Sexual Dimorphism in Interstitial Lung Disease.

Interstitial lung diseases (ILD) are a group of heterogeneous progressive pulmonary disorders, characterised by tissue remodelling and/or fibrotic scarring of the lung parenchyma. ILD patients experience lung function decline with progressive symptoms, poor response to treatment, reduced quality of life and high mortality. ILD can be idiopathic or associated with systemic or connective tissue diseases (CTD) but idiopathic pulmonary fibrosis (IPF) is the most common form. While IPF has a male predominance, women are affected more greatly by CTD and therefore associated ILDs. The mechanisms behind biological sex differences in these progressive lung diseases remain unclear. However, differences in environmental exposures, variable expression of X-chromosome related inflammatory genes and sex hormones play a role. Here, we will outline sex-related differences in the incidence, progression and mechanisms of action of these diseases and discuss existing and novel cellular and pre-clinical studies. Furthermore, we will highlight how sex-differences are not adequately considered in pre-clinical disease models, how gender bias exists in clinical diagnosis and how women are underrepresented in clinical trials. Future action on these observations will hopefully shed light on the role of biological sex in disease development, identify potential targets for intervention and increase female participant numbers in clinical trials.

Characteristics and Outcomes of People With Gout Hospitalized Due to COVID-19: Data From the COVID-19 Global Rheumatology Alliance Physician-Reported Registry.

OBJECTIVE: To describe people with gout who were diagnosed with coronavirus disease 2019 (COVID-19) and hospitalized and to characterize their outcomes. METHODS: Data on patients with gout hospitalized for COVID-19 between March 12, 2020, and October 25, 2021, were extracted from the COVID-19 Global Rheumatology Alliance registry. Descriptive statistics were used to describe the demographics, comorbidities, medication exposures, and COVID-19 outcomes including oxygenation or ventilation support and death. RESULTS: One hundred sixty-three patients with gout who developed COVID-19 and were hospitalized were included. The mean age was 63 years, and 85% were male. The majority of the group lived in the Western Pacific Region (35%) and North America (18%). Nearly half (46%) had two or more comorbidities, with hypertension (56%), cardiovascular disease (28%), diabetes mellitus (26%), chronic kidney disease (25%), and obesity (23%) being the most common. Glucocorticoids and colchicine were used pre-COVID-19 in 11% and 12% of the cohort, respectively. Over two thirds (68%) of the cohort required supplemental oxygen or ventilatory support during hospitalization. COVID-19-related death was reported in 16% of the overall cohort, with 73% of deaths documented in people with two or more comorbidities. CONCLUSION: This cohort of people with gout and COVID-19 who were hospitalized had high frequencies of ventilatory support and death. This suggests that patients with gout who were hospitalized for COVID-19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity.

A pilot study of burnout and long covid in senior specialist doctors.

BACKGROUND: Covid-19 has placed unprecedented demand on healthcare systems and on healthcare professionals. There have been concerns about the risk of distress, moral injury and burnout among healthcare professionals, especially doctors. AIM: To assess the effect of the ongoing Covid-19 pandemic on Irish doctors by investigating the incidence of burnout and long covid among senior medical staff in Ireland. METHODS: This is a cross-sectional pilot study of the prevalence of burnout and long covid among senior physicians. A survey was sent by email to members of the Irish Hospital Consultant's Association. The survey included measures of mental and physical health and the 2-item Maslach Burnout Scale (MBS-2). The study explored the experience of delivering health care in the context of a pandemic and experience of the long covid syndrome. RESULTS: A total of 114 responses were received. Three-quarters 77% (N = 88) screened positive for burnout on the MBS, with mean score of 5.6 (SD3.3), nearly double the cut-off for burnout. Nearly two-thirds (64%, n = 72) reported that Covid-19 has had an adverse effect on their mental health. One-quarter reported that they or colleagues had experience of 'long-covid' secondary to the virus. CONCLUSION: More comprehensive evaluation of the effect of the pandemic on front-line staff is needed to identify the extent of the problem and the factors which contribute to it. This will inform measures to mitigate these effects.

HIV and systemic lupus erythematosus: where immunodeficiency meets autoimmunity.

We report a case of a new diagnosis of systemic lupus erythematosus (SLE) in a patient with HIV who presented to the outpatient department with a fever, headache and lymphadenopathy. Cerebrospinal fluid analysis showed lymphocytic pleocytosis. Initial concerns were for an infectious process, and investigations for systemic and central nervous system infection were negative. Serum testing for ANA, dsDNA, nucleosome, anti-histone and ribosomal-P antibodies was positive. A magnetic brain imaging scan of the brain showed a well-circumscribed lesion in the right cerebellar peduncle on T2/FLAIR. The patient was commenced on prednisolone and rituximab, and had a good clinical response. The cerebellar lesion resolved and has not recurred with sequential imaging. SLE and HIV are both multi-systemic diseases which rarely co-occur. Autoimmune processes should be considered in HIV patients with multi-systemic symptoms and signs.

High prevalence of abnormalities on chest radiography in rheumatoid arthritis.

INTRODUCTION: Chest radiography (CXR) is commonly performed in rheumatoid arthritis (RA), particularly for the diagnosis of pulmonary disease. However, other structures are visible on CXR, abnormalities of which may contribute to morbidity and early mortality. This study was undertaken to evaluate the extent of CXR abnormalities in RA patients. METHODS: Consecutive out-patients meeting the 2010 ACR/EULAR classification criteria for RA were included. The most recent CXR was assessed by two independent reviewers. Abnormalities identified were recorded and compared to the formal CXR report. Predictors of abnormalities on CXR were assessed using chi-squared tests. SPSS 18.0 was used for statistical analysis. RESULTS: One hundred and ninety-eight patients were included. Mean age was 62 years (range 18-90). One hundred and nine (55.1%) were current or ex-smokers. One hundred and fifty-six (79%) patients were seropositive and 123 (62.1%) had joint erosions. A recent CXR was available in 163 (82%) cases. Abnormalities were identified in 129 (79.1%). Ninety-seven (60%) had bony abnormalities. Seventy-one (43.6%) had pulmonary abnormalities; old tuberculosis in 34 (20.9%), hyperinflation in 24 (14.7%), interstitial changes in 20 (13.3%), nodules in 4 (2.4%), consolidation in 2 (1.2%), and pneumothorax in 1 (0.6%). Cardiomegaly was identified in 37 (22.7%) and aortic calcification in 24 (14.7%). Age (p = 0.001), male gender (p = 0.01), and seropositivity (p = 0.04) were significantly associated with lung abnormalities. Cardiomegaly was associated with hypertension (p = 0.012) and ischaemic heart disease (p = 0.018). CONCLUSION: Abnormalities were identified in 79% of chest radiographs in RA patients. Sixty-six percent of these were not reported. Clinicians need to be aware of the need to check for abnormalities.Key Points• RA patients have a high prevalence of CXR abnormalities.• Many of these are of clinical significance.• Age, being male, and seropositivity were associated with lung abnormalities.

Management strategies and future directions for systemic lupus erythematosus in adults.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the loss of self-tolerance and formation of nuclear autoantigens and immune complexes resulting in inflammation of multiple organs. The clinical presentation of SLE is heterogeneous, can involve one or more organs, including the skin, kidneys, joints, and nervous system, and take a chronic or relapsing and remitting disease course. SLE is most common in women and in those of non-white ethnicity. Because of the multitude of presentations, manifestations, and serological abnormalities in patients with SLE, diagnosis can be challenging. Therapeutic approaches predominantly involve immunomodulation and immunosuppression and are targeted to the specific organ manifestation, with the aim of achieving low disease activity. Despite many treatment advances and improved diagnostics, SLE continues to cause substantial morbidity and premature mortality. Current management strategies, although helpful, are limited by high failure rates and toxicity. An overreliance on corticosteroid therapy contributes to much of the long-term organ damage. In this Seminar, we outline the classification criteria for SLE, current treatment strategies and medications, the evidence supporting their use, and explore potential future therapies.

Behaviour change interventions targeting physical activity in adults with fibromyalgia: a systematic review.

Physical activity (PA) and exercise programmes are recommended for the management of fibromyalgia. Despite positive effects on symptoms and function, PA promotion remains a significant clinical challenge. Behaviour change theories and techniques are recommended as part of complex health interventions; their integration into interventions aimed at PA behaviour in people with fibromyalgia is not known. This review explored behaviour change interventions targeting PA in adults with fibromyalgia. A systematic review was conducted; randomized and quasi-randomized controlled trials with at least one behaviour change intervention targeting PA were included. MEDLINE/OVID, EMBASE, PEDro, PsychINFO, CINAHL, Scopus, Web of Science, the Cochrane Central Register of Controlled Trials and relevant conference abstracts were searched. Two authors independently screened studies for inclusion and performed risk of bias assessments. Articles were reviewed for their use of behaviour change theory and behaviour change techniques (BCTs). The search identified 2491 records, from which eight studies (1416 participants) were included. PA and exercise behaviours were the primary focus of four interventions and were components of broader interventions in four studies. Behaviour change theories informed four interventions. Thirty-two different BCTs were used across studies. Five studies reported improvements in PA either post-intervention or at follow-up. Two studies used objective PA measures and seven studies used self-report measures. Short-term benefits in pain, quality of life, and physical fitness were also observed. Behaviour change interventions targeting PA in people with fibromyalgia have had limited success to date. With significant variations in intervention designs, the optimal intervention remains unknown.

Exercise and physical activity in systemic lupus erythematosus: A systematic review with meta-analyses.

Systemic lupus erythematosus (SLE) associates with enhanced cardiovascular (CV) risk frequently unexplained by traditional risk factors. Physical inactivity, common in SLE, likely contributes to the burden of CV risk and may also be a factor in co-morbid chronic fatigue. This systematic review evaluates whether exercise has a deleterious effect on disease activity in SLE, and explores effects on CV function and risk factors, physical fitness and function and health-related measures. MATERIALS AND METHODS: A systematic review, with meta-analyses, was conducted; quasi-randomised and randomised controlled trials in SLE comparing at least one exercise group to controls were included. MEDLINE/PubMed, EMBASE, PEDro, AMED, CINAHL, The Cochrane Central Register of Controlled Trials, and relevant conference abstracts were searched. Random-effects meta-analyses were used to pool extracted data as mean differences. Heterogeneity was evaluated with χ2 test and I2, with p < 0.05 considered significant. RESULTS: The search identified 3068 records, and 31 full-texts were assessed for eligibility. Eleven studies, including 469 participants, were included. Overall risk of bias of these studies was unclear. Exercise interventions were reported to be safe, while adverse effects were rare. Meta-analyses suggest that exercise does not adversely affect disease activity, positively influences depression, improves cardiorespiratory capacity and reduces fatigue, compared to controls. Exercise programmes had no significant effects on CV risk factors compared to controls. CONCLUSION: Therapeutic exercise programmes appear safe, and do not adversely affect disease activity. Fatigue, depression and physical fitness were improved following exercise-based interventions. A multimodal approach may be suggested, however the optimal exercise protocol remains unclear.

Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: Type I interferon (IFN) is implicated in the pathogenesis of systemic lupus erythematosus (SLE) and interferonopathies such as Aicardi-Goutières syndrome. A recently discovered DNA-activated type I IFN pathway, cyclic GMP-AMP synthase (cGAS), has been linked to Aicardi-Goutières syndrome and mouse models of lupus. The aim of this study was to determine whether the cGAS pathway contributes to type I IFN production in patients with SLE. METHODS: SLE disease activity was measured by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index. Expression of messenger RNA for cGAS and IFN-stimulated genes (ISGs) was determined by quantitative polymerase chain reaction analysis. Cyclic GMP-AMP (cGAMP) levels were examined by multiple reaction monitoring with ultra-performance liquid chromatography tandem mass spectrometry. RESULTS: Expression of cGAS in peripheral blood mononuclear cells (PBMCs) was significantly higher in SLE patients than in normal controls (n = 51 and n = 20 respectively; P < 0.01). There was a positive correlation between cGAS expression and the IFN score (P < 0.001). The expression of cGAS in PBMCs showed a dose response to type I IFN stimulation in vitro, consistent with it being an ISG. Targeted measurement of cGAMP by tandem mass spectrometry detected cGAMP in 15% of the SLE patients (7 of 48) but none of the normal (0 of 19) or rheumatoid arthritis (0 of 22) controls. Disease activity was higher in SLE patients with cGAMP versus those without cGAMP. CONCLUSION: Increased cGAS expression and cGAMP in a proportion of SLE patients indicates that the cGAS pathway should be considered as a contributor to type I IFN production. Whereas higher cGAS expression may be a consequence of exposure to type I IFN, detection of cGAMP in patients with increased disease activity indicates potential involvement of this pathway in disease expression.

Renal Cell Carcinoma: Accuracy of Multidetector Computed Tomography in the Assessment of Renal Sinus Fat Invasion.

PURPOSE: The purpose of this study was to evaluate the accuracy of multidetector computed tomography (MDCT) in the preoperative assessment of renal sinus fat invasion (RSFI) in patients with renal cell carcinoma (RCC) and to assess imaging features that improve detection of RSFI on CT. METHODS: This is a single-institution retrospective review of 53 consecutive patients with histologically proven RCC who underwent triple-phase preoperative contrast MDCT prior to partial or radical nephrectomy. Two experienced radiologists (R1 and R2), blinded to the final histology result, independently reviewed the preoperative MDCT studies to assess for RSFI. Histopathology was used as the gold standard for the presence of RSFI. RESULTS: Of 55 surgically resected RCCs that were evaluated with contrast-enhanced MDCT, 34.5% (19/55) of RCCs had RSFI on final histopathology. Multidetector CT demonstrated high sensitivity (R1, 100%; R2, 93.7%) for the detection of RSFI, but a low positive predictive value (R1, 40%; R2, 53%) and specificity (R1, 38.4%; R2, 66.6%). Interreader agreement for RSFI was moderate (κ = 0.56). Renal tumors were significantly larger in cases with RSFI (6.3 ± 3.219 cm) than tumors without RSFI (4.1 ± 2.9 cm) (P = 0.0275). Renal sinus fat invasion was more commonly associated to an irregular tumor margin at the tumor renal sinus fat interface (P < 0.001). CONCLUSIONS: Multidetector computed tomography demonstrates a high sensitivity but low positive predictive value in diagnosing RSFI with implications for prognosis and treatment planning. Tumor size, location, irregular tumor margin at the tumor/renal sinus interface, and invasion into pelvicaliceal structures can aid in the diagnosis of RSFI on preoperative MDCT.

Longitudinal Evaluation of Lipoprotein Variables in Systemic Lupus Erythematosus Reveals Adverse Changes with Disease Activity and Prednisone and More Favorable Profiles with Hydroxychloroquine Therapy.

OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerotic cardiovascular disease. Patients with SLE have adverse lipoprotein variables, but little is known about how these change with treatment and disease activity. The nuclear magnetic resonance LipoProfile test contains a glycoprotein signal-termed GlycA, an inflammatory marker, which has not been evaluated in SLE. We assessed patients longitudinally to determine how lipoproteins and GlycA change with active SLE. METHODS: Sera from selected clinical visits of patients in the Hopkins Lupus Cohort were analyzed for lipoprotein and GlycA levels. Univariate and multivariate analyses were performed to evaluate lipoprotein variables and their relationship to ethnicity, disease activity, prednisone use, and hydroxychloroquine (HCQ) therapy. RESULTS: Fifty-two patients were included over 229 visits. Adverse changes in lipoprotein variables with disease activity were demonstrated. For each point increase in the Systemic Lupus Erythematosus Disease Activity Index, there was a decrease in high-density lipoprotein (HDL) even after adjusting for corticosteroid use. Prednisone was associated with higher very low-density lipoprotein, low-density lipoprotein, HDL, and triglycerides. HCQ was associated with more favorable variables. GlycA levels were higher than in normal populations and increased with disease activity. CONCLUSION: Adverse changes in lipoprotein profiles were associated with SLE activity and prednisone therapy. This gives insight into mechanisms of atherosclerosis in SLE. Favorable lipoprotein variables occurred in those taking HCQ. GlycA increased with disease activity and was higher than in healthy populations.

Imaging as a potential outcome measure in gout studies: A systematic literature review.

OBJECTIVE: Despite major progress in the imaging of gout, it is unclear which domains these techniques can evaluate and whether imaging modalities have the potential to provide valid outcome measures. The aim of this study was to assess the use of imaging instruments in gout according to the Outcomes in Rheumatology Clinical Trials (OMERACT) filter to inform the development of imaging as an outcome measure. METHODS: A systematic literature search of imaging modalities for gout was undertaken. Articles were assessed by two reviewers to identify imaging domains and summarize information according to the OMERACT filter. RESULTS: The search identified 78 articles (one abstract). Modalities included were conventional radiography (CR) (16 articles), ultrasound (US) (29), conventional computed tomography (CT) (11), dual energy computed tomography (DECT) (20), and magnetic resonance imaging (MRI) (16). Three domains were identified as follows: urate deposition, joint damage, and inflammation. Although sufficient data were available to assess feasibility, validity, and reliability, comprehensive assessment of discrimination was not possible due to the paucity of prospective imaging studies. CR is widely accessible, inexpensive with a validated damage scoring system. US and MRI offer radiation-free methods of evaluating urate deposition, damage and inflammation, but may be limited by accessibility. DECT provides excellent definition of urate deposition and bone damage, but has restricted availability and requires radiation. CONCLUSIONS: Imaging methods can detect urate deposition, damage, and inflammation in gout. More than one modality may be required depending on the domains and therapeutic agent of interest. No single imaging method currently fulfils all aspects of the OMERACT filter for any domain.

Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence.

OBJECTIVE: Hydroxychloroquine (HCQ) is used for its effect on systemic lupus erythematosus (SLE) disease activity and longterm benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is disagreement about dosing; rheumatologists recommend weight-based dosing while some other specialists advocate height-based "ideal body weight" dosing. METHODS: Patients were prescribed HCQ not exceeding 6.5 mg/kg (max 400 mg/day). In hemodialysis, the dose was 200 mg after each session, and in renal insufficiency it was 200 mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the effect of measurement and counseling on adherence, we compared the proportion of patients with a level of 500 ng/ml or higher based on the number of prior assessments. RESULTS: The proportion of patients with HCQ levels in the therapeutic range differed significantly by age, sex, and Vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, subtherapeutic, and therapeutic levels, disease activity decreased (SLE Disease Activity Index 2.92, 2.36, and 2.20, p = 0.04 for trend). At first, 56% were therapeutic, and by the third measurement this increased to 80% (p ≤ 0.0001). CONCLUSION: There was a trend toward higher disease activity with lower HCQ levels. Renal failure dosing led to suboptimum levels. We show that weight-based dosing (max 400 mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling, and repeated testing can increase adherence rates.

Imaging as an Outcome Measure in Gout Studies: Report from the OMERACT Gout Working Group.

OBJECTIVE: The gout working group at the Outcome Measures in Rheumatology (OMERACT) 12 meeting in 2014 aimed to determine which imaging modalities show the most promise for use as measurement instruments for outcomes in studies of people with chronic gout and to identify the key foci for future research about the performance of these imaging techniques with respect to the OMERACT filter 2.0. METHODS: During the gout session, a systematic literature review of the data addressing imaging modalities including plain radiography (XR), conventional computed tomography (CT), dual-energy computed tomography (DECT), magnetic resonance imaging (MRI), and ultrasound (US) and the fulfillment of the OMERACT filter 2.0 was presented. RESULTS: The working group identified 3 relevant domains for imaging in gout studies: urate deposition (tophus burden), joint inflammation, and structural joint damage. CONCLUSION: The working group prioritized gaps in the data and identified a research agenda.

The effect of exercise on sleep and fatigue in rheumatoid arthritis: a randomized controlled study.

OBJECTIVE: Sleep disturbance and chronic fatigue are common in rheumatoid arthritis (RA) and contribute to disability, symptomatology, and healthcare use. It has long been recognized in other populations that exercise can improve sleep and diminish fatigue. The effect of exercise on sleep quality and fatigue in RA has not been evaluated. METHODS: Ours is a randomized controlled study in RA to determine the effect of an exercise program on sleep quality and fatigue. These were measured using the Pittsburgh Sleep Quality Index and the Fatigue Severity Scale. Patients were randomized to either a 12-week, home-based exercise intervention or usual care. The exercise program consisted of specific exercises to target individual deficiencies identified using the Health Assessment Questionnaire (HAQ) with cardiovascular work as per the guidelines. The intervention group was evaluated on a 3-week basis. Full evaluation was carried out at baseline and at 12 weeks. RESULTS: Forty patients were randomized to the intervention with 38 controls. In the exercise intervention group, there was a statistically significant improvement in HAQ (p = 0.00), pain (p = 0.05), stiffness (p = 0.05), sleep quality (p = 0.04), and fatigue (p = 0.04). In our control group, there was a statistically significant improvement demonstrated in their overall perceptions of the benefits of exercise, but none of the other variables. CONCLUSION: Our study demonstrates that an exercise program resulted in significant improvement in sleep quality and fatigue. This is particularly interesting given the importance of fatigue as an outcome measure in RA and gives us yet another reason to prescribe exercise in this population.