Machine learning and deep learning for the diagnosis and treatment of ankylosing spondylitis- a scoping review.

Background and objectives: Machine Learning (ML) and Deep Learning (DL) are novel technologies that can facilitate early diagnosis of Ankylosing Spondylitis (AS) and predict better patient-specific treatments. We aim to provide the current update on their use at different stages of AS diagnosis and treatment, describe different types of techniques used, dataset descriptions, contributions and limitations of existing work and ed to identify gaps in current knowledge for future works. Methods: We curated the data of this review from the PubMed database. We searched the full-text articles related to the use of ML/DL in the diagnosis and treatment of AS, for the period 2013-2023. Each article was manually scrutinized to be included or excluded for this review as per its relevance. Results: This review revealed that ML/DL technology is useful to assist and promote early diagnosis through AS patient characteristic profile creation, and identification of new AS-related biomarkers. They can help in forecasting the progression of AS and predict treatment responses to aid patient-specific treatment planning. However, there was a lack of sufficient-sized datasets sourced from multi-centres containing different types of diagnostic parameters. Also, there is less research on ML/DL-based AS treatment as compared to ML/DL-based AS diagnosis. Conclusion: ML/DL can facilitate an early diagnosis and patient-tailored treatment for effective handling of AS. Benefits are especially higher in places with a lack of diagnostic resources and human experts. The use of ML/DL-trained models for AS diagnosis and treatment can provide the necessary support to the otherwise overwhelming healthcare systems in a cost-effective and timely way.

Gut microbiome and metabolome to discover pathogenic bacteria and probiotics in ankylosing spondylitis.

Objective: Previous research has partially revealed distinct gut microbiota in ankylosing spondylitis (AS). In this study, we performed non-targeted fecal metabolomics in AS in order to discover the microbiome-metabolome interface in AS. Based on prospective cohort studies, we further explored the impact of the tumor necrosis factor inhibitor (TNFi) on the gut microbiota and metabolites in AS. Methods: To further understand the gut microbiota and metabolites in AS, along with the influence of TNFi, we initiated a prospective cohort study. Fecal samples were collected from 29 patients with AS before and after TNFi therapy and 31 healthy controls. Metagenomic and metabolomic experiments were performed on the fecal samples; moreover, validation experiments were conducted based on the association between the microbiota and metabolites. Results: A total of 7,703 species were annotated using the metagenomic sequencing system and by profiling the microbial community taxonomic composition, while 50,046 metabolites were identified using metabolite profiling. Differential microbials and metabolites were discovered between patients with AS and healthy controls. Moreover, TNFi was confirmed to partially restore the gut microbiota and the metabolites. Multi-omics analysis of the microbiota and metabolites was performed to determine the associations between the differential microbes and metabolites, identifying compounds such as oxypurinol and biotin, which were correlated with the inhibition of the pathogenic bacteria Ruminococcus gnavus and the promotion of the probiotic bacteria Bacteroides uniformis. Through experimental studies, the relationship between microbes and metabolites was further confirmed, and the impact of these two types of microbes on the enterocytes and the inflammatory cytokine interleukin-18 (IL-18) was explored. Conclusion: In summary, multi-omics exploration elucidated the impact of TNFi on the gut microbiota and metabolites and proposed a novel therapeutic perspective: supplementation of compounds to inhibit potential pathogenic bacteria and to promote potential probiotics, therefore controlling inflammation in AS.

Genetic variability of three common NK and γδ T cell receptor genes (FCγ3R, NCR3, and DNAM-1) and their role in Polish patients with rheumatoid arthritis and ankylosing spondylitis.

Various lymphocyte subpopulations, including NK cells as well as γδ T cells, have been considered an important element in the pathogenesis of autoimmune, inflammatory, rheumatic diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). The aim of this study was to assess the potential role of polymorphic variations in the genes coding for three NK and γδ T cell receptors: NCR3, FCγR3A, and DNAM-1 (rs1052248, rs396991, and rs763361, respectively) in the disease susceptibility and the efficacy of treatment with TNF inhibitors. The study included 461 patients with RA, 168 patients with AS, and 235 voluntary blood donors as controls. The NCR3 rs1052248 AA homozygosity prevailed in RA in patients lacking rheumatoid factor (p = 0.044) as well as in those who manifested the disease at a younger age (p = 0.005) and had higher CRP levels after 12 weeks of anti-TNF therapy (p = 0.021). The FCγR3A rs396991 polymorphism was associated with pain visual analogue scale (VAS) values before the initiation of anti-TNF treatment. Lower VAS values were observed in the GG homozygous RA patients (p = 0.024) and in AS patients with the TT genotype (p = 0.012). Moreover, AS heterozygous patients with the TG genotype presented higher CRP levels in the 12th week of anti-TNF treatment (p = 0.021). The findings suggest that the NCR3 rs1052248 AA homozygosity may have an adverse effect on RA, while the T allele potentially plays a protective role in the development of AS. Moreover, the rs1052248 T allele and TT genotype appear to have a favorable impact on the response to anti-TNF therapy in RA patients.

Haemophagocytic Lymphohistiocytosis Following the anti-PD-1 Nivolumab in a Patient with Gastric Cancer and Ankylosing Spondylitis.

Background: Autoimmune diseases are not contraindications for immune checkpoint inhibitors (ICI) therapy in patients with cancer. However, immune-related adverse events (irAEs) are frequently observed in patients receiving ICIs including dermatitis, thyroiditis, colitis, and pneumonitis. Thrombocytopenic purpura, aplasia, and haemophagocytic lymphohistiocytosis (HLH) are rarely observed during ICIs. Case description: We report the case of a male patient with pre-existing untreated HLA B27 and ankylosing spondylitis with gastric cancer and liver metastases. The 79-year-old man was treated with anti-HER2 trastuzumab and anti-PD-1 nivolumab. Seventeen days after the seventh cycle of treatment, he presented at the emergency department with acute fever, confusion, and hypotension. Laboratory results showed pancytopenia, and elevation of ferritin and triglyceride. No infections were detected. Although not seen in a bone marrow biopsy, clinical presentation, and absence of infection, together with an H-score of 263, indicated HLH. The patient was treated with dexamethasone for four days and discharged on a tapering dose of steroids. At the two-month follow-up, clinical presentation was normal and blood test almost normalised. At 8 months, no liver metastases were observed. Conclusions: In a patient with a pre-existing autoimmune condition, immunotherapy led to the development of HLH, which was controlled by glucocorticoid. Absence of the feature of haemophagocytosis in the bone marrow biopsy did not exclude the diagnosis, as HLH can occur in the spleen or in the liver. Glucocorticoid therapy did not prevent the anti-cancer effect of ICIs, and liver metastases disappeared 8 months post-HLH. This case warrants further research on the interplay between autoimmunity and ICI response, as well as ICI-induced irAEs. LEARNING POINTS: Haemophagocytic lymphohistiocytosis (HLH) post seventh cycle of trastuzumab (anti-HER2) and nivolumab (anti-PD-1) was controlled with glucocorticoid.Breach of tolerance was due to immunotherapy-induced HLH in a patient with pre-existing autoimmune condition (HLA B27- positive ankylosing spondylitis).There was a complete disappearance of liver metastases 8 months post-HLH.

Genetically Proxied Autoimmune Diseases and the Risk of Facial Aging.

Purpose: Previous studies have suggested a relationship between autoimmune diseases and the risk of facial skin aging. However, evidence from population-based studies on this topic is limited, leaving the causal association between these factors unknown. This study aimed to systematically evaluate the causal effects of 18 autoimmune diseases on the risk of facial skin aging, aim of providing strategies to mitigate early facial aging in patients with autoimmune diseases. Patients and Methods: We conducted univariate Mendelian randomization (UVMR) analyses to examine the causal relationship between 18 autoimmune diseases and facial aging using publicly available summary data from genome-wide association studies (GWASs). We also conducted multivariate Mendelian randomization (MVMR) analyses to adjust for confounding factors, including smoking, alcohol consumption, and body mass index (BMI). Results: The main inverse variance weighted (IVW) method revealed that genetically proxied ankylosing spondylitis (AS) (OR 1.017; 95% CI: 1.003-1.031; P=0.018), sicca syndrome (SS) (OR 1.008; 95% CI: 1.005-1.011; P= 2.66×10-6), systemic lupus erythematosus (SLE) (OR 1.006; 95% 1.001-1.011; P=0.014), multiple sclerosis (MS) (OR 1.004; 95% CI: 1.001-1.007; P=0.021), primary sclerosing cholangitis (PSC) (OR 1.002; 95% CI: 1.000-1.004; P=0.023), and celiac disease (CeD) (OR 1.002; 95% CI: 1.001-1.004; P=0.009) were significantly associated with higher risk of facial aging. After adjusting for potential confounding factors, the association persisted between AS, SLE, and CeD. Conclusion: These findings indicated that autoimmune diseases play a causal role in facial skin aging. Therefore, patients with autoimmune diseases should take appropriate measures to prevent early facial aging.

Bacteroides fragilis spondylitis after suspected oral ulcer: A Clinical Case and Comprehensive Literature Review.

This paper reports a case of Bacteroides fragilis induced spondylitis. Diagnosis was confirmed through blood culture and metagenomic sequencing of pus for pathogen detection. Due to persistent lumbar pain, surgical intervention became imperative, resulting in favorable postoperative outcomes. A detailed patient history revealed a severe episode of oral ulceration two weeks before symptom onset, although a direct link to the infection remained elusive. Leveraging insights from this case, we conducted a comprehensive literature review on B. fragilis spondylitis, elucidating clinical manifestations, diagnostic methodologies, and therapeutic strategies.

Determination of the Efficiency of Magnetic Resonance Imaging in the Evaluation of Compressive Myelopathy.

Background The phrase "compressive myelopathy" refers to compression of the spinal cord, either internally or externally. This compression might arise from various sources such as a herniated disc, post-traumatic compression, and epidural abscess as well as epidural or intradural neoplasms. Magnetic resonance imaging (MRI) plays a crucial role in differentiating between compressive and non-compressive myelopathy. After eliminating compressive lesions, attention is directed toward intrinsic cord-related causes of acute myelopathy including vascular, infectious, and inflammatory pathologies. Aims The study aimed to assess different etiologies of compressive myelopathy, analyze the MRI features of spinal cord compressive lesions, classify the lesions depending on site, and correlate MRI findings with intraoperative findings and histopathology in operated cases. Material & methods A total of 50 patients, who exhibited clinical symptoms indicative of compressive myelopathy sent to the Radiology department, Rangaraya Medical College (RMC), Kakinada for MRI spine were included in the study. It's an observational cross-sectional study. Statistical Package for Social Sciences (SPSS) version 22.0 (IBM Corp., Armonk, USA) was used for statistical calculations. Result Among the 50 cases of compressive myelopathy, the etiologies are distributed as follows: trauma (22 cases), infection (12 cases), primary neoplasm (eight cases), and secondary neoplasm (eight cases); extradural compressive lesions (84%) and Intradural-extramedullary lesions (16%). Conclusion Utilizing MRI successfully assessed the spinal cord integrity and characterized spinal tumors. Consequently, the study concludes that MRI is a highly definitive, sensitive, and accurate tool for evaluating compressive myelopathy.

A study of the association between single nucleotide polymorphisms of the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene and the risk of ankylosing spondylitis in Egyptians.

BACKGROUND: Ankylosing spondylitis (AS) is often regarded as the prototypical manifestation of spondylo-arthropathies that prevalently involves the axial skeleton with the potential attribution of ERAP2 polymorphisms to AS predisposition. The purpose of this study was to determine the genetic association between ERAP2 gene rs2910686, and rs2248374 single nucleotide polymorphisms (SNPs) and the risk of ankylosing spondylitis in the Egyptian population. METHODS AND RESULTS: A cross-sectional work involved 200 individuals: 100 AS individuals diagnosed based on modified New York criteria in 1984 with 100 healthy controls matched in age and gender. The study included a comprehensive evaluation of historical data, clinical examinations, and evaluation of the activity of the disease using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). A comprehensive laboratory and radiological evaluation were conducted, accompanied by an assessment and genotyping of the ERAP2 gene variants rs2248374 and rs2910686. This genotyping was performed utilizing a real-time allelic discrimination methodology.Highly statistically substantial variations existed among the AS patients and the healthy control group regarding rs2910686 and rs2248374 alleles. There was a statistically significant difference between rs2910686 and rs2248374 regarding BASDAI, BASFI, mSASSS, ASQoL, V.A.S, E.S.R, and BASMI in the active AS group. CONCLUSIONS: ERAP2 gene SNPs have been identified as valuable diagnostic biomarkers for AS patients in the Egyptian population being a sensitive and non-invasive approach for AS diagnosis especially rs2910686. Highly statistically significant variations existed among the AS patients and the healthy control group regarding rs2910686 alleles and genotypes.Further research is recommended to explore the potential therapeutic implications of these SNPs.

Literature review of non-pharmacological treatment for patients with axial spondyloarthritis.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disorder affecting the sacroiliac joints and axial spine. Along with pharmacotherapy, non-pharmacological interventions for axSpA are crucial and constitute the cornerstone of treatment. Here, we review the evidence for non-pharmacological treatment of axSpA as a basis for the 2023 Korean treatment recommendations for patients with axSpA. The effectiveness of the core non-pharmacological approaches, such as education, smoking cessation, and exercise, has been reaffirmed. High-quality research on surgical treatment is limited. However, total hip replacement is advised in patients with ongoing pain or disability and visible structural damage to the hip on imaging. Urgent spinal intervention should be considered in cases of acute spinal pain with neurological deficiency or concurrent unstable fractures. Evidence for complementary therapies, including spas and acupuncture, remains insufficient.

Biopsychosocial Management of Rural Ankylosing Spondylitis in a Pregnant Woman: A Case Report.

In a rural Japanese setting, this case report delves into managing a post-partum woman diagnosed with ankylosing spondyloarthritis (AS), showcasing the complexities of balancing effective pain relief with breastfeeding. The study highlights a multifaceted approach that incorporates medical treatment, psychosocial support, and comprehensive patient education, which are essential in rural healthcare where resources may be scarce. Initially managed with diclofenac due to its safer profile for breastfeeding, the patient's treatment was eventually escalated to adalimumab, aligning with improved circumstances regarding breastfeeding. This case emphasizes the critical role of holistic, patient-centered care in family medicine, particularly for managing maternal and child health chronic conditions. It illustrates how integrating mental health support, acknowledging patient fears, and educating families can significantly enhance patient care and outcomes. Through this approach, the report advocates for a broader application of family medicine principles to improve maternal and child health services in rural settings, demonstrating the importance of tailored healthcare strategies that consider patients' medical and emotional needs.

Frequency of fibromyalgianess in patients with rheumatoid arthritis and ankylosing spondylitis: A multicenter study of Turkish League Against Rheumatism (TLAR) network.

Objectives: This study aimed to evaluate the frequency of fibromyalgianess, fibromyalgia syndrome (FS), and widespread pain in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and their relationship with clinical and demographic parameters. Patients and methods: This cross-sectional multicenter trial was performed in 14 centers across Türkiye between June 2018 and November 2019. Out of 685 patients recruited from the accessible population, 661 patients (342 RA, 319 AS; 264 males, 397 females; mean age: 48.1±12.9 years; range, 17 to 88 years) met the selection criteria. In these cohorts, those who did not meet the criteria for FS and had widespread pain (widespread pain index ≥7) were evaluated as a separate group. Clinical status and demographic parameters of patients in both cohorts were evaluated as well as the evaluations of RA and AS patients with widespread pain (widespread pain index ≥7) and RA and AS patients with FS groups. In addition, correlations between polysymptomatic distress scale (PSD) scores and Visual Analog Scale (VAS), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and Disease Activity Score using 28 joint counts for RA patients and VAS, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Ankylosing Spondylitis Disease Activity Score (ASDAS) for AS patients were analyzed. Results: Frequencies of patients with FS and patients who had PSD scores ≥12 were 34.1% and 44.4% in all RA patients, respectively. Moreover, FS and PSD scores ≥12 were found in 29.2% and 36.9% of all AS patients, respectively. PSD scores of RA patients with FS were higher than all RA patients and RA patients with widespread pain. SDAI and CDAI scores of RA patients with FS were higher than all RA patients and RA patients with widespread pain. Similarly, PSD scores of AS patients with FS were higher than all AS patients and AS patients with widespread pain. ASDAS-erythrocyte sedimentation rate and BASDAI scores of AS patients with FS were found higher than all AS patients and AS patients with widespread pain. Conclusion: Disease activity scores, including pain in RA and AS, were higher in the presence of FS or fibromyalgianess. It may be related to clinical parameters, but cohort studies with long-term follow-up are needed to reveal causality. Additionally, to avoid overtreatment, coexistence of fibromyalgianess should be kept in mind in patients who have inflammatory diseases such as RA and AS, particularly with intractable widespread pain.

Aryl hydrocarbon receptor gene expression in ankylosing spondylitis and its correlation with interleukin-17, RAR-related orphan receptor gamma t expression, and disease activity indices.

Objectives: Considering the role of T helper (Th)17 cells in the pathogenesis of ankylosing spondylitis (AS), the aim of this study was to determine the correlation between aryl hydrocarbon receptor (AHR) gene expression and the expression of Th17-related genes including interleukin (IL)-17 and RAR-related orphan receptor gamma t (RORγt) transcription factor. Patients and methods: Thirty patients with AS (26 males, 4 females; mean age: 36.1±8.1 years) and 30 age- and sex-matched healthy individuals (26 males, 4 females; mean age: 36.2±14.6 years) were recruited for the case-control study between June 2021 and January 2022. Ribonucleic acid (RNA) was extracted from peripheral blood cells and expression levels of AHR, IL-17, RORγt, and AHR repressor (AHRR) genes were evaluated using real-time polymerase chain reaction technique. The serum level of IL-17 was evaluated with enzyme-linked immunosorbent assay. Results: The results showed a nonsignificant elevation of AHR, IL-17, and RORγt gene expression in the patient group compared to the control. There was a direct correlation between AHR gene expression and IL-17 and RORγt genes and a negative correlation between AHR and AHRR expression. Moreover, AHR gene expression showed a weak correlation with disease activity indices, including Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Global Score, and Ankylosing Spondylitis Quality of Life. Moreover, the serum level of IL-17 was higher in AS patients compared to the healthy group (p=0.02). Conclusion: Upregulated expression of the AHR gene in ankylosing spondylitis and its correlation with IL-17 and ROR-γ t gene expression suggests that it could be a potential diagnostic and therapeutic target for AS.

Correlation between clinical disease activity and sacroiliac magnetic resonance imaging detection in axial spondyloarthropathy.

Objectives: The study aimed to evaluate the correlation between the clinical disease activity of axial spondyloarthropathy (axSpA) and magnetic resonance imaging findings of the sacroiliac joint. Patients and methods: Thirty-two patients (21 males, 11 females; mean age: 39.3±9.2 years; range, 18 to 55 years) who were diagnosed with axSpA according to the Assessment in Spondyloarthritis International Society classification criteria between November 2015 and August 2017 were included in this cross-sectional study. Visual Analog Scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-erythrocyte sedimentation rate (ESR), and ASDAS-C-reactive protein (CRP) were used as the indicators of clinical activity. Magnetic resonance imaging of the sacroiliac joint was performed and the Spondyloarthritis Research Consortium of Canada (SPARCC) score was evaluated by a radiologist who was blinded to the clinical and laboratory parameters of the patients. Results: The mean duration of symptom onset was 9.3±7.7 years, and the mean duration of diagnosis was 3.6±2.8 years. Human leukocyte antigen (HLA)-B27 was positive in 16 (50%) patients. There was no correlation between the SPARCC score and VAS, BASDAI, MASES, BASFI, ASDAS-CRP, ASDAS-ESR, ESR, and CRP values (p>0.05). In the HLA-B27 subgroup analyses, a statistically significant correlation was found between HLA-B27-negative patients and SPARCC score (r=0.639, p=0.008). Conclusion: No relationship was found between other clinical disease parameters and sacroiliac joint imaging findings, except for the relationship between the SPARCC and BASDAI in HLA-B27- negative patients with axSpA.

Cervical tuberculosis treated with closed system abscess evacuation, and percutaneous laser disc decompression combined with secretome derived from umbilical cord mesenchymal stem cells: A case report.

INTRODUCTION AND IMPORTANCE: Minimal invasive surgery is preferred as it offers the same benefit with less tissue damage, especially in the cervical area where a lot of critical structure resides. Mesenchymal stem cells (MSCs) and its secretome provide a promising regenerative intervention to damaged tissue. We report a cervical spinal tuberculosis case with hemiparesis treated with minimally invasive surgery combined with a regenerative approach. CASE PRESENTATION: A 13-year-old boy presented with weakness in his left arm and left leg, accompanied by hemiparesthesia. The patient was unable to get up from bed, run, and jumpRadiology examination showed compression fracture, intervertebral disc retropulsion, spinal cord compression, and paravertebral cold abscess. The patient was treated with a single minimal invasive surgery consisting of closed system abscess evacuation, and percutaneous laser disc decompression combined with umbilical cord-derived mesenchymal stem cells. CLINICAL DISCUSSION: The pain, weakness, and numbness were gone two days after surgery. The patient could carry out normal activities, even doing sports such as mini soccer and badminton. This clinical improvement was obtained as he carried out some procedures. The cold abscess aspiration removed infection focus which prevents further vertebra destruction, PLDD which decompresses the retropulsed discs, and implantation of MSCs and secretomes which regenerate and strengthen the destructed bone and surrounding tissue. CONCLUSION: Closed system abscess evacuation, and percutaneous laser disc degeneration combined with secretome derived from UC-MSC are minimally-invasive strategies with promising results. Further studies are required to investigate its efficacy.

Comparative study of two laboratory techniques for the detection of HLA-B27 in patients with axial spondyloarthritis: a cross-sectional analysis.

BACKGROUND: The diagnostic and prognostic relevance of Human Leukocyte Antigen B-27 (HLA-B27) in Axial Spondyloarthritis (AxSpA) is undeniable, with 70% of Ankylosing Spondylitis (AS) patients carrying the B27 gene, contrasted with a mere 4.35% in the general population. Flow cytometry (FC) and Polymerase Chain Reaction (PCR) have emerged as the predominant techniques for routine HLA-B27 typing. While various studies have compared these methods, none have catered to the unique characteristics of the Brazilian demographic. Therefore, this research aims to compare FC and PCR in a Brazilian cohort diagnosed with AxSpA. METHODS: An analytical cross-sectional study was undertaken involving 62 AxSpA outpatients from a Brazilian University Hospital. Both FC and PCR-SSP assays were utilized to ascertain HLA-B27 typing. The outcomes (either confirming or refuting the allele's presence) underwent rigorous scrutiny. Agreement between the methodologies was assessed using the kappa statistic. A p-value of < 0.05 was deemed statistically significant. RESULTS: Of the participants, 90.3% (n = 56) were HLA-B27 positive according to FC, while 79% (n = 49) were identified as positive using the PCR method. FC exhibited a sensitivity rate of 98% paired with a specificity of 38.5%. The Positive Predictive Value for FC stood at 85.7%, and the Negative Predictive Value was 83.5%. Consequently, the overall accuracy of the FC method was gauged at 85.5%. A kappa coefficient of κ = 0.454 was derived. CONCLUSIONS: FC demonstrated noteworthy sensitivity and satisfactory accuracy in HLA-B27 detection, albeit with a reduced specificity when contrasted with PCR-SSP. Nevertheless, given its cost-effectiveness and streamlined operation relative to PCR, FC remains a pragmatic option for preliminary screening in clinical practice, especially in low-income regions. To optimize resource allocation, we advocate for a refined algorithm that initiates by assessing the relevance of HLA-B27 typing based on Choosing Wisely recommendations. It then leans on FC, and, if results are negative yet clinical suspicion persists, advances to PCR. This approach aims to balance diagnostic accuracy and financial prudence, particularly in regions contending with escalating medical costs.

Comparison of oxidative stress, lipid peroxidation and inflammatory markers between rheumatoid arthritis and ankylosing spondylitis patients.

Objectives: To measure the levels of superoxide dismutase and malondialdehyde along with erythrocyte sedimentation rate and C-reactive protein in patients of rheumatoid arthritis and ankylosing spondylitis. METHODS: The comparative, cross-sectional study was conducted from February 2 to December 30, 2022, at the Centre for Research in Experimental and Applied Medicine laboratory of the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Department of Rheumatology, Pak Emirates Military Hospital, Rawalpindi. The sample comprised healthy controls in group 1, patients of rheumatoid arthritis in group 2 and patients of ankylosing spondylitis in group 3. Blood samples were assessed for levels of superoxide dismutase, malondialdehyde, erythrocyte sedimentation rate and C-reactive protein. Data was analysed using SPSS 25. RESULTS: Of the 180 subjects, 60(33.3%) were in group 1; 32(53.3%) females and 28(46.7%) males with mean age 34.9±6.4 years. There were 60(33.3%) patients in group 2; 35(58.3%) females and 25(41.7%) males with mean age 46.0±11.1 years. There were 60(33.3%) patients in group 3, and all 60(100%) were males with mean age 35.9±6.9 years. Superoxide dismutase level was significantly low and malondialdehyde level was significantly high in groups 2 and 3 compared to group 1 (p<0.05). Erythrocyte sedimentation rate was the highest in group 2, followed by group 3 (p<0.05). C-reactive protein levels were the highest in group 2 and the lowest in group 3 (p<0.05). A significantly negative correlation (p<0.001) was found between superoxide dismutase and malondialdehyde. CONCLUSIONS: Oxidative stress played a pivotal role in chronic inflammatory rheumatic diseases, like rheumatoid arthritis and ankylosing spondylitis.

Giant Pseudotumour Following Ceramic on Polyethylene Total Hip Replacement.

Introduction: Metal reaction and pseudotumor formation are very rare complications following ceramic on polyethylene total hip replacement. Pseudotumors have been described in the case of metal on polyethylene as well as in metal on ceramic interfaces. We report the largest pseudotumor formation to be observed after a thorough literature review following ceramic on polyethylene total hip replacement in a case of ankylosing spondylitis and chronic kidney disease. Case report: The patient had reported 7 years following the index surgery with an uncemented total hip arthroplasty and presented with osteolytic changes of the right proximal femur and later was lost to follow-up due to the COVID-19 pandemic. The patient returned again 2 years later presenting with the pseudotumor. Owing to the presence of extensive osteolysis with gross necrotic muscle mass around the proximal one-third of femur and since bone stock was available, reconstruction of the hip joint was not considered and hence a right side hind-quarter amputation was performed. Conclusion: This immune reaction was possibly exacerbated due to the underlying ankylosing spondylitis and chronic kidney disease requires more stringent follow up protocols and early intervention. It is, thereby, necessary to evaluate patients with serial radiography following total hip replacement, especially those with conditions which could accelerate the immune responses to the metal. This could potentially avoid an amputation and allow for reconstruction of the hip with appropriate immunomodulation.

Exploring complement biomarkers in suspected axial spondyloarthritis.

OBJECTIVES: To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly diagnosed axSpA and chronic low back pain (cLBP) individuals. METHODS: Serum samples from 515 participants within the OptiRef cohort, including 151 axSpA patients and 364 cLBP patients, were measured using immunoassays for LPPs (mannan-binding lectin (MBL), collectin liver-1 (CL-L1), M-ficolin, H-ficolin and L-ficolin, MBL-associated serine proteases (MASP)-1, -2 and -3, MBL-associated proteins (MAp19 and MAp44) and the complement activation product C3dg). RESULTS: Serum levels of L-ficolin, MASP-2 and C3dg were elevated in axSpA patients, whereas levels of MASP-3 and CL-L1 were decreased, and this remained significant for C3dg and MASP-3 after adjustment for C reactive protein (CRP). A univariate regression analysis showed serum levels of CL-L1, MASP-2, MASP-3 and C3dg to predict the diagnosis of axSpA, and MASP-3 and C3dg remained significant in a multivariate logistic regression analysis. Assessment of the diagnostic potential showed that a combination of human leukocyte antigen B27 (HLA-B27) and measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, however, with a concomitant loss of sensitivity. CONCLUSIONS: Serum levels of complement activation, that is, C3dg, and MASP-3 differed significantly between axSpA and cLBP patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, this seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with axSpA diagnosis in multivariate logistic regression, suggesting an involvement of complement in the inflammatory processes and possibly pathogenesis in axSpA.

Spondylodiscitis: A Diagnostic and Management Dilemma.

Aims Spondylodiscitis (SpD), a debilitating infective condition of the spine, mandates early diagnosis and institution of appropriate therapy, for which accurate microbiology and histological evaluation of the affected tissue is vital. The objectives of the study were to assess the correlation between clinical and magnetic resonance imaging (MRI) findings with histopathology (HPE) and microbiology (MB) in clinically diagnosed spondylodiscitis. Settings and design This was a prospective study of 34 consecutive patients reporting at the outpatient department of a tertiary hospital with clinical and imaging features of SpD, who underwent image-guided/surgical biopsy of lesions. Methods and material The provisional diagnosis of SpD in all patients was made on the combined basis of clinical profile and MRI Spine findings. Tissue samples in all patients, obtained by either open surgery or CT-guided biopsy, were subjected to HPE and MB analysis.  Results SpD has a bimodal age distribution with the majority of patients being males in the fourth to fifth decades. Only raised erythrocyte sedimentation rate (ESR) was consistently seen amongst laboratory parameters, with leucocytosis being added pointer towards pyogenic etiology. MRI remained the imaging modality of choice for SpD but was not dependable for etiologic differentiation. On HPE and MB evaluations, 24 patients (71%) had findings consistent with infective SpD, while combined results augmented etiologic confirmation for 28 patients (82.4%). HPE was more sensitive than traditional MB methods to determine etiology in SpD, but the addition of the GeneXpert (Cepheid, Sunnyvale, California, United States) technique improved the MB positivity rate, especially in patients with tubercular SpD. Six patients (17.6%) with both negative HPE and MB results were categorized as 'Non-specific' SpD. Conclusions SpD poses a challenge to determine the etiology for the administration of specific antimicrobial therapy. A stratified standard institutional approach needs adoption to systematically evaluate SpD patients by having a high index of clinical suspicion, early imaging, followed by tissue biopsy for HPE and MB. Despite efforts to reach a diagnosis, a subset of patients without conclusive etiologic agent identification would remain as 'Non-specific', needing empiric antibiotic treatment based on clinico-radiologic profile.

Investigation of the Shared Biomarkers in Heterotopic Ossification Between Ossification of the Ligamentum Flavum and Ankylosing Spondylitis.

STUDY DESIGN: Bioinformatics analysis of Gene Expression Omnibus (GEO). BACKGROUND: Ossification of the ligamentum flavum (OLF) and ankylosing spondylitis (AS) represent intricate conditions marked by the gradual progression of endochondral ossification. This investigation endeavors to unveil common biomarkers associated with heterotopic ossification and explore the potential molecular regulatory mechanisms. METHODS: Microarray and RNA-sequencing datasets retrieved from the Gene Expression Omnibus (GEO) repository were harnessed to discern differentially expressed genes (DEGs) within the OLF and AS datasets. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) was implemented to pinpoint co-expression modules linked to OLF and AS. Common genes were further subjected to an examination of functional pathway enrichment. Moreover, hub intersection genes were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by an evaluation of diagnostic performance in external OLF and AS cohorts. Lastly, an analysis of immune cell infiltration was conducted to scrutinize the correlation of immune cell presence with shared biomarkers in OLF and AS. RESULTS: A total of 1353 and 91 Differentially Expressed Genes (DEGs) were identified in OLF and AS, respectively. Using the Weighted Gene Co-expression Network Analysis (WGCNA), 2 modules were found to be notably significant for OLF and AS. The integrative bioinformatic analysis revealed 3 hub genes (MAB21L2, MEGF10, ISLR) as shared risk biomarkers, with MAB21L2 being the central focus. Receiver Operating Characteristic (ROC) analysis exhibited a strong diagnostic potential for these hub genes. Gene Ontology (GO) analysis indicated their involvement in the positive regulation of myoblast proliferation. Notably, MAB21L2 was singled out as the optimal common biomarker for OLF and AS. Furthermore, an analysis of immune infiltration demonstrated a correlation between MAB21L2 expression and changes in immune cells. Activated CD8 T cells were identified as shared differential immune infiltrating cells significantly linked to MAB21L2 in both OLF and AS. CONCLUSION: This study represents the first instance of identifying MAB21L2 as a prospective diagnostic marker for patients contending with OLF associated with AS. The research results indicate that the ECM-receptor interaction and the cell-cell adhesion may play a role in both disease processes. This newfound knowledge not only enhances our understanding of the pathogenesis behind spinal ligament ossification but also uncovers potential targets for therapeutic interventions.