Nonoperative Treatment of a Periprosthetic Gout Flare in the Setting of a Positive Alpha-Defensin Result.
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ABSTRACT:
SUBMITTER: Phillips DS
PROVIDER: S-EPMC8141601 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Gout flares require monosodium urate (MSU) to activate the NLRP3 inflammasome and secrete sufficient IL-1β. However, MSU alone is not sufficient to cause a flare. This is supported by the evidence that most patients with hyperuricemia do not develop gout throughout their lives. Recent studies have shown that, besides MSU, various purine metabolites, including adenosine triphosphate, adenosine diphosphate, and adenosine bind to different purine receptors for regulating IL-1β secretion implicated in the pathogenesis of gout flares. Purine metabolites such as adenosine triphosphate mainly activate the NLRP3 inflammasome through P2X ion channel receptors, which stimulates IL-1β secretion and induces gout flares, while some purine metabolites such as adenosine diphosphate and adenosine mainly act on the G protein-coupled receptors exerting pro-inflammatory or anti-inflammatory effects to regulate the onset and resolution of a gout flare. Given that the purine signaling pathway exerts different regulatory effects on inflammation and that, during the inflammatory process of a gout flare, an altered expression of purine metabolites and their receptors was observed in response to the changes in the internal environment. Thus, the purine signaling pathway is involved in regulating gout flare and resolution. This study was conducted to review and elucidate the role of various purine metabolites and purinergic receptors during the process.
| S-EPMC8671294 | biostudies-literature
Project description:BackgroundGout is an inflammatory arthritis and is characterized by the accumulation of deposited monosodium urate (MSU) crystals in the joints. miRNAs may act as key regulators of gout pathogenesis. The aim of our study was to explore the underlying role and molecular mechanism of miR-3146 in the formation of neutrophil extracellular traps (NETs) during the pathogenesis of gout.MethodsThe expression of miR-3146 and sirtuin 1 (SIRT1) was determined by real-time reverse transcription-polymerase chain reaction and Western blot, respectively. The luciferase reporter assay was performed to identify the targeting relationship between miR-3146 and SIRT1. Reactive oxygen species (ROS) production was detected by fluorescent staining. NETs formation was demonstrated via immunofluorescence staining and ELISA method. Gout model was induced in rats to verify the effects of miR-3146 inhibition on histopathological changes and NETs.ResultsHere, we found miR-3146 expression was dramatically increased in neutrophils of patients with gout, which was accompanied with the higher levels of NETs. MSU crystals significantly increased miR-3146 expression and ROS production in neutrophils. The NETs process was also triggered by MSU crystals. Furthermore, we verified the interaction between miR-3146 and SIRT1. Additionally, antagomir-3146-based therapy effectively inhibited the formation of NETs in rats with gout.ConclusionOur findings indicated that miR-3146-mediated NETs formation may play a potential role in the pathogenesis of gout. These results suggested that miR-3146 could be used as a potential therapeutic target for the treatment of gout.
| S-EPMC8605122 | biostudies-literature
Project description:BACKGROUND:Alpha defensin was proposed as a new biomarker in synovial fluid for the diagnostic workup of failed joint prostheses. To our knowledge, no comparative study of the performance of the quantitative enzyme-linked immunosorbent assay (ELISA) and qualitative lateral flow alpha defensin test has been reported. QUESTIONS/PURPOSES:(1) Using the proposed European Bone and Joint Infection Society (EBJIS) criteria for defining periprosthetic joint infection (PJI), is there a difference in the diagnostic accuracy of quantitative ELISA and qualitative lateral flow alpha defensin tests? (2) Is there a difference in the performance of the two alpha defensin tests when using three definition classification systems (Musculoskeletal Infection Society [MSIS], Infectious Diseases Society of America [IDSA], and proposed EBJIS)? METHODS:In this retrospective study of samples collected earlier as part of a related longitudinal study, we included patients in whom aspiration of the prosthetic hip or knee was performed as routine investigation before every revision arthroplasty. Between October 2016 and April 2017, a total of 73 patients were eligible for inclusion. As a result of an insufficient fluid volume for analysis (< 5 mL), two patients were excluded. Among the 71 patients in the final analysis, 54 had a knee and 17 a hip arthroplasty. Using the proposed EBJIS criteria, PJI was diagnosed in 22 patients (31%) and aseptic failure in 49 (69%). The alpha defensin ELISA and lateral flow tests were performed in synovial fluid. Patients were classified as having PJI or aseptic failure using the MSIS, the IDSA, and the proposed EBJIS criteria. Sensitivity and specificity of ELISA and the lateral flow alpha defensin test were calculated. Based on receiver operating characteristic analysis, area under the curve values were compared. RESULTS:When measured against the proposed EBJIS criteria, the sensitivity of alpha defensin ELISA and the lateral flow test was low and not different from one another with the numbers available at 50% (95% confidence interval [CI], 31%-69%) and 46% (95% CI, 27%-65%; p = 0.857), respectively, whereas both methods showed high specificity (98% [95% CI, 88%-100%]; p = 1.000). For sensitivity, the highest values were seen when compared against the MSIS criteria (ELISA: 85% [95% CI, 56%-97%], lateral flow: 77% [95% CI]; p = 0.871), intermediate with IDSA criteria (ELISA: 73% [95% CI, 48%-89%], lateral flow: 67% [95% CI]; p = 0.867), and lowest with proposed EBJIS criteria (ELISA: 50% [95% CI, 31%-69%], lateral flow: 46% [95% CI]; p = 0.763). Specificity, however, was high regardless of the criteria used, where ELISA and lateral flow produced results that were not different (MSIS: 98% [95% CI, 90%-100%], IDSA: 98% [95% CI, 90%-100%], EBJIS: 98% [95% CI, 88%-100%]; p = 1.000). The area under the curve of alpha defensin ELISA and the lateral flow test was similar, regardless of the definition criteria used (EBJIS: p = 0.566; IDSA: p = 0.425; MSIS: p = 0.339). CONCLUSIONS:There is no difference between the quantitative and qualitative alpha defensin test for confirmation of PJI, irrespective of applied definition criteria. Having the advantage of providing results within 10 minutes without the need for a laboratory facility, the qualitative test may be of interest in the intraoperative setting, however, at a cost of higher test expense. LEVEL OF EVIDENCE:Level I, diagnostic study.
| S-EPMC6259762 | biostudies-literature
Project description:BackgroundSynovial fluid proteins had been applied as diagnostic biomarkers for periprosthetic joint infection (PJI) in recent research papers. Thus, this meta-analysis aimed to estimate the diagnostic efficiency of synovial fluid ?-defensin and leukocyte esterase (LE) for PJI.MethodsWe conducted our systematic review by searching the keywords in online databases such as PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to October 2018. Inclusion criteria were as follows: patients who have undergone knee, hip, or shoulder joint replacements; ?-defensin or leukocyte esterase (LE strip) of synovial fluid was detected as the biomarker for PJI diagnosis; and Musculoskeletal Infection Society (MSIS) or utilizing a combination of clinical data was considered as the gold standard. Diagnostic parameters including sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary of receiver operating characteristics curve (AUSROC) were calculated for the included studies to evaluate the synovial fluid ?-defensin and LE for PJI diagnosis.ResultsAfter full-text review, 28 studies were qualified for this systematic review, 16 studies used ?-defensin and the other 12 were conducted using LE strip. The pooled sensitivity, specificity, and DOR of LE strip were 87% (95% CI 84-90%), 96% (95% CI 95-97%), and 170.09 (95% CI 97.63-296.32), respectively, while the pooled sensitivity, specificity, and DOR of ?-defensin were 87% (95% CI 83-90%), 97% (95% CI 96-98%), and 158.18 (95% CI 74.26-336.91), respectively. The AUSROC for LE strip and ?-defensin were 0.9818 and 0.9685, respectively.ConclusionBoth LE strip and ?-defensin of synovial fluid provide rapid and convenient diagnosis for PJI. Sensitivity of ?-defensin and LE strip are the same, while both these two methods have high specificity in clinical practice.
| S-EPMC6921602 | biostudies-literature
Project description:Methods of gout flare reporting in research settings are inconsistent and poorly defined. The aim of this study was to describe patterns of gout flare and assess the concurrent validity of different methods of flare reporting in a gout clinical trial. Daily flare diary entries including self-report of flare and pain scale from a randomised controlled trial of 120 patients with gout were analysed. Detailed pain-by-time plots for each participant were inspected and analysed for different methods of flare reporting for both self-report and the classification tree (CART)-defined flare developed by Gaffo in 2012. Concurrent validity for different methods of flare reporting were analysed. Although the single gout flare had a 'typical' average pattern (peak on day 1 and resolution over 14 days), individual pain-by-time plots showed wide variation in pain intensity, duration and frequency of flares. Over the four-month study period, there were 84/120 (70%) participants who experienced at least one self-reported flare that was not a 'typical' flare. The time to first self-reported flare correlated poorly with other measures of gout activity and other methods of flare reporting. The number of days with flare (either self-reported or Gaffo-defined) and the area under the pain-by-time curve correlated most strongly with other measures of disease severity. There is wide variation in the patterns of flare over time in individuals with gout, leading to challenges for flare reporting in clinical trials. Time-dependent reporting strategies such as number of days with flare or area under the pain-by-time curve correlate well with other measures of gout disease severity and may provide a more accurate measure of flare burden. Clinical trial number: ACTRN12609000479202, registered 17/06/2009.
| S-EPMC6615178 | biostudies-other
Project description:We present a case of chronic periprosthetic hip infection diagnosed using the Musculoskeletal Infection Society criteria as the gold standard. The alpha-defensin test was falsely negative. The diagnostic workup of the patient is detailed, along with a discussion regarding the potential reasons behind the misleading alpha-defensin results. To our knowledge, this is the first reported case of a false-negative alpha-defensin test in the setting of an open sinus tract communicating with a culture-positive total hip implant. The alpha-defensin test should be interpreted cautiously, along with all relevant pertinent clinical data. In certain cases, similar to those described here, the Musculoskeletal Infection Society criteria may perform better than this particular biomarker.
| S-EPMC5712026 | biostudies-literature
Project description:In the past few decades, gout has increased not only in prevalence, but also in clinical complexity, the latter accentuated in part by a dearth of novel advances in treatments for hyperuricemia and gouty arthritis. Fortunately, recent research reviewed here, much of it founded on elegant translational studies of the past decade, highlights how gout can be better managed with cost-effective, well-established therapies. In addition, the advent of both new urate-lowering and anti-inflammatory drugs, also reviewed here, promises for improved management of refractory gout, including in subjects with co-morbidities such as chronic kidney disease. Effectively delivering improved management of hyperuricemia and gout will require a frame shift in practice patterns, including increased recognition of the implications of refractory disease and frequent noncompliance of patients with gout, and understanding the evidence basis for therapeutic targets in serum urate-lowering and gouty inflammation.
| S-EPMC2745774 | biostudies-literature
Project description:ObjectiveOur objective was to determine whether initiation of febuxostat during an acute gout flare prolongs the current episode.MethodsIn this randomized, placebo-controlled, single-blinded, multicentre trial, patients with acute gout flares within 72 h were randomized (1:1) to the placebo and febuxostat (40 mg/day) groups. All patients were administered diclofenac (150 mg/day) for 7 days and then open-labelled on the eighth day. Febuxostat 40 mg daily and diclofenac 75 mg daily were administered from day 8 through 28 for the remission period. The dose of diclofenac was 150 mg/day before remission in both arms, and the original protocol was maintained until remission. The primary outcome was 'days to resolution'.ResultsWe randomized 140 patients, 70 into each arm. The mean days to resolution was 5.98 days [median 7.00, interquartile range (IQR) 2.45 days] for the placebo and 6.50 days (median 7.00, IQR 3.67 days) for the febuxostat group (P = 0.578). The rate of resolution within 7 days was 84.38% for the placebo group and 76.92% for the febuxostat group (P = 0.284). There were no statistically significant differences in joint pain, swelling, tenderness and erythema scores at days 1, 3, 5 and 7. The mean serum uric acid levels were 507.54 and 362.62 μmol/l for the placebo and febuxostat group, respectively, on day 7 (P = 0.000). The rate of recurrent gout flares was 10.00% for the placebo group and 6.56% for the febuxostat group from day 8 through 28 (P = 0.492).ConclusionInitiation of febuxostat administration during an acute gout flare did not prolong the duration of acute flares.Trial registrationChinese Clinical Trial Registry, http://www.chictr.org.cn/, ChiCTR1800015962.
| S-EPMC8409997 | biostudies-literature
Project description:The small intestinal epithelium produces numerous antimicrobial peptides and proteins, including abundant enteric ?-defensins. Although they most commonly function as potent antivirals in cell culture, enteric ?-defensins have also been shown to enhance some viral infections in vitro. Efforts to determine the physiologic relevance of enhanced infection have been limited by the absence of a suitable cell culture system. To address this issue, here we use primary stem cell-derived small intestinal enteroids to examine the impact of naturally secreted ?-defensins on infection by the enteric mouse pathogen, mouse adenovirus 2 (MAdV-2). MAdV-2 infection was increased when enteroids were inoculated across an ?-defensin gradient in a manner that mimics oral infection but not when ?-defensin levels were absent or bypassed through other routes of inoculation. This increased infection was a result of receptor-independent binding of virus to the cell surface. The enteroid experiments accurately predicted increased MAdV-2 shedding in the feces of wild type mice compared to mice lacking functional ?-defensins. Thus, our studies have shown that viral infection enhanced by enteric ?-defensins may reflect the evolution of some viruses to utilize these host proteins to promote their own infection.
| S-EPMC5489213 | biostudies-literature
Project description:Gout typically presents as an acute, self-limiting inflammatory monoarthritis. Based on single-cell RNA sequencing (scRNA-seq), we profiled peripheral blood mononuclear cells (PBMCs) from the same patients with gout flare and gout remission We identified the dynamics of cell abundance, gene expression patterns and biological processes underlying the immune dysregulation of each cell compartment. The single-cell landscape of both innate and adaptive immune responses provides new insights into pathogenesis and therapy of gout flare.
2023-01-01 | GSE211783 | GEO