Patient-Reported Fatigue Associated with Joint Histopathology in Rheumatoid Arthritis.

Objective: Fatigue is important for patients with rheumatoid arthritis (RA) but is poorly understood. We sought to study associations of fatigue with clinical features, disease activity, and synovial histology.

Methods: Patients meeting the American College of Rheumatology/EULAR 1987 and/or 2010 RA criteria were recruited before elective total joint replacement.

Deep topic modeling of spatial transcriptomics in the rheumatoid arthritis synovium identifies distinct classes of ectopic lymphoid structures.

Single-cell RNA sequencing studies have revealed the heterogeneity of cell states present in the rheumatoid arthritis (RA) synovium. However, it remains unclear how these cell types interact with one another and how synovial microenvironments shape observed cell states. Here, we use spatial transcriptomics (ST) to define stable microenvironments across eight synovial tissue samples from six RA patients and characterize the cellular composition of ectopic lymphoid structures (ELS).

Automated multi-scale computational pathotyping (AMSCP) of inflamed synovial tissue.

Rheumatoid arthritis (RA) is a complex immune-mediated inflammatory disorder in which patients suffer from inflammatory-erosive arthritis. Recent advances on histopathology heterogeneity of RA synovial tissue revealed three distinct phenotypes based on cellular composition (pauci-immune, diffuse and lymphoid), suggesting that distinct etiologies warrant specific targeted therapy which motivates a need for cost effective phenotyping tools in preclinical and clinical settings. To this end, we developed an automated multi-scale computational pathotyping (AMSCP) pipeline for both human and mouse synovial tissue with two distinct components that can be leveraged together or independently: (1) segmentation of different tissue types to characterize tissue-level changes, and (2) cell type classification within each tissue compartment that assesses change across disease states.

An Intermittent Fasting Intervention for Black Adults Can Be Feasibly Implemented in Black Churches: A Cluster Randomized Controlled Pilot Study.

Background: Intensive lifestyle interventions, including modest reductions in daily caloric intake (ie, continuous calorie energy reduction [CER]), are recommended by US national professional health organizations (eg, American Heart Association). However, they are less effective in Black communities. A burgeoning literature has reported the promise of intermittent fasting (IF) as an alternative strategy for weight loss.

Synovial fibroblast gene expression is associated with sensory nerve growth and pain in rheumatoid arthritis.

It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We developed a machine-learning approach (graph-based gene expression module identification or GbGMI) to identify an 815-gene expression module associated with pain in synovial biopsy samples from patients with established RA who had limited synovial inflammation at arthroplasty. We then validated this finding in an independent cohort of synovial biopsy samples from patients who had early untreated RA with little inflammation.

Outcomes of a Dietary Intervention to Reduce Bladder Cancer Recurrence and Progression in Survivors of Non-Muscle-Invasive Bladder Cancer.

Background: As one of the 10 most common cancers in the United States, bladder cancer is the most expensive cancer to treat. Most bladder cancers (70%-80%) are diagnosed at early stages as non-muscle-invasive bladder cancer (NMIBC), which can be removed. However, 50% to 80% of NMIBC recurs within 5 years, and 15% to 30% progresses with poor survival.

Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.

Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction. There is currently no cure for rheumatoid arthritis, and the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity. Here, to deconstruct the cell states and pathways that characterize this pathogenic heterogeneity, we profiled the full spectrum of cells in inflamed synovium from patients with rheumatoid arthritis.

Machine Learning Reveals Synovial Fibroblast Genes Associated with Pain Affect Sensory Nerve Growth in Rheumatoid Arthritis.

Unlabelled: It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We identified a module of 815 genes associated with pain, using a novel machine learning approach, Graph-based Gene expression Module Identification (GbGMI), in samples from patients with longstanding RA, but limited synovial inflammation at arthroplasty, and validated this finding in an independent cohort of synovial biopsy samples from early, untreated RA patients. Single-cell RNA-seq analyses indicated these genes were most robustly expressed by lining layer fibroblasts and receptor-ligand interaction analysis predicted robust lining layer fibroblast crosstalk with pain sensitive CGRP+ dorsal root ganglion sensory neurons.

Clonally expanded CD38 cytotoxic CD8 T cells define the T cell infiltrate in checkpoint inhibitor-associated arthritis.

Immune checkpoint inhibitor (ICI) therapies used to treat cancer, such as anti-PD-1 antibodies, can induce autoimmune conditions in some individuals. The T cell mechanisms mediating such iatrogenic autoimmunity and their overlap with spontaneous autoimmune diseases remain unclear. Here, we compared T cells from the joints of 20 patients with an inflammatory arthritis induced by ICI therapy (ICI-arthritis) with two archetypal autoimmune arthritides, rheumatoid arthritis (RA) and psoriatic arthritis (PsA).

Computer Vision Analysis of Rheumatoid Arthritis Synovium Reveals Lymphocytic Inflammation Is Associated With Immunoglobulin Skewing in Blood.

Objective: We sought to develop computer vision methods to quantify aggregates of cells in synovial tissue and compare these with clinical and gene expression parameters.

Methods: We assembled a computer vision pipeline to quantify five features encompassing synovial cell density and aggregates and compared these with pathologist scores, disease classification, autoantibody status, and RNA expression in a cohort of 156 patients with rheumatoid arthritis (RA) and 149 patients with osteoarthritis (OA).

Results: All five features were associated with pathologist scores of synovial lymphocytic inflammation (P < 0.

Drivers of heterogeneity in synovial fibroblasts in rheumatoid arthritis.

Inflammation of non-barrier immunologically quiescent tissues is associated with a massive influx of blood-borne innate and adaptive immune cells. Cues from the latter are likely to alter and expand activated states of the resident cells. However, local communications between immigrant and resident cell types in human inflammatory disease remain poorly understood.

Machine learning identification of thresholds to discriminate osteoarthritis and rheumatoid arthritis synovial inflammation.

Background: We sought to identify features that distinguish osteoarthritis (OA) and rheumatoid arthritis (RA) hematoxylin and eosin (H&E)-stained synovial tissue samples.

Methods: We compared fourteen pathologist-scored histology features and computer vision-quantified cell density (147 OA and 60 RA patients) in H&E-stained synovial tissue samples from total knee replacement (TKR) explants. A random forest model was trained using disease state (OA vs RA) as a classifier and histology features and/or computer vision-quantified cell density as inputs.

Dynamic spectrum of ectopic lymphoid B cell activation and hypermutation in the RA synovium characterized by NR4A nuclear receptor expression.

Ectopic lymphoid structures (ELS) can develop in rheumatoid arthritis (RA) synovial tissue, but the precise pathways of B cell activation and selection are not well understood. Here, we identify a synovial B cell population characterized by co-expression of a family of orphan nuclear receptors (NR4A1-3), which is highly enriched in RA synovial tissue. A transcriptomic profile of NR4A synovial B cells significantly overlaps with germinal center light zone B cells and an accrual of somatic hypermutation that correlates with loss of naive B cell state.

Rheumatoid Arthritis Synovial Inflammation Quantification Using Computer Vision.

Objective: We quantified inflammatory burden in rheumatoid arthritis (RA) synovial tissue by using computer vision to automate the process of counting individual nuclei in hematoxylin and eosin images.

Methods: We adapted and applied computer vision algorithms to quantify nuclei density (count of nuclei per unit area of tissue) on synovial tissue from arthroplasty samples. A pathologist validated algorithm results by labeling nuclei in synovial images that were mislabeled or missed by the algorithm.

Rosai-Dorfman Disease of Bone and Soft Tissue.

Context.—: Rosai-Dorfman disease is a rare histiocytic proliferative disorder of unknown pathogenesis that may be diagnostically difficult in extranodal sites. It is commonly an unsuspected diagnosis when arising in bone and soft tissue, especially when it presents without associated lymphadenopathy.

Prevalence of Occult Infections in Posterior Instrumented Spinal Fusion.

Study Design: This is a prospective observational study.

Objective: The aim of this study is to determine the rate of occult infection after instrumented spine surgery in presumed aseptic patients.

Summary Of Background Data: The reported incidence rate of delayed/occult infection determined by positive culture swabs after instrumented spine surgery in prospective studies is 0.

Subarticular Inflammatory Pseudoabscesses: A Pathologic Study With Clinical Correlation.

Abnormal accumulation of neutrophils in a subarticular bone usually raises the concern for osteomyelitis or septic arthritis, a disabling and potentially life-threatening medical condition. At the pathology department of a specialized orthopedic institute, we observed a distinct pattern of subarticular inflammation mimicking infection characterized by collections of neutrophils, macrophages, and fibrin in pseudocystic spaces of variable size and extent in the superficial subarticular bone not accompanied by granulation tissue or necrosis. We coined the term "inflammatory pseudoabscess" to describe these accumulations.

Rheumatoid Arthritis Morning Stiffness Is Associated With Synovial Fibrin and Neutrophils.

Objective: Morning stiffness is a hallmark symptom of rheumatoid arthritis (RA), but its etiology is poorly understood. This study was undertaken to determine whether any histologic features of synovium are associated with this symptom.

Methods: Data on patient-reported morning stiffness duration and severity, and Disease Activity Score in 28 joints (DAS28) were collected from 176 patients with RA undergoing arthroplasty.

Rheumatoid Arthritis Flares After Total Hip and Total Knee Arthroplasty: Outcomes at One Year.

Objective: Most patients with rheumatoid arthritis (RA) undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) have active RA and report postoperative flares; whether RA disease activity or flares increase the risk of worse pain and function scores 1 year later is unknown.

Methods: Patients with RA were enrolled before THA/TKA. Patient-reported outcomes, including the Hip disability and Osteoarthritis Outcome Score (HOOS)/Knee Injury and Osteoarthritis Outcome Score (KOOS) and physician assessments of disease characteristics and activity (Disease Activity Score in 28 joints [DAS28] and Clinical Disease Activity Index), were collected before surgery.

Lytic Lesion in the Proximal Humerus After a Flu Shot: A Case Report.

Case: There has been a recent campaign to vaccinate patients in an effort to prevent widespread flu pandemic. Although the complication rate after vaccine is low, there have been reports of Guillain-Barré syndrome and shoulder injury related to vaccine administration (SIRVA). In this case presentation, we discuss a patient who developed a large lytic lesion in the proximal humerus after a deeply administered flu shot.

HBEGF macrophages in rheumatoid arthritis induce fibroblast invasiveness.

Macrophages tailor their function according to the signals found in tissue microenvironments, assuming a wide spectrum of phenotypes. A detailed understanding of macrophage phenotypes in human tissues is limited. Using single-cell RNA sequencing, we defined distinct macrophage subsets in the joints of patients with the autoimmune disease rheumatoid arthritis (RA), which affects ~1% of the population.