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Frontiers in Immunology 2024The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of studies investigating the circulating concentrations of bilirubin, the end product of heme metabolism and a potent endogenous antioxidant with anti-inflammatory properties, in patients with RDs and healthy controls. The electronic databases PubMed, Scopus, and Web of Science were searched from inception to 31 December 2023 for relevant articles. We evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 17 eligible studies, all with low risk of bias, compared to controls, patients with RDs had significantly lower concentrations of total bilirubin (standard mean difference, SMD=-0.68, 95% CI -0.91 to -0.44, p<0.001; I = 92.5%, p<0.001; low certainty of evidence), direct (conjugated) bilirubin (SMD=-0.67, 95% CI -0.92 to -0.41, p<0.001; I = 81.7%, p<0.001; very low certainty of evidence), and the active antioxidant and anti-inflammatory indirect (unconjugated) form of bilirubin (SMD=-0.71, 95% CI -1.18 to -0.24, p=0.003; I = 95.1%, p<0.001; very low certainty of evidence). The results of the meta-analysis were stable in sensitivity analysis. In meta-regression, there were no significant associations between the SMD of total bilirubin and several clinical and demographic characteristics, including age, male to female ratio, number of participants, liver enzymes and erythrocyte sedimentation rate. In subgroup analysis, the SMD of total bilirubin was significant across a range of RDs, including rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, and myositis. Therefore, the results of our systematic review and meta-analysis suggests that the reductions in bilirubin concentrations observed in patients with RDs reflect a state of impaired antioxidant and anti-inflammatory defence due to bilirubin consumption and highlight the promising role of this endogenous product as a biomarker of RDs.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023500649.
Topics: Humans; Bilirubin; Biomarkers; Rheumatic Diseases; Oxidative Stress; Female
PubMed: 38947324
DOI: 10.3389/fimmu.2024.1369284 -
Frontiers in Immunology 2024The topic of fertility in women with spondyloarthritis (SpA) has been scarcely investigated to date. Recent systematic reviews and registry studies have brought renewed... (Review)
Review
The topic of fertility in women with spondyloarthritis (SpA) has been scarcely investigated to date. Recent systematic reviews and registry studies have brought renewed attention to the plight of women of childbearing age with rheumatic diseases, in particular SpA. Fertility may be impacted by physical impairment, hormonal imbalances and psychological distress. Several studies observed a reduction in anti-Müllerian hormone in women with SpA, reflecting a reduced ovarian reserve (OR). Furthermore, disease activity and the use of certain therapies can alter fertility, and this is reflected in a prolonged time-to-pregnancy (TTP), a validated outcome measure that can evaluate the status of subfertility. The employment of glucocorticoids or non-steroidal anti-inflammatory drugs has also been linked to reduced fertility, whereas the use of biologics, especially tumour necrosis factor inhibitors (TNFi), is not associated with a prolonged TTP. In all women of childbearing age with rheumatic diseases, preconception counselling is paramount, and a referral to a reproductive specialist should be considered in the presence of multiple factors that may influence fertility. A comprehensive evaluation involving a multidisciplinary team of rheumatologists, gynaecologists, and often psychologists is warranted. In this narrative review, we collected the currently available literature focusing on fertility issues in women affected by SpA, providing data on fertility outcomes, hormonal imbalance, and therapeutic concerns.
Topics: Humans; Female; Spondylarthritis; Pregnancy; Fertility; Infertility, Female; Adult; Ovarian Reserve
PubMed: 38947314
DOI: 10.3389/fimmu.2024.1412174 -
Frontiers in Immunology 2024Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from...
Severe thermal and major traumatic injury results in elevated plasma concentrations of total heme that are associated with poor clinical outcomes and systemic immune suppression.
BACKGROUND
Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from injured muscle and lysed red blood cells, heme is a damage associated molecular pattern with potent immune modulatory properties. Here, we measured plasma concentrations of total heme in over 200 traumatic and thermally-injured patients in order to examine its relationship with clinical outcomes and post-injury immune suppression.
METHODS
Blood samples were collected from 98 burns (≥15% total body surface area) and 147 traumatically-injured (injury severity score ≥8) patients across the ultra-early (≤1 hour) and acute (4-72 hours) post-injury settings. Pro-inflammatory cytokine production by lipopolysaccharide (LPS) challenged whole blood leukocytes was studied, and plasma concentrations of total heme, and its scavengers haptoglobin, hemopexin and albumin measured, alongside the expression of heme-oxygenase-1 (HO-1) in peripheral blood mononuclear cells (PBMCs). LPS-induced tumour necrosis factor-alpha (TNF-α) production by THP-1 cells and monocytes following heme treatment was also examined.
RESULTS
Burns and traumatic injury resulted in significantly elevated plasma concentrations of heme, which coincided with reduced levels of hemopexin and albumin, and correlated positively with circulating levels of pro and anti-inflammatory cytokines. PBMCs isolated from trauma patients 4-12 and 48-72 hours post-injury exhibited increased HO-1 gene expression. Non-survivors of burn injury and patients who developed sepsis, presented on day 1 with significantly elevated heme levels, with a difference of 6.5 µM in heme concentrations corresponding to a relative 52% increase in the odds of post-burn mortality. On day 1 post-burn, heme levels were negatively associated with LPS-induced TNF-α and interleukin-6 production by whole blood leukocytes. THP-1 cells and monocytes pre-treated with heme exhibited significantly reduced TNF-α production following LPS stimulation. This impairment was associated with decreased gene transcription, reduced activation of extracellular signal-regulated kinase 1/2 and an impaired glycolytic response.
CONCLUSIONS
Major injury results in elevated plasma concentrations of total heme that may contribute to the development of endotoxin tolerance and increase the risk of poor clinical outcomes. Restoration of the heme scavenging system could be a therapeutic approach by which to improve immune function post-injury.
Topics: Humans; Heme; Burns; Male; Adult; Female; Middle Aged; Cytokines; Wounds and Injuries; Young Adult; Aged; THP-1 Cells; Leukocytes, Mononuclear; Biomarkers; Lipopolysaccharides; Heme Oxygenase-1
PubMed: 38947312
DOI: 10.3389/fimmu.2024.1416820 -
Orthopedic Reviews 2024Osteoarthritis of the carpometacarpal (CMC) is considered a common musculoskeletal disorder. The treatment of carpometacarpal osteoarthritis could be either by...
BACKGROUND
Osteoarthritis of the carpometacarpal (CMC) is considered a common musculoskeletal disorder. The treatment of carpometacarpal osteoarthritis could be either by conservative or surgical methods. surgical treatment, there are various alternatives, including trapeziectomy and arthroplasty. This study aims to perform a systematic review of the literature to determine the functional outcomes associated with trapeziectomy and arthroplasty in CMC arthritis.
OBJECTIVES
To determine the functional outcomes associated with trapeziectomy and arthroplasty in CMC arthritis patients.
METHODS
A systematic review was conducted according to PRISMA guidelines and performed on August 2022 by one independent reviewer (author) using PubMed database, EBSCO Host, EMBASE, and ScienceDirect. The literature search will be based on (PICO) criteria, as mentioned in the following: Patients with any carpometacarpal arthritis; with the intervention of using carpometacarpal arthroplasty as their method of surgery; control with trapeziectomy and primary outcome of functional outcome. Clinical outcomes using patient-reported outcome measures and complications were included. The quality of the included studies was evaluated with Cochrane risk-of-bias assessment tools. Quantitative analysis was performed by Review Manager 5.4.
RESULTS
Three studies met the inclusion criteria for the systematic review. Both treatments resulted in significant improvements in functional scores. When matching patients according to preoperative function, patients receiving arthroplasty had better postoperative function (Quick DASH: trapeziectomy = 25.1, ARPE = 16.8).
CONCLUSION
This study showed that variable results of clinical outcomes improved after trapezeictomy and arthroplasty in patients with CMC arthritis. Evidence showed that arthroplasty allows for a better improvement in functional outcome.
PubMed: 38947179
DOI: 10.52965/001c.117651 -
Research Square Jun 2024Purpose ( )-4-[ F]fluoroglutamine ([ F]FGln) is a promising metabolic imaging marker in cancer. Based on the fact that major inflammatory cells are heavily dependent...
Purpose ( )-4-[ F]fluoroglutamine ([ F]FGln) is a promising metabolic imaging marker in cancer. Based on the fact that major inflammatory cells are heavily dependent on glutamine metabolism like cancer cells, we explored the potential utility of [ F]FGln as a metabolic imaging marker for inflammation in two rat models: carrageenan-induced paw edema (CIPE) and collagen-induced arthritis (CIA). Procedures: The CIPE model (n = 4) was generated by injecting 200 µL of 3% carrageenan solution into the left hind paw three hours before the PET. The CIA model (n = 4) was generated by injecting 200 µg of collagen emulsion subcutaneously at the tail base 3-4 weeks before the PET. A qualitative scoring system was used to assess the severity of paw inflammation. After a CT scan, 15.7 ± 4.9 MBq of [ F]FGln was injected via the tail vein, followed by a dynamic micro-PET scan for 90 minutes under anesthesia with isoflurane. The standard uptake value of [ F]FGln was measured by placing a volume of interest in each paw. The non-injected right hind paws of the CIPE model rats served as controls for both models. The paws with CIA were pathologically examined after PET. Results In CIPE models, uptake in the injected paw was higher compared to the non-injected paw by 52-83%. In CIA models, uptake in the paws with severe inflammation was higher than the averaged controls by 54-173%, while that with mild and no inflammation was slightly higher (33%) and lower (-7%), respectively. Combined overall, the [ F]FGln uptake in CIA showed a significant positive correlation with inflammation severity ( = 0.88, = 0.009). The pathological findings confirmed profound inflammation in CIA. Conclusions [ F]FGln uptake was increased in both acute and chronic inflammation, and the uptake level was significantly correlated with the severity, suggesting its potential utility as a novel metabolic imaging marker for inflammation.
PubMed: 38947024
DOI: 10.21203/rs.3.rs-4493375/v1 -
Osteoarthritis and Cartilage Open Sep 2024Osteoarthritis prevalence differs between women and men; whether this is the result of differences in pre-morbid articular or peri-articular anatomical morphotypes... (Review)
Review
OBJECTIVE
Osteoarthritis prevalence differs between women and men; whether this is the result of differences in pre-morbid articular or peri-articular anatomical morphotypes remains enigmatic. Albeit sex within humans cannot be reduced to female/male, this review focusses to the sexual dimorphism of peri-articular tissues, given lack of literature on non-binary subjects.
METHODS
Based on a Pubmed search and input from experts, we selected relevant articles based on the authors' judgement of relevance, interest, and quality; no "hard" bibliometric measures were used to evaluate the quality or importance of the work. Emphasis was on clinical studies, with most (imaging) data being available for the knee and thigh.
RESULTS
The literature on sexual dimorphism of peri-articular tissues is reviewed: 1) bone size/shape, 2) subchondral/subarticular bone, 3) synovial membrane and infra-patellar fad-pad (IPFP), 4) muscle/adipose tissue, and 5) peri-articular tissue response to treatment.
CONCLUSIONS
Relevant sex-specific differences exist for 3D bone shape and IPFP size, even after normalization to body weight. Presence of effusion- and Hoffa-synovitis is associated with greater risk of incident knee osteoarthritis in overweight women, but not in men. When normalized to bone size, men exhibit greater muscle, and women greater adipose tissue measures relative to the opposite sex. Reduced thigh muscle specific strength is associated with incident knee osteoarthritis and knee replacement in women, but not in men. These observations may explain why women with muscle strength deficits have a poorer prognosis than men with similar deficits. A "one size/sex fits all" approach must be urgently abandoned in osteoarthritis research.
PubMed: 38946793
DOI: 10.1016/j.ocarto.2024.100485 -
Orthopaedic Surgery Jul 2024The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to...
OBJECTIVES
The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to investigate whether similar benefits can be observed in patients with rheumatoid arthritis undergoing total joint arthroplasty. Specifically, we aim to explore the impact of perioperative glucocorticoid use on postoperative complications, opioid consumption, incidence of hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission in this patient population.
METHODS
Approval for the study protocol was obtained from the Medical Research Ethics Committee at Sichuan University, aligning with the principles outlined in the Declaration of Helsinki. We retrospectively analyzed a consecutive series of patients with rheumatoid arthritis who underwent total joint arthroplasty at our medical center between November 2009 and April 2021 and who were not on chronic glucocorticoid therapy before surgery. Those who received glucocorticoids at any time during hospitalization were compared to those who did not in terms of acute complications within 90 days after surgery as well as postoperative rescue opioid consumption, hypotension, and hyperglycemia during hospitalization. The two groups were also compared in terms of overall duration of hospitalization, all-cause mortality within 30 days, and readmission for any reason within 90 days. Continuous data were assessed for significance using the independent-samples t test. Categorical data were assessed using the Pearson chi-squared test.
RESULTS
Of the 849 patients included in the analysis, 598 administered perioperative glucocorticoids and 251 did not. Prior to surgery, the two groups did not differ significantly in any clinicodemographic variable that we examined. The incidence of acute postoperative complications (2.3% vs. 4.0%, p = 0.187) and acute postoperative infection (2.0% vs. 2.8%, p = 0.482) was comparable between those who received perioperative glucocorticoids and those who did not, but the former group exhibited a significantly lower incidence of rescue opioid use (17.9% vs. 44.6%, p < 0.001) as well as significantly lower total rescue opioid consumption (4.7 ± 2.1 mg vs. 8.9 ± 4.6 mg, p < 0.001). However, the two groups showed similar incidences of postoperative hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission.
CONCLUSION
Perioperative glucocorticoids may reduce the need for rescue opioids after total joint arthroplasty of rheumatoid arthritis patients, without increasing the incidence of acute complications, hypotension or hyperglycemia.
PubMed: 38946692
DOI: 10.1111/os.14150 -
Autoimmunity Dec 2024Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic...
BACKGROUND
Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA.
OBJECTIVE
This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms.
METHODS
An injury cell model was established by treating chondrocytes with IL-1β. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 .
RESULTS
Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2.
CONCLUSION
Osteocyte-derived exosomal DLX2 alleviated IL-1β-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.
Topics: Exosomes; Animals; Osteoarthritis; Mice; Transcription Factors; Homeodomain Proteins; Osteocytes; Wnt Signaling Pathway; Chondrocytes; Disease Models, Animal; Humans; Interleukin-1beta; Cartilage, Articular; Apoptosis; Cartilage; Male; Cell Movement; Cell Survival
PubMed: 38946534
DOI: 10.1080/08916934.2024.2364686 -
Revista Espanola de Quimioterapia :... Jun 2024
PubMed: 38946479
DOI: 10.37201/req/030.2024 -
Physiotherapy Theory and Practice Jul 2024The relationship between psychosocial factors and bodily pain in people with knee osteoarthritis (KOA) is unclear.
INTRODUCTION
The relationship between psychosocial factors and bodily pain in people with knee osteoarthritis (KOA) is unclear.
PURPOSE
To examine whether widespread pain was associated with poorer self-efficacy, more anxiety, depression, and kinesiophobia in people with KOA.
METHODS
This was a cross-sectional study based on data from Good Life with osteoArthritis in Denmark (GLA:D®). The association between widespread pain (multiple pain sites) and self-efficacy (Arthritis Self-Efficacy Scale), anxiety and depression (item from the EQ-5D-5 L), and kinesiophobia (yes/no) was examined using multiple linear tobit or logistic regression models.
RESULTS
Among 19,323 participants, 10% had no widespread pain, 37% had 2 pain sites, 26% had 3-4 pain sites, and 27% had ≥5 pain sites. Widespread pain was associated with poorer self-efficacy (-0.9 to -8.3 points), and the association was stronger with increasing number of pain sites (p-value <.001). Significant increasing odds ratios (ORs) were observed for having anxiety or depression with 3-4 pain sites (OR 1.29, 95% CI 1.12; 1.49) and ≥5 pain sites (OR 1.80, 95% CI 1.56; 2.07). Having 2 and 3-4 pain sites were associated with lower odds of kinesiophobia compared to having no widespread pain.
CONCLUSION
Widespread pain was associated with lower self-efficacy and more anxiety and depression but also lower kinesiophobia in people with KOA.
PubMed: 38946473
DOI: 10.1080/09593985.2024.2372381