-
BMC Musculoskeletal Disorders Jun 2024Ankylosing spondylitis (AS) with radiographic damage is more prevalent in men than in women. IL-17, which is mainly secreted from peripheral blood mononuclear cells...
BACKGROUND
Ankylosing spondylitis (AS) with radiographic damage is more prevalent in men than in women. IL-17, which is mainly secreted from peripheral blood mononuclear cells (PBMCs), plays an important role in the development of AS. Its expression is different between male and female. However, it is still unclear whether sex dimorphism of IL-17 contribute to sex differences in AS.
METHODS
GSE221786, GSE73754, GSE25101, GSE181364 and GSE205812 datasets were collected from the Gene Expression Omnibus (GEO) database. Differential expressed genes (DEGs) were analyzed with the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods. CIBERSORTx and EcoTyper algorithms were used for immune infiltration analyses. Machine learning based on the XGBoost algorithm model was used to identify the impact of DEGs. The Connectivity Map (CMAP) database was used as a drug discovery tool for exploring potential drugs based on the DEGs.
RESULTS
According to immune infiltration analyses, T cells accounted for the largest proportion of IL-17-secreting PBMCs, and KEGG analyses suggested an enhanced activation of mast cells among male AS patients, whereas the expression of TNF was higher in female AS patients. Other signaling pathways, including those involving metastasis-associated 1 family member 3 (MAT3) or proteasome, were found to be more activated in male AS patients. Regarding metabolic patterns, oxidative phosphorylation pathways and lipid oxidation were significantly upregulated in male AS patients. In XGBoost algorithm model, DEGs including METRN and TMC4 played important roles in the disease process. we integrated the CMAP database for systematic analyses of polypharmacology and drug repurposing, which indicated that atorvastatin, famciclocir, ATN-161 and taselisib may be applicable to the treatment of AS.
CONCLUSIONS
We analyzed the sex dimorphism of IL-17-secreting PBMCs in AS. The results showed that mast cell activation was stronger in males, while the expression of TNF was higher in females. In addition, through machine learning and the CMAP database, we found that genes such as METRN and TMC4 may promote the development of AS, and drugs such as atorvastatin potentially could be used for AS treatment.
Topics: Humans; Female; Male; Interleukin-17; Spondylitis, Ankylosing; Machine Learning; Leukocytes, Mononuclear; Sex Characteristics; Computational Biology; Databases, Genetic; Gene Expression Profiling
PubMed: 38914997
DOI: 10.1186/s12891-024-07589-6 -
Journal of Maxillofacial and Oral... Jun 2024To evaluate the variation in the position of the mandibular foramen and mandibular canal in patients with and without temporomandibular joint ankylosis.
AIM
To evaluate the variation in the position of the mandibular foramen and mandibular canal in patients with and without temporomandibular joint ankylosis.
MATERIALS AND METHODS
100 temporomandibular joints were evaluated of which 50 joints were ankylosed joints (Group A) and the rest 50 were normal joints (Group B) without ankylosis. These groups were further divided into those with growing potential (less than 18 years) and those without growing potential (above 18 years). The position of the mandibular foramen was measured from its center to the glenoid fossa, sigmoid notch, coronoid notch, gonion and posterior border on CBCT scans. The position of the mandibular canal was measured from the outer aspect of the canal to the lower border of the mandible, buccal and lingual cortical plates and the alveolus in the region of the 1st, 2nd and 3rd molars.
RESULTS
The mean distance of the foramen from the base of the skull in Group A was 19.01 mm while the same for Group B was 31.26 mm. The mandibular foramen was found to be closer to the occlusal plane (5.43 mm) in Group A as compared to the mean distance of 6.21 mm reported in Group B. There was no significant difference in the position of the foramen from the posterior border, gonion and sigmoid notch between the groups. The mental foramen was seen more commonly posterior to the 2nd premolar and closer to the first molar region in Group A while in Group B it was seen anterior or near the 2nd premolar. In Group A, the mean distance of the canal to the buccal cortical plate in the 1st and 2nd molar regions was 3.65 mm and 5.76 mm, respectively, while in Group B it was 6.09 mm and 6.59 mm. The canal was further away from the lower border in ankylosis cases (8.79 mm) than the control group (7.41 mm). On comparing the unaffected side in unilateral cases with the normal mandible, the canal and the foramen location were similar to that of a normal mandible with the values in the lower range that is usually seen in normal mandibles.
CONCLUSION
Ankylosis of the mandible is a debilitating condition especially when it develops in an individual prior completion of growth as it can affect the mandibular anatomy. Understanding the variations that accompany a deranged mandible can assist the surgeon in planning of surgical procedures in a manner that limits the possible complications resulting from surgery.
PubMed: 38911403
DOI: 10.1007/s12663-023-02072-6 -
Cureus May 2024Temporomandibular joint (TMJ) ankylosis results in malocclusion, poor feeding, difficulty in maintaining oral hygiene, and facial esthetic deformity. The basic surgical...
Temporomandibular joint (TMJ) ankylosis results in malocclusion, poor feeding, difficulty in maintaining oral hygiene, and facial esthetic deformity. The basic surgical objectives in the treatment of TMJ ankylosis are to establish joint movement, prevent relapse, and achieve normal growth and development. Here, we present an operated case ofsurgical correction of mandibular hypoplasia; however, the patient came back after three years due to unsatisfactory results and underwent bilateral coronoidectomy and gap arthroplasty. Bones were osteotomized at the LeFort I level and the maxillary segment was down-fractured and mobilized to bring into occlusion with the mandible. In the present case, the lower pharyngeal airway changed from 5 mm pre-treatment to 10 mm post-treatment, and the facial angle was changed from 73 to 84 post-treatment. Assessment of the pharyngeal airway is done with a high suspicion of obstructive sleep apnea and facial deformity is mandatory in the management of TMJ ankylosis.
PubMed: 38910750
DOI: 10.7759/cureus.60857 -
Cureus May 2024Temporomandibular joint (TMJ) ankylosis is generally characterised by a complex aetiology, with several contributing causes, including infections, autoimmune diseases,...
Temporomandibular joint (TMJ) ankylosis is generally characterised by a complex aetiology, with several contributing causes, including infections, autoimmune diseases, trauma, and congenital anomalies. This case report describes a three-year-old female suffering from traumatic temporomandibular ankylosis with retrognathia, severe mouth-opening restriction, and obstructive sleep apnea (OSA). The present case highlights the difficulties with TMJ ankylosis, especially when access to healthcare is sought out late and delayed diagnosis is prevalent. Mandibular distraction osteogenesis and awake fiberoptic intubation were used in the surgical and anaesthetic management of this case, with the otorhinolaryngology team on standby to perform a tracheostomy if required, highlighting the necessity of a multidisciplinary approach in such cases. Patients with TMJ ankylosis have significant life-altering changes, including psychological stress, chewing difficulty, speech difficulties, facial distortion, and speech impediment. When OSA progresses, it also presents more health risks. For the purpose of treating TMJ ankylosis, avoiding serious problems, and enhancing patient well-being, prompt diagnosis and therapy are crucial. In order to optimise patient results, this case study highlights the need for knowledge and research in the treatment of TMJ ankylosis as well as the requirement of medical professionals working together in a synergistic way.
PubMed: 38910731
DOI: 10.7759/cureus.60828 -
Oral and Maxillofacial Surgery Jun 2024In the digital era, the internet is the go-to source of information, and patients often seek insights on medical conditions like TMJ ankylosis. YouTube, a popular...
PURPOSE
In the digital era, the internet is the go-to source of information, and patients often seek insights on medical conditions like TMJ ankylosis. YouTube, a popular platform, is widely used for this purpose. However, YouTube's lack of regulation means it can host unreliable content. Hence, the primary objective of this study is to assess the scientific quality of YouTube videos concerning TMJ ankylosis.
MATERIALS AND METHODS
This study analyzed 59 TMJ ankylosis-related videos. Two Oral and Maxillofacial Surgery specialists assessed these videos. Data on the video source, duration, upload date, the time elapsed since upload, total views, likes, dislikes and comments, Interaction index, and viewing rate were collected and analyzed. Video quality was assessed using the Global Quality Scale (GQS) and the Quality Criteria for Consumer Health Information (DISCERN), comparing health professionals and non-health professionals.
RESULTS
Health professional's videos were better in terms of GQS 3.21 ± 0.94 and DISCERN score 3.03 ± 0.75 as compared to the non-health professional videos GQS 3.0 ± 1.04, and DISCERN 2.81 ± 1.13. Health professional group videos had more reliability and better quality than the non-health professional group (p < 0.01).
CONCLUSION
YouTube should not be relied on as a trustworthy source for high-quality and reliable information regarding TMJ ankylosis videos. Healthcare professionals must be prepared to address any ambiguous or misleading information and to prioritize building trustworthy relationships with patients through accurate diagnostic and therapeutic processes.
PubMed: 38910212
DOI: 10.1007/s10006-024-01270-x -
Bone Research Jun 2024Stem/progenitor cells differentiate into different cell lineages during organ development and morphogenesis. Signaling pathway networks and mechanotransduction are...
Stem/progenitor cells differentiate into different cell lineages during organ development and morphogenesis. Signaling pathway networks and mechanotransduction are important factors to guide the lineage commitment of stem/progenitor cells during craniofacial tissue morphogenesis. Here, we used tooth root development as a model to explore the roles of FGF signaling and mechanotransduction as well as their interaction in regulating the progenitor cell fate decision. We show that Fgfr1 is expressed in the mesenchymal progenitor cells and their progeny during tooth root development. Loss of Fgfr1 in Gli1 progenitors leads to hyperproliferation and differentiation, which causes narrowed periodontal ligament (PDL) space with abnormal cementum/bone formation leading to ankylosis. We further show that aberrant activation of WNT signaling and mechanosensitive channel Piezo2 occurs after loss of FGF signaling in Gli1-Cre;Fgfr1 mice. Overexpression of Piezo2 leads to increased osteoblastic differentiation and decreased Piezo2 leads to downregulation of WNT signaling. Mechanistically, an FGF/PIEZO2/WNT signaling cascade plays a crucial role in modulating the fate of progenitors during root morphogenesis. Downregulation of WNT signaling rescues tooth ankylosis in Fgfr1 mutant mice. Collectively, our findings uncover the mechanism by which FGF signaling regulates the fate decisions of stem/progenitor cells, and the interactions among signaling pathways and mechanotransduction during tooth root development, providing insights for future tooth root regeneration.
Topics: Animals; Wnt Signaling Pathway; Tooth Root; Mechanotransduction, Cellular; Fibroblast Growth Factors; Mice; Cell Differentiation; Stem Cells; Receptor, Fibroblast Growth Factor, Type 1; Ion Channels
PubMed: 38910207
DOI: 10.1038/s41413-024-00345-5 -
Scientific Reports Jun 2024Sarcopenia is linked to chronic inflammation and muscle wasting. This research aims to compare the screening accuracy of tools for sarcopenia in axial spondyloarthritis... (Comparative Study)
Comparative Study
Sarcopenia is linked to chronic inflammation and muscle wasting. This research aims to compare the screening accuracy of tools for sarcopenia in axial spondyloarthritis (axSpA). A cross-sectional study involving 104 axSpA patients was conducted at Phramongkutklao Hospital between January 2020 and February 2021. Sarcopenia was diagnosed according to the AWGS 2019 criteria. Appendicular skeletal muscle mass was measured using DXA. SARC-F, SARC-CalF, and SARC-F+EBM, muscle strength, and physical performance were assessed. The screening tests were evaluated using ROC curves. The optimal cutoffs were identified with the Youden index. Most patients were male (74%), with a mean (SD) age and disease duration of 42.6 (12.22) and 8.3 (8.5), respectively. The prevalence of sarcopenia was 22.1%. The AUCs (95% CI) for calf circumference, SARC-F, SARC-CalF, SARC-F+EBM, handgrip strength, chair stand time, gait speed, and time and go test were 0.830 (0.734, 0.925), 0.509 (0.373-0.645), 0.782 (0.670-0.894), 0.856 (0.758-0.954), 0.710 (0.594-0.825), 0.640 (0.508-0.772), 0.689 (0.539-0.839), and 0.711 (0.576-0.846), respectively. The optimal cutoffs for SARC-F, SARC-CalF, and SARC-F+EBM were 1, 10, and 10, with sensitivity/specificity of 81.0%/29.7%, 90.5%/68.9%, and 77.3%/87.2%, respectively. Calf circumference, SARC-CalF, and SARC-F+EBM had the best performance to screen for sarcopenia in axSpA patients. Lowering the thresholds would potentially enhance the performances of SARC-CalF and SARC-F+EBM.
Topics: Humans; Sarcopenia; Male; Female; Adult; Cross-Sectional Studies; Middle Aged; Axial Spondyloarthritis; Hand Strength; Muscle Strength; Muscle, Skeletal; Mass Screening; ROC Curve; Prevalence
PubMed: 38909047
DOI: 10.1038/s41598-024-65120-2 -
European Journal of Dermatology : EJD Apr 2024Previous studies reveal that psoriatic arthritis (PsA) and ankylosing spondylitis (AS) share susceptibility genes, such as HLA-B27, demonstrating a degree of genetic...
Previous studies reveal that psoriatic arthritis (PsA) and ankylosing spondylitis (AS) share susceptibility genes, such as HLA-B27, demonstrating a degree of genetic overlap between these diseases. Recent studies have identified a number of novel AS and PsA genetic susceptibility loci, but data on these loci in Chinese PsA patients are limited. To identify candidate genes that confer susceptibility to PsA in Chinese patients with PsA, psoriasis vulgaris (PsV), and healthy controls. Sixteen susceptibility loci, reported in a genome-wide association study of AS, and nine susceptibility loci, reported in candidate gene studies of PsA, were examined. Single-nucleotide polymorphisms (SNPs) were genotyped in 503 patients with PsA, 496 patients with PsV, and 979 healthy controls using the SNPscanTM multiplex SNP genotyping platform. PLINK software and logistic regression analysis were used to estimate the statistical significance of associations. PPP2R3C (rs8006884) was shown to significantly associate with PsA+PsV (p = 1.92×10-3, OR = 1.28) and was suggested to associate with PsV (p = 0.03, OR = 1.19). A suggestive association was also observed between IL-23R (rs12141575) and PsA as well as with axial PsA based on subtype analysis, KIF3A (rs2897442) and PsV, and ERN1 (rs196941) or IFIH1 (rs984971) and axial PsA. Our results suggest that PPP2R3C confers susceptibility to PsA and PsV, and that this gene may be related to the pathogenesis of psoriatic lesions and arthritis. Moreover, our results indicate a possible association between IL-23R, ERN1, or IFIH1 and subtypes of PsA, and between KIF3A and PsV.
Topics: Humans; Arthritis, Psoriatic; Spondylitis, Ankylosing; Male; Polymorphism, Single Nucleotide; Female; Genetic Predisposition to Disease; Asian People; Adult; Middle Aged; Case-Control Studies; China; Receptors, Interleukin; Protein Phosphatase 2; Genotype; Genome-Wide Association Study; Psoriasis; East Asian People
PubMed: 38907550
DOI: 10.1684/ejd.2024.4641 -
Clinical Orthopaedics and Related... Jun 2024Notable surgeon-to-surgeon variation in rates of uncommon surgery can reflect appropriate concentration of expertise with technically difficult or risky procedures that...
BACKGROUND
Notable surgeon-to-surgeon variation in rates of uncommon surgery can reflect appropriate concentration of expertise with technically difficult or risky procedures that address problematic impairment due to objective pathophysiology. Examples include vascularized tissue transfer or transplantation to address complex tissue loss and release of bony elbow ankylosis. Perhaps more problematic is notable variation in straightforward, discretionary surgeries intended to alleviate pain, offered in the absence of objectively measurable pathophysiology, and without experimental evidence of benefit over placebo and other nonspecific effects. Evidence of concentration of this type of surgery in the hands of a few surgeons might point to inordinate influence of surgeon opinions on patient behavior. A study of variation in operations for upper extremity peripheral mononeuropathy has the potential to uncover potentially problematic variation. There are billing codes specific to common surgeries that can benefit patients with objectively verifiable neuropathies. And there are billing codes that represent less common nerve decompression surgeries that in many cases are offered in the absence of both objective evidence of pathophysiology as well as experimental evidence that surgery alleviates pain better than simulated surgery.
QUESTIONS/PURPOSES
We asked the following questions: (1) Among surgeons who billed a mean of at least 10 carpal tunnel releases (CTRs) per year in patients with Medicare insurance in the United States, how many also performed at least one less common peripheral nerve release and cubital tunnel release (CubTR) per year? (2) Among surgeons who billed a mean of at least one less common peripheral nerve release or CubTR on average per year, what is the median and range of the number of less common peripheral nerve releases and CubTRs and the relative proportion of these compared with CTRs per year? (3) Are there any differences in gender, specialty, and number of CTRs and CubTRs between surgeons who performed at least one less common nerve decompression and surgeons who, on average, performed none?
METHODS
Using the Medicare Physician & Other Practitioners - by Provider and Service database, we identified surgeons who perform a minimum of 10 CTRs per year. Because this database has all surgeries billed to Medicare performed in any setting by individual surgeons, it is well suited to the study of surgeon-specific operative rates among Medicare patients. Among 7259 clinicians who billed one or more nerve procedure to Medicare between January 2013 and December 2019, we excluded 120 nonsurgical clinicians, 47 podiatrists, and 1561 clinicians who billed procedures as an organization. Among the remaining 5531 surgeons, 5439 performed at least 10 CTRs on average per year, which we considered representative of surgeons who include nerve decompression surgery as a part of their practice. Among these 5439 surgeons, we calculated the mean number of CTRs, CubTRs, and less common peripheral nerve releases (including decompression of a digital nerve, nerve in hand or wrist, ulnar nerve at the wrist, brachial plexus, and unspecified nerve) per year between 2013 and 2019. Decompression of the median nerve at the carpal tunnel, the ulnar nerve at the cubital tunnel, and, much less frequently, the ulnar nerve at the wrist typically addresses measurable neuropathy. The other nerve releases are often performed for illnesses characterized by pain that are defined, in part, by the absence of experimentally verifiable pathophysiology such as radial tunnel and pronator (or lacertus) syndromes. We counted the number of surgeons who billed an average of at least one less common peripheral nerve release and CubTR per year; the median and range of the number of less common nerve releases and CubTRs and their relative proportion among those subsets of surgeons; and differences in the number of surgeons who performed one or none less common surgery by gender, specialty, and volume of CTR/CubTR surgery.
RESULTS
Of 5439 surgeons who performed a mean of at least 10 CTRs per year, 2% (93) performed a mean of at least one less common peripheral nerve release per year among patients on Medicare, 14% (775) at least one CubTR, and 1% (47) performed both. Surgeons who performed a mean of at least one less common peripheral nerve release per year performed a median (IQR) of 7 (3 to 17) per year (with a maximum of 153 per year), representing approximately one less common peripheral nerve release for every five CTRs. Sixty-five percent (4076 of 6272) of all less common nerve procedures were performed by the top 20 billing surgeons. Gender was not associated with doing one or more uncommon nerve releases (women 1% [6 of 413], men 2% [87 of 5026]; p = 0.84), but specialty was, with plastic surgeons leading (6% [20 of 340] compared with 1% [73 of 5087] for other types of surgeons; p < 0.001).
CONCLUSION
The observation that a relatively small number of surgeons perform a large majority of the surgery for nerve syndromes conceptualized as accounting for arm pain suggests that most surgeons are cautious about ascribing pain to conceptual nerve compression syndromes and offering surgery.
CLINICAL RELEVANCE
An approach to surgical care founded on ethical principles regards this type of notable variation as a signal of inordinate influence of surgeon opinion on patient behavior, suggesting that professional conduct may be supported by safeguards such as checklists that help guide patients to choices consistent with their values unclouded by surgeon beliefs, false hope, and common misconceptions.
PubMed: 38905446
DOI: 10.1097/CORR.0000000000003162 -
Scientific Reports Jun 2024Clinical data on the use of tumour necrosis factor inhibitors (TNFi) in late-onset ankylosing spondylitis (LoAS) are limited. The present study aimed to evaluate...
Clinical data on the use of tumour necrosis factor inhibitors (TNFi) in late-onset ankylosing spondylitis (LoAS) are limited. The present study aimed to evaluate efficacy, safety, and treatment adherence associated with the initial use of TNFi therapy in biologic naive patients diagnosed with LoAS. Patients whose age of onset was ≥ 45 years and < 45 years were classified as having LoAS and YoAS, respectively, based on the age of symptom onset. There were 2573 patients with YoAS and 281 LoAS. Baseline disease activity measures were similar between the groups. No significant differences were seen between the two groups in response to treatment and in remaining on the first TNFi at 6, 12 and 24 months. In the LoAS group, the analysis showed that TNFi discontinuation was linked to VAS pain score (HR 1.04; 95% CI 1.01-1.06). Patient groups had similar rates of adverse events (YoAS: 8.7% vs. LoAS: 11.7%). In both biologic naive LoAS and YoAS patients, the study showed that the initial TNFi therapy was equally effective and safe.
Topics: Humans; Spondylitis, Ankylosing; Male; Female; Middle Aged; Registries; Adult; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Age of Onset; Antirheumatic Agents; Tumor Necrosis Factor-alpha
PubMed: 38902436
DOI: 10.1038/s41598-024-65180-4