Impact of COVID-19 pandemic on social isolation and loneliness among minority populations.

BACKGROUND: The impact of social isolation and loneliness (SIL) was heightened during the COVID-19 pandemic. Although the pandemic disproportionately affected racial/ ethnic minorities, no studies have investigated the ramifications of the pandemic on SIL among these populations. This study aimed to determine the prevalence and pervasiveness of SIL during the COVID-19 pandemic on minority communities. MATERIALS AND METHODS: This was a single center, cross sectional study conducted by scientists from the University of Rochester Medical Center (URMC) working in collaboration with members of the Rochester community. Adult patients presenting to the emergency department at URMC who identified themselves as belonging to minority communities were asked to complete a survey that comprised questions from the Lubben Social Network Scale-6 and questions from the Campaign to End Loneliness Measurement Tool. We analyzed the percentage of SIL and conducted linear regression models to study the association between these outcomes and race/ ethnicity, age, gender, chronic disease status and the frequency of hospitalizations. RESULTS: A total of 1,029 subjects completed the survey. Social isolation was reported by 375 (37%) persons. Those of Latinx ethnicity had higher prevalence of social isolation (41%) compared to those of Black/African American race (36%) and also had higher degrees of isolation (14.8%) (15.42; p = 0.07). Loneliness was documented by 215 (21%) for the cohort with no differences based on race or ethnicity. CONCLUSIONS: Social isolation was common among minority communities during the pandemic but loneliness was less pervasive. The study highlights the need to address the specific needs of these populations.

Dendritic cell-specific transmembrane protein is required for synovitis and bone resorption in inflammatory arthritis.

Objective: Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) is essential for the formation of fully functional multinucleated osteoclasts. DC-STAMP deficient mice, under physiological conditions, exhibit osteopetrosis and develop systemic autoimmunity with age. However, the function of DC-STAMP in inflammation is currently unknown. We examined whether genetic ablation of DC-STAMP attenuates synovitis and bone erosion in TNF transgenic (Tg) and K/BxN serum-induced murine rheumatoid arthritis. Methods: We evaluated arthritis onset in Tg(hTNF) mice lacking DC-STAMP and 50:50 chimeric mice by visual examination, measurement of ankle width, micro-CT-scan analysis and quantitation of the area occupied by osteoclasts in bone sections. To further investigate the cellular and molecular events modulated by DC-STAMP, we measured serum cytokines, determined changes in cytokine mRNA expression by monocytes activated with IL4 or LPS/IFNγ and enumerated immune cells in inflamed mouse joints. Results: Synovitis, bone loss and matrix destruction are markedly reduced in Dcstamp-/-;Tg(hTNF) mice. These mice had significantly lower CCL2 and murine TNF serum levels and exhibited impaired monocyte joint migration compared to Tg(hTNF) mice. The reduced arthritic severity in Dcstamp deficient mice was associated with compromised monocyte chemotaxis, cytokine production, and M2 polarization. Conclusion: These results reveal that DC-STAMP modulates both bone resorption and inflammation and may serve as an activity biomarker and therapeutic target in inflammatory arthritis and metabolic bone disease.

Role of RANKL in bone diseases.

Bone remodeling is a tightly regulated process of osteoclast-mediated bone resorption, balanced by osteoblast-mediated bone formation. Disruption of this balance can lead to increased bone turnover, resulting in excessive bone loss or extra bone formation and consequent skeletal disease. The receptor activator of nuclear factor kappaB ligand (RANKL) (along with its receptor), the receptor activator of nuclear factor kappaB and its natural decoy receptor, osteoprotegerin, are the final effector proteins of osteoclastic bone resorption. Here, I provide an overview of recent studies that highlight the key role of RANKL in the pathophysiology of several bone diseases and discuss the novel therapeutic approaches afforded by the modulation of RANKL.

Bone loss in the spondyloarthropathies: role of osteoclast, RANKL, RANK and OPG in the spondyloarthropathies.

Bone loss is a common finding in the spondyloarthropathies. It may be localized and present as erosions or be generalized and cause osteoporosis. The pathogenesis of bone loss in the spondyloarthropathies is yet to be fully understood. There is however increasing evidence to support a role for the osteoclasts in bone erosions. Similarly a balance between the receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) levels is thought to regulate osteoclastic activity and therefore bone loss in the inflammatory arthritides. In this chapter we will review the recent literature on the role of osteoclasts and the RANKL/OPG system in the various spondyloarthropathies and try to formulate a hypothesis for the possible mechanism of bone loss in this group of inflammatory rheumatic disease.

Adopting the Quadruple Aim: The University of Rochester Medical Center Experience: Moving from Physician Burnout to Physician Resilience.

BACKGROUND: The high rates of burnout among medical professionals in the United States are well documented. The reasons for burnout and the factors that contribute to physician resilience among health care providers in academic centers, however, are less well studied. METHODS: Health care providers at a large academic center were surveyed to measure their degree of burnout and callousness and identify associated factors. Additional questions evaluated features linked to resilience. The survey assessed demographic variables, work characteristics, qualifications, experience, and citizenship. RESULTS: A total of 528 surveys were sent out; 469 providers responded, and 444 (84%) completed the survey. High burnout was reported by 214 providers (45.6%), and callousness was noted among 163 (34.8%). Rates of burnout and callousness were higher among advanced practice providers than physicians. Lack of support, lack of respect, and problems with work-life balance were themes significantly associated with a risk for burnout. Rates of burnout (P < .05) and callousness (P < .001) were also significantly higher among those who spent more than 80% of their time in patient care. Participation in patient care was the most sustaining factor, followed by teamwork, scholarly activities, autonomy, and medicine as a calling. CONCLUSIONS: Academic physicians enjoy patient care and value scholarly activities, but lack of support, lack of respect, workload, and problems with work-life balance prevent them from finding a sense of meaning in their professional work. Changes at the organizational level are needed to overcome these impediments and recreate joy in the practice of medicine.

Etanercept in psoriatic arthritis.

Psoriatic arthritis (PsA), an inflammatory arthritis associated with psoriasis, can lead to disability from progressive joint destruction and bony fusion. To date, conventional disease modifying antirheumatic drugs (DMARDS) have not convincingly lessened joint pain and inflammation in PsA and there is very little data on the limitation of radiographic progression with these agents. The biological agent etanercept (Enbrel, Amgen, Inc, Thousand Oaks, California, USA) is a soluble TNF receptor fusion protein with proven efficacy in the treatment of rheumatoid arthritis (RA). In a Phase II and Phase III trial, conducted in moderate-to-severe PsA, etanercept significantly reduced joint pain and swelling and lowered the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. A significant decline in structural damage was observed as early as 6 months after starting the drug. Etanercept also improved quality of life measures (Health Assesment Questionnaire [HAQ] and global assessment scores). Up to a third of patients experienced transient injection-site reactions. Rare cases of opportunistic infection, demyelinating disorders and aplastic anaemia have been reported, but a causal link has not been established. In summary, etanercept is a safe and effective agent for the treatment of PsA and represents a major advance in the therapy of this potentially crippling disease.

Treatment update on spondyloarthropathy. From NSAIDs and DMARDs to anti-TNF-alpha agents.

Traditionally, nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic agents (DMARDs) have been used to control the symptoms of spondyloarthropathy. With the advent of anti-tumor necrosis factor alpha (anti-TNF-alpha) agents, however, it is now possible to slow disease progression, improve overall function, and provide symptomatic relief of arthritis, skin lesions, and bowel inflammation associated with these disorders. Here, Drs Anandarajah and Ritchlin explore the effectiveness of conventional therapies as well as biologic agents that are currently available or under development.

Decreased influenza-specific B cell responses in rheumatoid arthritis patients treated with anti-tumor necrosis factor.

INTRODUCTION: As a group, rheumatoid arthritis (RA) patients exhibit increased risk of infection, and those treated with anti-tumor necrosis factor (TNF) therapy are at further risk. This increased susceptibility may result from a compromised humoral immune response. Therefore, we asked if short-term effector (d5-d10) and memory (1 month or later) B cell responses to antigen were compromised in RA patients treated with anti-TNF therapy. METHODS: Peripheral blood samples were obtained from RA patients, including a subset treated with anti-TNF, and from healthy controls to examine influenza-specific responses following seasonal influenza vaccination. Serum antibody was measured by hemagglutination inhibition assay. The frequency of influenza vaccine-specific antibody secreting cells and memory B cells was measured by EliSpot. Plasmablast (CD19+IgD-CD27hiCD38hi) induction was measured by flow cytometry. RESULTS: Compared with healthy controls, RA patients treated with anti-TNF exhibited significantly decreased influenza-specific serum antibody and memory B cell responses throughout multiple years of the study. The short-term influenza-specific effector B cell response was also significantly decreased in RA patients treated with anti-TNF as compared with healthy controls, and correlated with decreased influenza-specific memory B cells and serum antibody present at one month following vaccination. CONCLUSIONS: RA patients treated with anti-TNF exhibit a compromised immune response to influenza vaccine, consisting of impaired effector and consequently memory B cell and antibody responses. The results suggest that the increased incidence and severity of infection observed in this patient population could be a consequence of diminished antigen-responsiveness. Therefore, this patient population would likely benefit from repeat vaccination and from vaccines with enhanced immunogenicity.

Comparative analysis of disease activity measures, use of biologic agents, body mass index, radiographic features, and bone density in psoriatic arthritis and rheumatoid arthritis patients followed in a large U.S. disease registry.

OBJECTIVE: To compare disease activity, radiographic features, and bone density in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) matched cohorts. METHODS: Disease activity and radiographic data in the Consortium of Rheumatology Researchers of North America database from 2001 to 2008 were compared for 2481 patients with PsA and 17,107 patients with RA subsequently matched for age, gender, and disease duration. Radiographic outcomes included presence of erosions, and joint deformity. In addition, bone mineral density (BMD) scores for lumbar spine (L-spine) and femoral neck were compared using the same matching criteria plus weight and smoking status. RESULTS: Tender (4.5 vs 3.4, p < 0.001) and swollen (4.4 vs 2.9, p < 0.012) joint counts, and modified Health Assessment Questionnaire scores were significantly higher (0.4 vs 0.3, p < 0.001) in patients with RA compared with patients with PsA. Patient general health and pain scores were also higher in patients with RA vs patients with PsA. Joint erosions (47.4% vs 37.6%, p = 0.020) and deformity (25.2% vs 21.6%, p = 0.021) were more prevalent in RA than PsA. In multivariate analysis, a reduced prevalence of erosions in PsA vs RA was noted (OR 0.609, p < 0.001). After matching, T-scores for L-spine (-0.54 vs -0.36, p = 0.077) and femoral neck (-0.88 vs -0.93, p = 0.643) were similar in patients with RA and patients with PsA, although body weight was a major confounder. CONCLUSION: The level of disease activity and radiographic damage was significantly higher for RA vs PsA subjects, although the magnitude of differences was relatively small. BMD levels were comparable between cohorts. Outcomes in patients with PsA and patients with RA may be more similar than previously reported.

The diagnosis and treatment of early psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disorder associated with a heterogeneous disease presentation, varied disease expression and an unpredictable but often chronically destructive clinical course. Joint damage can occur early in the disease; indeed, several imaging modalities have demonstrated subclinical joint involvement in psoriasis patients without musculoskeletal signs or symptoms. Efforts are underway to validate questionnaires that will enable dermatologists to screen patients with psoriasis for the presence of musculoskeletal disease. To date, the use of therapies in patients with early PsA has not been reported in randomized controlled trials. Moreover, conventional agents are partially effective in established PsA but, in general, trials with DMARDS have not included validated outcome measures for the different manifestations of PsA. Tumor necrosis factor antagonists can alleviate the signs and symptoms of established psoriatic arthritis and inhibit radiographic progression, but the therapeutic impact of early intervention with these agents requires further study. The extent of disease and the presence of comorbidities should be used to guide treatment decisions and to minimize adverse events.

Anti-RANKL therapy for inflammatory bone disorders: Mechanisms and potential clinical applications.

Focal bone loss around inflamed joints in patients with autoimmune disease, such as rheumatoid arthritis, remains a serious clinical problem. The recent elucidation of the RANK/RANK-ligand/OPG pathway and its role as the final effector of osteoclastogenesis and bone resorption has brought a tremendous understanding of the pathophysiology of inflammatory bone loss, and has heightened expectation of a novel intervention. Here, we review the etiology of inflammatory bone loss, the RANK/RANK-ligand/OPG pathway, and the clinical development of anti-RANK-ligand therapy.

Pathogenesis of psoriatic arthritis.

PURPOSE OF REVIEW: Psoriatic arthritis is an inflammatory arthritis associated with psoriasis that is more common and severe than initially appreciated. The success of biologic agents in psoriatic arthritis has sparked great interest in this disorder, although the disease pathogenesis is poorly understood. This review focuses on recent advances in the genetic factors and immune pathways that have been implicated in susceptibility to disease. In addition, recent studies examining the mechanisms that underlie angiogenesis, enthesitis, and bone resorption in psoriatic arthritis are discussed. RECENT FINDINGS: Studies performed on several different populations indicate that the MHC class I allele Cw6 is associated with both early-onset psoriasis and psoriatic arthritis. Mutations in the caspase-activating recruitment domain 15 locus on chromosome 16 are also associated with psoriatic arthritis, providing support for a model involving innate immune mechanisms. Evidence for a CD8 antigen-driven acquired immune response in psoriatic synovium and blood was reported. The finding of elevated levels of vascular endothelial growth factor and angiopoietin 2 in psoriatic arthritis synovial vasculature may provide insights into events responsible for the tortuous vessel morphology, a histologic feature characteristic of psoriatic joints. Tumor necrosis factor (TNF)-alpha is a critical factor mediating inflammation in the synovium, enthesis, and bone. In particular, osteoclasts resorb bone via a receptor activator of nuclear factor kappaB-receptor activator of nuclear factor kappaB ligand signaling pathway that is potentiated by TNF-alpha. The lessening of bone marrow edema after anti-TNF therapy provides further support for the importance of this cytokine in disease pathogenesis. SUMMARY: Recent studies provide additional support for distinct pathogenetic mechanisms in psoriatic arthritis that arise from a complex interplay between genetic and environmental factors. Histopathologic data and results from clinical trials highlight the predominance of TNF-mediated inflammation in psoriatic joint tissues.