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Medicine Jun 2024Our aim is to evaluate serum Raftlin levels as a biomarker for diagnosing and monitoring disease activity in patients with axial spondyloarthritis (axSpA) and Psoriatic... (Observational Study)
Observational Study
Our aim is to evaluate serum Raftlin levels as a biomarker for diagnosing and monitoring disease activity in patients with axial spondyloarthritis (axSpA) and Psoriatic arthritis (PsA). This trial included 40 axSpA patients, 40 PsA patients, and 40 healthy participants as the control group. Disease activity was assessed with Ankylosing Spondylitis Disease Activity Score for axSpA patients and The Disease Activity Index for Psoriatic Arthritis for PsA patients. The Spondyloarthritis Research Consortium of Canada index, health assessment questionnaire-disability index, and numeric rating scale were used to evaluate the enthesitis severity, disability, and pain status of all patients. Serum Raftlin levels were determined using the ELISA method. The 3 groups had no statistical differences regarding gender, age, weight, height, BMI, educational status, and exercise habits. The axSpA group had higher Raftlin levels than the PsA and control groups, and Raftlin levels were statistically significant in predicting the likelihood of axSpA. We found no statistically significant differences between the PsA and control groups. We found no statistically significant difference in Raftlin levels in HLA-B27 positive versus HLA-B27 negative patients in both axSpA and PsA groups. Our results also did not detect any correlation of Raftlin levels with Ankylosing Spondylitis Disease Activity Score, C-reactive protein, erythrocyte sedimentation rate, health assessment questionnaire-disability index, numeric rating scale, and Spondyloarthritis Research Consortium of Canada index in axSpA patients. Receiver operating characteristic analysis determined that Raftlin level ≥ 6.31 ng/mL discriminates axSpA from normal individuals with 92.5% sensitivity, 59% specificity, and an area under the curve of 0.738. Our results demonstrate that although serum Raftlin levels are elevated in axSpA patients, Raftlin cannot be used as an alone diagnostic marker for axSpA. Furthermore, it was not found to be related to the monitoring of disease activity, the level of pain, disability, or severity of enthesitis. This study is prospectively registered at www.clinicaltrials.gov (ID: NCT05771389).
Topics: Humans; Male; Female; Biomarkers; Arthritis, Psoriatic; Adult; Axial Spondyloarthritis; Severity of Illness Index; Middle Aged; Membrane Proteins; Case-Control Studies
PubMed: 38941376
DOI: 10.1097/MD.0000000000038770 -
Medicine Jun 2024As chronic autoimmune inflammatory diseases, rheumatoid arthritis (RA) and Crohn disease (CD) are closely associated and display a significant positive correlation....
As chronic autoimmune inflammatory diseases, rheumatoid arthritis (RA) and Crohn disease (CD) are closely associated and display a significant positive correlation. However, the underlying mechanisms and disease markers responsible for their cooccurrence remain unknown and have not been systematically studied. Therefore, this study aimed to identify key molecules and pathways commonly involved in both RA and CD through bioinformatic analysis of public sequencing databases. Datasets for RA and CD were downloaded from the GEO database. Overlapping genes were identified using weighted gene co-expression network analysis and differential analysis crossover, and enrichment analysis was conducted for these genes. Protein-protein interaction networks were then constructed using these overlapping genes to identify hub genes. Expression validation and receiver operating characteristic curve validation were performed for these hub genes using different datasets. Additionally, the immune cell correlation, single-cell expression cluster, and the immune cell expression cluster of the core gene were analyzed. Furthermore, upstream shared microRNAs (miRNA) were predicted and a miRNA-gene network was constructed. Finally, drug candidates were analyzed and predicted. These core genes were found to be positively correlated with multiple immune cells that are infiltrated by the disease. Analysis of gene expression clusters revealed that these genes were mostly associated with inflammatory and immune responses. The miRNA-genes network analysis suggested that hsa-miR-31-5p may play an important role in the common mechanism of RA and CD. Finally, tamibarotene, retinoic acid, and benzo[a]pyrene were identified as potential treatment options for patients with both RA and CD. This bioinformatics study has identified ITGB2, LCP2, and PLEK as key diagnostic genes in patients with both RA and CD. The study has further confirmed that inflammation and immune response play a central role in the development of both RA and CD. Interestingly, the study has highlighted hsa-miR-31-5p as a potential key player in the common mechanism of both diseases, representing a new direction in research and a potential therapeutic target. These shared genes, potential mechanisms, and regulatory networks offer new opportunities for further research and may provide hope for future treatment of patients with both RA and CD.
Topics: Humans; Crohn Disease; Arthritis, Rheumatoid; Computational Biology; MicroRNAs; Protein Interaction Maps; Gene Regulatory Networks; Biomarkers; Gene Expression Profiling
PubMed: 38941374
DOI: 10.1097/MD.0000000000038690 -
Health Technology Assessment... Jun 2024Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a non-acute anterior cruciate ligament injury can be non-surgical (rehabilitation) or surgical (reconstruction). However, insufficient evidence exists to guide treatment.
OBJECTIVE(S)
To determine in patients with non-acute anterior cruciate ligament injury and symptoms of instability whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically and cost-effective than non-surgical management (rehabilitation).
DESIGN
A pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. Due to the nature of the interventions, no blinding could be carried out.
SETTING
Twenty-nine NHS orthopaedic units in the United Kingdom.
PARTICIPANTS
Participants with a symptomatic (instability) non-acute anterior cruciate ligament-injured knee.
INTERVENTIONS
Patients in the surgical management arm underwent surgical anterior cruciate ligament reconstruction as soon as possible and without any further rehabilitation. Patients in the rehabilitation arm attended physiotherapy sessions and only were listed for reconstructive surgery on continued instability following rehabilitation. Surgery following initial rehabilitation was an expected outcome for many patients and within protocol.
MAIN OUTCOME MEASURES
The primary outcome was the Knee Injury and Osteoarthritis Outcome Score 4 at 18 months post randomisation. Secondary outcomes included return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee-specific quality of life and resource usage.
RESULTS
Three hundred and sixteen participants were recruited between February 2017 and April 2020 with 156 randomised to surgical management and 160 to rehabilitation. Forty-one per cent ( = 65) of those allocated to rehabilitation underwent subsequent reconstruction within 18 months with 38% ( = 61) completing rehabilitation and not undergoing surgery. Seventy-two per cent ( = 113) of those allocated to surgery underwent reconstruction within 18 months. Follow-up at the primary outcome time point was 78% ( = 248; surgical, = 128; rehabilitation, = 120). Both groups improved over time. Adjusted mean Knee Injury and Osteoarthritis Outcome Score 4 scores at 18 months had increased to 73.0 in the surgical arm and to 64.6 in the rehabilitation arm. The adjusted mean difference was 7.9 (95% confidence interval 2.5 to 13.2; = 0.005) in favour of surgical management. The per-protocol analyses supported the intention-to-treat results, with all treatment effects favouring surgical management at a level reaching statistical significance. There was a significant difference in Tegner Activity Score at 18 months. Sixty-eight per cent ( = 65) of surgery patients did not reach their expected activity level compared to 73% ( = 63) in the rehabilitation arm. There were no differences between groups in surgical complications ( = 1 surgery, = 2 rehab) or clinical events ( = 11 surgery, = 12 rehab). Of surgery patients, 82.9% were satisfied compared to 68.1% of rehabilitation patients. Health economic analysis found that surgical management led to improved health-related quality of life compared to non-surgical management (0.052 quality-adjusted life-years, = 0.177), but with higher NHS healthcare costs (£1107, < 0.001). The incremental cost-effectiveness ratio for the surgical management programme versus rehabilitation was £19,346 per quality-adjusted life-year gained. Using £20,000-30,000 per quality-adjusted life-year thresholds, surgical management is cost-effective in the UK setting with a probability of being the most cost-effective option at 51% and 72%, respectively.
LIMITATIONS
Not all surgical patients underwent reconstruction, but this did not affect trial interpretation. The adherence to physiotherapy was patchy, but the trial was designed as pragmatic.
CONCLUSIONS
Surgical management (reconstruction) for non-acute anterior cruciate ligament-injured patients was superior to non-surgical management (rehabilitation). Although physiotherapy can still provide benefit, later-presenting non-acute anterior cruciate ligament-injured patients benefit more from surgical reconstruction without delaying for a prior period of rehabilitation.
FUTURE WORK
Confirmatory studies and those to explore the influence of fidelity and compliance will be useful.
TRIAL REGISTRATION
This trial is registered as Current Controlled Trials ISRCTN10110685; ClinicalTrials.gov Identifier: NCT02980367.
FUNDING
This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/140/63) and is published in full in ; Vol. 28, No. 27. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Male; Female; Anterior Cruciate Ligament Injuries; Adult; United Kingdom; Cost-Benefit Analysis; Anterior Cruciate Ligament Reconstruction; Quality of Life; Quality-Adjusted Life Years; Middle Aged; Young Adult; State Medicine; Joint Instability; Adolescent; Technology Assessment, Biomedical
PubMed: 38940695
DOI: 10.3310/VDKB6009 -
Journal of Global Health Jun 2024Understanding chronic disease prevalence, patterns, and co-occurrence is pivotal for effective health care planning and disease prevention strategies. In this paper, we...
BACKGROUND
Understanding chronic disease prevalence, patterns, and co-occurrence is pivotal for effective health care planning and disease prevention strategies. In this paper, we aimed to identify the clustering of major non-communicable diseases among Indian adults aged ≥50 years based on their self-reported diagnosed non-communicable disease status and to find the risk factors that heighten the risk of developing the identified disease clusters.
METHODS
We utilised data from the nationally representative survey Study on Global AGEing and Adult Health (SAGE Wave-2). The eligible sample size was 6298 adults aged ≥50 years. We conducted the latent class analysis to uncover latent subgroups of multimorbidity and the multinomial logistic regression to identify the factors linked to observed latent class membership.
RESULTS
The latent class analysis grouped our sample of men and women >49 years old into three groups - mild multimorbidity risk (41%), moderate multimorbidity risk (30%), and severe multimorbidity risk (29%). In the mild multimorbidity risk group, the most prevalent diseases were asthma and arthritis, and the major prevalent disease in the moderate multimorbidity risk group was low near/distance vision, followed by depression, asthma, and lung disease. Angina, diabetes, hypertension, and stroke were the major diseases in the severe multimorbidity risk category. Individuals with higher ages had an 18% and 15% higher risk of having moderate multimorbidity and severe multimorbidity compared to those in the mild multimorbidity category. Females were more likely to have a moderate risk (3.36 times) and 2.82 times more likely to have severe multimorbidity risk.
CONCLUSIONS
The clustering of diseases highlights the importance of integrated disease management in primary care settings and improving the health care system to accommodate the individual's needs. Implementing preventive measures and tailored interventions, strengthening the health and wellness centres, and delivering comprehensive primary health care services for secondary and tertiary level hospitalisation may cater to the needs of multimorbid patients.
Topics: Humans; Female; Male; India; Middle Aged; Chronic Disease; Aged; Risk Factors; Multimorbidity; Cluster Analysis; Latent Class Analysis; Prevalence; Noncommunicable Diseases; Health Surveys
PubMed: 38940270
DOI: 10.7189/jogh.14.04079 -
Frontiers in Bioscience (Landmark... Jun 2024Persistent hyperuricemia can lead to the generation and deposition of monosodium urate (MSU) crystals. This can trigger gouty arthritis (GA), which in turn induces...
BACKGROUND
Persistent hyperuricemia can lead to the generation and deposition of monosodium urate (MSU) crystals. This can trigger gouty arthritis (GA), which in turn induces inflammation. Activation of the Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome plays a critical role in the onset and progression of GA. Autophagy may have a dual effect on GA with regard to the NLRP3 inflammasome. Therefore, the present study aimed to gain a deeper comprehension of the interaction between autophagy and NLRP3 inflammasome activation is imperative for developing more efficacious treatments for GA.
METHODS
Peripheral blood monocytes (PBMCs) were first isolated from GA patients and healthy controls and underwent bulk RNA sequencing analysis. Overexpression and knockdown of dual specificity phosphatase 1 (DUSP1) was performed in THP-1 monocytes to investigate its role in the immune response and mitochondrial damage. The luciferase assay and Western blot analysis were used to study the interaction between autophagy and NLRP3 inflammasome activation.
RESULTS
Bulk RNA sequencing analysis showed significant upregulation of DUSP1 expression in PBMCs from GA patients compared to healthy controls. This result was subsequently verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR). DUSP1 expression in human THP-1 monocytes was also shown to increase after MSU treatment. Downregulation of DUSP1 expression increased the secretion of inflammatory cytokines after MSU treatment, whereas the overexpression of DUSP1 decreased the secretion levels. Lipopolysaccharides (LPS) combined with adenosine-triphosphate (ATP) led to mitochondrial damage, which was rescued by overexpressing DUSP1. DUSP1 overexpression further increased the level of autophagy following MSU treatment, whereas downregulation of DUSP1 decreased autophagy. Treatment with the autophagy inhibitor 3-Methyladenine (3-MA) restored inflammatory cytokine secretion levels in the DUSP1 overexpression group. MSU caused pronounced pathological ankle swelling . However, DUSP1 overexpression significantly mitigated this phenotype, accompanied by significant downregulation of inflammatory cytokine secretion levels in the joint tissues.
CONCLUSIONS
This study revealed a novel function and mechanism for DUSP1 in promoting autophagy to mitigate the MSU-induced immune response in GA. This finding suggests potential diagnostic biomarkers and anti-inflammatory targets for more effective GA therapy.
Topics: Humans; Autophagy; Dual Specificity Phosphatase 1; Arthritis, Gouty; Uric Acid; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; THP-1 Cells; Male; Monocytes; Case-Control Studies; Female; Leukocytes, Mononuclear; Middle Aged
PubMed: 38940057
DOI: 10.31083/j.fbl2906222 -
Psoriasis (Auckland, N.Z.) 2024Patients with psoriasis (PsO) and psoriatic arthritis (PsA) are at increased risk of herpes zoster (HZ), but healthcare resource use (HRU) and costs relating to HZ in...
PURPOSE
Patients with psoriasis (PsO) and psoriatic arthritis (PsA) are at increased risk of herpes zoster (HZ), but healthcare resource use (HRU) and costs relating to HZ in adults with PsA are unknown. We aimed to estimate the incidence of HZ among adults with PsA vs without psoriatic disease and the additional HRU and costs among patients with PsA with vs without HZ.
PATIENTS AND METHODS
This retrospective, longitudinal, cohort study estimated HZ incidence in PsA+ vs PsO-/PsA- cohorts and HRU and medical/pharmacy costs among PsA+/HZ+ vs PsA+/HZ- cohorts comprised of adults from Optum's de-identified Clinformatics Data Mart Database during 2015-2020. For the HRU/cost analyses, index was the date of first HZ diagnosis (PsA+/HZ+ cohort) or was randomly assigned (PsA+/HZ- cohort). Generalized linear models were used for adjusted comparisons between cohorts.
RESULTS
HZ incidence was higher in the PsA+ (n = 57,126) vs PsO-/PsA- (n = 23,837,237) cohort (14.85 vs 7.67 per 1000 person-years; adjusted incidence rate ratio [aIRR]: 1.23; 95% confidence interval [CI]: 1.16-1.30). Numbers of outpatient visits, emergency department visits, and inpatient admissions were significantly higher in the PsA+/HZ+ (n = 1045) vs PsA+/HZ- (n = 36,091) cohorts during the first month after HZ diagnosis (outpatient: aIRR: 1.74; 95% CI: 1.63-1.86; emergency department: 3.14; 95% CI: 2.46-4.02; inpatient: aIRR: 2.61; 95% CI: 1.89-3.61). Mean all-cause per-patient costs were significantly higher in the PsA+/HZ+ vs PsA+/HZ- cohorts during the first month after index ($6493 vs $4521; adjusted cost difference: $2012; 95% CI: $1204-$3007). HRU and costs were numerically higher in the PsA+/HZ+ cohort during the first 3 and 12 months.
CONCLUSION
These findings, which provide evidence on the increased incidence and HRU and economic burden associated with HZ among adults with PsA, could be used to inform clinical practice and decision-making.
PubMed: 38939905
DOI: 10.2147/PTT.S430151 -
JACC. Advances Apr 2024Statins are highly effective for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and mortality. Data on the benefit of statins in adults with heart...
BACKGROUND
Statins are highly effective for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and mortality. Data on the benefit of statins in adults with heart failure with preserved ejection fraction (HFpEF) and without ASCVD are limited.
OBJECTIVES
The purpose of this study was to determine whether statins are associated with a lower risk of mortality and major adverse cardiovascular events (MACE) in HFpEF.
METHODS
Veterans Health Administration data from 2002 to 2016, linked to Medicare and Medicaid claims and pharmaceutical data, were collected. Patients had a new HFpEF diagnosis and no known ASCVD or prior statin use at baseline. Cox proportional hazards models were fit to evaluate the association of new statin use with outcomes (all-cause mortality and MACE). Propensity score overlap weighting (PSW) was used to balance baseline characteristics.
RESULTS
Among 7,970 Veterans, 47% initiated a statin over a mean 6.0-year follow-up. At HFpEF diagnosis, mean age was 69 ± 12 years, 96% were male, 67% were White, 14% were Black, and mean EF was 60% ± 6%. Before PSW, statin users were younger with more prevalent metabolic syndrome, arthritis, and other chronic conditions. All characteristics were balanced after PSW. There were 5,314 deaths and 4,859 MACE events. After PSW, the hazard for all-cause mortality for statin users vs nonusers was 22% lower (HR: 0.78; 95% CI: 0.73-0.83). The HR for MACE was 0.79 (95% CI: 0.74-0.84), 0.69 (95% CI: 0.60-0.80) for all-cause hospitalization, and 0.72 (95% CI: 0.59-0.88) for HF hospitalization.
CONCLUSIONS
New statin use was associated with reduced all-cause mortality, MACE, and hospitalization in Veterans with HFpEF without prevalent ASCVD.
PubMed: 38939680
DOI: 10.1016/j.jacadv.2024.100869 -
Cureus May 2024Palmar fasciitis and polyarthritis syndrome (PFPAS) is an exceedingly rare rheumatologic condition characterized by fibrotic changes in the palmar fascia with joint...
Palmar fasciitis and polyarthritis syndrome (PFPAS) is an exceedingly rare rheumatologic condition characterized by fibrotic changes in the palmar fascia with joint pains. It is known to be associated with gynecological malignancy, especially ovarian adenocarcinoma, gastric cancer, pancreatic, prostate, breast, and lung cancer. We present a unique case of a 75-year-old Caucasian female with PFPAS preceding the diagnosis of ovarian cancer by eight months. Our case highlights the importance of considering PFPAS as a potential paraneoplastic syndrome. It underscores the need for increased awareness and further studies to enhance the early detection of underlying malignancies in patients presenting with similar nonspecific hand symptoms.
PubMed: 38939277
DOI: 10.7759/cureus.61248 -
Chemical Science Jun 2024Secreted phospholipase A2 (sPLA2) is a Ca-dependent, widely distributed enzyme superfamily in almost all mammalian tissues and bacteria. It is also a critical component...
Secreted phospholipase A2 (sPLA2) is a Ca-dependent, widely distributed enzyme superfamily in almost all mammalian tissues and bacteria. It is also a critical component of the venom of nearly all snakes, as well as many invertebrate species. In non-venomous contexts, sPLA2 assumes significance in cellular signaling pathways by binding cell membranes and catalyzing ester bond hydrolysis at the sn-2 position of phospholipids. Elevated levels of GIIA sPLA2 have been detected in the synovial fluid of arthritis patients, where it exhibits a pro-inflammatory function. Consequently, identifying sPLA2 inhibitors holds promise for creating highly effective pharmaceutical treatments. Beyond arthritis, the similarities among GIIA sPLA2s offer an opportunity for developing treatments against snakebite envenoming, the deadliest neglected tropical disease. Despite decades of study, the details of PLA2 membrane-binding, substrate-binding, and reaction mechanism remain elusive, demanding a comprehensive understanding of the sPLA2 catalytic mechanism. This study explores two reaction mechanism hypotheses, involving one or two water molecules, and distinct roles for the Ca cofactor. Our research focuses on the human synovial sPLA2 enzyme bound to lipid bilayers of varying phospholipid compositions, and employing adiabatic QM/MM and QM/MM MD umbrella sampling methods to energetically and geometrically characterize the structures found along both reaction pathways. Our studies demonstrate the higher frequency of productive conformations within the single-water pathway, also revealing a lower free energy barrier for hydrolyzing POPC. Furthermore, we observe that the TS of this concerted one-step reaction closely resembles transition state geometries observed in X-ray crystallography complexes featuring high-affinity transition state analogue inhibitors.
PubMed: 38939148
DOI: 10.1039/d4sc02315c -
BioMedicine 2024Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and synovial joint destruction.
INTRODUCTION
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and synovial joint destruction.
AIMS
The current study investigated the possible beneficial effect of zinc oxide nanoparticles doped curcumin (ZnONPs-DC) on the recovery of RA and antioxidant status of experimental rabbits.
METHODS
RA was induced in experimental rabbits by injecting complete Freund's adjuvant and collagen type-II emulsion (100 μL/kg body weight) in the base of their tail. Arthritic rabbits were orally treated with ZnONPs, curcumin, and ZnONPs-DC(250 μL/kg bodyweight). Serumsamples fromthe control and study groupswere collected before and afterRAinduction and after treatment. The sera were subjected to analysis of biological markers of RA and antioxidant status.
RESULTS
The complete Freund's adjuvant and collagen type II treatment resulted in positive rheumatoid factor and C-reactive protein elevated oxidative stress and decreased antioxidant potential. Each treatment showed the absence of rheumatoid factor and C-reactive protein decreased oxidative stress and improved antioxidant potential compared to the control. However, ZnONPs-DC treatment showed a comparatively higher decline in serum malondialdehyde MDA content and an elevation in the antioxidant activity of RA animals.
CONCLUSIONS
In conclusion, using zinc oxide nanoparticles-doped curcumin may be an effective anti-arthritic and anti-inflammatory drug in controlling RA.
PubMed: 38939093
DOI: 10.37796/2211-8039.1446