Knee Hurt

Category: Knee Arthritis

  • National trends in the prevalence of rheumatoid arthritis and osteoarthritis in South Korea, 1998–2021

    Patient selection and data collection

    This study used data from the Korea National Health and Nutrition Examination Survey (KNHANES), conducted between 1998 and 2021 by the Korea Centers for Disease Control and Prevention Agency (KDCA).10,11. The study population included adults aged ≥ 19 years and data collected included information on age, gender, place of residence, body mass index (BMI), education level, income, alcohol consumption, smoking status and history of RA and OA.12. We focused our research on the adult population, which is over 19 years old in South Korea. A nationally representative sample of 163,221 participants was used to examine the prevalence of RA and OA before and during the COVID-19 pandemic. The survey was conducted over 24 years and the number of participants surveyed in each year group was as follows: 51,515 in 1998-2001; 26,996 in 2005-2007; 20,070 in 2008–2010; 17,601 in 2011–2013; 17,129 in 2014–2016; 18,469 in 2017–2019; 5839 in 2020; and 5,602 in 2021.

    The study protocol was approved by the Institutional Review Board of Kyung Hee University (KHUH 2022-06-042) and KDCA, and all participants provided written informed consent. Furthermore, the KNHANES provides accessible public access to its data, which can be used as a valuable resource for various epidemiological studies. This study followed the ethical guidelines established by relevant national and institutional review boards for human research and adhered to the 1975 Declaration of Helsinki, as amended in 2008.

    Determination of RA and OA

    The aim of our study was to investigate the risk factors associated with the two most common forms of arthritis, RA and OA, over a 24-year period, from 1998 to 2021. To achieve our research objective, we collected a large number surveyed participants and asked them the question, “Have you ever been diagnosed with RA or OA by a doctor?” Based on their answers, we divided the participants into three groups: RA, OA, and both13. We collected data on several potential risk factors associated with the development of RA and OA, such as age, gender, lifestyle habits and socio-economic status. We conducted statistical analyzes to examine the associations between these risk factors and the development of RA and OA and to identify patterns or trends that have emerged over 24 years.

    Covariates

    Covariates included age (19–29, 30–39, 40–49, 50–59, 60–69, 70–79, and ≥ 80 years), gender, region of residence (urban and rural)14,15,16, BMI group, household income (lowest, second, third, and highest quartiles), education level (primary school or less, middle school, high school, and college or higher education), alcohol consumption (1–5 days/month, ≥ 6 days/month, and non-drinker) and smoking status (non-smoker, ex-smoker and smoker). BMI was subdivided into underweight (< 18.5 kg/m2).2), normal weight (18.5–22.9 kg/m2), overweight (23–25 kg/m22), and obese (≥ 25.0 kg/m2) according to Asia-Pacific guidelines17,18.

    static analysis

    The results of this study were presented using qualitative data, expressed in proportions or percentages. Weighted multivariate regression model analyzes were conducted to compare the estimates of each related factor before and during the COVID-19 pandemic, using weighted odds ratios (ORs) with 95% confidence intervals (CIs).19. The prevalence of RA and OA was calculated using data from the KNHANES, spanning the period 1998 to 2021, stratified by year group. A weighted complex sampling analysis was performed to ensure accurate estimation. Binomial or linear logistic regression models were used to calculate the ORs with 95% CIs or β coefficients with 95% CIs. To ensure the robustness of the main findings, a stratification analysis was performed in all regression models using variables such as gender, education level, region of residence and income. Furthermore, the ratio of ORs was calculated to estimate the interaction duration of each risk factor and identify groups that were more vulnerable to the patient with RA and OA during the pandemic. Overall, this study aimed to provide a comprehensive analysis of the impact of the COVID-19 pandemic on the prevalence of RA and OA and to identify the factors contributing to vulnerability to these conditions. The SAS software (version 9.4; SAS Institute, Cary, NC, USA) was used for statistical analyses, with a two-sided test, and a p-value ≤ 0.05 was considered statistically significant19.

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  • Research links lower testosterone levels to an increased risk of arthritis

    Research links lower testosterone levels to an increased risk of arthritis

    In a recent study published in Scientific Reports, researchers determined the relationship between serological testosterone levels and arthritis in adults in the United States (US).

    Research: Lower serum testosterone is associated with an increased risk of arthritis. Image credits: airdone/Shutterstock.comStudy: Lower serum testosterone is associated with an increased risk of arthritis. Image credits: airdone/Shutterstock.com

    Background

    Arthritis is a joint disease that affects the hyaline articular cartilage, surrounding tissues and subchondral bone. Hormonal variables, such as testosterone, have been linked to the growth and development of knee osteoarthritis (KOA).

    Studies have shown that androgens activate non-genetic and non-genetic mechanisms, with the most rapid evidence being a rapid increase in intercellular calcium concentration.

    Physiological testosterone doses have been shown to improve cartilage production in men with advanced osteoarthritis, and treatment with testosterone replacement improves articular cartilage regeneration in affected individuals.

    According to research, androgens are also involved in the formation and development of osteoblasts. However, there is minimal evidence for sex-specific relationships between serological testosterone expression and OA, and the association between plasma testosterone in arthritic individuals and disease progression is not clear.

    About the study

    In the current study, researchers examined the influence of serological testosterone levels on the pathophysiology of arthritis.

    Data from 10,439 adults who participated in the 2013–2016 National Health and Nutrition Examination Survey (NHANES) were analyzed using multivariable logistic regression modeling, performed to determine odds ratios (ORs).

    The model estimates are adjusted for covariates such as age, gender, race, education level, marital status, income, alcohol consumption, smoking status, test reports, laboratory findings, survey responses, and comorbidities (such as diabetes, cardiovascular disease, and hypertension). ).

    In addition, generalized additivity modeling and smoothed curve fitting were performed. The database samples were selected using stratified multistage sampling.

    Data collection methods include home interviews to collect demographic, nutritional and health-related data, and medical examinations to collect laboratory data [including sex hormone binding globulin (SHBG) and estradiol] and physical assessment data [including body mass index (BMI) and waistline].

    Individuals were asked whether they had been diagnosed with arthritis by doctors or other medical professionals, and if so, they were asked to report the type of condition as rheumatoid arthritis, osteoarthritis, or other.

    The Centers for Disease Control and Prevention (CDC) isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS) technique was used to determine TT concentrations.

    Results

    Initially, 20,146 individuals were identified, of whom 5,380 and 4,327 were excluded due to missing data on serological testosterone levels and development of arthritis, respectively. Of the 10,439 study participants, 48% were male, with an average age of 47 years and an average serum testosterone level of 215. Of the participants, 27% developed arthritis.

    Arthritis patients showed lower serum testosterone than their non-arthritic counterparts, in line with previous studies. The findings from linear regression analysis showed a statistically significant negative association between serological testosterone levels and arthritis.

    Similarly, the fourth quarter univariable analyzes using the first quarter as reference showed a significantly lower risk of developing arthritis.

    Specifically, sensitivity analyzes using quartiles of serum testosterone resulted in odds ratios of 1.0, 0.9, 0.5, and 0.5 for the first quartile, second quartile, third quartile, and fourth quartile, respectively, in the fully adjusted model.

    Individuals in the top quartile of serum testosterone levels showed a 51% lower risk of developing arthritis compared to individuals in the lowest quartile.

    Smoothed curve fitting showed a non-linear relationship between the development of arthritis and serological testosterone levels. The subgroup analyzes showed that the negative association between serological testosterone and the development of arthritis was statistically more significant in older female smokers with comorbidities and body mass index (BMI) values ​​of 30 kg per m2 and above.

    Testosterone and estradiol are natural immunosuppressants that suppress antibody and cell-mediated immunity while acting as anti-inflammatory agents. Because women have more active immunity than men, they play a crucial role in lowering men’s susceptibility to autoimmune diseases.

    The primary androgen, testosterone, binds to specialized intracellular receptors to create active forms of testosterone receptor complexes. Androgen and estrogen receptors are present in both male and female osteoblasts, and testosterone binds to both to regulate bone calcium.

    Decreased testosterone levels can affect cartilage metabolism via ion channels and androgen receptors, resulting in cartilage and KOA breakdown. The activation of androgen receptors (AR) and estrogen receptors (ER) has a profound influence on bone metabolism.

    Testosterone increases the glycosaminoglycan content in the extracellular matrix of the chondrocytes, improves the coverage of type II collagen on the cartilage surface and influences the development of the fibrocartilage structures.

    Low testosterone levels may be the cause of obesity rather than its consequence, with BMI having a causal influence on serum testosterone in the hypothalamic-pituitary-gonadal axis.

    Conclusion

    Overall, the study results indicated that lower levels of serum testosterone were associated with an increased risk of developing arthritis.

    The in-depth investigation of the negative and non-linear association between serological testosterone levels and the development of arthritis was related to BMI and sex.

    The findings could impact the prevention and treatment of arthritis. However, further research is needed to elucidate the mechanisms underlying the impact of serum testosterone on the development of arthritis.

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  • Study sheds new light on the variety of cellular causes of rheumatoid arthritis

    Study sheds new light on the variety of cellular causes of rheumatoid arthritis

    shutterstock 390538711 6b3c40fdd32742caa54307db3553cab1

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation leading to pain, joint damage and disability, affecting approximately 18 million people worldwide. Although RA therapies targeting specific inflammatory pathways have emerged, only some patients’ symptoms improve with treatment, highlighting the need for multiple treatment approaches tailored to different disease subtypes. To more precisely define the cellular causes of RA, an international research consortium, co-led by researchers from the Broad Institute of MIT and Harvard and Brigham and Women’s Hospital, a founding member of the Mass General Brigham health care system, analyzed tissues from RA donors to the at the single-cell level, integrating multiple forms of analysis to stratify RA based on six subtypes of inflammation. Findings, published in Natureshed new light on the variety of cellular causes of RA, which may lead to more targeted, effective and patient-tailored therapeutic approaches.

    “In treating people with rheumatoid arthritis, we struggle to find the right treatment for the right patient,” says corresponding author Soumya Raychaudhuri, MD, PhD, of the Brigham’s Division of Rheumatology, Inflammation and Immunity and the Broad Institute, where he is an institute member. “We wanted to determine why some subgroups of patients do not respond to conventional treatments by looking at the subtypes of inflammation. We did this from many different angles, using multiple advanced, single-cell techniques and by integrating the results in a way that is has not been done before for an inflammatory disease.”

    The study findings represent a major milestone in the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus program, a public-private partnership launched in 2014 to advance the understanding of autoimmune diseases at the molecular and cellular levels and identify promising drug targets to identify. Working with researchers and physicians in the US and Britain, the researchers analyzed 79 donor samples of synovial tissue, the inflamed tissue in RA that normally helps soften and support joints. In particular, the researchers examined tissue from patients with new disease and from patients who did not respond to treatment to better identify both the initial causes of RA and those of refractory diseases.

    To ‘deconstruct’ RA pathology at the cellular level, the researchers combined surface protein data and histological analysis with multiple forms of single-cell RNA sequencing and bulk RNA sequencing. Despite the variety of methods used to analyze more than 314,000 cells, the researchers consistently found evidence of six major types of inflammation, which they stratified by associated cell type, called cell type abundance phenotypes (CTAPs). Although some CTAPS, such as those enriched in T and B cells, would be expected to be used for an autoimmune disease like RA, the researchers were surprised to see that CTAPs were associated with structural cells such as fibroblasts and endothelial cells, with relatively few inflammatory leukocytes. They also found that patients’ CTAPs were dynamic and could change over time in response to treatment.

    In the future, the researchers want to expand their knowledge of the cell types involved in RA by studying how interconnections between cells promote disease states. Furthermore, they hope that this work will advance the analysis of synovial tissues in RA patients, which is not currently standard practice. Although blood tests are more common in RA patients, findings from this study and others emphasize that the cellular profile of synovial tissue differs substantially from that of blood.

    What this study shows is that tissue matters. Our findings point to the value of obtaining synovial tissue biopsies to evaluate the nature of the pathological process, which can be so different among patients. Future clinical trials will benefit greatly from assessing tissue characteristics in addition to responses to therapy. By providing this atlas of cell types and pathways involved in RA, we are better able to pursue our goal of precision medicine: being able to select the right drug for the right patient and achieve a high response rate.”


    Michael Brenner, MD, co-senior author, Brigham’s Division of Rheumatology, Inflammation and Immunity

    Source:

    Brigham and Women’s Hospital

    Magazine reference:

    Zhang, F., et al. (2023). Deconstruction of the synovium of rheumatoid arthritis defines inflammatory subtypes. Nature. doi.org/10.1038/s41586-023-06708-y.

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  • Deconstruction of the synovium of rheumatoid arthritis defines inflammatory subtypes

  • Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Fan Zhang, Anna Helena Jonsson, Aparna Nathan, Nghia Millard, Michelle Curtis, Qian Xiao, Maria Gutierrez-Arcelus, Gerald FM Watts, Dana Weisenfeld, Kathryne E. Marks, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kathryn Weinand, Ellen M. Gravallese, Adam Chicoine, Kazuyoshi Ishigaki, Gregory Keras, Ilya Korsunsky, Zhihan J. Li, Yuhong Li, Yakir Reshef, Saori Sakaue, Zhu Zhu, Katherine P. Liao, Kevin Wei, Deepak A. Rao, Michael B. Brenner and Soumya Raychaudhuri

  • Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA

    Fan Zhang, Aparna Nathan, Nghia Millard, Michelle Curtis, Qian Xiao, Maria Gutierrez-Arcelus, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kathryn Weinand, Kazuyoshi Ishigaki, Ilya Korsunsky, Yakir Reshef, Saori Sakaue & Soumya Raychaudhuri

  • Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Fan Zhang, Aparna Nathan, Nghia Millard, Michelle Curtis, Qian Xiao, Maria Gutierrez-Arcelus, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kathryn Weinand, Kazuyoshi Ishigaki, Ilya Korsunsky, Yakir Reshef, Saori Sakaue & Soumya Raychaudhuri

  • Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA

    Fan Zhang, Aparna Nathan, Nghia Millard, Michelle Curtis, Qian Xiao, Maria Gutierrez-Arcelus, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kamil Slowikowski, Kathryn Weinand, Kazuyoshi Ishigaki, Ilya Korsunsky, Yakir Reshef, Saori Sakaue, Katherine P. Liao & Soumya Raychaudhuri

  • Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Fan Zhang, Aparna Nathan, Nghia Millard, Michelle Curtis, Qian Xiao, Maria Gutierrez-Arcelus, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kamil Slowikowski, Kathryn Weinand, Kazuyoshi Ishigaki, Ilya Korsunsky, Yakir Reshef, Saori Sakaue & Soumya Raychaudhuri

  • Department of Rheumatology and the Center for Health Artificial Intelligence, University of Colorado School of Medicine, Aurora, CO, USA

    Fan Zhang

  • Division of Immunology, Department of Pediatrics, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA

    Maria Gutierrez-Arcelus

  • Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network, Bethesda, MD, USA

    William Apruzzese

  • Rheumatology Research Group, Institute of Inflammation and Aging, University of Birmingham, Birmingham, UK

    Saba Nayar, Mark Maybury, Ilfita Sahbudin, Hayley L. Carr, Karim Raza, Dagmar Scheel-Toellner & Andrew Filer

  • Birmingham Tissue Analytics, Institute of Translational Medicine, University of Birmingham, Birmingham, UK

    Saba Nayar and Andrew Filer

  • Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.

    Javier Rangel-Moreno, Nida Meednu, Darren Tabechian, Jennifer Albrecht, Jennifer L. Barnas, Debbie Campbell, Christopher Ritchlin & Jennifer H. Anolik

  • Hospital for Special Surgery, New York, NY, USA

    Ian Mantel, Dana E. Orange, S. Louis Bridges Jr., Lionel B. Ivashkiv, Amit Lakhanpal, Anvita Singaraju, Melanie H. Smith, Susan M. Goodman, Vivian P. Bykerk & Laura T. Donlin

  • Weill Cornell Medicine, New York, NY, USA

    Ian Mantel, S. Louis Bridges Jr., Lionel B. Ivashkiv, Amit Lakhanpal, Anvita Singaraju, Susan M. Goodman, Vivian P. Bykerk & Laura T. Donlin

  • Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital (MGH), Boston, MA, USA.

    Kamil Slowikowski

  • Laboratory of Molecular Neuro-Oncology, Rockefeller University, New York, NY, USA

    Dana E. Orange

  • Department of Rheumatology, Columbia University College of Physicians and Surgeons, New York, NY, USA

    Laura Geraldino-Pardilla & Joan M. Bathon

  • Department of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA

    Kevin D. Deane, Jennifer A. Seifert, Larry W. Moreland, and V. Michael Holers

  • Department of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA.

    Arnoldas Ceponis, Gary S. Firestein, and David L. Boyle

  • NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK

    Mark Maybury, Ilfita Sahbudin, Hayley L. Carr, Karim Raza, Dagmar Scheel-Toellner & Andrew Filer

  • Department of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Ami Ben-Artzi, Lindsy Forbess and Michael H. Weisman

  • Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Arthur M. Mandelin II & Harris Perlman

  • Center for Experimental Medicine and Rheumatology, EULAR Center of Excellence, William Harvey Research Institute, Queen Mary University of London, London, UK

    Alessandra Nerviani, Myles J. Lewis, Felice Rivellese & Costantino Pitzalis

  • Barts Health NHS Trust, Barts Biomedical Research Center (BRC), National Institute for Health and Care Research (NIHR), London, UK

    Alessandra Nerviani, Myles J. Lewis, Felice Rivellese & Costantino Pitzalis

  • Department of Biomedical Sciences, Humanitas University and Humanitas Research Hospital, Milan, Italy

    Constantine Pitzalis

  • Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

    Laura B. Hughes

  • Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, NY, USA

    Diane Horowitz and Peter K. Gregersen

  • Department of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, NY, USA

    Edward DiCarlo

  • Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA

    Brendan F Boyce

  • Department of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Mandy J. McGeachy & Larry W. Moreland

  • Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Andrew Cordle and Aaron Wyse

  • Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

    Patrick Dunn

  • Northrop Grumman Health Solutions, Rockville, MD, USA

    Patrick Dunn

  • Division of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    Joel M. Guthridge and Judith A. James

  • Laboratory of Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

    Kazuyoshi Ishigaki

  • Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    James A. Lederer

  • Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.

    Andrew McDavid

  • Division of Immunology and Rheumatology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.

    William H. Robinson, Paul J. Utz, and Michael H. Weisman

LG-P., KDD, DT, AC, GSF, MM, IS, AB-A., AMM, A. Nerviani, FR, CP, LBH and DH recruited patients and obtained synovial tissues. LWM, SMG, HP, VMH, AF, VPB, and JHA contributed to sample acquisition and processing and design of the AMP study. ED, EMG and BFB performed histological assessment of tissues. DW, KPL, AF, and VPB compiled and analyzed histological and clinical data. WA provided project management and compiled histological and clinical data. K. Wei, AHJ, GFMW, A. Nathan, and MBB designed and implemented the tissue disaggregation, cell sorting, and single-cell sequencing pipeline. AHJ, K. Wei, and GFMW oversaw and executed the tissue disaggregation pipeline. S.N., J.R.-M. and N. Meednu. performed immunofluorescence microscopy and analyzed these data together with MC and AHJKEM and IM performed and analyzed functional cellular assays. MJL, FR, and CP contributed unpublished clinical trial data. FZ, A. Nathan, N. Millard, MC, QX, MG-A., JBK, K. Weinand, JM, LR, and SR performed computational and statistical analyses. AHJ, K. Wei, MBB, JHA, LTD, DAR, FZ, A. Nathan, SR, DEO, JR-M. and AF provided input on cellular analysis and interpretation. DEO, JR-M., AF and JHA provided input for histological analyses. N. Millard and KS implemented the website. SR, MBB, JHA, LTD, and DAR supervised the study. FZ, AHJ, A. Nathan, N. Millard, QX, and SR wrote the first draft. FZ, AHJ, A. Nathan, K. Wei, N. Millard, DAR, LTD, JHA, MBB, and SR edited the draft. Members of the AMP RA/SLE Network contributed to this work by managing patient recruitment, managing clinical data, obtaining and processing synovial tissue samples, managing biorepositories, performing histological or computational analyses, providing software code, providing website support and/or providing input for data analysis. and interpretation. All authors participated in editing the final manuscript.

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  • The use of TNF inhibitors during pregnancy is not associated with worse fetal or obstetric outcomes

    The use of TNF inhibitors during pregnancy is not associated with worse fetal or obstetric outcomes

    Pregnancy

    According to new research at ACR Convergence 2023, the annual meeting of the American College of Rheumatology (ACR), use of tumor necrosis factor inhibitors during pregnancy is not associated with worse fetal or obstetric outcomes and may reduce the risk of serious maternal infections during pregnancy ( Abstract #0477).

    Tumor necrosis factor (TNF) inhibitors such as adalimumab and infliximab are often prescribed for inflammatory forms of arthritis that have not improved with other treatments. Although research shows the drugs are safe during pregnancy, many women stop taking them for fear of harming the fetus. Unlike other medications used for inflammatory arthritis, such as methotrexate, which can cause serious fetal complications, TNF inhibitors are not known teratogens (an agent that causes abnormalities after fetal exposure during pregnancy).

    To further test the safety of persistent TNF inhibitors during pregnancy, Anna Molto, MD, PhD, HDR, a rheumatologist and researcher at Cochin Hospital in Paris, France, and her colleagues used data from a nationwide French health insurance database to create a ​​to emulate a randomized database. clinical trial (RCT). This type of research relies on observational data to conduct a study when a gold standard RCT may not be ethical or feasible.

    The researchers identified more than 2,000 women treated with TNF inhibitors for rheumatoid arthritis (579 patients) or spondyloarthritis (1,503 patients) between 2008 and 2017. Each had a singleton pregnancy, with 1,497 (72%) stopping treatment when they learned they were pregnant. The average age of the women at the start of pregnancy was 31 years±5 years and the average duration of illness was 4 ±5 years.

    The results showed no statistically significant difference in poor obstetric, fetal or infant outcomes, including spontaneous abortion (a loss of pregnancy naturally before twenty weeks of gestation), medical termination of pregnancy, preeclampsia or eclampsia, gestational diabetes, premature birth, small birth weight or serious birth defects.

    Interestingly, women who continued to use TNF inhibitors were less likely to be hospitalized for serious infections during pregnancy during six weeks postpartum compared to those who stopped treatment (0.2 versus 1.3 percent, respectively). Molto says this finding was the most surprising.

    “Although we had assumed that pregnancy outcomes would be at least comparable in both groups, we did not expect that there would be a lower risk of maternal infections in patients who continued TNFi, as the risk of infection is known to be higher with these treatments” , she says. She speculates that the finding may be due to lower concomitant use of corticosteroids, but does not yet have results to confirm her theory.

    Regarding the overall study results, Molto says: “These data add to the increasingly reassuring data on the use of TNFi during pregnancy. And most importantly, if a rheumatologist is considering stopping a TNFi during pregnancy because of the risk of infection, this study suggests that this may not be justified.”

    Molto acknowledges the limitations of relying on claims data, noting that disease activity cannot be measured, but also points out that the use of a national database ensures that “all French participants are included, [thereby avoiding] selection bias.”

    The next step, Molto says, is to test the hypothesis in a randomized controlled trial.

    This study was carried out thanks to the funding program of the French Ministry of Health.

    Source:

    American College of Rheumatology

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  • Research shows that there is a doubled risk of fractures in patients with acute calcium pyrophosphate crystal arthritis

    Research shows that there is a doubled risk of fractures in patients with acute calcium pyrophosphate crystal arthritis

    Arthritis

    Researchers will present the first-ever study on fractures and calcium pyrophosphate deposition disease at ACR Convergence 2023, the annual meeting of the American College of Rheumatology (ACR). They report a doubled risk of fracture in patients with acute calcium pyrophosphate crystal arthritis compared with those without the disease (Abstract #0235).

    Calcium pyrophosphate deposition disease (CPPD) occurs when calcium pyrophosphate (CPP) crystals form near cartilage cells, sometimes leading to joint inflammation, pain, and swelling. It is often called pseudogout because of its clinical similarity to gout, yet much less is known about CPPD than about gout and other forms of inflammatory arthritis.

    Rheumatologist Sara Tedeschi, MD, MPH, her colleagues at Brigham and Women’s Hospital in Boston, and fellow at the Medical College of Wisconsin, wanted to expand the knowledge base by investigating whether patients with CPPD disease are at increased risk for fractures. Previous studies had shown a link between low bone density and CPPD. Recent data from experimental models suggest that increased formation of osteoclast (cells that break down old bone) due to loss of function of osteoprotegerin (a protein that normally inhibits bone resorption) may contribute to the pathogenesis of the disease.

    To find out more, Tedeschi and her team conducted a matched cohort study using electronic health records (EHR) from Mass General Brigham’s health care system. The study included more than 1,100 patients who had at least one episode of acute CPP crystal arthritis; the acute inflammatory form of CPPD – between 1991 and 2017. They were compared with more than 3,300 comparison researchers who did not have acute CPP crystal arthritis, although they could have other types of arthritis. The average age in both groups was 73 years, and more than half were women.

    The index date for patients with CPP crystal arthritis was either the first mention of pseudogout in their chart or the first synovial fluid analysis with the finding of CPP crystals. The period from registration of the EPD to the index date was at least 180 days. The index date for the matched comparators was a medical encounter within 30 days of the matched pseudogout patient’s index date.

    The primary outcome of the study was the first fragility fracture (fractures resulting from a fall from standing height or lower) at the humerus, wrist, hip or pelvis. Secondary outcomes were the first fracture at each of these anatomic locations. For patients with more than one fracture, only the earliest fracture was used. Fragility fractures were identified using published algorithms with a positive predictive value of greater than 90%.

    The researchers estimated the incidence rates and incidence ratios for each type of fracture and for fractures at each individual body location. They used Cox models (a statistical technique that can be used to measure time-to-event results on one or more predictors) to estimate adjusted risk ratios for fractures. Patients who had rheumatoid arthritis (RA) or were prescribed corticosteroid or osteoporosis treatment were excluded from the sensitivity analyzes in an attempt to rule out the influence of these diagnoses/medications, which are known to increase the risk of fracture.

    The researchers found that the fracture rate was twice as high in the acute crystal CPP arthritis cohort as in the comparison group, after adjusting for traditional fracture risk factors: 11.2 per 1,000 person-years versus 5.6 per 1,000 person-years. The disparity between the two groups increased over time and the sensitivity analyzes yielded similar findings.

    Tedeschi says the increased risk of fractures wasn’t particularly surprising, but the difference was large. Also surprising, she says, was “that differences in fracture risk were seen, of similar magnitude, after excluding patients who had used corticosteroids in the 90 days before the index date.” [Moreover]Fracture rates varied within the first months of follow-up, indicating a pre-existing difference in bone health between cohorts.”

    Tedeschi notes that the study does not indicate whether patients with acute CPP crystal arthritis had repeat episodes or used corticosteroids after the index date, either of which could influence the findings. She adds that they could not assess falls, which would affect fracture risk and may have differed between CPPD and comparators. She concludes by noting: “The analysis did not assess vertebral fractures as they may be asymptomatic and not captured in diagnosis codes.”

    Yet the findings are clear: patients with acute CPP crystal arthritis have a doubled risk of fragility fractures.

    “At the very least, we hope that physicians will consider assessing bone mineral density in patients with CPPD to determine whether osteoporosis treatment is necessary,” says Tedeschi.

    This research was supported by grants from the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

    Source:

    American College of Rheumatology

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  • Salivary gland abnormalities in primary Sjögren’s become more serious over time, research shows

    Salivary gland abnormalities in primary Sjögren’s become more serious over time, research shows

    shutterstock 312351317 82a9e0224160430890b6b34a2b64af19

    New research at ACR Convergence 2023, the annual meeting of the American College of Rheumatology (ACR), shows that ultrasound-detected salivary gland abnormalities in primary Sjögren’s become more severe over time and that the slowly progressive disease likely begins long before it reaches the is first. detected (summary #1371).

    Sjögren’s disease, also called primary Sjögren’s syndrome, is a systemic autoimmune disease. It is characterized by inflammation of the tear and salivary glands, leading to chronic dry eyes and mouth. Fatigue is common and about a third of patients have complications affecting the lungs, skin, kidneys and joints. Up to 60% of patients may develop systemic symptoms.

    Salivary gland ultrasound (SGUS) is a safe and non-invasive method for diagnosing and monitoring Sjögren’s disease. Still, it’s unclear whether the abnormalities it detects become more notable over time. Valérie Devauchelle-Pensec, M.D., Ph.D., professor of rheumatology in the Department of Clinical Immunology and Rheumatology at the University of Brest Occidentale and Cavale Blanche Hospital in Brest, France, designed a cross-sectional international study to find out.

    I have been caring for patients with Sjögren’s disease for years and I am always surprised that when I see them at the beginning of their disease, their first ultrasound scan of the salivary gland shows severe lesions. I also have many patients with rheumatoid arthritis. In rheumatoid arthritis, the joints are destroyed, but not at the onset of the disease. Sjögren’s seems different. I wondered, ‘When does the disease really start and do the lesions evolve over time or not?’ Many of my colleagues, who are experts in Sjögren’s and ultrasound, agreed to participate [in the study].”


    Valérie Devauchelle-Pensec, MD, Ph.D., professor of rheumatology, department of clinical immunology and rheumatology at the University of Brest Occidentale

    Between May 2019 and February 2022, 247 patients from 11 international centers consecutively participated in the study. Most were women, with an average age of 58 years. Nearly 100% of patients reported dry mouth; 75% had abnormal saliva production and 85% were positive for anti-SSA autoantibodies, a hallmark of Sjögren’s. The median EULAR Sjögren’s disease activity score (ESSDAI) was 3, indicating low disease activity.

    Ultrasound-detected functional abnormalities of the parotid and submandibular gland were classified according to the most recent Outcome Measures in Rheumatology (OMERACT) score, a four-grade semiquantitative scoring system. The patients were then grouped according to the duration of illness from the onset of dry mouth symptoms.

    • Group A: less than five years (47 patients)

    • Group B: five to nine years (69 patients)

    • Group C: 10 to 20 years (78 patients)

    • Group D: More than 20 years (53 patients)

    When the researchers looked at the most serious node for each patient, they found a significant association between disease duration and the OMERACT score. The odds ratio for progression over a five-year interval was 1.23.

    There was no statistical difference between the groups with regard to the various ultrasound parameters, with the exception of the proportion of hyperechoic bands, which are associated with damage in established Sjögren’s patients.

    “We hypothesized that hyperechoic bands represent the slow fibroadipose evolution of the disease,” says Devauchelle-Pensec. “To me, this means that Sjögren’s disease starts long before we find it, so it is important to treat patients early.”

    She adds that the study highlights the importance of adding ultrasound findings to the classification criteria for Sjögren’s syndrome and the need for a better understanding of when the disease begins.

    Source:

    American College of Rheumatology

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  • New training program expands access to rheumatology care for Native American communities

    New training program expands access to rheumatology care for Native American communities

    Rheumatology

    New research at ACR Convergence 2023, the annual meeting of the American College of Rheumatology (ACR), describes the expansion of a new program to train primary care physicians (PCPs) in the diagnosis and treatment of rheumatoid arthritis (RA) in Native American communities that little or no access to rheumatology care (Abstract #2455).

    Despite the high prevalence of RA and other rheumatologic diseases among Native Americans, many Native American communities lack adequate access to subspecialty care. As a result, the responsibility for treatment has shifted to primary care providers, who often lack confidence in prescribing RA medications or managing the disease. To help offset the critical shortage of rheumatologists, the Rheumatology Access Expansion (RAE) Initiative launched RA ECHO (Extension for Community Healthcare Outcomes) in 2021, a 12-week training program to teach Navajo Nation PCPs how to diagnose and treat RA. The goal was to improve outcomes and reduce entrenched disparities in healthcare. This year, the project expanded to tribes in 15 states.

    We successfully offered the RA ECHO curriculum three times on the Navajo Nation from 2021-2022. For our fourth cohort – Spring 2023 – we have dramatically expanded our target audience and invited healthcare professionals serving Native American communities across the country to participate.”


    Jennifer Mandal, MD, assistant professor at the University of California, San Francisco (UCSF) and director of the RAE Initiative

    Mandal says she and her team worked with an organization called Indian Country ECHO to recruit participants for cohort four.

    “We knew that Indian Country ECHO’s established lines of communication with tribes across the country would allow us to reach a much broader audience for our RA ECHO program. And indeed, when Indian Country ECHO put out a call for interested health care providers the response was overwhelming in attending our program. Over 100 providers responded that they would like to participate, and after the final dates and times were selected, 50 providers registered,” says Mandal.

    Most participants were PCPs, but pharmacists, community health care representatives, and providers from non-primary care settings such as emergency medicine, ophthalmology, and orthopedics also enrolled.

    The Spring 2023 program followed the same format as the first three: 12 weekly interactive classes held virtually, with approximately 30 minutes of high-level didactics on key aspects of RA diagnosis and management, followed by case-based discussion. Participants were encouraged to bring their own anonymized patient cases to class. In addition to the weekly sessions, there were also biweekly virtual ‘office hours’, where participants could interact with a panel of rheumatologists.

    To measure how successful the training actually was, the RAE Initiative team collected data on PCP responses to tests and surveys. Before and after each of the four programs (cohort five is currently underway), participants completed a medical knowledge test about RA and surveys about their confidence in the diagnosis and treatment of RA on a five-point Likert scale. Starting in cohort three, participants were also asked to rate changes in their own clinical behavior, such as how often they performed joint screening exams or blood tests before starting immunosuppressants.

    Pre- and post-intervention scores were available for more than one-third of participants. When data across cohorts were pooled, test scores increased by 26% and PCP confidence increased by more than one point on the Likert scale. Nearly 80% of participants reported that they performed important clinical behaviors related to the diagnosis and treatment of RA “more often” or “much more often” after taking the course.

    While the results are encouraging, Mandal says one limitation is that they did not look directly at patient outcomes.

    “While the RAE Initiative team hopes to eventually measure patient health data, it is critical to recognize that, due to centuries of exploitation, there is widespread mistrust of requests for access to private medical records in the Navajo community. Before seeking out personal health information, we strive to prioritize respectful and considerate handling of sensitive information, while still striving to achieve our educational and empowerment goals.”

    In the meantime, she lists other next steps, including:

    • Creating educational materials for RA patients that are culturally and linguistically tailored to the Navajo community

    • Organizing in-person training for community health representatives in Navajo Nation to increase awareness about joint health and different types of arthritis

    • Creating online training resources for PCPs who want to learn more about common rheumatologic diseases

    • Creating a new ECHO training program for spondyloarthritis

    Mandal hopes that the RA ECHO program can serve as a model for creating similar rheumatology training programs for other communities with limited access to rheumatologists, saying, “We are eager to collaborate with others who are interested in joining this important mission to expand access to rheumatology care.”

    This work was funded by a grant from the Bristol Myers Squibb Foundation.

    Source:

    American College of Rheumatology

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  • A deep learning system accurately identifies joint space narrowing and erosions on hand X-rays

    A deep learning system accurately identifies joint space narrowing and erosions on hand X-rays

    shutterstock 390538711 6b3c40fdd32742caa54307db3553cab1

    New research at ACR Convergence 2023, the annual meeting of the American College of Rheumatology (ACR), shows that a deep learning system can accurately identify and predict joint space narrowing and erosions in hand x-rays of patients with rheumatoid arthritis (RA) (Abstract #0745) .

    X-rays are the most commonly used imaging technique for detecting and monitoring RA in the hand. Radiologists often use the well-validated Sharp/van der Heidje (SvH) method to evaluate joint space narrowing and erosions by assessing specific locations in each hand and wrist. However, scoring SvH is time-consuming and requires expertise that is not always available. This has led to increased use of deep learning (also called machine learning) to analyze hand X-ray data in RA.

    According to Carol Hitchon, MD, FRCPC, MSc, associate professor at the University of Manitoba and clinical scientist in rheumatology and lead co-author of the study: “Machine learning offers a powerful and complementary approach to traditional RA detection and diagnosis methods. It improves the accuracy, efficiency and objectivity of RA radiograph assessment, while providing the opportunity for early detection of damage and valuable insights into the disease.”

    For the current study, Hitchon and colleagues aimed to develop and validate a deep learning system for the automated detection of joints and prediction of SvH scores on hand radiographs of patients with RA.

    They used a convolutional neural network (CNN)-based algorithm called You Only Look Once (YOLO). CNN is a deep learning neural network commonly used in computer vision and recognition tasks and has been successfully used in medical image classification. YOLO is a type of CNN model specifically designed for real-time object detection in images and videos and known for its speed and efficiency in image processing. Hitchon and colleagues used a recent version of YOLOv516, which they showed to be more than 90% accurate in detecting hand joints.

    The YOLO model was trained to detect joints in 240 training and evaluation pediatric hand radiographs from the Radiologic Society of North America database.

    The researchers boxed and labeled the different joints of interest: proximal interphalangeal, metacarpophalangeal, wrist, distal radius, and distal ulna. The joint detection model was validated with 54 clinician-labeled radiographs from four adult RA patients followed for more than ten years.

    Researchers then applied a vision transformer model (VTM) to predict the erosion and joint space narrowing score of each joint. Hitchon explains that a VTM is a deep learning architecture designed to efficiently process and understand sets of data.

    It works by splitting an image into small chunks, transforming or flattening the chunks into a sequence, creating low-dimensional linear embeddings from the flattened spots, adding the positional embedding, and then running the encoded sequence into a standard transformer encoder for the remaining prediction task. “


    Carol Hitchon, MD, FRCPC, MSc, Associate Professor, University of Manitoba

    The VTM was validated using more than 2,200 hand radiographs from 381 RA patients to whom the physician assigned SvH scores. Patients were from the Canadian Early Arthritis Cohort, a multicenter Canadian study. These scored radiographs were used as the gold standard for this study.

    The joint detection model was trained to detect the entire wrist, but the researchers had SvH scores for individual wrist joints, so they trained a separate model to detect joint space narrowing and erosion in each joint.

    When they evaluated the accuracy of their models, they found:

    • The joint detection model accurately identified target joints. The F1 score for children was 0.991 and the F1 score for adults was 0.812. (In machine learning, the F1 score is a metric that measures the accuracy of a model).

    • VTM predictions for joint space narrowing and erosion were very accurate. The principal square error, which evaluates the accuracy of predictions, was 0.91 and 0.93, respectively.

    • The multitask models predicted SvH erosion and joint space narrowing scores of individual wrist joints with moderate accuracy (0.6 to 0.91).

    Hitchon says they weren’t surprised by the performance of their model.

    “The AI ​​technologies we applied in this study have been successfully and widely used in other domains, some of which have been commercialized. Compared to the model’s performance in other domains, our performance is relatively low in predicting X-ray scores for some joint types, such as the wrist. [This] may be due to the relatively small sample size in our study or to the complexity of the anatomy of the wrist joint,” she notes.

    Hitchon also says the model’s performance does not match that of human radiologists for joints such as the wrist.

    “The AI ​​models cannot replace human radiologists at this stage, but they will be excellent complementary tools that can improve the overall quality and efficiency of radiograph scoring analysis when used in conjunction with the radiologist’s judgment. [these models] may be applicable to the interpretation of large volumes of radiographs in clinical trials.”

    The study has two major limitations: X-rays were obtained from cohorts composed almost entirely of white women, and the findings may not apply to races and ethnicities traditionally underrepresented in research studies. Hitchon acknowledges that the findings need to be replicated in other groups. The model also lacks the ability to learn and become more accurate with subsequent images, although Hitchon says they are developing a new deep learning framework so that the model continuously learns as new data is available.

    This study received local funding from the Health Science Center Foundation, a hospital charity in Winnipeg, Manitoba, Canada. One of the co-authors, Pingzhao Hu, is supported by the Canada Research Chair Program. The Canadian Early Arthritis Cohort, which provided one set of radiographs, is funded by multiple sources.

    Source:

    American College of Rheumatology

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  • Research shows that depression increases the risk of disability in patients with rheumatoid arthritis

    Research shows that depression increases the risk of disability in patients with rheumatoid arthritis

    In a review published in Nature Reviews Rheumatologyresearchers discussed the interactions between central and peripheral immunobiological mechanisms associated with rheumatoid arthritis (RA) and major depressive disorder (MDD).

    They further described the role of inflammatory proteins, the effect of peripheral inflammation on different parts of the brain, and the relationship between changes in the brain and inflammation-induced depression.

    Study: Immune mechanisms of depression in rheumatoid arthritis. Image credits: pikselstock/Shutterstock.comStudy: Immune mechanisms of depression in rheumatoid arthritis. Image credits: pikselstock/Shutterstock.com

    Background

    RA is a chronic autoimmune inflammatory disease that negatively affects synovial joints and several other organs. Depression is a common, clinically heterogeneous condition that affects all other patients with RA. There is increasing evidence that RA and depression have overlapping features and can be modulated by each other.

    Data suggest that depression is a risk factor for RA, and that patients diagnosed with RA at a young age are more susceptible to depression. Furthermore, RA patients with depression are observed to exhibit functional progression as well as decreased response to treatment, leading to poor outcomes. However, the precise biological mechanisms underlying this association are not clearly understood.

    Therefore, this review focuses on understanding the link between these two conditions and the underlying mechanisms, while exploring the interplay between the nervous system and the immune system in RA patients.

    Shared cytokines in RA and depression

    Proinflammatory cytokines amplified in RA are also known to be causally linked to depression. Several cytokines have been implicated in RA and depression, including interleukin (IL)-16, IL-18, IL-1, IL-6, and tumor necrosis factor (TNF).

    Peripheral immune signals to the brain

    The peripheral immune system signals the brain through two known pathways: neural and humoral. In the neural pathway, molecules that mediate inflammation can bind and activate receptors on sensory neurons, including those in the dorsal root ganglia (DRG) and the vagus nerve.

    The activated sensory neurons then send the signal back to the cerebral cortex of the brain via the spinal cord. The signal is then passed on to higher brain centers, which modulate the immune system locally and systemically.

    Through the humoral pathway, immune cells release molecules capable of crossing the blood-brain barrier (BBB) ​​and affecting brain cells or activating the endothelial cells of BBB.

    As observed in experimental studies in mice, this pathway leads to the release of chemokines involved in neuronal plasticity, resulting in depression-like behavior and cognitive impairment.

    Immune responses in the brain

    In the brain, existing neural cells and recruited immune cells release various inflammatory proteins that support neuroimmune communication. When cytokines and chemokines are released by neurons, microglia, astrocytes, peripheral immune cells and endothelial cells, they influence neurological and immunological processes.

    For example, during inflammation, the recruitment of peripheral monocytes to the brain is associated with dendritic remodeling and cognitive impairment, potentially leading to depression. Chronic peripheral inflammation in RA induces local microglial activation in the brain, leading to altered microglial expression.

    Although microglia are often associated with inflammatory changes in the brain, recent studies indicate a more complex role for microglia in neurological health.

    Contrary to previous belief, microglia found in the brain, according to studies in mice, originate not only from peripheral blood, but also from meninges and bone marrow in the skull. However, there is a lack of studies examining this aspect in humans.

    Astrocytes also play a role in brain inflammation. Activation of astrocytes by cytokines from microglia has been shown to result in the release of neurotoxic factors that influence neuronal health and behavior.

    Mechanisms linking depression and inflammation

    Immune-related inflammation has been implicated in the pathophysiology of depression. In RA, several pathways are activated, which can lead to inflammation-related behavior.

    These pathways include inflammasome activation, the kynurenine pathway, neuroplasticity, and the pathways of the glutamatergic and serotonergic systems.

    Regional variation in the brain

    Although regional changes in the brain and the underlying mechanisms continue to be studied, mainly using animal models, neuroimaging studies in humans have significantly improved our understanding of inflammation-related changes in the brain.

    Advances in magnetic resonance imaging (MRI) have provided insights into the role of inflammation in depression beyond traditional structural assessments and histology-based studies. Emerging evidence suggests that the brain regions affected by inflammation and depression are the striatum, hippocampus, amygdala, and insula.

    Conclusion

    This review article provides a comprehensive overview of the association between immune mechanisms and depression in patients with rheumatoid arthritis. It highlights the need for further research in this area.

    Furthermore, data from clinical trials suggest that immune modulation may be a promising approach for treating comorbid depression in patients with rheumatoid arthritis, potentially reducing the global burden of this debilitating condition.

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