evaluated using immunohistochemistry and isolated and characterised using flow cytometry. RNA was isolated from γδT-cell subsets and analysed by qPCR. Entheseal γδT-cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, anti-CD3/28 or IL-23 and IL-17A production was measured by high-sensitivity ELISA and qPCR. RESULTS: Entheseal γδT-cells were confirmed immunohistochemically with Vδ1 and Vδ2 subsets that are cytometrically defined. Transcript profiles of both cell populations suggested tissue residency and immunomodulatory status. Entheseal Vδ2 cells expressed high relative abundance of IL-23/17-associated transcripts including IL-23R, RORC and CCR6, whereas the Vδ1 subset almost completely lacked detectable IL-23R transcript. Following PMA stimulation IL-17A was detectable in both Vδ1 and Vδ2 subsets, and following CD3/CD28 stimulation both subsets showed IL-17A and IL-17F transcripts with neither transcript being detectable in the Vδ1 subset following IL-23 stimulation. CONCLUSION: Spinal entheseal Vδ1 and Vδ2 subsets are tissue resident cells with inducible IL-17A production with evidence that the Vδ1 subset does so independently of IL-23R expression.


Subject(s)
Enthesopathy/immunology , Interleukin-17/biosynthesis , Intraepithelial Lymphocytes/metabolism , Receptors, Interleukin/metabolism , T-Lymphocyte Subsets/metabolism , Humans
5.
Ann Rheum Dis ; 78(7): 929-933, 2019 07.
Article in English | MEDLINE | ID: mdl-31018959

ABSTRACT

OBJECTIVE: We investigated whether the normal human spinal enthesis contained resident myeloid cell populations, capable of producing pivotal proinflammatory cytokines including tumour necrosis factor (TNF) and interleukin (IL)-23 and determined whether these could be modified by PDE4 inhibition. METHODS: Normal human enthesis soft tissue (ST) and adjacent perientheseal bone (PEB) (n=15) were evaluated using immunohistochemistry (IHC), digested for myeloid cell phenotyping, sorted and stimulated with different adjuvants (lipopolysaccharide and mannan). Stimulated enthesis fractions were analysed for inducible production of spondyloarthropathy disease-relevant mediators (IL-23 full protein, TNF, IL-1ß and CCL20). Myeloid populations were also compared with matched blood populations for further mRNA analysis and the effect of PDE4 inhibition was assessed. RESULTS: A myeloid cell population (CD45+ HLADR+ CD14+ CD11c+) phenotype was isolated from both the ST and adjacent PEB and termed 'CD14+ myeloid cells' with tissue localisation confirmed by CD14+ IHC. The CD14- fraction contained a CD123+ HLADR+ CD11c- cell population (plasmacytoid dendritic cells). The CD14+ population was the dominant entheseal producer of IL-23, IL-1ß, TNF and CCL20. IL-23 and TNF from the CD14+ population could be downregulated by a PDE4I and other agents (histamine and 8-Bromo-cAMP) which elevate cAMP. Entheseal CD14+ cells had a broadly similar gene expression profile to the corresponding CD14+ population from matched blood but showed significantly lower CCR2 gene expression. CONCLUSIONS: The human enthesis contains a CD14+ myeloid population that produces most of the inducible IL-23, IL-1ß, TNF and CCL20. This population has similar gene expression profile to the matched blood CD14+ population.


Subject(s)
Connective Tissue Cells/metabolism , Interleukin-23/biosynthesis , Myeloid Cells/metabolism , Chemokine CCL20/biosynthesis , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Dendritic Cells/metabolism , Humans , Immunohistochemistry , Interleukin-1beta/biosynthesis , Lipopolysaccharide Receptors/metabolism , Tumor Necrosis Factor-alpha/biosynthesis
7.
Cureus ; 16(1): e53100, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38414690

ABSTRACT

PURPOSE: Magnetic resonance imaging (MRI) is the gold standard investigation for lumbosacral degenerative disc disease. However, there is controversy regarding the clinical value of repeating an MRI scan within 12 months when a patient presents with recurring or changing symptoms. This study measures rates of radiological change in a real-world cohort to guide clinicians when deciding to repeat a scan. METHODS: All patients over a 10-year window in one general hospital who underwent two lumbosacral MRI scans for degenerative disc disease within 12 months of each other were included in the study. All MRI reports were manually reviewed. The level of main vertebral pathology was recorded, along with the location of a disc prolapse. Time intervals between the two scans were calculated, and these were collated into 30-day intervals for analysis. The repeat scans were categorized into three groups: no change, radiological improvement, and radiological deterioration. Patients who had clinically significant deterioration in the form of cauda equina compression on MRI scans were recorded. FINDINGS: Four hundred and eighty-one patients were included for analysis. Three hundred and ninety (81%) showed no change in MRI findings, 18 (3.7%) had improvements in their repeat scans, and 73 (15.3%) demonstrated deterioration in their repeat scans. Of the 73 patients with radiological deterioration, three patients (0.62% of the total) required urgent surgical intervention for cauda equina syndrome (CES). CONCLUSIONS: Though there is no alternative to detailed clinical assessment in determining whether a repeat MRI scan is indicated, the findings demonstrate that repeating MRI within 12 months for patients with lumbosacral degenerative disc disease has a low chance of altering the management plan. Over the 10-year period, only three patients required an urgent change to their clinical management. We believe this data can help guide clinical decision-making when considering a repeat scan.

8.
Bone Jt Open ; 3(1): 85-92, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35084206

ABSTRACT

The development of spinal deformity in children with underlying neurodisability can affect their ability to function and impact on their quality of life, as well as compromise provision of nursing care. Patients with neuromuscular spinal deformity are among the most challenging due to the number and complexity of medical comorbidities that increase the risk for severe intraoperative or postoperative complications. A multidisciplinary approach is mandatory at every stage to ensure that all nonoperative measures have been applied, and that the treatment goals have been clearly defined and agreed with the family. This will involve input from multiple specialities, including allied healthcare professionals, such as physiotherapists and wheelchair services. Surgery should be considered when there is significant impact on the patients' quality of life, which is usually due to poor sitting balance, back or costo-pelvic pain, respiratory complications, or problems with self-care and feeding. Meticulous preoperative assessment is required, along with careful consideration of the nature of the deformity and the problems that it is causing. Surgery can achieve good curve correction and results in high levels of satisfaction from the patients and their caregivers. Modern modular posterior instrumentation systems allow an effective deformity correction. However, the risks of surgery remain high, and involvement of the family at all stages of decision-making is required in order to balance the risks and anticipated gains of the procedure, and to select those patients who can mostly benefit from spinal correction.

9.
Bone Joint J ; 104-B(6): 715-720, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35638217

ABSTRACT

AIMS: The aim of the study was to determine if there was a direct correlation between the pain and disability experienced by patients and size of their disc prolapse, measured by the disc's cross-sectional area on T2 axial MRI scans. METHODS: Patients were asked to prospectively complete visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores on the day of their MRI scan. All patients with primary disc herniation were included. Exclusion criteria included recurrent disc herniation, cauda equina syndrome, or any other associated spinal pathology. T2 weighted MRI scans were reviewed on picture archiving and communications software. The T2 axial image showing the disc protrusion with the largest cross sectional area was used for measurements. The area of the disc and canal were measured at this level. The size of the disc was measured as a percentage of the cross-sectional area of the spinal canal on the chosen image. The VAS leg pain and ODI scores were each correlated with the size of the disc using the Pearson correlation coefficient (PCC). Intraobserver reliability for MRI measurement was assessed using the interclass correlation coefficient (ICC). We assessed if the position of the disc prolapse (central, lateral recess, or foraminal) altered the symptoms described by the patient. The VAS and ODI scores from central and lateral recess disc prolapses were compared. RESULTS: A total of 56 patients (mean age 41.1 years (22.8 to 70.3)) were included. A high degree of intraobserver reliability was observed for MRI measurement: single measure ICC was 0.99 (95% confidence interval (CI) from 0.97 to 0.99 (p < 0.001)). The PCC comparing VAS leg scores with canal occupancy for herniated disc was 0.056. The PCC comparing ODI for herniated disc was 0.070. We found 13 disc prolapses centrally and 43 lateral recess prolapses. There were no foraminal prolapses in this group. The position of the prolapse was not found to be related to the mean VAS score or ODI experienced by the patients (VAS, p = 0.251; ODI, p = 0.093). CONCLUSION: The results of the statistical analysis show that there is no direct correlation between the size or position of the disc prolapse and a patient's symptoms. The symptoms experienced by patients should be the primary concern in deciding to perform discectomy. Cite this article: Bone Joint J 2022;104-B(6):715-720.


Subject(s)
Intervertebral Disc Displacement , Adult , Humans , Intervertebral Disc Displacement/complications , Intervertebral Disc Displacement/diagnostic imaging , Leg , Lumbar Vertebrae/surgery , Pain , Prolapse , Reproducibility of Results
10.
Bone Joint J ; 103-B(8): 1400-1404, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34334046

ABSTRACT

AIMS: The aim of this study was to determine whether there is an increased prevalence of scoliosis in patients who have suffered from a haematopoietic malignancy in childhood. METHODS: Patients with a history of lymphoma or leukaemia with a current age between 12 and 25 years were identified from the regional paediatric oncology database. The medical records and radiological findings were reviewed, and any spinal deformity identified. The treatment of the malignancy and the spinal deformity, if any, was noted. RESULTS: From a cohort of 346 patients, 19 (5.5%) had radiological evidence of scoliosis, defined as a Cobb angle of > 10°. A total of five patients (1.4% of the total cohort) had a Cobb angle of > 40°, all of whom had corrective surgery. No patient with scoliosis had other pathology as a possible cause of the scoliosis and all had been treated with high doses of steroids for leukaemia, either acute or chronic myeloid, or acute lymphoblastic. CONCLUSION: There is an increased prevalence of idiopathic-like scoliosis and larger curves (Cobb angle of > 40°) associated with childhood leukaemia, which has not been previously reported in the literature. Causative factors may relate to the underlying disease process and/or its treatment. Cite this article: Bone Joint J 2021;103-B(8):1400-1404.


Subject(s)
Leukemia , Lymphoma , Scoliosis/epidemiology , Adolescent , Adult , Child , Cohort Studies , Female , Humans , Leukemia/therapy , Lymphoma/therapy , Male , Prevalence , Young Adult
11.
Cureus ; 13(3): e13703, 2021 Mar 04.
Article in English | MEDLINE | ID: mdl-33824837

ABSTRACT

Pyogenic subdural spinal collections are rare but an important pathology to recognise and manage appropriately. We report the case of a 56-year-old female who developed a posterior subdural spinal collection associated with local discitis. There was no direct communication between the infected disc and subdural space, and the collection was located posteriorly within the subdural space which makes this case all the more unusual. We discuss the need for spinal subdural collections to be considered as a differential in patients with back pain and lower limb neurology (especially when there is a known spinal infective focus), the importance of careful interpretation of imaging, and the pathophysiological mechanisms and organisms known to cause spinal subdural collections.

12.
J Clin Orthop Trauma ; 23: 101672, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34790562

ABSTRACT

BACKGROUND: This study aims to assess the quantity and quality of available literature on surgical treatment outcomes of spinal stenosis in adult and paediatric achondroplasia patients through a systematic review of literature and to investigate the suitability of conducting a meta-analysis on outcomes of surgical treatment. METHODS: Online databases were searched according to PRISMA guidelines. No restrictions regarding study design, sample size, previous treatment, or publication date were implemented. The following terms: "Spinal stenosis", "Spinal Decompression", "Spinal fusion", each term separately combined with the term "Achondroplasia" were used. Quality of the included studies were assessed used the Modified Coleman method. RESULTS: Five adult and four paediatric single-sample non-comparative studies were identified for inclusion (176 adult and 102 paediatric patients). Meta-analyses assessed the proportion of patients achieving full resolution of symptoms to be 0.51 (95% CI 0.00 to 1.00); the proportion of patients achieving full or partial resolution of symptoms to be 0.90 (95% CI 0.84 to 0.97); the proportion of procedures requiring re-operation to be 0.42 (95% CI 0.34 to 0.50; and the proportion of procedures involving dural tears to be 0.20 (95% CI 0.02 to 0.39). Statistical heterogeneity was very high for full resolution of symptoms and requirement for dural repair; and very low for other outcomes. CONCLUSIONS: The available literature on this population and condition is sparse, highly heterogenous, and is generally of low quality limiting the value of meta-analysis. Overall, outcomes of surgical decompression of symptomatic spinal stenosis in achondroplasia patients show consistent degree of resolution of symptoms. Duration of symptoms prior to surgical treatment appears to play an important role in the overall outcome of treatment. Therefore, a delay in diagnosis and treatment can potentially be detrimental in achieving a better outcome.

13.
Cells ; 10(2)2021 02 06.
Article in English | MEDLINE | ID: mdl-33562025

ABSTRACT

OBJECTIVE: The spondylarthritides (SpA) are intimately linked to new bone formation and IL-17A and TNF pathways. We investigated spinal soft tissue and bone mesenchymal stem cell (MSC) responses to IL-17A and TNF, including their osteogenesis, adipogenesis, and stromal supportive function and ability to support lymphocyte recruitment. METHODS: Normal spinal peri-entheseal bone (PEB) and entheseal soft tissue (EST) were characterized for MSCs by immunophenotypic, osteogenic, chondrogenic, and adipogenic differentiation criteria. Functional and gene transcriptomic analysis was carried out on undifferentiated, adipo- differentiated, and osteo-differentiated MSCs. The enthesis C-C Motif Chemokine Ligand 20-C-C Motif Chemokine Receptor 6 (CCL20-CCR6) axis was investigated at transcript and protein levels to ascertain whether entheseal MSCs influence local immune cell populations. RESULTS: Cultured MSCs from both PEB and EST displayed a tri-lineage differentiation ability. EST MSCs exhibited 4.9-fold greater adipogenesis (p < 0.001) and a 3-fold lower osteogenic capacity (p < 0.05). IL-17A induced greater osteogenesis in PEB MSCs compared to EST MSCs. IL-17A suppressed adipogenic differentiation, with a significant decrease in fatty acid-binding protein 4 (FABP4), peroxisome proliferator-activated receptor gamma (PPARγ), Cell Death Inducing DFFA Like Effector C (CIDEC), and Perilipin-1 (PLIN1). IL-17A significantly increased the CCL20 transcript (p < 0.01) and protein expression (p < 0.001) in MSCs supporting a role in type 17 lymphocyte recruitment. CONCLUSIONS: Normal spinal enthesis harbors resident MSCs with different in vitro functionalities in bone and soft tissue, especially in response to IL-17A, which enhanced osteogenesis and CCL20 production and reduced adipogenesis compared to unstimulated MSCs. This MSC-stromal-enthesis immune system may be a hitherto unappreciated mechanism of "fine tuning" tissue repair responses at the enthesis in health and could be relevant for SpA understanding.


Subject(s)
Adipogenesis , Interleukin-17/pharmacology , Mesenchymal Stem Cells/cytology , Osteogenesis , Spinal Cord/cytology , Stromal Cells/cytology , Tumor Necrosis Factor-alpha/pharmacology , Adipogenesis/drug effects , Adipogenesis/genetics , Aged , Bone and Bones/cytology , Chemokine CCL20/metabolism , Cytokines/metabolism , Female , Humans , Male , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Osteogenesis/drug effects , Osteogenesis/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, CCR6/metabolism , Stromal Cells/drug effects
14.
Front Immunol ; 12: 635018, 2021.
Article in English | MEDLINE | ID: mdl-33936047

ABSTRACT

Objective: Bacterial and viral infectious triggers are linked to spondyloarthritis (SpA) including psoriatic arthritis (PsA) development, likely via dendritic cell activation. We investigated spinal entheseal plasmacytoid dendritic cells (pDCs) toll-like receptor (TLR)-7 and 9 activation and therapeutic modulation, including JAK inhibition. We also investigated if COVID-19 infection, a potent TLR-7 stimulator triggered PsA flares. Methods: Normal entheseal pDCs were characterized and stimulated with imiquimod and CpG oligodeoxynucleotides (ODN) to evaluate TNF and IFNα production. NanoString gene expression assay of total pDCs RNA was performed pre- and post- ODN stimulation. Pharmacological inhibition of induced IFNα protein was performed with Tofacitinib and PDE4 inhibition. The impact of SARS-CoV2 viral infection on PsA flares was evaluated. Results: CD45+HLA-DR+CD123+CD303+CD11c- entheseal pDCs were more numerous than blood pDCs (1.9 ± 0.8% vs 0.2 ± 0.07% of CD45+ cells, p=0.008) and showed inducible IFNα and TNF protein following ODN/imiquimod stimulation and were the sole entheseal IFNα producers. NanoString data identified 11 significantly upregulated differentially expressed genes (DEGs) including TNF in stimulated pDCs. Canonical pathway analysis revealed activation of dendritic cell maturation, NF-κB signaling, toll-like receptor signaling and JAK/STAT signaling pathways following ODN stimulation. Both tofacitinib and PDE4i strongly attenuated ODN induced IFNα. DAPSA scores elevations occurred in 18 PsA cases with SARS-CoV2 infection (9.7 ± 4 pre-infection and 35.3 ± 7.5 during infection). Conclusion: Entheseal pDCs link microbes to TNF/IFNα production. SARS-CoV-2 infection is associated with PsA Flares and JAK inhibition suppressed activated entheseal plasmacytoid dendritic Type-1 interferon responses as pointers towards a novel mechanism of PsA and SpA-related arthropathy.


Subject(s)
Arthritis, Psoriatic/complications , COVID-19/complications , Dendritic Cells/metabolism , Interferon-alpha/metabolism , Janus Kinases/antagonists & inhibitors , Adjuvants, Immunologic/pharmacology , Adult , Aged , COVID-19/genetics , COVID-19/metabolism , Computational Biology , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Dendritic Cells/drug effects , Female , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Humans , Imiquimod/pharmacology , Janus Kinases/metabolism , Male , Middle Aged , NF-kappa B/metabolism , Oligonucleotides/pharmacology , Phosphodiesterase 4 Inhibitors/pharmacology , Piperidines/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Signal Transduction/drug effects , Signal Transduction/genetics , Toll-Like Receptor 7/metabolism , Toll-Like Receptor 9/metabolism , Transcriptome , Tumor Necrosis Factor-alpha/metabolism
15.
Gynecol Obstet Invest ; 68(3): 213-6, 2009.
Article in English | MEDLINE | ID: mdl-19729940

ABSTRACT

BACKGROUND: Tuberculous paraplegia as a consequence of spinal infiltration in pregnancy is reported to be rare. Analysis of the current literature produces few case studies that report successful outcomes. Delay in diagnosis and treatment may ultimately result in an irreversible neurological deficit. The potential implications of progression are paraplegia and a significant associated morbidity to the fetus if delivered premature. METHODS: Two cases of spinal tuberculosis in pregnancy are reported with description of clinical presentation, neuroradiographic findings and treatment. RESULTS: Both patients made good recoveries after undergoing cesarean section followed by urgent spinal cord decompression and fixation for progression of neurology. On review at 2 years, neither patient had any permanent neurological deficit. Both children suffered no deleterious effects from treatment of the mothers. CONCLUSIONS: A treatment strategy to successfully treat this group of patients is recommended. Although there is a place for both chemotherapeutic and surgical intervention in the treatment of spinal tuberculosis, the authors suggest initiation of treatment with chemotherapy and close neurological monitoring of the patient, unless deterioration in neurological status mandates surgery. Furthermore, the use of steroids for fetal maturation should be used with caution.


Subject(s)
Mycobacterium tuberculosis/isolation & purification , Paraparesis/surgery , Pregnancy Complications, Infectious/surgery , Tuberculosis, Spinal/surgery , Adult , Cesarean Section , Decompression, Surgical , Female , Humans , Paraparesis/microbiology , Pregnancy , Pregnancy Complications, Infectious/microbiology , Pregnancy Trimester, Third , Tuberculosis, Spinal/microbiology , Young Adult
16.
J Trauma ; 65(3): 646-52, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18784579

ABSTRACT

BACKGROUND: Recently, increasing emphasis is being placed upon assessment of the inflammatory status of the patient. Serum inflammatory cytokines, particularly IL-6, have been used as an adjunct to this assessment. Another method uses a combination of simple laboratory and clinical data to provide an assessment of the patient's current level of systemic inflammation, the SIRS. The aim of this study was to investigate, in a group of adult trauma patients, the relationship between the interleukin-6 (IL-6) concentration, the systemic inflammatory response score (SIRS) and outcome. METHODS: In patients with femoral shaft fracture, serum IL-6 levels and clinical parameters were recorded prospectively on admission and on days 1, 3, 5, and 7. Clinical course, the SIRS score and complications were documented. Nonparametric tests were used to assess relationships between variables and receiver operator characteristic (ROC) curves were used to examine their predictive values. Significance was assumed at the p < 0.05 level. RESULTS: Forty-eight patients were included in the final analysis, with a median new injury severity score (NISS) of 31.5 (range, 9-75). The presence of a "SIRS state" detected early (day 1 and 3) positively correlated with the IL-6 measurement from the same period (p < 0.001). ROC curve analysis revealed elevated IL-6 to be significantly diagnostic of a SIRS state (p < 0.001) at all times. Early (days 0 and 1), an IL-6 value above 200 pg/dL diagnosed a SIRS state with an 83% sensitivity and a 75% specificity (area under ROC curve 0.76, p < 0.0001). Both a SIRS state and an IL-6 > 300 pg/mL was associated with a significantly increased risk of complication (pneumonia, MOF, death). Both systems were found to be significantly diagnostic of these complications using ROC curve analysis. CONCLUSIONS: The IL-6 concentration and SIRS score are useful adjuncts to clinical evaluation of the injured patient. In the early phase, they are closely correlated with the NISS and each other. A cutoff value of 200 pg/dL was shown to be significantly diagnostic of a SIRS state. Significant correlations between adverse events and both the IL-6 level and SIRS state are demonstrated.


Subject(s)
Femoral Fractures/blood , Interleukin-6/blood , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/diagnosis , Adolescent , Adult , Aged , Female , Femoral Fractures/complications , Femoral Fractures/therapy , Fracture Fixation , Humans , Injury Severity Score , Length of Stay , Male , Middle Aged , Predictive Value of Tests , ROC Curve , Systemic Inflammatory Response Syndrome/etiology
17.
World J Orthop ; 9(9): 138-148, 2018 Sep 18.
Article in English | MEDLINE | ID: mdl-30254970

ABSTRACT

AIM: To present our results on the use of a single rod instrumentation correction technique in a small number of patients with major medical co-morbidities. METHODS: This study was a prospective single surgeon series. Patients were treated with single rod hybrid constructs and had a minimum 2-year follow-up. Indications included complex underlying co-morbidities, conversion of growing rods to definitive fusion, and moderate adolescent idiopathic primarily thoracic scoliosis with severe eczema and low body mass index (BMI). RESULTS: We included 99 consecutive patients. Mean age at surgery was 12.8 years (SD 3.5 years). Mean scoliosis correction was 62% (SD 15%) from 73° (SD 22°) to 28° (SD 15°). Mean surgical time was 153 min (SD 34 min), and blood loss was 530 mL (SD 327 mL); 20% BV (SD 13%). Mean clinical and radiological follow-up was 3.2 years (range: 2-12) post-operatively. Complications included rod failure, which occurred in three of our complex patients with severe syndromic or congenital kyphoscoliosis (3%). Only one of these three patients required revision surgery to address a non-union. Our revision rate was 2% (including a distal junctional kyphosis in a Marfan's syndrome patient). CONCLUSION: The single rod technique has achieved satisfactory deformity correction and a low rate of complications in patients with specific indications and severe underlying medical conditions. In these children with significant co-morbidities, where the risks of scoliosis surgery are significantly increased, this technique has achieved low operative time, blood loss, and associated surgical morbidity.

18.
J Child Neurol ; 32(7): 657-662, 2017 06.
Article in English | MEDLINE | ID: mdl-28395573

ABSTRACT

This study aims to identify the risk factors leading to the development of severe scoliosis among children with cerebral palsy. A cross-sectional descriptive study of 70 children (aged 12-18 years) with severe spastic and/or dystonic cerebral palsy treated in a single specialist unit is described. Statistical analysis included Fisher exact test and logistic regression analysis to identify risk factors. Severe scoliosis is more likely to occur in patients with intractable epilepsy ( P = .008), poor gross motor functional assessment scores ( P = .018), limb spasticity ( P = .045), a history of previous hip surgery ( P = .048), and nonambulatory patients ( P = .013). Logistic regression model confirms the major risk factors are previous hip surgery ( P = .001), moderate to severe epilepsy ( P = .007), and female gender ( P = .03). History of previous hip surgery, intractable epilepsy, and female gender are predictors of developing severe scoliosis in children with cerebral palsy. This knowledge should aid in the early diagnosis of scoliosis and timely referral to specialist services.


Subject(s)
Cerebral Palsy/complications , Epilepsy/complications , Scoliosis/etiology , Adolescent , Cerebral Palsy/physiopathology , Child , Cross-Sectional Studies , Epilepsy/physiopathology , Female , Humans , Male , Risk Factors , Scoliosis/physiopathology , Sex Factors
19.
Case Rep Emerg Med ; 2016: 6718679, 2016.
Article in English | MEDLINE | ID: mdl-27807487

ABSTRACT

We report two cases of failed attempts at closed reduction of high-energy tibial fractures with an associated fibula fracture. The first case was a 39-year-old male involved in high-speed motorbike collision, while the second was a 14-year-old male who injured his leg following a fall of three metres. Emergency medical services at the scenes of the accidents reported a 90-degree valgus deformity of the injured limb and both limbs were realigned on scene and stabilized. Adequate alignment of the tibia could not be achieved by manipulation under sedation or anaesthesia. Open reduction and exposure of the fracture sites revealed that the distal fibula fragment was "transposed" and entrapped in the medulla of the proximal tibial fragment. Reduction required simulation of the mechanism of injury in order to disengage the fragments and allow reduction. Tibiofibula transposition is a rare complication of high-energy lower limb fractures which has not previously been reported and may prevent adequate closed reduction. Impaction of the distal fibula within the tibial medulla occurs as the limb is realigned by paramedic staff before transfer to hospital. We recommend that when this complication is identified the patient is transferred to the operating room for open reduction and stabilization of the fracture.

20.
World J Orthop ; 7(12): 808-813, 2016 Dec 18.
Article in English | MEDLINE | ID: mdl-28032033

ABSTRACT

AIM: To investigate whether autologous blood transfusion (ABT) drains and intra-operative cell salvage reduced donor blood transfusion requirements during scoliosis surgery. METHODS: Retrospective data collection on transfusion requirements of patients undergoing scoliosis surgery is between January 2006 and March 2010. There were three distinct phases of transfusion practice over this time: Group A received "traditional treatment" with allogeneic red cell transfusion (ARCT) in response to an intra- or post-operative anaemia (Hb < 8 g/dL or a symptomatic anaemia); Group B received intra-operative cell salvage in addition to "traditional treatment". In group C, ABT wound drains were used together with both intra-operative cell salvage and "traditional treatment". RESULTS: Data from 97 procedures on 77 patients, there was no difference in mean preoperative haemoglobin levels between the groups (A: 13.1 g/dL; B: 13.49 g/dL; C: 13.66 g/dL). Allogeneic red cell transfusion was required for 22 of the 37 procedures (59%) in group A, 17 of 30 (57%) in group B and 16 of 30 (53%) in group C. There was an overall 6% reduction in the proportion of patients requiring an ARCT between groups A and C but this was not statistically significant (χ2 = 0.398). Patients in group C received fewer units (mean 2.19) than group B (mean 2.94) (P = 0.984) and significantly fewer than those in group A (mean 3.82) (P = 0.0322). Mean length of inpatient stay was lower in group C (8.65 d) than in groups B (12.83) or A (12.62). CONCLUSION: When used alongside measures to minimise blood loss during surgery, ABT drains and intra-operative cell salvage leads to a reduced need for donor blood transfusion in patients undergoing scoliosis surgery.

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