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ID PMID Title PublicationDate abstract
33247940 Increased expression of interleukin-21-inducible genes in minor salivary glands are associ 2021 Jun 18 OBJECTIVE: To determine the upregulation of IL-21-inducible genes in minor salivary glands (MSGs) in 28 primary SS (pSS) patients and 12 non-pSS subjects and correlate it with disease characteristics. METHODS: RNA sequencing was utilized to compare IL-21-inducible genes expression in the MSGs between pSS and non-pSS subjects. The subgroups were characterized according to the IL-21 score calculated by seven IL-21-inducible genes. Furthermore, the disease characteristics and transcripts implicated in hypoxia and interferon signalling were assessed in two pSS subgroups. RESULTS: We observed that the expression of the IL-21-inducible genes (IL-21, IL-21R, JAK3, STAT1, HLA-B, CCR7 and CXCL10), the so-called IL-21 signature genes, was significantly increased in pSS patients. The upregulation of JAK3 expression may be induced by hypomethylation of the JAK3 promoter in pSS patients and putatively associated with POU2F2. The patients with increased IL-21 signature gene expression showed an increased EULAR Sjögren's Syndrome Disease Activity Index score and increased enrichment of B cells, memory B cells, CD4+ T cells and CD8+ T cells. Furthermore, the IL-21 scores in the anti-SSA+, SSB+, ANA+ and high IgG samples were higher than those in the respective antibody-negative samples and normal IgG. In addition, we found both hypoxia and IFN-relevant genes showed strong correlation with IL-21 signature gene expression, indicating their interaction in pSS. CONCLUSION: IL-21 signature gene was associated with typical disease characteristics in pSS, which provides insight into the contribution of the IL-21 signalling pathway to the pathogenesis of the disease and might provide a novel treatment strategy for this subtype of pSS.
35347914 Research progress on inflammatory mechanism of primary Sjögren syndrome. 2021 Dec 25 Primary Sjögren syndrome is an autoimmune disease, in which a large number of lymphocytes infiltrate the exocrine glands and cause gland dysfunction. Its pathogenesis is related to the chronic inflammation of the exocrine glands caused by genetic factors, immunodeficiency or viral infection. Long-term inflammation leads to accelerated apoptosis of epithelial cells, disordered gland structure, increased expression of proinflammatory cytokine such as CXC subfamily ligand (CXCL) 12, CXCL13, B cell-activating factor (BAF), interleukin (IL)-6, interferon (IFN)-γ and tumor necrosis factor (TNF)-α in submandibular gland. With the action of antigen-presenting cells such as dendritic cells and macrophages, lymphocytes (mainly B cells) are induced to mature in secondary lymphoid organs and migrate to the submandibular gland to promotes the formation of germinal centers and the synthesis of autoantibodies. Meanwhile, innate lymphocytes, vascular endothelial cells and mucosa-associated constant T cells as important immune cells, also participated in the inflammatory response of the submandibular gland in primary Sjögren syndrome through different mechanisms. This process involves the activation of multiple signal pathways such as JAK/STAT, MAPK/ERK, PI3K/AKT/mTOR, PD-1/PD-L1, TLR/MyD88/NF-κB, BAF/BAF-R and IFN. These signaling pathways interact with each other and are intricately complex, causing lymphocytes to continuously activate and invade the submandibular glands. This article reviews the latest literature to clarify the mechanism of submandibular gland inflammation in primary Sjögren syndrome, and to provide insights for further research.
33063091 Takotsubo syndrome and rheumatic diseases-a critical systematic review. 2021 Jan 5 Since its description in 1990, Takotsubo syndrome (TTS), an acute cardiac condition triggered by physical or emotional stress, has been believed to be related to catecholamine surge from overwhelming sympathetic activity. While symptomatology, biochemical features, ECG and echocardiogram alterations are largely indistinguishable from acute coronary syndrome, the absence of culprit coronary lesions often necessitates further investigations, uncovering underlying inflammatory processes. Mechanistically, animal models of TTS reveal early neutrophil infiltration followed by staged ingression of two subtypes of macrophages (M1, M2) mediating initial acute inflammatory changes (M1), followed by switching to anti-inflammatory signals (M2) that enhance myocardial tissue recovery. Here, we begin with a description of two TTS patients with primary Sjögren's syndrome and Takayasu's arteritis, followed by a systematic literature review that summarizes the demographic and clinical features of TTS patients with rheumatological conditions. Potential impact of disease manifestations and treatment of rheumatological conditions on TTS are critically discussed.
32757000 Elevated circulating pro-inflammatory low-density granulocytes in adult-onset Still's dise 2021 Jan 5 OBJECTIVES: Neutrophilia is a hallmark of adult-onset Still's disease (AOSD). This study aimed to investigate the role of a distinct subset of granulocytes, the low-density granulocytes (LDGs) in the pathogenesis of AOSD. METHODS: A total of 56 patients with AOSD were included in the study. LDGs were quantified by flow cytometry. Correlations between LDGs with disease activity and laboratory parameters were determined by Spearman's nonparametric test. The cellular sources of the pro-inflammatory cytokines in AOSD were determined by intracellular staining. RESULTS: Active AOSD patients displayed significantly higher levels of LDGs compared with inactive AOSD patients and healthy controls (HCs) (P<0.001). Circulating LDGs were significantly correlated with CRP, ESR and the modified Pouchot score in patients with AOSD (P<0.01). The levels of LDGs were significantly decreased after the active AOSD patients achieved disease remission (P=0.0391). CD14+ monocytes constituted over 90% IL-1β+ peripheral blood mononuclear cells (PBMCs) and over 80% TNF-α+ PBMCs in both active AOSD patients and HCs, respectively. In active AOSD, CD14+ monocytes accounted for 24.6% to 75.0% of IL-6+ PBMCs, while LDGs comprised 22.8% to 72.2% of IL-6+ PBMCs. In contrast, over 90% IL-6+ PBMCs were CD14+ monocytes in HCs. A significant correlation was identified between the levels of LDGs and serum IL-6 levels in AOSD (P<0.0001). CONCLUSION: Active AOSD is associated with elevated levels of a pro-inflammatory subset of neutrophils, the LDGs that produce IL-6. Our data highlight an unappreciated role of LDGs in the aberrant innate immune responses in AOSD.
32657632 Novel Cytokine Multiplex Assay for Tear Fluid Analysis in Sjogren's Syndrome. 2021 Nov 17 Purpose: Sjögren's syndrome (SS) is an autoimmune disease associated with ocular surface inflammation. The goals of this study were to establish a novel bead-based protein microarray for simultaneous analysis of 11 cytokines from tear fluid collected with Schirmer strips from patients with SS.Methods: Three to ten microliter of tear fluid was collected with Schirmer strips from both eyes of 13 healthy controls and 12 SS patients. Tear fluid was eluted from the Schirmer strips, total protein and concentrations of 11 different cytokines were analyzed.Results: The multiplex assay demonstrated high assay sensitivity with LoDs between 1.4 and 55.3 pg/µl with mean CVs between 3.7% and 9.7%. Statistically significant upregulation (p < .005) of eight cytokines was observed in SS patients compared to controls. Additionally, four patient cytokine values showed a significant inverse correlation (r<-0.7) with Schirmer strip readings.Conclusion: The assay offers analytical reliability for quantification of biomarkers in small amounts of tear fluid with potential utility for treatment monitoring of SS and other types of Dry Eye Disease.
33909180 Neuromyelitis Optica Spectrum Disorders (NMOSD) and Connective Tissue Disease (CTD): an Up 2021 Apr 28 PURPOSE OF REVIEW: To review the pathophysiology, presentation, and treatment of neuromyelitis optica spectrum disorder (NMOSD) and its association with systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). RECENT FINDINGS: NMOSD is an autoimmune disorder of the central nervous system that primarily targets astrocytes. Although the prevalence is unknown, the coexistence of NMOSD and SLE/SS is well-recognized. Patients with both NMOSD and SLE or SS require may require unique approaches to diagnosis and management. Coexistence of NMOSD and SLE/SS is important for the rheumatologist and neurologist to be able to recognize. For the rheumatologist, NMOSD and its neurologic symptoms represent a distinct disease process from neurologic complications of the patient's underlying connective tissue disease, and it requires distinct acute and chronic management. For the neurologist, the coexistence of SLE and SS can help to establish a diagnosis of NMOSD, or in some situations, the development of neurologic symptoms secondary to NMOSD can lead to the diagnosis of connective tissue disease.
33751488 Expanding the etiologic spectrum of spastic ataxia syndrome: chronic infection with human 2021 Apr Human T-lymphotropic virus type-1 (HTLV-1) is a neglected infection most often associated with an indolent process. However, a subset of HTLV-1 seropositive patients face the risk to develop life-threatening T-cell lymphoma/leukemia, or the highly disabling and incurable HTLV1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Over the years, other complications to HTLV-1 have been proposed and debated intensely. One of these, although rare, associations include cerebellar ataxia occurring most often in Japanese patients with manifest HAM/TSP. Here we present a HTLV-1 seropositive patient from the Middle East featuring a slowly progressive cerebellar syndrome with cerebellar atrophy but not evidence of spastic paraparesis. In addition, this patient suffered from autoimmune conditions such as Sjögren’s syndrome and vitiligo which are putatively associated with HTLV-1.
33655792 Severe pulmonary arterial hypertension and massive ascites in a patient with systemic lupu 2021 Mar BACKGROUND: Pulmonary arterial hypertension (PAH), is a rare manifestation of systemic lupus erythematosus (SLE), characterized by pulmonary arterial remodeling leading to right ventricular failure and death. To date, optimal management of SLE-associated PAH should be clarified, especially regarding the respective places of immunosuppressants and PAH vasodilator treatments. CASE REPORT: We report the case of a 48-year-old woman with SLE and secondary Sjogren syndrome, associated with severe PAH and lupus peritonitis with massive ascites, who showed a remarkable response, both for SLE flare and PAH, to a treatment combining immunosuppressants and pulmonary arterial vasodilator treatment. CONCLUSION: This observation highlights the interest of combining immunosuppressive therapy in SLE-PAH, whose modalities in association with PAH treatments should be clarified.
33085747 Patient-based reliability of the Outcome Measures in Rheumatology (OMERACT) ultrasound sco 2021 May 14 BACKGROUND: To assess the reliability of the consensually agreed US definitions of major salivary gland lesions and the US scoring system for salivary gland assessment in patients with SS. METHODS: Nine experienced sonographers scanned and read the US images of both parotid glands (PGs) and submandibular glands (SMGs) in eight patients with primary and secondary SS in two rounds. A consensually agreed four-grade semi-quantitative scoring was applied in B-mode for morphological lesions: grade 0, normal; grade 1, mild inhomogeneity without anechoic or hypoechoic areas; grade 2, moderate inhomogeneity with focal anechoic or hypoechoic areas; grade 3, severe inhomogeneity with diffuse an- or hypoechoic areas occupying the entire gland or fibrous gland. The presence or absence of typical SS lesions, i.e. the Sjögren's signature, was scored binary. Intra- and interreader reliabilities were computed using weighted and unweighted Cohen's and Light's κ coefficients. RESULTS: The mean prevalence of grades 0-3 in PG were 43, 17, 23 and 31% and 28, 14, 33 and 32% for the SMGs, respectively. The weighted κ for intrareader reliability ranged from 0.44 to 1 for grading and 0.64 to 1 for the Sjögren's signature of PG and 0.59 to 1 and -0.09 to 0.6 for SMGs, respectively. The interreader reliability κ for grading in PG was 0.62 (95% CI 0.47, 0.74) and for Sjögren's signature it was 0.36 (95% CI 0, 0.43); in SMG it was 0.62 (95% CI 0.47, 0.72) and 0.03 (95% CI 0, 0.07) respectively. CONCLUSIONS: The consensually agreed novel US scoring system for major salivary gland lesions showed substantial intra- and interreader reliability in patients with SS. The reliability of the Sjögren's signature was moderate.
35145508 The Role of IgG4 in Autoimmunity and Rheumatic Diseases. 2021 The distinguishing of the IgG4-related disease (IgG4-RD) from among other rheumatic diseases has brought attention to the IgG4 subclass of immunoglobulins. It is the least numerous subclass among immunoglobulins G. In general, IgG4 is considered to be non-inflammatory and tolerance inducing, due to its unique structure. However, in IgG4-RD this antibody plays a pathogenic role in activation of the fibrinogenesis and of the inflammatory process; there are also suggestions that it may be a marker of an abnormal inflammatory response. The importance of IgG4 for the pathogenesis of allergic diseases, with a vital role of its ratio to immunoglobulin E (IgE/IgG4 ratio), has been known for years. The role of IgG4 in the course and pathogenesis of rheumatic diseases is still being researched and is not yet fully understood. Increased IgG4 levels have been revealed in rheumatoid arthritis, although no clear link between this phenomenon and disease activity has been demonstrated. There are articles on the potential importance of IgG4 concentration (of both elevated and decreased serum levels) in Sjogren's syndrome. Additionally, anti-nuclear IgG4 antibody significant titers have been detected in SLE patients, and it has been suggested that the effect of these antibodies on complement consumption and the production of proinflammatory cytokines may play a role in inhibiting the progression of SLE. IgG4 plays a role in autoimmune diseases other than rheumatic diseases, such as pemphigus, bullous pemphigoid, idiopathic membranous glomerulonephritis, or myasthenia gravis, but also in helmints infections. Research shows the importance of IgG4 in malignancy of neoplasms. Melanoma cells are known to stimulate IgG4 production through a modified Th2-based inflammatory response. The role of this immunoglobulin in cholangiocarcinoma is also considered as possible. The aim of this review article is to discuss the current knowledge of IgG4 not only from the perspective of the IgG4-RD but also from a point of view of other autoimmune diseases with particular emphasis on rheumatic diseases.
34653934 Interleukin-4-carrying small extracellular vesicles with a high potential as anti-inflamma 2021 Nov Interleukin-4 (IL4), a Th2-type cytokine that can drive M2 macrophage polarization, is expected to be used as an anti-inflammatory therapy agent as M2 polarization of macrophages can ameliorate chronic inflammation. However, several problems, such as the low effectiveness and side effects, have hampered the clinical application. To safely and effectively use IL4, an efficient delivery of IL4 to target cells, macrophages, is necessary. Small extracellular vesicles (sEVs) are promising candidates as macrophage delivery carriers because they are efficiently recognized by macrophages. In addition, considering the property of IL4 signaling, for which the internalization of IL4 receptor into the cellular compartment is important, and sEV uptake mechanism by macrophages, sEVs are expected to amplify IL4 signaling. In this study, we developed IL4-carrying sEVs (IL4-sEVs) by genetically engineering sEV-producing cells. We investigated the bioactivity of IL4-sEVs using RAW264.7 macrophages and their potential for therapeutic application to the treatment of an inflammatory disease using collagen-induced arthritis model mice. IL4-sEVs exhibited stronger anti-inflammatory effects on M1-polarized macrophages through M2 polarization of macrophages than those of soluble IL4 proteins. Moreover, IL4-sEVs exhibited more effective therapeutic effects on rheumatoid arthritis than those of IL4. These results indicate that IL4-carrying sEVs are promising anti-inflammatory therapeutics.
34514945 Effect and underlying mechanism of morin on the pharmacokinetics of diclofenac sodium in r 2021 Oct 1. Morin, a natural flavonol, is present in many plants. It has anti-inflammatory and immunomodulatory activities and is often used as an adjuvant treatment for arthritis. Diclofenac sodium is the first-choice drug in the treatment of rheumatoid arthritis. However, the herb-drug interaction (HDI) between morin and diclofenac sodium remains unclear.2. The aim of the present research was to investigate whether and how morin affect the pharmacokinetic profile of diclofenac sodium.3. The enzyme kinetic and pharmacokinetic studies showed that morin significantly accelerated the metabolism and reduced systemic exposure of diclofenac sodium. Interestingly, the effect of morin on the pharmacokinetic profile of diclofenac sodium was not in a dose-dependent manner. Therefore, the effect of morin on P-glycoprotein (P-gp) was further investigated.4. The results implied that the influence mechanism of morin on the pharmacokinetic of diclofenac sodium might be related to CYP2C9 and P-gp. Attention should be paid to the risk of HDI between morin and diclofenac sodium in clinical practice.
34345021 Importance of lymphocyte-stromal cell interactions in autoimmune and inflammatory rheumati 2021 Sep Interactions between lymphocytes and stromal cells have an important role in immune cell development and responses. During inflammation, stromal cells contribute to inflammation, from induction to chronicity or resolution, through direct cell interactions and through the secretion of pro-inflammatory and anti-inflammatory mediators. Stromal cells are imprinted with tissue-specific phenotypes and contribute to site-specific lymphocyte recruitment. During chronic inflammation, the modified pro-inflammatory microenvironment leads to changes in the stromal cells, which acquire a pathogenic phenotype. At the site of inflammation, infiltrating B cells and T cells interact with stromal cells. These interactions induce a plasma cell-like phenotype in B cells and T cells, associated with secretion of immunoglobulins and inflammatory cytokines, respectively. B cells and T cells also influence the stromal cells, inducing cell proliferation, molecular changes and cytokine production. This positive feedback loop contributes to disease chronicity. This Review describes the importance of these cell interactions in chronic inflammation, with a focus on human disease, using three selected autoimmune and inflammatory diseases: rheumatoid arthritis, psoriatic arthritis (and psoriasis) and systemic lupus erythematosus. Understanding the importance and disease specificity of these interactions could provide new therapeutic options.
34276042 Editorial: Tocilizumab, a Humanized Therapeutic IL-6 Receptor (IL-6R) Monoclonal Antibody, 2021 Jul 19 Vaccinated, non-vaccinated, and immunosuppressed individuals will continue to be infected with SARS-CoV-2. Therefore, there is a priority to develop treatments that reduce the severity of COVID-19 in patients who require hospital admission. Interleukin-6 (IL-6) is a proinflammatory cytokine. In 2011, a humanized monoclonal antibody to the IL-6 receptor (IL-6R), tocilizumab, was approved by the US Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis, and Castleman's disease. In 2017, tocilizumab was approved to treat chimeric antigen receptor (CAR) T-cell therapy-induced cytokine release syndrome (CRS). In 2021, the results of the REMAP-CAP clinical trial (NCT02735707) and the COVID-19 Therapy (RECOVERY) clinical trial (NCT04381936) supported FDA Emergency Use Authorization (EUA) for tocilizumab to treat hospitalized patients with moderate and severe COVID-19. Monoclonal antibodies are currently in clinical development or undergoing clinical trials to treat COVID-19. Further clinical trials will provide safety and efficacy data on targeting IL-6 and IL-6R and provide rationales for more personalized combination treatments to control the systemic effects of SARS-CoV-2 infection in hospitalized patients with moderate and severe COVID-19. This Editorial aims to present the background to the recent authorization of tocilizumab, a humanized therapeutic monoclonal antibody to the IL-6 receptor (IL-6R), for hospitalized patients with moderate and severe COVID-19 and future combination therapies.
33427615 Non-medical switching from reference to biosimilar etanercept - no evidence for nocebo eff 2021 Nov OBJECTIVES: To evaluate the effectiveness and safety of non-medical switching from reference to biosimilar etanercept in adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) using different information strategies before switching. METHODS: Data of adult patients with RA, PsA or axSpA who had received reference etanercept were retrospectively analysed. Whether or not patients were informed about the switch from reference to biosimilar etanercept was left to the discretion of the treating rheumatologist. Disease activity and function were regularly assessed in two consecutive visits (week 12 and 24). The scores documented at week 12 week after the switch were defined as primary outcome. Adverse drug events (ADE) were documented. RESULTS: Data of 84 patients were available (44 RA, 25 axSpA and 15 PsA patients), of whom 24 had been informed about the planned switch (28.5%). The scores at week 12 of disease activity and function remained rather unchanged. Neither outcomes nor frequency of ADE were influenced by information strategy. The retention rate was high (96.4% at week 12, 87.6% at week 24). Seven patients were lost to follow-up, and six patients discontinued due to inefficacy or ADE. 18 ADEs were reported in 10 patients (12%). In 3 patients (3.6%) who had 5 ADEs in the first 12 weeks the reference etanercept was successfully readministered. CONCLUSIONS: Systematic switch from reference to biosimilar etanercept was not associated with changes in disease activity or function in. This was independent of information on the switch transmitted to the patients.
34429051 Systematic Review on Treatment Trials of Tocilizumab: A Repurposing Drug against COVID-19. 2021 BACKGROUND: Coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a global issue today. There exists an ongoing health crisis all over the world, and efficacious drugs against COVID-19 are not available yet. Therefore, on an urgent basis, scientists are looking for safe and efficacious drugs against SARSCoV- 2. METHODS: The reported individual patient data and clinical outcomes, including the rate of recovery and mortality, patients' characteristics, and complications, are reviewed. Randomized controlled trials, single-center cohort studies, and different case studies are provided, and the PICO model is used to illustrate the outcomes. RESULTS: There exist several FDA (U.S Food and Drug Administration) approved anti coronavirus drugs that sometimes are unsuccessful in curing COVID-19 critical conditions. It has been observed that a humanized monoclonal antibody, Tocilizumab (licensed for the treatment of rheumatoid arthritis), targeting the interleukin-6 (IL-6) receptor, has an integral role in the treatment of COVID-19. CONCLUSION: The cause behind the mortality of COVID-19 patients was found to be the Cytokine Release Syndrome (CRS). Therefore, besides other antiviral drugs, the utilization of tocilizumab should also be considered as it can effectively block IL-6 and reduce the inflammatory signal.
34347576 Emerging roles of IL-34 in neurodegenerative and neurological infectious disease. 2021 Aug 18 Neurological infections are often devastating in their clinical presentation. Although significant advances have made in neuroimaging techniques and molecular tools for diagnosis, as well as in anti-infective therapy, these diseases always difficult to diagnose and treat. Neuroparasitic infections and virus infections lead to neurological infections. In the nervous system, various cytokines and chemokines act as neuroinflammatory agents, neuromodulators, regulate neurodevelopment, and synaptic transmission. Among the most important cytokines, interleukins (ILs) are a large group of immunomodulatory proteins that elicit a wide variety of responses in cells and tissues. These ILs are involved in pro and anti-inflammatory effects, systemic inflammation, immune system modulation and play crucial roles in fighting cancer, infectious disease, and neurological disorders. Interleukin-34 (IL-34) identified by screening a comprehensive human protein library containing ∼3400 secreted and extracellular domain proteins in a human monocyte viability assay. Recent evidence has disclosed the crucial roles of IL-34 in the proliferation and differentiation of mononuclear phagocyte lineage cells, osteoclastogenesis, and inflammation. Additionally, IL-34 plays an important role in development, homeostasis, and disease. Dysregulation in IL-34 function can lead to various inflammatory and infectious diseases (e.g. Inflammatory bowel disease, liver fibrosis, Systemic Lupus erythematosus, rheumatoid arthritis), neurological disorders (e.g. Alzheimer disease) and neurological infectious disease (e.g. West Nile virus disease). In this review, we explore the biological role of IL-34 in addition to various impairments caused by dysregulation in IL-34 and discuss their potential links that may lead to important therapeutic and/or preventive strategies for these disorders.
34109072 Preliminary Report of Arthroscopically Assisted Sauvé-Kapandji Procedure for Distal Radio 2021 Jun Background  The arthroscopically assisted Sauvé-Kapandji (S-K) procedure has been described as a safe and promising technique for distal radioulnar joint (DRUJ) arthrodesis. Our purpose was to investigate the advantages and disadvantages of the arthroscopically assisted S-K procedure. Methods  Eight patients underwent an arthroscopically assisted S-K procedure. All patients were diagnosed as DRUJ osteoarthritis (OA), including six primary DRUJ OA, one OA following a distal radius fracture, and one rheumatoid arthritis (RA). Arthroscopy was performed in neutral forearm rotation with vertical traction. The surface of the DRUJ was debrided through arthroscopy to expose the subchondral surface, and the DRUJ was fixed with a cannulated screw and Kirschner wire (K-wire) with zero or minus ulnar variance in the same posture. Bone graft was not performed. Results  Bone union was achieved at 2 to 3.5 months postoperatively. At an average of 17-month follow-up, the pain intensity on 10-point numerical rating scale (NRS) decreased from 10 preoperatively to 0.4 postoperatively, average range of pronation significantly improved from 77 degrees to 89 degrees, and average grip strength as a percentage of contralateral side improved from 76 to 104%. Conclusion  Satisfactory outcomes were achieved with the arthroscopically assisted S-K procedure. Advantages of this procedure included the ability to achieve union without bone grafting, preservation of the extensor mechanism integrity, and easy reduction of the ulnar head due to its wrist positioning. No major complications were encountered. Disadvantages included its required use of arthroscopic technique and potential contraindication for cases with severe deformity at the sigmoid notch. Level of Evidence  This is a Level IV, therapeutic study.
34122597 Metabolomic Analysis of the Urine from Rats with Collagen-Induced Arthritis with the Effec 2021 Rheumatoid arthritis (RA) is a chronic autoimmune disease with high incidence and high disability and recurrence rates. Caulophyllum robustum Maxim (C. robustum) is a traditional Chinese medicine (TCM) with main effective parts (CRME) commonly used for RA treatment. To explore the mechanism of CRME in RA, we used metabolomics to investigate the effect of CRME intervention on urine metabolism in rats with collagen-induced arthritis (CIA). CIA rats were randomly divided into normal control, CIA model, and CRME groups. A metabolomics approach, using Ultra-Performance Liquid Chromatography-Quadrupole-Time-of-Flight/Mass Spectrometry, was developed to perform urinary metabolic profiling. Differential metabolites were identified by comparing the CIA model and CRME groups. Preliminarily, 56 significant differential metabolites were identified in urine, and 20 metabolic pathways were disturbed by the CIA. The amount of 16 different metabolites changed in urine after CRME intervention. The production of these metabolites involves tryptophan, tyrosine, energy, cholesterol, and vitamin metabolism. CRME has anti-inflammatory and immunosuppressive effects in CIA model rats. By examining the endogenous metabolite levels, we identified potential CRME targets and pathways involved in the treatment of RA. The results of our metabolic studies indicate that CRME regulates amino acid, vitamin, energy, and lipid metabolism pathways to treat RA and may provide a new explanation for the anti-RA mechanism of CRME.
34088568 Synchronous Periprosthetic Joint Infections: High Mortality, Reinfection, and Reoperation. 2021 Oct BACKGROUND: Synchronous periprosthetic joint infections (PJIs) are a catastrophic complication with potentially high mortality. We aimed to report mortality, risk of reinfection, revision, reoperation, and implant survivorship after synchronous PJIs. METHODS: We identified 34 patients treated for PJI in more than one joint within a single 90-day period from 1990 to 2018. PJIs involved bilateral knee arthroplasty (27), bilateral hip arthroplasty (4), 1 knee arthroplasty and 1 elbow arthroplasty (1), 1 knee arthroplasty and 1 shoulder arthroplasty (1), and bilateral hip and knee arthroplasty (1). Irrigation and debridement with component retention was performed in 23 patients, implant resection in 10 patients, and a combination of irrigation and debridement with component retention and implant resection in 1 patient. A competing risk model was used to analyze implant survivorship, and Kaplan-Meier survival was used for patient mortality. Mean follow-up was 6 years. RESULTS: Mortality was high at 18% at 30 days and 27% at 1 year. The 1-year cumulative incidence of any reinfection was 13% and 27% at 5 years. The 1-year cumulative incidence of any revision or implant removal was 6% and 20% at 5 years. The 1-year cumulative incidence of unplanned reoperation was 25% and 35% at 5 years. Rheumatoid arthritis was associated with increased risk of mortality (HR 7, P < .01), as was liver disease (HR 4, P = .02). CONCLUSION: In the largest series to date, patients with synchronous PJIs had a high 30-day mortality rate of 18%, and one-fourth underwent unplanned reoperation within the first year.