-
Medical Science Monitor : International... Jul 2024BACKGROUND The Lisfranc ligament is crucial for maintaining the transverse and longitudinal arch of the foot. Owing to the disruption between the medial cuneiform bone...
BACKGROUND The Lisfranc ligament is crucial for maintaining the transverse and longitudinal arch of the foot. Owing to the disruption between the medial cuneiform bone and the base of the second metatarsal bone, the currently preferred fixation method remains controversial. Our fixation technique involves screwing one anchor to the medial and intermediate cuneiform bones and using the anchor to carry the ligament to bind the Lisfranc joint and first and second metatarsal joints altogether for elastic fixation. This study evaluated the clinical and functional outcomes of InternalBrace fixation for Lisfranc injury. MATERIAL AND METHODS This retrospective study included 58 patients who underwent InternalBrace fixation for Lisfranc injury between January 2019 and September 2022 by an experienced surgeon. One-way analysis of variance or t test was used. Preoperative classification was performed according to the Myerson classification with imaging data. Postoperative follow-up was performed based on intraoperative blood loss, fracture healing time, visual analog scale (VAS) score, the American Orthopedic Foot and Ankle Society (AOFAS) score, Tegner score, and complications. RESULTS Surgery was completed in all patients, and follow-up was performed. The patients' ages ranged from 19 to 62 years (average: 34.6±9.4 years). The postoperative follow-up time was 12-24 months (average: 16.9±3.0 months). The average time for fracture healing was 12.8±3.0 (10-24) weeks. The VAS, AOFAS, and Tegner scores significantly improved postoperatively (from 5.33±1.0 (3-7) to 1.24±0.57 (0-2); 28.02±6.70 (18-51) to 91.59±4.76 (82-96); and 2.40±0.67 (1-4) to 6.53±0.54 (6-7), respectively), which was statistically significant (P<0.01), and the good rate of AOFAS was 91.4%. The postoperative complications were traumatic arthritis, incision infection, and temporary dorsal foot numbness, which gradually recovered. No other rejection reactions or Lisfranc fracture/dislocations recurrence occurred during the follow-up period. CONCLUSIONS InternalBrace fixation for Lisfranc injury is beneficial for restoring Lisfranc joint stability and function and allows for early and more aggressive rehabilitation for patients, with fewer surgical complications.
Topics: Humans; Retrospective Studies; Adult; Female; Male; Middle Aged; Fracture Fixation, Internal; Metatarsal Bones; Young Adult; Foot Injuries; Treatment Outcome; Ligaments, Articular
PubMed: 38954596
DOI: 10.12659/MSM.943537 -
JCI Insight Jul 2024Rheumatoid arthritis (RA) management lean toward achieving remission or low-disease activity. In this study, we conducted single-cell RNA sequencing (scRNAseq) of...
Rheumatoid arthritis (RA) management lean toward achieving remission or low-disease activity. In this study, we conducted single-cell RNA sequencing (scRNAseq) of peripheral blood mononuclear cells (PBMCs) from 36 individuals (18 RA patients and 18 matched controls, accounting for age, sex, race, and ethnicity), to identify disease-relevant cell subsets and cell type-specific signatures associated with disease activity. Our analysis revealed 18 distinct PBMC subsets, including an IFITM3 overexpressing Interferon-activated (IFN-activated) monocyte subset. We observed an increase in CD4+ T effector memory cells in patients with moderate to high disease activity (DAS28-CRP ≥ 3.2), and a decrease in non-classical monocytes in patients with low disease activity or remission (DAS28-CRP < 3.2). Pseudobulk analysis by cell type identified 168 differentially expressed genes between RA and matched controls, with a downregulation of pro-inflammatory genes in the gamma-delta T cells subset, alteration of genes associated with RA predisposition in the IFN-activated subset, and non-classical monocytes. Additionally, we identified a gene signature associated with moderate-high disease activity, characterized by upregulation of pro-inflammatory genes such as TNF, JUN, EGR1, IFIT2, MAFB, G0S2, and downregulation of genes including HLA-DQB1, HLA-DRB5, TNFSF13B. Notably, cell-cell communication analysis revealed an upregulation of signaling pathways, including VISTA, in both moderate-high and remission-low disease activity contexts. Our findings provide valuable insights into the systemic cellular and molecular mechanisms underlying RA disease activity.
PubMed: 38954480
DOI: 10.1172/jci.insight.178499 -
Clinical Rheumatology Jul 2024Herpes zoster (HZ) risk is increased in rheumatoid arthritis (RA) patients receiving Janus kinase inhibitors (JAKi) therapy. Identifying and evaluating the risk factors...
Prior herpes zoster occurrence and high-dose corticosteroids increase herpes zoster risk in rheumatoid arthritis patients receiving janus kinase inhibitors in a retrospective and observational study.
Herpes zoster (HZ) risk is increased in rheumatoid arthritis (RA) patients receiving Janus kinase inhibitors (JAKi) therapy. Identifying and evaluating the risk factors of HZ development in patients receiving JAKi therapy would be clinically helpful. We investigated HZ's incidence rates (IR), identified the risk factors, and further assessed their influence on HZ development in RA patients undergoing JAKi therapy. We retrospectively evaluated 249 RA patients who received JAKi therapy between 2015 and 2023. Data regarding clinical characteristics, HZ reactivation, HZ vaccination status, and concomitant medication use were collected. Among 249 JAKi-treated patients, 44 developed new-onset HZ (tofacitinib, 28/142; baricitinib, 6/35; upadacitinib,10/72), with an IR of 5.11/100patient-years. Multivariate analysis revealed significant predictors of HZ development: a long JAKi exposure period, prior HZ or COVID-19 history, and concomitant high-dose corticosteroids use. The interval between JAKi initiation and HZ development was significantly shorter in patients with prior HZ history than in those without (median, 6.5 months versus 33.5 months, p < 0.001), suggesting "biphasic" emergence of HZ. Only one patient who had experienced an HZ episode while receiving JAKi developed recurrent HZ. None of the seventeen patients immunized with the non-live recombinant zoster vaccine developed HZ. Our JAKi-treated patients had elevated HZ risks, a class effect across different JAKi. A long exposure period, prior history of HZ or COVID-19, and concomitant high-dose corticosteroid treatment may further increase the risk. The emergence of HZ shows a biphasic pattern: early HZ development in patients with prior HZ and late development in those without. Key Points • An increased risk of HZ was observed in Taiwanese RA patients treated with JAKi, presenting as a class effect. • Patients with a long JAKi exposure period, prior history of HZ or COVID-19, and concomitant use of high-dose corticosteroids were at high risk of HZ while receiving JAKi therapy. • The interval between JAKi initiation and HZ occurrence was shorter in patients with prior HZ than in those without, showing "biphasic" emergence.
PubMed: 38954278
DOI: 10.1007/s10067-024-07041-z -
Drugs Jul 2024Early intervention has been the cornerstone of improving outcomes in patients with rheumatoid arthritis. Over the past decade, the boundaries have been pushed in an...
Early intervention has been the cornerstone of improving outcomes in patients with rheumatoid arthritis. Over the past decade, the boundaries have been pushed in an attempt to achieve effective prevention strategies in those who are at high risk of developing rheumatoid arthritis. Core risk factors including the presence of serum anti-citrullinated protein antibodies, arthralgia and subclinical inflammation on imaging are highly predictive of arthritis development. The influence of air pollution, diet and the role of microbiome on disease progression are less clear. In turn, therapeutic focus has shifted to an earlier pre-arthritis phase of the disease continuum where the clinically apparent arthritis may potentially be intercepted. Seven proof-of-concept interventional trials in at-risk individuals have been conducted so far. Whether true prevention of rheumatoid arthritis is possible remains elusive. Promising signals towards permanent disease modulation and improvement in symptom burden were seen with some immunomodulatory therapies, whilst others were unsuccessful. Long-term follow-up is required to ascertain a true effect. Looking forward, a better understanding of the natural history and underlying biological mechanisms of arthritis development and more accurate, validated risk stratification is needed.
PubMed: 38954266
DOI: 10.1007/s40265-024-02061-0 -
Interdisciplinary Sciences,... Jul 2024To elucidate the genetic basis of complex diseases, it is crucial to discover the single-nucleotide polymorphisms (SNPs) contributing to disease susceptibility. This is...
To elucidate the genetic basis of complex diseases, it is crucial to discover the single-nucleotide polymorphisms (SNPs) contributing to disease susceptibility. This is particularly challenging for high-order SNP epistatic interactions (HEIs), which exhibit small individual effects but potentially large joint effects. These interactions are difficult to detect due to the vast search space, encompassing billions of possible combinations, and the computational complexity of evaluating them. This study proposes a novel explicit-encoding-based multitasking harmony search algorithm (MTHS-EE-DHEI) specifically designed to address this challenge. The algorithm operates in three stages. First, a harmony search algorithm is employed, utilizing four lightweight evaluation functions, such as Bayesian network and entropy, to efficiently explore potential SNP combinations related to disease status. Second, a G-test statistical method is applied to filter out insignificant SNP combinations. Finally, two machine learning-based methods, multifactor dimensionality reduction (MDR) as well as random forest (RF), are employed to validate the classification performance of the remaining significant SNP combinations. This research aims to demonstrate the effectiveness of MTHS-EE-DHEI in identifying HEIs compared to existing methods, potentially providing valuable insights into the genetic architecture of complex diseases. The performance of MTHS-EE-DHEI was evaluated on twenty simulated disease datasets and three real-world datasets encompassing age-related macular degeneration (AMD), rheumatoid arthritis (RA), and breast cancer (BC). The results demonstrably indicate that MTHS-EE-DHEI outperforms four state-of-the-art algorithms in terms of both detection power and computational efficiency. The source code is available at https://github.com/shouhengtuo/MTHS-EE-DHEI.git .
PubMed: 38954231
DOI: 10.1007/s12539-024-00621-2 -
Zeitschrift Fur Rheumatologie Jul 2024This study aimed to examine the effects of a remote video-based cervical stabilization exercise program on cervical proprioception, functional status, and...
OBJECTIVE
This study aimed to examine the effects of a remote video-based cervical stabilization exercise program on cervical proprioception, functional status, and disease-related quality of life in patients with rheumatoid arthritis (RA).
DESIGN
Patients with RA were evaluated regarding cervical joint positioning error, cervical region functional status (Neck Disability Index), general functional status (Health Assessment Questionnaire), and disease-related quality of life (Rheumatoid Arthritis Quality of Life Scale). Patients were randomized to exercise (n = 14, 10 female) and control (n = 12, 9 female) groups. Patients in the exercise group performed a video-based home exercise program consisting of progressive cervical stabilization exercises three times a week for six weeks in addition to their routine medication. The patients in the control group continued their routine medication only. Evaluations were repeated in both groups in the seventh week following the baseline evaluation.
RESULTS
Groups were similar at baseline (p > 0.05). Patients in both groups had low disease activity (DAS-28 CRP ≤ 3.2). The remote video-based exercise program led to significant improvements in cervical proprioception, functional status, and disease-related quality of life (p < 0.05). No significant changes were detected in any parameters in the control group (p > 0.05). Obtained changes were superior in the exercise group compared to the control group (d > 1.00, p < 0.05).
CONCLUSION
Cervical stabilization exercises may increase cervical proprioception, improve functional status, and enhance disease-related quality of life in patients with RA when administered as a remote program.
TRIAL NUMBER
https://clinicaltrials.gov/study/NCT04948775 , NCT04948775.
PubMed: 38953936
DOI: 10.1007/s00393-024-01543-6 -
Nanomedicine (London, England) Jul 2024This study focused on developing a topical gel incorporating lornoxicam-loaded poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) blend nanoparticles to...
This study focused on developing a topical gel incorporating lornoxicam-loaded poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) blend nanoparticles to mitigate gastrointestinal (GIT) side effects and enhance therapeutic efficacy. Synthesized nanoparticles were subjected to characterization, permeation studies, and acute oral toxicity analysis post-incorporation into the gel using a S/O/W double emulsion solvent. The nanoparticles displayed a smooth, spherical morphology (170-321 nm) with increased entrapment efficiency (96.2%). LOX exhibited a permeation rate of 70-94% from the nanoparticle-infused gel, demonstrating favorable biocompatibility at the cellular level. The formulated gel, enriched with nanoparticles, holds promising prospects for drug-delivery systems and promising improved therapeutic outcomes for LOX.
PubMed: 38953843
DOI: 10.1080/17435889.2024.2359356 -
Ugeskrift For Laeger Jun 2024This case report describes laryngeal oedema occurring in a 35-year-old woman with chronic bowel-associated dermatosis-arthritis syndrome, and stenosis of the left main...
This case report describes laryngeal oedema occurring in a 35-year-old woman with chronic bowel-associated dermatosis-arthritis syndrome, and stenosis of the left main bronchus. The oedema was attributed to persistent cough exacerbated by delayed treatment and intubation-related irritation. Evaluations ruled out inflammatory, autoimmune, and malignant causes. Literature lacks on specific descriptions of cough-induced laryngeal oedema, emphasizing the need for a multidisciplinary approach and early intervention in complex cases to prevent severe hospitalizations in patients with known serious conditions and symptom exacerbation.
Topics: Humans; Adult; Female; Cough; Laryngeal Edema; Respiration, Artificial; Intubation, Intratracheal
PubMed: 38953687
DOI: 10.61409/V12230792 -
Frontiers in Immunology 2024
Topics: Humans; Allergy and Immunology; Animals; Microbiology
PubMed: 38953029
DOI: 10.3389/fimmu.2024.1436631 -
Journal of Pain Research 2024Joint pain is one of the most commonly reported pain types in the United States. In the case of patients suffering from inflammatory diseases such as osteoarthritis (OA)...
PURPOSE
Joint pain is one of the most commonly reported pain types in the United States. In the case of patients suffering from inflammatory diseases such as osteoarthritis (OA) and gout, persistent inflammation due to long-term overexpression of several key cytokines has been linked to neuronal hypersensitivity and damage within the joints. Ultimately, a subset of patients develop chronic pain. Pharmacologic treatment of joint pain involves the use of analgesics such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, antidepressants, as well as intra-articular injections of corticosteroids and hyaluronic acid. However, NSAIDs are short-acting and fail to alleviate severe pain, opioids are generally ineffective at managing chronic pain, and all therapeutic options involve increased risks of serious side effects.
METHODS
We explored the therapeutic and analgesic effects of transforming growth factor-β-activated kinase 1 (TAK1) inhibition in both the monoiodoacetate (MIA) and monosodium urate (MSU) models of joint pain as an innovative strategy for alleviating chronic inflammatory pain. Mechanical allodynia (Von Frey), weight-bearing and histological changes were measured in separate groups of rats receiving either the selective TAK1 inhibitor, HS-276, gabapentin or vehicle.
RESULTS
Our data support that TAK1 inhibition effectively prevented the development of mechanical allodynia and differential weight-bearing in the MIA model. In the MSU model of gouty arthritis, treatment with HS-276 significantly reduced mechanical allodynia and knee edema in female rats, but not male rats. Histological evaluation of effected joints in both models showed that HS-276 treatment significantly reduced disease-induced degradation of the joint.
CONCLUSION
Our results support that TAK1 is a critical signaling node in inflammatory joint diseases such as OA and gouty arthritis. Selective pharmacological inhibition significantly attenuated several aspects of the disease, including joint degeneration and mechanical pain. Thus, TAK1 is a novel therapeutic target for the treatment of painful inflammatory joint diseases.
PERSPECTIVE
This article reports on the therapeutic potential of TAK1 in the treatment of chronic inflammatory joint diseases such as OA and gout. Using the selective TAK1 inhibitor, HS-276, we show the therapeutic and analgesic effects of TAK1 inhibition in two preclinical murine models of inflammatory joint pain.
PubMed: 38952995
DOI: 10.2147/JPR.S451409