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ID PMID Title PublicationDate abstract
34397604 Safety updates in novel therapeutics for pediatric rheumatic disease. 2021 Sep 1 PURPOSE OF REVIEW: Biologics and novel targeted therapeutics have transformed the management of pediatric rheumatic diseases over the past two decades; however, questions about short-term and long-term safety remain. Safety data gathered from recent clinical trials, long-term extensions of prior trials, registries, and other real-world evidence are summarized here for biologics and novel therapeutics commonly prescribed for pediatric rheumatic diseases. RECENT FINDINGS: With nearly 20 years of therapeutic experience, tumor necrosis inhibitors (TNFi) are generally well tolerated, although infections, malignancy, and development of new autoimmunity remain a concern. Risk of infections may be higher in IL-1 and IL-6 inhibitors, and lower in abatacept, compared with TNFi. Safety data for B-cell-targeted therapeutics and janus kinase inhibitors are emerging, but remain limited, especially in children. SUMMARY: Biologic and novel targeted therapeutics offer a promising future for children with pediatric rheumatic disease. However, long-term safety data in children remain limited for several agents. With any therapeutic option, both short-term and long-term safety concerns must be weighed against individual clinical needs when choosing the optimal treatment for each child.
33512089 Characterization and Function of Tumor Necrosis Factor and Interleukin-6-Induced Osteoclas 2021 Jul OBJECTIVE: We have previously reported that stimulation of mouse bone marrow-derived macrophages with tumor necrosis factor (TNF) and interleukin-6 (IL-6) induces differentiation of osteoclast-like cells. We undertook this study to clarify the characterization and function of human TNF and IL-6-induced osteoclasts using peripheral blood collected from patients with rheumatoid arthritis (RA) and healthy donors. METHODS: Peripheral blood monocytes were cultured with a combination of TNF and IL-6, TNF alone, IL-6 alone, or with RANKL, and their bone resorption ability was evaluated. Expression levels of NFATc1, proinflammatory cytokines, and matrix metalloproteinase 3 were analyzed. The effects of NFAT inhibitor and JAK inhibitor were examined. Furthermore, the relationship between the number of TNF and IL-6-induced osteoclasts or RANKL-induced osteoclasts differentiated from peripheral blood mononuclear cells (PBMCs) in patients with RA and the modified total Sharp score (mTSS) or whole-body bone mineral density (BMD) was examined. RESULTS: Peripheral blood monocytes stimulated with a TNF and IL-6-induced osteoclasts were shown to demonstrate the ability to absorb bone matrix. Cell differentiation was not inhibited by the addition of osteoprotegerin. Stimulation with a combination of TNF and IL-6 promoted NFATc1 expression, whereas the NFAT and JAK inhibitors prevented TNF and IL-6-induced osteoclast formation. Expression levels of IL1β, TNF, IL12p40, and MMP3 were significantly increased in TNF and IL-6-induced osteoclasts, but not in RANKL-induced osteoclasts. The number of TNF and IL-6-induced osteoclasts differentiated from PBMCs in patients with RA positively correlated with the mTSS, whereas RANKL-induced osteoclast numbers negatively correlated with the whole-body BMD of the same patients. CONCLUSION: Our results demonstrate that TNF and IL-6-induced osteoclasts may contribute to the pathology of inflammatory arthritis associated with joint destruction, such as RA.
33579724 IgG Epitopes Processed and Presented by IgG(+) B Cells Induce Suppression by Human Thymic- 2021 Mar 15 We described a human regulatory T cell (Treg) population activated by IgG(+) B cells presenting peptides of the heavy C region (Fc) via processing of the surface IgG underlying a model for B cell-Treg cooperation in the human immune regulation. Functionally, Treg inhibited the polarization of naive T cells toward a proinflammatory phenotype in both a cognate and a noncognate fashion. Their fine specificities were similar in healthy donors and patients with rheumatoid arthritis, a systemic autoimmune disease. Four immunodominant Fc peptides bound multiple HLA class II alleles and were recognized by most subjects in the two cohorts. The presentation of Fc peptides that stimulate Treg through the processing of IgG by dendritic cells (DC) occurred in myeloid DC classical DC 1 and classical DC 2. Different routes of Ag processing of the IgG impacted Treg expansion in rheumatoid arthritis patients.
34638855 The Germinal Center Milieu in Rheumatoid Arthritis: The Immunological Drummer or Dancer? 2021 Sep 29 Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, affecting approximately 1% of the general population. To alleviate symptoms and ameliorate joint damage, chronic use of immunosuppressives is needed. However, these treatments are only partially effective and may lead to unwanted side effects. Therefore, a more profound understanding of the pathophysiology might lead to more effective therapies, or better still, a cure. The presence of autoantibodies in RA indicates that B cells might have a pivotal role in the disease. This concept is further supported by the fact that a diverse antibody response to various arthritis-related epitopes is associated with arthritis development. In this context, attention has focused in recent years on the role of Germinal Centers (GCs) in RA. Since GCs act as the main anatomic location of somatic hypermutations, and, thus, contributing to the diversity and specificity of (auto) antibodies, it has been speculated that defects in germinal center reactions might be crucial in the initiation and maintenance of auto-immune events. In this paper, we discuss current evidence that various processes within GCs can result in the aberrant production of B cells that possess autoreactive properties and might result in the production of RA related autoantibodies. Secondly, we discuss various (pre-)clinical studies that have targeted various GC processes as novel therapies for RA treatment.
33789488 Total ankle arthroplasty. 2021 Apr AIMS: We report the medium-term outcomes of a consecutive series of 118 Zenith total ankle arthroplasties (TAAs) from a single, non-designer centre. METHODS: Between December 2010 and May 2016, 118 consecutive Zenith prostheses were implanted in 114 patients. Demographic, clinical, and patient-reported outcome measures (PROMs) data were collected. The endpoint of the study was failure of the implant requiring revision of one or all of the components. Kaplan-Meier survival curves were generated with 95% confidence intervals (CIs) and the rate of failure calculated for each year. RESULTS: Eight patients (ten ankles) died during follow-up, but none required revision. Of the surviving 106 patients (108 ankles: rheumatoid arthritis (RA), n = 15; osteoarthritis (OA), n = 93), 38 were women and 68 were men, with a mean age of 68.2 years (48 to 86) at the time of surgery. Mean follow-up was 5.1 years (2.1 to 9.0). A total of ten implants failed (8.5%), thus requiring revision. The implant survival at seven years, using revision as an endpoint, was 88.2% (95% CI 100% to 72.9%). There was a mean improvement in Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ) from 85.0 to 32.8 and visual analogue scale (VAS) scores from 7.0 to 3.2, and overall satisfaction was 89%. The three commonest complications were malleolar fracture (14.4%, n = 17), wound healing (13.6%, n = 16), and superficial infection (12.7%, n = 15). The commonest reason for revision was aseptic loosening. No patients in our study were revised for deep infection. CONCLUSION: Our results show that Zenith survival rates are comparable with those in the literature for other implants and in the National Joint Registry (NJR). Overall patient satisfaction was high as were functional outcomes. However, the data highlight potential complications associated with this surgery. The authors believe that these figures support ankle arthroplasty as an option in the treatment of ankle arthritis. Cite this article: Bone Joint J 2021;103-B(4):696-703.
34517888 Gut microbial determinants of clinically important improvement in patients with rheumatoid 2021 Sep 14 BACKGROUND: Rapid advances in the past decade have shown that dysbiosis of the gut microbiome is a key hallmark of rheumatoid arthritis (RA). Yet, the relationship between the gut microbiome and clinical improvement in RA disease activity remains unclear. In this study, we explored the gut microbiome of patients with RA to identify features that are associated with, as well as predictive of, minimum clinically important improvement (MCII) in disease activity. METHODS: We conducted a retrospective, observational cohort study on patients diagnosed with RA between 1988 and 2014. Whole metagenome shotgun sequencing was performed on 64 stool samples, which were collected from 32 patients with RA at two separate time-points approximately 6-12 months apart. The Clinical Disease Activity Index (CDAI) of each patient was measured at both time-points to assess achievement of MCII; depending on this clinical status, patients were distinguished into two groups: MCII+ (who achieved MCII; n = 12) and MCII- (who did not achieve MCII; n = 20). Multiple linear regression models were used to identify microbial taxa and biochemical pathways associated with MCII while controlling for potentially confounding factors. Lastly, a deep-learning neural network was trained upon gut microbiome, clinical, and demographic data at baseline to classify patients according to MCII status, thereby enabling the prediction of whether a patient will achieve MCII at follow-up. RESULTS: We found age to be the largest determinant of the overall compositional variance in the gut microbiome (R(2) = 7.7%, P = 0.001, PERMANOVA). Interestingly, the next factor identified to explain the most variance in the gut microbiome was MCII status (R(2) = 3.8%, P = 0.005). Additionally, by looking at patients' baseline gut microbiome profiles, we observed significantly different microbiome traits between patients who eventually showed MCII and those who did not. Taxonomic features include alpha- and beta-diversity measures, as well as several microbial taxa, such as Coprococcus, Bilophila sp. 4_1_30, and Eubacterium sp. 3_1_31. Notably, patients who achieved clinical improvement had higher alpha-diversity in their gut microbiomes at both baseline and follow-up visits. Functional profiling identified fifteen biochemical pathways, most of which were involved in the biosynthesis of L-arginine, L-methionine, and tetrahydrofolate, to be differentially abundant between the MCII patient groups. Moreover, MCII+ and MCII- groups showed significantly different fold-changes (from baseline to follow-up) in eight microbial taxa and in seven biochemical pathways. These results could suggest that, depending on the clinical course, gut microbiomes not only start at different ecological states, but also are on separate trajectories. Finally, the neural network proved to be highly effective in predicting which patients will achieve MCII (balanced accuracy = 90.0%, leave-one-out cross-validation), demonstrating potential clinical utility of gut microbiome profiles. CONCLUSIONS: Our findings confirm the presence of taxonomic and functional signatures of the gut microbiome associated with MCII in RA patients. Ultimately, modifying the gut microbiome to enhance clinical outcome may hold promise as a future treatment for RA.
32669445 Abdominal Obesity in Comparison with General Obesity and Risk of Developing Rheumatoid Art 2021 Feb OBJECTIVE: Being overweight or obese increases rheumatoid arthritis (RA) risk among women, particularly among those diagnosed at a younger age. Abdominal obesity may contribute to systemic inflammation more than general obesity; thus, we investigated whether abdominal obesity, compared to general obesity, predicted RA risk in 2 prospective cohorts: the Nurses' Health Study (NHS) and NHS II. METHODS: We followed 50,682 women (1986-2014) in NHS and 47,597 women (1993-2015) in NHS II, without RA at baseline. Waist circumference (WC), BMI, health outcomes, and covariate data were collected through biennial questionnaires. Incident RA cases and serologic status were identified by chart review. We examined the associations of WC and BMI with RA risk using time-varying Cox proportional hazards models. We repeated analyses restricted to age ≤ 55 years. RESULTS: During 28 years of follow-up, we identified 844 incident RA cases (527 NHS, 317 NHS II). Women with WC > 88 cm (35 in) had increased RA risk (HR 1.22, 95% CI 1.06-1.41). A similar association was observed for seropositive RA, which was stronger among young and middle-aged women. Further adjustment for BMI attenuated the association to null. In contrast, BMI was associated with RA (HR(BMI ≥ 30 vs < 25) 1.33, 95% CI 1.05-1.68) and seropositive RA, even after adjusting for WC, and, as in WC analyses, this association was stronger among young and middle-aged women. CONCLUSION: Abdominal obesity was associated with increased RA risk, particularly for seropositive RA, among young and middle-aged women; however, it did not independently contribute to RA risk beyond general obesity.
33590829 Upadacitinib improves patient-reported outcomes vs placebo or adalimumab in patients with 2021 Dec 1 OBJECTIVE: To evaluate the impact of upadacitinib vs placebo and adalimumab treatment, on patient-reported outcomes (PROs) in SELECT-COMPARE in an active RA population with inadequate responses to MTX (MTX-IR). METHODS: PROs in patients receiving upadacitinib (15 mg QD), placebo, or adalimumab (40 mg EOW) while on background MTX were evaluated over 48 weeks. PROs included Patient Global Assessment of Disease Activity (PtGA) and pain by visual analogue scale (VAS), the HAQ Disability Index (HAQ-DI), the 36-Item Short Form Survey (SF-36), morning (AM) stiffness duration and severity, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and work instability. Least squares mean (LSM) changes and proportions of patients reporting improvements ≥ minimal clinically important differences (MCIDs) and scores ≥ normative values were evaluated. RESULTS: Upadacitinib and adalimumab resulted in greater LSM changes from baseline vs placebo across all PROs (P < 0.05) at week 12, and pain and AM stiffness severity (P < 0.05) at week 2. More upadacitinib- vs placebo-treated (P < 0.05) and similar percentages of upadacitinib- vs adalimumab-treated patients reported improvements ≥ MCID across all PROs at week 12. Upadacitinib vs adalimumab resulted in greater LSM changes from baseline in PtGA, pain, HAQ-DI, stiffness severity, FACIT-F, and the SF-36 Physical Component Summary (PCS) (all P < 0.05) at week 12. More upadacitinib- vs adalimumab-treated patients reported scores ≥ normative values in HAQ-DI and SF-36 PCS (P < 0.05) at week 12. More upadacitinib- vs adalimumab-treated patients maintained clinically meaningful improvements in PtGA, pain, HAQ-DI, FACIT-F, and AM stiffness through 48 weeks. CONCLUSION: In MTX-IR patients with RA, treatment with upadacitinib resulted in statistically significant and clinically meaningful improvements in PROs equivalent to or greater than with adalimumab. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02629159.
33944985 Rheumatoid factor and falsely elevated results in commercial immunoassays: data from an ea 2021 Sep The aim of the study was to  assess RF cross-reactivity to animal antibodies used in immunoassays, and to test if selected commercial immunoassays are vulnerable to interference from RF, causing false test results. Our study included samples from patients with RF-positive rheumatoid arthritis (RA) and controls (patients with RF-negative RA and psoriatic arthritis), included in an early arthritis-cohort. Reactivity to mouse IgG1, mouse IgG2a, rabbit IgG, bovine IgG, sheep/goat IgG and human IgG was analysed using in-house interference assays. RF-positive sera with strong reactivity to mouse IgG1 were analysed in three commercial immunoassays. To reveal interference, results before and after addition of blocking aggregated murine IgG1 were compared. Samples from 124 RF-positive RA patients and 66 controls were tested. We found considerably stronger reactivity toward animal antibodies, particularly mouse IgG1 (73% vs. 12%) and rabbit IgG (81% vs. 6%), in sera from RF-positive RA-patients compared to controls (p < 0.001). After selecting samples for testing in commercial assays, interference was revealed in 6/30 sera in the Architect β-hCG assay, 7/10 sera in the 27-plex cytokine assays, and in 2/33 samples in the Elecsys Soluble Transferrin Receptor assay. Our study revealed considerable RF reactivity to animal antibodies used in immunoassays and RF was associated with falsely elevated results in immunoassays used in clinical care and research. Clinicians, laboratorians, researchers and assay manufacturers must be alert to the risk of falsely elevated test results in RF-positive RA patients.
34557202 NOX2-Deficient Neutrophils Facilitate Joint Inflammation Through Higher Pro-Inflammatory a 2021 Immune-mediated arthritis is an important chronic inflammatory disease of joints causing debilitating morbidity in affected patients. The mechanisms underlying immune-mediated arthritis have been intensively investigated, however the cellular and molecular factors contributing to the joint inflammation in different redox conditions have not been clearly elucidated. Previous research showed that phagocyte-produced reactive oxygen species (ROS) plays an anti-inflammatory role in K/BxN serum-transfer arthritis and NOX2-deficient mice tend to have more severe arthritis. Although many leukocytes play critical roles in the development of immune-mediated arthritis, the role of neutrophils, which are the main producers of ROS in inflammation, is still controversial. We hence assessed the immunomodulatory function of neutrophils from arthritic joints of NOX2-deficient and wild type mice in this study. We found more neutrophils accumulation in NOX2-deficient inflamed joints. RNA-sequencing and quantitative PCR revealed significantly increased expression of acute inflammation genes including IL1b, Cxcl2, Cxcl3, Cxcl10 and Mmp3 in activated neutrophils from the inflamed joints of NOX2-deficient mice. Moreover, gene set enrichment analysis (GSEA) showed enriched gene signatures in type I and II IFN responses, IL-6-JAK-STAT3 signaling pathway and TNF-α signaling pathway via NF-κB in NOX2-deficient neutrophils. In addition, we found that NOX2-deficient neutrophils expressed lower levels of PD-L1 and were less suppressive than WT neutrophils. Moreover, treatment of PD-L1-Fc decreased cytokine expression and ameliorated the severity of inflammatory arthritis. Our results suggest that NOX2-derived ROS is critical for regulating the function and gene expression in arthritic neutrophils. Both the strong pro-inflammatory and weakened anti-inflammatory functions of neutrophils due to abnormal redox regulation may be targets of treatment for immune-mediated arthritis.
32909390 Mediterranean Diet and Risk of Rheumatoid Arthritis: Findings From the French E3N-EPIC Coh 2021 Jan OBJECTIVE: The Mediterranean diet has been reported to be associated with a significant reduction in risk of noncommunicable diseases. We undertook this study to assess the relationship between adherence to the Mediterranean diet and the risk of rheumatoid arthritis (RA), especially in high-risk individuals. METHODS: The E3N study (Etude Epidémiologique Auprès des Femmes de la Mutuelle Générale de l'Education Nationale) is a French prospective cohort study that has included 98,995 women since 1990. Dietary data were collected via a validated food frequency questionnaire in 1993. Adherence to the Mediterranean diet was assessed using a 9-unit dietary score evaluating consumption of vegetables, legumes, cereal products, fish, meat, dairy products, olive oil, and alcohol. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident RA were estimated using Cox proportional hazards regression models adjusted for age and the main potential confounders, including smoking. RESULTS: Among 62,629 women, we identified 480 incident cases of RA. In the entire study population, the Mediterranean diet adherence score was not associated with RA risk (HR 0.86 [95% CI 0.67-1.09] for high score versus low score; P for trend = 0.09); however, among ever-smokers, a higher score was associated with a decreased risk of RA (HR 0.91 [95% CI 0.84-0.99] for 1-point increase in score; P = 0.03). In ever-smokers, the absolute risks of RA in those with high scores and those with low scores were 38.3 and 51.5 per 100,000 person-years, respectively, compared to 35.8 per 100,000 person-years in never-smokers with high Mediterranean diet scores. CONCLUSION: Our results suggest that adherence to the Mediterranean diet could reduce the high risk of RA among ever-smoking women. Our results must be confirmed in future research.
34531306 A core set of risk factors in individuals at risk of rheumatoid arthritis: a systematic li 2021 Sep BACKGROUND: There is significant interest in determining risk factors in individuals at risk of rheumatoid arthritis (RA). A core set of risk factors for clinical arthritis development has not been defined. METHODS: A literature search and systematic literature review (SLR) was conducted to identify risk factors in individuals at risk of RA using Medline, Embase, PubMed and Central databases. RESULTS: 3854 articles were identified by the literature search. After screening of titles, 138 abstracts were reviewed and 96 articles finally included. Fifty-three articles included data on risk factors including autoantibodies, subclinical inflammation on imaging, clinical features, serum and cellular biomarkers and genetic markers. Risk factors were dependent on the at-risk population. There was good evidence for serum anticitrullinated protein antibodies (ACPA) levels, as risk factors for arthritis in all at-risk populations (n=13 articles). Subclinical inflammation on ultrasound (n=12) and MRI (n=6) was reported as a risk factor in multiple studies in at-risk individuals with musculoskeletal (MSK) symptoms and undifferentiated arthritis (UA). Clinical features were reported as a risk factor in at-risk individuals with MSK symptoms and UA (n=13). Other risk factors, including serum and cellular markers were less frequently reported. CONCLUSIONS: Risk factors for arthritis development in RA are specific to the at-risk population. Serum ACPA confers risk in all populations; subclinical inflammation on imaging and clinical features confer risk in at-risk individuals with MSK symptoms. This SLR informed the EULAR taskforce for points to consider on conducting clinical trials and studies in individuals at risk of RA.
33558877 Rheumatologic disorders in patients undergoing esophageal manometry: prevalence, symptom c 2021 Aug 10 Rheumatologic disorders (RDs) can have gastrointestinal (GI) manifestations. Systemic sclerosis (SSc) patients often have upper GI symptoms from absent esophageal contractility (AC). Upper GI symptom characteristics and high-resolution esophageal manometry with impedance (HREMI) findings of other RDs have not been well studied. We aimed to: (i) determine the prevalence of RD in patients undergoing HREMI and (ii) assess the symptom characteristics and manometric findings of these patients. Patients undergoing HREMI (July 2018 to March 2020) rated their GI symptoms' severity. Healthy volunteers (HVs) also underwent HREMI. Of the 1,003 patients, 90 (9%) had RD (mean age: 55.3 ± 1.4 years, 73.3% females), most commonly SSc (n = 27), rheumatoid arthritis (RA, n = 20), and systemic lupus erythematosus (SLE, n = 11). The most severe upper GI symptoms in patients with RD were heartburn, regurgitation, nausea, and dysphagia, with no significant differences in their severities between SSc, RA, and SLE. RD patients had higher upper esophageal sphincter (UES) pressures, lower distal contractile integral (DCI), lower bolus clearance, and more frequent hiatal hernia (HH) on HREMI (all P < 0.05) than HVs. Over half (61.1%) of patients with RD had esophageal motility disorders, most commonly AC (n = 25), ineffective esophageal motility (IEM; n = 18), and esophagogastric junction (EGJ) obstructive disorders (n = 11). Among patients undergoing HREMI, 9% had RD. Upper GI symptom severities did not distinguish different RDs. Patients with RD had higher UES pressures, weaker DCI, lower bolus clearance, and more frequent HH than HVs. Although AC and IEM were most common motility disorders, a considerable minority (12.2%) of our RD patients had EGJ obstructive disorders.
33685930 Reduced cardiorespiratory fitness is a mediator of excess all-cause mortality in rheumatoi 2021 Mar OBJECTIVES: Investigate if low cardiorespiratory fitness (CRF) was associated with and acted as a mediator of excess all-cause mortality rate in persons suffering from rheumatoid arthritis (RA) compared with the general population. METHODS: All-cause mortality was analysed using Cox regression modelling in patients with RA (n=348) and controls (n=60 938) who took part in the second (1995-1997) and third (2006-2008) waves of the longitudinal population-based Trøndelag Health Study in Norway. A mediation analysis was performed to investigate if excess relative risk of mortality in RA was mediated by low estimated CRF (eCRF). RESULTS: During the follow-up until 31 December 2018 (mean 19.3 years), the mortality rate among patients with RA (n=127, 36.5%) was higher than among controls (n=12 942, 21.2%) (p<0.001). Among controls and patients with RA, 51% and 26%, respectively, had eCRF above the median for their age and sex (p<0.001). The final Cox model included RA status and eCRF, adjusted for hypertension, body mass index, smoking, cholesterol, diabetes and creatinine. eCRF below median for sex and age category was associated with increased mortality (p<0.001). The total excess relative risk of mortality in patients with RA was 28% (95% CI 2% to 55%, p=0.035), in which RA itself contributed 5% and the direct and indirect contributions of low eCRF accounted for 23%. CONCLUSIONS: Low eCRF was an important mediator of the increased all-cause mortality rate found in RA. Our data indicate that patients with RA should be given advice to perform physical activity that increases CRF, along with optimised treatment with antirheumatic drugs, from the time of diagnosis.
34632743 [About a pediatric patients cohort followed in the adult rheumatology department of CHU Li 2021 Oct We realized an observational retrospective study about pediatric patients (between 1 to 18 years) followed at the CHU Liège in an adult rheumatologic service during the last 14 years. This study identified 102 patients who developed the first symptoms during infancy, identifying 39 different diseases. Mainly, we identify cases of idiopathic juvenile arthritis, rheumatoid arthritis, spondylarthropathies, systemic lupus erythematosus, systemic vasculitis, connective tissue diseases, bone diseases, and phosphocalcic metabolic disorders. These observations highlight the difficulties to classify inflammatory articular diseases in young patients. Furthermore, this article may be helpful to identify some specificities in the pediatric population who suffers from rheumatologic diseases and some essential factors to make an optimal transition to adult medicine.
33592182 Pneumothorax Due to a Nontraumatic Thoracic Wall Rupture Due to Steroid-Induced Muscle Was 2021 Oct Spontaneous pneumothorax can be classified into primary and secondary variants. A 58-year-old patient presented with a 7-week history of severe coughing and chest pain. He noticed progressive swelling of the face and the upper part of the body. His medical history revealed osteoporosis and severe rheumatoid arthritis treated with steroids and disease-modifying antirheumatic drugs. Computed tomography of the thorax revealed complete rupture of the thoracic wall through costae 9 and 10 with lung herniation. The defect was closed using dual mesh and the pneumothorax was treated. Two weeks after surgery, the subcutaneous emphysema resolved and the patient was discharged from the hospital.
34505213 Lifestyle factors in patients with rheumatoid arthritis-a cross-sectional study on two Sca 2022 Feb INTRODUCTION: The risk for cardiovascular diseases and other comorbidities increases with the number of unhealthy lifestyle factors in the general population. However, information on the combined number of unhealthy lifestyle factors in people with rheumatoid arthritis (RA) is scarce. OBJECTIVES: To study lifestyle factors and the association between disease impact and two or more unhealthy lifestyle factors in two Scandinavian cohorts with RA. METHODS: We analysed data from two cohorts, Danish (n = 566; mean age 61.82 (SD 11.13) years; 72% women) and Swedish (n = 955; mean age 66.38 (SD 12.90) years; 73% women). Lifestyle factors (tobacco use, BMI, alcohol consumption and physical activity) were dichotomised as healthy vs. unhealthy (range 0-4 unhealthy factors). The association between disease impact and two or more unhealthy lifestyle factors was analysed using logistic regression. RESULTS: Sixty-six percent of Danish and 47% of Swedish respondents reported two or more unhealthy lifestyle factors, most commonly, being overweight/obese and physical inactivity. For Danish participants, two or more unhealthy lifestyle factors were associated with (OR and 95% CI) male gender (1.86; 1.21-2.85), cardiovascular diseases (1.90; 1.28-2.82) and disease duration (0.97; 0.95-0.99). Corresponding findings for the Swedish cohort were male gender (1.42; 1.07-1.89), pain (1.10; 1.04-1.15), fatigue (1.09; 1.04-1.15), physical functioning (1.64; 1.28-2.10) and quality of life (0.35; 0.20-0.60). CONCLUSION: Many patients, most often male, in both cohorts had two or more unhealthy lifestyle factors. The number of unhealthy lifestyle factors indicates a multifaceted relationship with disease impact.
32406914 A novel deep learning method for predictive modeling of microbiome data. 2021 May 20 With the development and decreasing cost of next-generation sequencing technologies, the study of the human microbiome has become a rapid expanding research field, which provides an unprecedented opportunity in various clinical applications such as drug response predictions and disease diagnosis. It is thus essential and desirable to build a prediction model for clinical outcomes based on microbiome data that usually consist of taxon abundance and a phylogenetic tree. Importantly, all microbial species are not uniformly distributed in the phylogenetic tree but tend to be clustered at different phylogenetic depths. Therefore, the phylogenetic tree represents a unique correlation structure of microbiome, which can be an important prior to improve the prediction performance. However, prediction methods that consider the phylogenetic tree in an efficient and rigorous way are under-developed. Here, we develop a novel deep learning prediction method MDeep (microbiome-based deep learning method) to predict both continuous and binary outcomes. Conceptually, MDeep designs convolutional layers to mimic taxonomic ranks with multiple convolutional filters on each convolutional layer to capture the phylogenetic correlation among microbial species in a local receptive field and maintain the correlation structure across different convolutional layers via feature mapping. Taken together, the convolutional layers with its built-in convolutional filters capture microbial signals at different taxonomic levels while encouraging local smoothing and preserving local connectivity induced by the phylogenetic tree. We use both simulation studies and real data applications to demonstrate that MDeep outperforms competing methods in both regression and binary classifications. Availability and Implementation: MDeep software is available at https://github.com/lichen-lab/MDeep Contact:chen61@iu.edu.
32734406 Multiple coronary aneurysms and acute myocardial infarction in a female patient with rhupu 2021 Mar Coronary artery aneurysms (CAA) are an infrequent cause of coronary artery disease in both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), most occurring as a result of acute coronary syndromes (ACS). Until now, no cases of CAA have been described in a patient with rhupus syndrome (RhS). Differentiating whether CAA stem from primary vasculitis, atherosclerosis, or a combination of both continues to pose a significant challenge. We present the first described clinical case of a 43-year-old patient with RhS and multiple CAA identified by the presentation of an acute myocardial infarction. The presence of multiple cardiovascular risk factors and the absence of inflammatory findings, both in PET-CT and arterial biopsy, favored an atherosclerotic versus a vasculitic etiology of the CAA. At the time of the aneurysms diagnosis, the patient showed no signs of SLE activity and only moderate RA activity, which underscores the importance of screening for silent coronary aneurysms in these patients, even in subjects exhibiting little apparent activity from their underlying disease. This case also exemplifies the severe impact of atherosclerotic burdens on such patients, demanding vigilance and aggressiveness in its prevention, early diagnosis, and treatment. We hypothesize that RhS could engender an even greater risk of presenting CAA than either SLE or RA on their own, which therefore warrants more careful follow-up in these patients.
33404652 Changes in the pharmacological management of rheumatoid arthritis over two decades. 2021 Sep 1 OBJECTIVES: To assess whether modern management of RA has reduced the prescription of oral corticosteroids and NSAIDs and to evaluate use of pharmacological prophylaxis strategies. METHODS: Using the Clinical Practice Research Datalink, we explored long-term (≥3/12 months; ≥6/12 in sub-analyses) DMARD, corticosteroid and NSAID prescribing (annually, in the year post-diagnosis and across the patient's life course to 15 years post-diagnosis), annual proportion with co-prescribing for prophylaxis of associated bone (corticosteroids, women only) and gastrointestinal (NSAIDs) comorbidity. RESULTS: Reported incidence of RA was 5.98 (0.37) per 10 000 person-years and prevalence was 0.91% (0.014) in 2017. In 71 411 RA patients, long-term DMARD prescribing initially rose post-diagnosis from 41.6% in 1998 to 67.9% in 2009. Corticosteroid prescribing changed little, overall [22.2% in 1998, 19.1% in 2016; incident risk ratio (IRR) 0.92, 95% CI: 0.82, 1.03] and across the life course from the first to fifteenth year (22.2% to 16.9%). NSAID prescribing declined from 57.7% in 1998, and significantly so from 2008, to 27.1% in 2016 (IRR 0.50, 95% CI: 0.44, 0.56). This continued across the life course (41.2% to 28.4%). Bone prophylaxis increased to 68.1% in 2008 before declining to 56.4% in 2017; gastrointestinal prophylaxis increased from 11.5% in 1998 to 62.6% in 2017. Sub-analyses showed consistent patterns. CONCLUSION: Despite modern treatment strategies, corticosteroid prescribing in RA patients remains substantial and persists beyond 6 months once initiated. Rheumatologists need to determine causes and develop strategies to reduce corticosteroid use to minimize adverse event occurrence.