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ID PMID Title PublicationDate abstract
32741737 Chinese herbal medicine SS-1 inhibits T cell activation and abrogates T(H) responses in Sj 2021 Jan BACKGROUND/PURPOSE: Sjögren's syndrome (SS) is an autoimmune disease and its conventional treatment has exhibited limited therapeutic efficacy. Traditional Chinese medicine has been demonstrated to ameliorate the sicca symptoms of SS by decreasing the level of T(H)1 and T(H)2 cytokines and increasing salivary flow rate. A newly designed traditional Chinese medicine, SS-1, showed improved efficacy in alleviating the dryness symptoms of SS patients in the National Taiwan SS cohort investigation. Here, we investigated the effect of SS-1 on T cell responses. METHODS: SS-1 was authenticated and its major compounds were verified by high-performance liquid chromatography. We examined the effects of SS-1 on the activation and T(H)1, T(H)2, and T(H)17 polarization of murine T cells. We also determined the level of T(H)1, T(H)2, and T(H)17 cytokine RNA in peripheral blood mononuclear cells of SS patients before and after SS-1 treatment. RESULTS: SS-1 treatment inhibits the activation and T(H)1, T(H)2, and IL-17A(+)IFNγ(+) T(H) polarization of murine T cells. SS-1 treatment also significantly reduces IFN-γ, IL-4, and IL-13 expression, and moderately reduces IL-17A expression in peripheral blood mononuclear cells of SS patients. CONCLUSION: Our results suggest that SS-1 inhibits T cell activation and diminishes T(H)1, T(H)2, and IL-17(+)IFN-γ(+) T(H) responses in SS patients.
33227058 Investigation of anti-inflammatory effects of bee venom in experimentally induced adjuvant 2020 OBJECTIVES: Rheumatoid arthritis is a multisystemic inflammatory disease characterized by destruction of the joints. An effective treatment method of the disease has not been developed yet. The aim of the present study is to evaluate the effects of bee (Apis mellifera anatoliaca) venom (BV) on serum inflammatory parameters, serum antioxidant load and clinical parameters of experimentally induced adjuvant arthritis in rats. MATERIAL AND METHODS: A total of 35 Wistar albino male rats were used. The animals were divided into 5 groups. First group animals served as negative controls. The second, third, fourth and fifth groups were used for experimental arthritis induction. Following clinical development of arthritis, the first group was subcutaneously administered 0.2 ml of physiological saline, and the second, third and fourth groups were treated subcutaneously with 2 µg/kg, 4 µg/kg and 20 µg/kg once a week three times. Physiological saline injected fifth group animals were used as a sham-treatment group. Clinical observations and evaluation of arthritis were made at the 15(th) day, and at the end of the experiment. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, paraoxonase, serum aryl esterase, high-sensitivity C reactive protein, interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) were determined in cardiac blood samples taken at the end of the 29(th) day. RESULTS: From the data, total oxidant level (TOL) and oxidative stress index (OSI) were calculated. Significant improvements were observed in the clinical signs of arthritis and inflammatory markers such as in IL-1β, TNF-α, IL-6 and TOL and OSI in the 20.0 µg/kg BV-administered group. Bee venom administration did not cause any significant increase in ALT and AST values or signs of liver toxicity. CONCLUSIONS: Bee venom treatment was effective in alleviation of symptoms of the experimental rat adjuvant arthritis by means of clinical observation and serum inflammatory markers.
32439392 National Analysis of Coronary Artery Bypass Grafting in Autoimmune Connective Tissue Disea 2020 Dec BACKGROUND: Autoimmune connective tissue diseases (CTDs) are associated with accelerated atherosclerosis and inflammation, while often requiring immunosuppression. Large-scale outcomes of coronary artery bypass graft (CABG) surgery in this population have not been reported thus far. This study characterized trends in use of CABG in patients with CTDs and the impact of the disease on mortality, in-hospital complications, length of stay, and costs. METHODS: The 2005 to 2015 National Inpatient Sample was used to identify all adult patients undergoing isolated CABG. The CTDs cohort included rheumatoid arthritis, lupus erythematosus, and antiphospholipid syndrome (APLS), among others. Hierarchical multivariable logistic models were used to calculate the independent impact of CTDs on clinical outcomes and costs. RESULTS: Of an estimated 2,101,591 patients, 41,567 (1.8%) were diagnosed with CTDs (rheumatoid arthritis, 58%; systemic lupus erythematosus, 12%; APLS, 11%) Although the overall annual use of CABG decreased, the proportion of patients with CTDs receiving the operation significantly increased. After adjusting for patient and hospital characteristics, CTDs were not associated with increased mortality (adjusted odds ratio [AOR], 0.91; P = .34) but were protective against cardiovascular (AOR, 0.92; P < .003), neurologic (AOR, 0.81; P = .01), and infectious (AOR, 0.80; P = .01) complications. The diagnosis of CTDs was also predictive of reduced length of hospital stay (β-coefficient = -0.40; P < .001) and costs (β-coefficient, -$1200; P = .01). On subgroup analysis patients with APLS had significantly increased odds of mortality (AOR, 1.5) and increased renal (AOR, 1.3), infectious (AOR, 1.7), and thromboembolic (AOR, 4.3) complications (all P < .05). CONCLUSIONS: CABG in patients with CTDs provides acceptable outcomes and paradoxically improved resource use. However CABG in patients with APLS warrants careful consideration given inferior outcomes.
32616791 Tofacitinib treatment aggravates Staphylococcus aureus septic arthritis, but attenuates se 2020 Jul 2 Tofacitinib, a janus kinase inhibitor, is a novel immunosuppressive drug for treatment of rheumatoid arthritis (RA). Septic arthritis (SA) and sepsis caused by Staphylococcus aureus (S. aureus), for which RA patients are at risk, are infections with high mortality. The aim of this study was to investigate the effect of tofacitinib on S. aureus infections using mouse models. In vitro tofacitinib treated mouse splenocytes were stimulated with S. aureus derived stimuli. Mice pre-treated with tofacitinib were inoculated intravenously with either arthritogenic- or septic doses of S. aureus. Arthritis severity and mortality were compared between groups. Additionally, pre-treated mice were challenged with staphylococcal toxin TSST-1 to induce shock. Tofacitinib inhibited splenocyte proliferation and IFN-γ production in response to TSST-1 and dead S. aureus. In SA, tofacitinib treatment aggravated arthritis with more severe bone erosions. However, in sepsis, treated mice displayed significantly prolonged survival compared to controls. Similarly, in staphylococcal enterotoxin-induced shock tofacitinib pre-treatment, but not late treatment dramatically reduced mortality, which was accompanied by decreased levels of TNF-α and IFN-γ. Our findings show that tofacitinib treatment increase susceptibility of SA in mice, but has a positive effect on survival in S. aureus-induced sepsis and a strong protective effect in toxin-induced shock.
33331307 [Clinical characteristics and biological treatment of adult patient with juvenile idiopath 2020 Dec 18 OBJECTIVE: To explore the clinical characteristics and biological treatment of juvenile Idiopathic arthritis (JIA) after adulthood. METHODS: Selected 358 patients with previous medical history diagnosed by JIA who were hospitalized in the Department of Rheumatology and Immunology, West China Hospital of Sichuan University from January 1, 2009 to January 1, 2019. Perform retrospective analysis of basic information, clinical symptoms, diagnostic indicators, treatment plans, outpatient follow-up (inpatients require outpatient follow-up treatment) and diagnosis and treatment process of 90 eligible cases included, and observe different ages and different courses of disease. The clinical characteristics of young and middle-aged idiopathic arthritis in adults and the outpatient situation of using biological agents for 6 months. RESULTS: According to age, they were divided into ≤26 years old group (42 cases) and >26 years old group (48 cases). Under examination [rheumatoid factor (RF), anti-nuclear antibody (ANA), anti-neutrophil antibody (ANCA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin 6 (IL-6), hemoglobin (HGB), white blood cell count (WBC), human leukocyte antigen-B27 (HLA-B27), complement 3 (C3), etc.], concurrent in terms of symptoms, treatment and prognosis, the ≤26-year-old group was generally lighter than the >26-year-old group; that was, the older the age, the heavier the onset of inflammation and other symptoms, the more complications, the worse the treatment effect, and the worse the prognosis, and there were statistical differences academic significance (P < 0.05). According to the course of disease, they were divided into ≤19 years group (46 cases) and >19 years group (44 cases). In terms of examination (RF, ANA, ANCA, ESR, CRP, IL-1β, IL-6, HGB, HLA-B27, C3, etc.), complications, treatment and prognosis, the course of disease ≤19 years group was compared with the disease course> 19 years group Overall mild; that was, the longer the course of the disease, the more severe the onset of symptoms such as inflammation, the more complications, the worse the treatment effect, and the worse the prognosis, P < 0.05, the difference was statistically significant. After 6 months of outpatient treatment with biological agents, it was found that biological agents could improve some of the patients' clinical symptoms and delay the further development of the disease. Compared with the non-biological agent treatment group (48 cases), the biological agent group (42 cases) benefited, and the difference was statistically significant (P < 0.05). CONCLUSION: Through retrospective analysis, this article believes that although adult JIA is diagnosed as connective tissue disease, it has special clinical characteristics with the course of the disease and age. Therefore, it should be recommended to give special attention to JIA patients after adulthood, require regular medical treatment in the adult rheumatology department, according to the corresponding connective tissue disease or JIA diagnosis, and standard treatment; at the same time, pay attention to the history of JIA. In the comparison of biological and non-biological treatment, it is proved that biological treatment can effectively improve some of the clinical symptoms of JIA patients after adulthood. Therefore, it is recommended that biological treatment be used as soon as possible if economic conditions permit to delay the development of the disease.
33347356 Therapeutic blockade of CXCR2 rapidly clears inflammation in arthritis and atopic dermatit 2020 Jan Neutrophils are the most abundant effector cells of the innate immune system and represent the first line of defense against infection. However, in many common pathologies, including autoimmune diseases, excessive recruitment and activation of neutrophils can drive a chronic inflammatory response leading to unwanted tissue destruction. Several strategies have been investigated to tackle pathologic neutrophil biology, and thus provide a novel therapy for chronic inflammatory diseases. The chemokine receptor CXCR2 plays a crucial role in regulating neutrophil homeostasis and is a promising pharmaceutical target. In this study, we report the discovery and validation of a humanized anti-human CXCR2 monoclonal antibody. To enable in vivo studies, we developed a surrogate anti-mouse CXCR2 antibody, as well as a human knock-in CXCR2 mouse. When administered in models of atopic dermatitis (AD) and rheumatoid arthritis (RA), the antibodies rapidly clear inflammation. Our findings support further developments of anti-CXCR2 mAb approaches not only for RA and AD, but also for other neutrophil-mediated inflammatory conditions where neutrophils are pathogenic and medical needs are unmet.
31988013 Investigation of the mechanism of action of Porana sinensis Hemsl. against gout arthritis 2020 Apr 24 ETHNOPHARMACOLOGICAL RELEVANCE: Porana sinensis Hemsl. has been widely used to treat joint pain and rheumatoid arthritis in traditional Chinese medicine (TCM). Although evidence exists to support a pharmacological action of P. sinensis for the treatment of gout arthritis (GA), the underlying mechanism of action remains unknown due to it being a multi-component and multi-target agent. AIM OF THE STUDY: To clarify the active compounds and mechanism of P. sinensis against GA. MATERIALS AND METHODS: The present study combined network pharmacology with experiments to clarify the mechanism of P. sinensis against GA. A protein-protein interaction network for gout was constructed to identify the potential drug targets, and molecular docking was subsequently performed to determine whether the protein was a target for the compounds of P. sinensis. KEGG pathway analysis was then conducted to elucidate the pathway involved in the P. sinensis-mediated treatment of gout. A rat model of GA was used to further investigate the mechanism of P. sinensis against GA. RESULTS: The network pharmacology study indicates that coumarins and chlorogenic acids of P. sinensis may serve as additives to GA treatment. P. sinensis played a role in the treatment of GA by regulating the PI3K-Akt, MAPK, NF-kappa B and toll-like receptor pathways and so on. Moreover, experimental validation suggests that P. sinensis extract significantly suppressed the expression of TLR2 and MyD88 mRNA, regulating the release of cytokines (IL-1β, IL-4 and TGF-β), lowering lipid peroxidation (MDA) and increasing antioxidant status (SOD). CONCLUSION: The present study clarifies the mechanism of P. sinensis against GA, and provides evidence to support its clinical use.
31820687 Evaluation of Anti-inflammatory Effects of Choerospondias axillaris Fruit's Methanolic Ext 2020 BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune, systemic disease mainly affecting joints. Presently, there is no specific treatment/ drug available for curing RA except few supportive medicines. Therefore, the focus has been shifted to medicinal plants for the treatment of such diseases. Choerospondias axillaris commonly known as Lupsi/Lapsi and has been reported to have several properties for the treatment of various diseases. OBJECTIVE: The present study has been conducted to explore the anti-inflammatory effects of Choerospondias axillaris fruit extract on Synoviocytes (FLS) and Collagen-Induced Arthritis (CIA) rat model. METHODS: Methanolic extract of the Choerospondias axillaris fruit was used for determining phytochemical, antioxidant and anti-inflammatory properties. Antioxidant activity of Choerospondias axillaris fruit was determined by free radicals scavenging assays and bioactive compounds were identified via LC-MS/MS analysis. Anti-inflammatory effect was investigated in RA and Osteo Arthritis (OA) primary cells and also in Collagen Induced Arthritis (CIA) rat models. Further, the medicinal properties of anti-inflammatory bioactive compounds were supported by docking studies. RESULTS: In-vitro and in-vivo studies showed significant decrease in the levels of inflammatory cytokines. Docking analysis revealed that quercetin inhibits TNF-α having -9.1 kcal/mol binding energy and 10.13 μM inhibitory constant. Quercetin also inhibits IL-6 having -6.6 kcal/mol binding energy and 21.9 μM inhibitory constant. CONCLUSION: Observed results suggest that the underutilized fruit Choerospondias axillaris can be used to reduce the inflammation of inflammatory diseases like RA.
32924009 B-Cell-Targeted 3DNA Nanotherapy Against Indoleamine 2,3-Dioxygenase 2 (IDO2) Ameliorates 2020 Jan The tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase 2 (IDO2) has been identified as an immunomodulatory agent promoting autoimmunity in preclinical models. As such, finding ways to target the expression of IDO2 in B cells promises a new avenue for therapy for debilitating autoimmune disorders such as rheumatoid arthritis. IDO2, like many drivers of disease, is an intracellular protein expressed in a range of cells, and thus therapeutic inhibition of IDO2 requires a mechanism for targeting this intracellular protein in specific cell types. DNA nanostructures are a promising novel way of delivering small molecule drugs, antibodies, or siRNAs to the cytoplasm of a cell. These soluble, branched structures can carry cell-specific targeting moieties along with their therapeutic deliverable. Here, we examined a 3DNA nanocarrier specifically targeted to B cells with an anti-CD19 antibody. We find that this 3DNA is successfully delivered to and internalized in B cells. To test whether these nanostructures can deliver an efficacious therapeutic dose to alter autoimmune responses, a modified anti-IDO2 siRNA was attached to B-cell-directed 3DNA nanocarriers and tested in an established preclinical model of autoimmune arthritis, KRN.g7. The anti-IDO2 3DNA formulation ameliorates arthritis in this system, delaying the onset of joint swelling and reducing total arthritis severity. As such, a 3DNA nanocarrier system shows promise for delivery of targeted, specific, low-dose therapy for autoimmune disease.
32908452 CypB-CD147 Signaling Is Involved in Crosstalk between Cartilage and FLS in Collagen-Induce 2020 To investigate the crosstalk between cartilage and fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), we adopted an in vitro coculture system model of collagen-induced arthritis (CIA) cartilage and CIA FLS monolayer. CIA rat samples of the synovium and femur head were collected for isolation of FLS and coculture system. Cartilages were treated with vehicle (Ctrl group), 10 ng/mL interleukin- (IL-) 1α (IL-1α group), and 10 ng/mL IL-1α plus 10 μM dexamethasone (Dex group) for 3 days before coculture with FLS for further 2 days. After the coculture, FLS were collected to determine the influences of articular cartilage on synoviocytes. Whether the CypB-CD147 signaling pathway is involved in the interactions between cartilage and FLS is assayed. Results showed that IL-1α-stimulated CIA cartilage promoted the proliferation and reduced the apoptosis of FLS. Increased inflammatory cytokines and decreased p57 expression were found in cocultured FLS stimulated by IL-1α-challenged CIA cartilage. Upregulation of NF-κB and I-κB kinase β (IKK-β) and downregulation of the inhibitor of NF-κBα (I-κBα) protein were observed in cocultured FLS. After coculture, significant increases in the expression of cyclophilin B (CypB) and CD147 were observed in CIA cartilage and FLS, respectively. Furthermore, results of immunofluorescence staining showed that the anti-CD147 antibody significantly suppressed p65 nuclear translocation in cocultured FLS stimulated by IL-1α-challenged CIA cartilage. In conclusion, inflammatory effects in the cartilage-FLS coculture system are associated with the CypB-CD147 mediating NF-κB pathway which may further enhance the inflammation in RA.
33104286 Comorbidities Before and After the Diagnosis of Rheumatoid Arthritis: A Matched Longitu 2020 Nov OBJECTIVE: To determine the contribution of rheumatoid arthritis (RA) to conditions and medical events. A secondary objective is to quantify this association before and after the introduction of biologic medications. METHODS: All data were collected as health administrative data in Ontario, Canada. Patients with RA (n = 136 678) matched 1:1 to a pool of possible controls without RA from 1995 to 2016. The study was a retrospective longitudinal observational administrative data-based cohort study with cases (RA) and controls (two non-RA comparator groups). The main exposure was new-onset RA identified by a validated diagnosis algorithm. The secondary exposure was the calendar year, which provided a natural experiment to compare years in which biologics were unavailable (pre-2001) to increasing utilization over time. The main outcomes were counts of 27 Johns Hopkins Expanded Diagnostic Cluster Comorbid Conditions. Outcomes were reported as counts and percentage differences between cases and matched controls. RESULTS: Patients experienced increases in conditions and medical events up to 5 years before RA disease incidence-4.9 conditions per patient-year compared with 4.6 conditions per patient-year in matched controls. Comorbidities increased to 8.7 conditions per patient-year in the year of RA incidence but were lower in the years after diagnosis-6.9 conditions per patient-year at 5 years postdiagnosis. CONCLUSION: This study reframes the clinical manifestations of RA with detailed data on the marginal contribution of RA to conditions and medical events. These results show that a large portion of disease burden is due to the indirect effects of RA.
33288543 Integration of the Transcriptome and Genome-Wide Landscape of BRD2 and BRD4 Binding Motifs 2021 Jan 15 Fibroblast-like synoviocytes (FLS), one of the main cell types of the rheumatoid arthritis (RA) synovium, possess phenotypic and molecular characteristics of transformed cells. JQ1, an inhibitor of the bromodomain and extra terminal domain family that includes BRD2, BRD3, BRD4, and BRDt, has shown efficacy in models of arthritis. We demonstrate that the active isomer of JQ1 but not its inactive isomer inhibits IL-1β-induced RA-FLS activation and proliferation. To understand the mechanism of JQ1 action, we subjected JQ1-treated RA-FLS to transcriptional profiling and determined BRD2 and BRD4 cistromes by identifying their global chromatin binding sites. In addition, assay for transposable accessible chromatin by high throughput sequencing was employed to identify open and closed regions of chromatin in JQ1-treated RA-FLS. Through an integrated analysis of expression profiling, Brd2/Brd4 cistrome data, and changes in chromatin accessibility, we found that JQ1 inhibited key BRD2/BRD4 superenhancer genes, downregulated multiple crucial inflammatory pathways, and altered the genome-wide occupancy of critical transcription factors involved in inflammatory signaling. Our results suggest a pleiotropic effect of JQ1 on pathways that have shown to be individually efficacious in RA (in vitro, in vivo, and/or in humans) and provide a strong rationale for targeting BRD2/BRD4 for disease treatment and interception.
32180808 The Micro-Immunotherapy Medicine 2LARTH® Reduces Inflammation and Symptoms of Rheumatoid 2020 BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damages as well as pain and disability. In order to prevent disease progression, reduce pain, and major symptoms of RA, one good strategy consists in targeting proinflammatory cytokines that have the key role in the vicious circle of synovial inflammation and pain. The micro-immunotherapy medicine (MIM) 2LARTH® targets cytokines involved in inflammation. AIM: The aim of the study is to evaluate the effect of the MIM compared to vehicle in an in vivo model of RA, induced in mice after immunization with articular bovine type II collagen. METHODS: Vehicle and MIM were dissolved in pure water (1 capsule in 100 ml) and 100 µl was given by gavage daily for 14 days. To evaluate the severity of arthritis, wrist and ankle thickness was determined, paw edema was measured, and a clinical score from 0 to 4 was established. Furthermore, histological analysis was performed. To evaluate systemic inflammation, circulating levels of IL-1β and TNF-α were measured by ELISA. RESULTS: Ankle thickness was found to be significantly reduced in MIM-treated mice compared to vehicle-treated mice (P < 0.05) and compared to untreated me (P < 0.05) and compared to untreated me (P < 0.05) and compared to untreated me (β and TNF-α were measured by ELISA. P < 0.05) and compared to untreated me (. CONCLUSION: The results indicate that the tested medicine reduces inflammation, histological, and clinical signs of RA in a CIA model.
32684761 Juvenile idiopathic arthritis in a center in the Western Anatolia region in Turkey. 2020 AIM: To demonstrate the demographic data, subgroup distributions, responses to treatment and outcomes of long-term follow-up in patients who were followed up and treated in our clinics with a diagnosis of juvenile idiopathic arthritis, and to compare these data with national and international data. MATERIAL AND METHODS: The files of 116 patients who had been diagnosed as having juvenile idiopathic arthritis, were initiated on treatment and presented for regular follow-up visits between January 2012 and January 2018, were examined. Their demographic findings, treatments, active/inactive disease states (on-medication and off-medication) and treatment response states were evaluated. RESULTS: According to the International League of Associations for Rheumatology criteria, the subtypes were specified as enthesitis-related arthritis (n=38), oligoarticular (n=37), rheumatoid factor (-) polyarticular (n=17), systemic (n=15), rheumatoid factor (+) polyarticular (n=5), and psoriatic juvenile idiopathic arthritis (n=4). In total, the female/male ratio was found to be 1.5. The mean delay time between the first complaint and the diagnosis was found to be 5.7±5.2 months. The patients with systemic type were diagnosed at the earliest, while the patients with polyarticular and enthesitis-related subtypes were diagnosed at the latest. Thirty-two percent of the patients were treated with methotrexate alone, and 38% were given additional biologic drugs. In both treatment groups, the time to achieve inactive disease was the shortest in the oligoarticular group and the longest in the enthesitis-related arthritis group. In the study period, 38 patients were in remission off-medication (the highest rate (53.3%) was observed in the systemic group) and 71 patients were in remission on-medication (the highest rate (70.2%) was observed in the oligoarticular group). Remission was obtained in 94% of the patients. CONCLUSION: Enthesitis which is the remarkable finding of enthesitis-related arthritis, should not be overlooked in routine physical examination. Awareness of enthesitis can contribute to the prevention of diagnostic delay in children with enthesitis-related arthritis.
32095896 C-reactive protein is not a screening tool for late periprosthetic joint infection. 2020 Feb 24 BACKGROUND: Preoperative diagnosis of periprosthetic joint infection (PJI) is important because of the therapeutic consequences. The aim of the present study is to investigate whether the serum C-reactive protein (CRP) level can be used as a screening tool for late PJI. MATERIALS AND METHODS: A cohort of 390 patients with revision surgery of total hip prostheses (200) or total knee prostheses (190) was assessed for late PJI by determining CRP serum level and performing preoperative aspiration with cultivation and intraoperative tissue analyses with cultivation and histologic examination, using the Musculoskeletal Infection Society (MSIS) and International Consensus Meeting (ICM) criteria. RESULTS: A total of 180 joints were rated as PJI (prevalence 46%). Of these, 42.8% (77) showed a CRP level below 10 mg/L and 28.3% (51) showed a normal CRP level of less than 5 mg/L. The 76.9% of the cases with slow-growing bacteria showed a CRP level below 10 mg/L, and 61.5% showed a normal CRP level. CONCLUSIONS: Serum CRP level should not be used as a screening tool to rule out late PJI. LEVEL OF EVIDENCE: Level 2 (diagnostic study).
32432638 Ultrasound-targeted microbubble destruction augmented synergistic therapy of rheumatoid ar 2020 Jun 24 Rheumatoid arthritis (RA) can lead to joint destruction and deformity, which is a significant cause of the loss of the young and middle-aged labor force. However, the treatment of RA is still filled with challenges. Though dexamethasone, one of the glucocorticoids, is commonly used in the treatment of RA, its clinical use is limited because of the required high-dose and long-term use, unsatisfactory therapeutic effects, and various side-effects. Ultrasound-targeted microbubble destruction (UTMD) can augment the ultrasonic cavitation effects and trigger drug release from targeted nanocarriers in the synovial cavity, which makes it a more effective synergistic treatment strategy for RA. In this work, we aim to utilize the UTMD effect to augment the synergistic therapy of RA by using polyethylene glycol (PEG)-modified folate (FA)-conjugated liposomes (LPs) loaded with dexamethasone sodium phosphate (DexSP) (DexSP@LPs-PEG-FA). The UTMD-mediated DexSP@LPs-PEG-FA for targeted delivery of DexSP including a synergistic ultrasonic cavitation effect and drug therapy were investigated through in vitro RAW264.7 cell experiments and in vivo collagen-induced arthritis SD rat model animal experiments. The results show the DexSP release from targeted liposomes was improved under the UTMD effect. Likewise, the folate-conjugated liposomes displayed targeting association to RAW264.7 cells. Together with the application of ultrasound and microbubbles, liposomes-delivered DexSP potently reduced joints swelling, bone erosion, and inflammation in both joints and serum with a low dose. These results demonstrated that UTMD-mediated folate-conjugated liposomes are not only a promising method for targeted synergistic treatment of RA but also may show high potential for serving as nanomedicines for many other biomedical fields.
32929546 Clinical and radiological outcomes after arthrodesis of the first metatarsophalangeal join 2021 Mar PURPOSE: The main aim of this study was to investigate the correlation between radiographic findings and clinical outcomes following the first metatarsophalangeal (MTP) joint arthrodesis. METHODS: In a comparative retrospective study, on 46 patients (48 ft), the correlation between post-operative radiographic findings including hallux valgus angle (HVA) and first MTP dorsiflexion angle (MTPDA) and clinical outcomes including VAS pain, modified AOFAS hallux score, and FFI questionnaire were evaluated. Moreover, clinical outcomes were compared between cases with pre-operative diagnosis of first MTP inflammatory arthritis, hallux valgus, hallux varus, and grade 3 and 4 of hallux rigidus. The effect of first MTP arthrodesis on Meary's angle and intermetatarsal angle (IMA) were found out. RESULTS: The mean age of the patients was 56.3 ± 9.1 (range, 29-69) years, including 42 (91.3%) females and 4 (8.7%) males. We had fusion rate of 97.9%, one asymptomatic nonunion case (2.1%). Totally, mean scores of modified AOFAS hallux score, FFI percentage, and VAS pain were 88.9 ± 12.6, 9.4 ± 16.5, and 1.23 ± 2.24, respectively. Hallux varus was associated with the most favourable outcomes; whereas, patients with first MTP arthritis got the worst outcome. Regression analysis test between clinical outcomes and HVA > 15° and first MTPDA >15° showed correlation coefficient of almost zero. No statistically significant differences were found between the clinical outcomes of grade 3 and 4 of hallux rigidus (p value of modified AOFAS hallux score, FFI percentage, and VAS pain: 0.879, 0.906, and 0.298, respectively). Mean of HVA and IMA reduction in 15 hallux valgus underwent first MTP fusion were 34.4° and 8.4°, respectively. Meary's angle increased about 4° with statistically significant difference (p value 0.001). CONCLUSION: Patients with first MTP fusion > 15° in coronal and transverse plans could have acceptable clinical outcomes. The clinical outcome of first MTP arthrodesis for grade 3 hallux rigidus is comparable with grade 4. First MTP fusion would have positive effect on IMA and Meary's angle.
31648078 The role of sphingosine 1-phosphate metabolism in bone and joint pathologies and ectopic c 2020 Jan Sphingolipids display important functions in various pathologies such as cancer, obesity, diabetes, cardiovascular or neurodegenerative diseases. Sphingosine, sphingosine 1-phosphate (S1P), and ceramide are the central molecules of sphingolipid metabolism. Sphingosine kinases 1 and 2 (SK1 and SK2) catalyze the conversion of the sphingolipid metabolite sphingosine into S1P. The balance between the levels of S1P and its metabolic precursors ceramide and sphingosine has been considered as a switch that could determine whether a cell proliferates or dies. This balance, also called « sphingolipid rheostat », is mainly under the control of SKs. Several studies have recently pointed out the contribution of SK/S1P metabolic pathway in skeletal development, mineralization and bone homeostasis. Indeed, SK/S1P metabolism participates in different diseases including rheumatoid arthritis, spondyloarthritis, osteoarthritis, osteoporosis, cancer-derived bone metastasis or calcification disorders as vascular calcification. In this review, we will summarize the most important data regarding the implication of SK/S1P axis in bone and joint diseases and ectopic calcification, and discuss the therapeutic potential of targeting SK/S1P metabolism for the treatment of these pathologies.
32864627 Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of 2020 Nov BACKGROUND: Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis. METHODS: In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I (2) value was less than 0·4. FINDINGS: The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12-2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22-3·95]), chest pain or angina (1·15 [1·05-1·26]), and heart failure (1·22 [1·02-1·45]). INTERPRETATION: Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit-risk trade-off when counselling those on hydroxychloroquine treatment. FUNDING: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, NIHR Senior Research Fellowship programme, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research and Development, IQVIA, Korea Health Industry Development Institute through the Ministry of Health and Welfare Republic of Korea, Versus Arthritis, UK Medical Research Council Doctoral Training Partnership, Foundation Alfonso Martin Escudero, Innovation Fund Denmark, Novo Nordisk Foundation, Singapore Ministry of Health's National Medical Research Council Open Fund Large Collaborative Grant, VINCI, Innovative Medicines Initiative 2 Joint Undertaking, EU's Horizon 2020 research and innovation programme, and European Federation of Pharmaceutical Industries and Associations.
32770403 Relationship between synoptic weather type and emergency department visits for different t 2020 Nov Many people around the world are impacted by some form of bodily pain. Outside factors, such as weather, are thought to help trigger pain, especially in those who have pain-related conditions. When it comes to human health and comfort, understanding the potential external factors that aide in triggering pain is essential. Identifying such factors makes prevention and treatment of pain more feasible. This study focused on how those who suffer from various pain-related conditions (fibromyalgia, rheumatoid arthritis, osteoarthritis, and general back pain) are impacted by different synoptic weather types (i.e., air masses). Synoptic weather types and emergency department (ED) visits for pain in select central North Carolina counties were collected over a seven-year period to determine a potential relationship. Bootstrapped confidence intervals revealed that moist tropical weather types resulted in the highest number of ED visits for each of the conditions examined, while moist polar weather types often resulted in the fewest. The barometric pressure changes associated with transitional weather types, which are often associated with fronts, did not have any significant relationships with pain.