Syntenin-1-mediated arthritogenicity is advanced by reprogramming RA metabolic macrophages and Th1 cells.

OBJECTIVES: Syntenin-1, a novel endogenous ligand, was discovered to be enriched in rheumatoid arthritis (RA) specimens compared with osteoarthritis synovial fluid and normal synovial tissue (ST). However, the cellular origin, immunoregulation and molecular mechanism of syntenin-1 are undescribed in RA. METHODS: RA patient myeloid and lymphoid cells, as well as preclinical models, were used to investigate the impact of syntenin-1/syndecan-1 on the inflammatory and metabolic landscape. RESULTS: Syntenin-1 and syndecan-1 (SDC-1) co-localise on RA ST macrophages (MΦs) and endothelial cells. Intriguingly, blood syntenin-1 and ST SDC-1 transcriptome are linked to cyclic citrullinated peptide, erythrocyte sedimentation rate, ST thickness and bone erosion. Metabolic CD14+CD86+GLUT1+MΦs reprogrammed by syntenin-1 exhibit a wide range of proinflammatory interferon transcription factors, monokines and glycolytic factors, along with reduced oxidative intermediates that are downregulated by blockade of SDC-1, glucose uptake and/or mTOR signalling. Inversely, IL-5R and PDZ1 inhibition are ineffective on RA MΦs-reprogrammed by syntenin-1. In syntenin-1-induced arthritis, F4/80+iNOS+RAPTOR+MΦs represent glycolytic RA MΦs, by amplifying the inflammatory and glycolytic networks. Those networks are abrogated in SDC-1-/- animals, while joint prorepair monokines are unaffected and the oxidative metabolites are moderately replenished. In RA cells and/or preclinical model, syntenin-1-induced arthritogenicity is dependent on mTOR-activated MΦ remodelling and its ability to cross-regulate Th1 cells via IL-12 and IL-18 induction. Moreover, RA and joint myeloid cells exposed to Syntenin-1 are primed to transform into osteoclasts via SDC-1 ligation and RANK, CTSK and NFATc1 transcriptional upregulation. CONCLUSION: The syntenin-1/SDC-1 pathway plays a critical role in the inflammatory and metabolic landscape of RA through glycolytic MΦ and Th1 cell cross-regulation (graphical abstract).

Orthopedic Articular and Periarticular Joint Infections.

Acute nontraumatic joint pain has an extensive differential. Emergency physicians must be adept at identifying limb and potentially life-threatening infection. Chief among these is septic arthritis. In addition to knowing how these joint infections typically present, clinicians need to be aware of host and pathogen factors that can lead to more insidious presentations and how these factors impact the interpretation of diagnostic tests.

From Acute Infection to Prolonged Health Consequences: Understanding Health Disparities and Economic Implications in Long COVID Worldwide.

The COVID-19 pandemic has resulted in a growing number of patients experiencing persistent symptoms and physiological changes after recovering from acute SARS-CoV-2 infection, known as Long COVID. Long COVID is characterized by recurring symptoms and inflammation across multiple organ systems. Diagnosis can be challenging, influenced by factors like demographics, comorbidities, and immune responses. Long COVID impacts various organ systems and can have neuropsychological effects. Health disparities, particularly related to race, contribute to a higher burden of infection and ongoing symptoms in minority populations. Managing Long COVID entails addressing a spectrum of symptoms that encompass physical, cognitive, and psychological aspects. The recovery period for patients with Long COVID can vary significantly, influenced by factors like the severity of the disease, hospitalization, comorbidities, and age. Currently, there are no universally effective treatments, although certain interventions show promise, necessitating further research. Self-management and rehabilitation programs can provide relief, but more research is needed to establish their effectiveness. Preventive measures such as vaccination and the use of antiviral medications and metformin. It is imperative to conduct further research to develop evidence-based guidelines and gain a better understanding of the long-term implications of COVID-19. Long COVID could have substantial economic impact on the labor market, productivity, healthcare expenditures, and overall economic growth. To address the challenges patients with long-term complications face, there is a focus on strategies like promoting telework and flexible work arrangements to accommodate diverse symptoms, particularly chronic fatigue and other Long COVID effects. In conclusion, this review emphasizes the multifaceted complexity of Long COVID and the ongoing need to address its potential long-term health and economic impacts.

Bullous Systemic Lupus Erythematosus Successfully Treated With Intravenous Immunoglobulin and Mycophenolate Mofetil.

Bullous systemic lupus erythematosus (BSLE) is a rare autoimmune blistering disorder of cutaneous lupus erythematosus (CLE) that typically manifests as an acute vesiculobullous eruption in a patient with systemic lupus erythematosus (SLE). Also, it can rarely present as the initial clinical manifestation of SLE. There is no established US Food and Drug Administration (FDA) therapy for BSLE. We report a case of a 71-year-old Hispanic woman with SLE and lupus nephritis classes III and V who presented to the hospital with a worsening rash with painful, ruptured blisters involving the upper arms, chest, and back. Our patient did not respond to topical or systemic steroids but improved rapidly to combination therapy with intravenous immunoglobulin (IVIg) and mycophenolate mofetil (MMF).

Cervical CT-Dependent Diagnosis of Crowned Dens Syndrome in Calcium Pyrophosphate Dihydrate Crystal Deposition Disease.

PURPOSE: The purpose of this study is to assess the presence of crowned dens syndrome in patients with calcium pyrophosphate disease. We report 34 patients with crowned dens syndrome in one of the largest series from a single tertiary medical center in North America. METHODS: A retrospective chart review was conducted at the University of Kansas Medical Center from November 1, 2005-November 1, 2017. A total of 191 patients with calcium pyrophosphate disease were identified. The available cervical computed tomography scans were analyzed by a musculoskeletal radiologist for the presence of periodontoid calcifications and erosions. RESULTS: Of the 191 patients with calcium pyrophosphate disease, 57 had cervical computed tomography scans; 34 of them (34/57, 59.64%) had periodontoid calcifications. Only 12/34 patients were formally evaluated and diagnosed by rheumatologists with crowned dens syndrome. Twenty-two of 34 were either not seen by a rheumatologist or were not diagnosed with crowned dens syndrome. The median age was 78.5 years, with 73.52% over 70 years old; 24/34 (70.58%) were female; 17/34 patients (50%) were symptomatic; 28/34 (82.35%) had additional sites of chondrocalcinosis on available radiographs; 8 (28.57%) had 3 or more sites of chondrocalcinosis in typical calcium pyrophosphate disease locations. Six patients did not have any radiographs. CONCLUSION: Crowned dens syndrome is an under-recognized entity that should be considered in elderly patients with neck pain in the setting of calcium pyrophosphate disease. Our data demonstrated a high percentage (about 60%) of patients with calcium pyrophosphate disease who had cervical computed tomography findings consistent with crowned dens syndrome. This underscores the importance of performing cervical computed tomography when evaluating patients with neck pain and calcium pyrophosphate disease.

Ganoderma lucidum suppresses endothelial cell cytotoxicity and proteinuria in persistent proteinuric focal segmental glomerulosclerosis (FSGS) nephrosis.

A persistent proteinuria is commonly observed in nephrotic patient with focal segmental glomerulosclerosis (FSGS) under treatment with prednisolone+/-cyclophosphamide or with vasodilators (ACEI+AII receptor antagonist, calcium channel blocker and antiplatelet agent). Fourteen such patients with persistent proteinuria were subject to be treated with Ganoderma lucidum. Initial study revealed an enhanced endothelial cell cytotoxicity induced by patient's serum, and an altered immunocirculatory balance with predominant proinflammatory cytokine TNF alpha activity in the presence of defective anti-inflammatory cytokine interleukin-10. Treatment with Ganoderma lucidum suppressed endothelial cell cytotoxicity, restored immunocirculatory balance and successfully suppressed proteinuria in all of these 14 patients.