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Katherine Dutton,1 Geoffrey Littlejohn21Department of Rheumatology, Townsville Hospital, Douglas, QLD, Australia; 2Department of Medicine, Monash University, Melbourne, VIC, AustraliaAbstract: Complex regional pain syndrome has long been recognized as a severe and high impact chronic pain disorder. However, the condition has historically been difficult to define and classify and little attention has been given to where complex regional pain syndrome sits within other apparently similar chronic pain disorders, such as fibromyalgia and regional pain syndrome. In this review challenges in regard to nomenclature, definitions, and classification of complex regional pain syndrome are reviewed and suggestions are provided about future directions.Keywords: complex regional pain syndromes, fibromyalgia, causalgia, classification

Objectives: ANA-associated rheumatic and musculoskeletal (MSK) diseases (RMDs) [SLE, primary SS (pSS), scleroderma, inflammatory myositis, MCTD and UCTD] make up a disease spectrum with overlapping clinical and immunological features. MSK inflammation is common and impactful across ANA-associated RMDs. The objectives of this study were to evaluate MSK inflammation (ANA-associated arthritis) prevalence in a multidisease ANA-associated RMD study, assess its clinical impact across ANA-associated RMD diagnoses, propose new basket groupings of patients, and evaluate immunological profiles in legacy and new basket contexts., Methods: An observational study enrolled patients with ANA-associated RMDs. Demographic variables, comorbidities, therapies, disease activity instruments [BILAG, SLEDAI, the EULAR SS disease activity index (ESSDAI), physician visual analogue scale (VAS)], patient-reported outcomes [SF36, FACIT-Fatigue, EQ5D, ICECAP-A, Work Productivity and Activity impairment (WPAI), patient VAS] and the biomarker profile (six-gene expression scores, flow cytometry, autoantibody profile) were analysed. Reclustering utilized Gaussian mixture modelling (GMM). The clinical and immune features of new and legacy clusters were compared., Results: Inflammatory MSK symptoms were prevalent across ANA-associated RMDs, in 213/294 patients. In ANA-associated arthritis patients, most variables did not differ between diagnoses, with the exception of the EQ5D-5L index and mobility domains (lower in MCTD/pSS, both P < 0.05). FM and OA prevalence were similar across diagnoses. Therapy use differed significantly, the use of biologics being greatest in SLE (P < 0.05). GMM yielded two multidisease clusters: High MSK disease activity (n = 89) and low MSK disease activity (n = 124). The high MSK disease activity cluster included all patients with active joint swelling, and they had significantly higher prednisolone usage, physician global assessment (PGA), Sm/RNP/SmRNP/chromatin positivity, Tetherin mean fluorescence intensity (MFI), and IFN Score-A activity, along with numerically lower FM and OA prevalence., Conclusion: We defined ANA-associated arthritis, a more clinically and immunologically homogeneous population than existing RMD populations for trials, and a more prevalent population for therapies in the clinic., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Climate change is altering the functioning of foundational ecosystems. While the direct effects of warming are expected to influence individual species, the indirect effects of warming on species interactions remain poorly understood. In marine systems, as tropical herbivores undergo poleward range expansion, they may change food web structure and alter the functioning of key habitats. While this process ('tropicalization') has been documented within declining kelp forests, we have a limited understanding of how this process might unfold across other systems. Here we use a network of sites spanning 23° of latitude to explore the effects of increased herbivory (simulated via leaf clipping) on the structure of a foundational marine plant (turtlegrass). By working across its geographic range, we also show how gradients in light, temperature and nutrients modified plant responses. We found that turtlegrass near its northern boundary was increasingly affected (reduced productivity) by herbivory and that this response was driven by latitudinal gradients in light (low insolation at high latitudes). By contrast, low-latitude meadows tolerated herbivory due to high insolation which enhanced plant carbohydrates. We show that as herbivores undergo range expansion, turtlegrass meadows at their northern limit display reduced resilience and may be under threat of ecological collapse., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Progress in psychopathy research has been hampered by ongoing contention about its fundamental cause. The Impaired Integration theory of psychopathy provides an attention-based account of information integration abnormalities. We set out to evaluate the suggested mechanism via an innovative application of the well-established illusory conjunction paradigm. Two hundred participants were recruited by utilizing a psychopathic-trait-maximization technique, sampling individuals from an ex-prisoner and a population sample. We found no support for information integration deficits in psychopathic individuals (BF₁₀ = 0.156), and the absence of a relationship between psychopathic traits and illusory conjunctions remained when accounting for confounding variables. These findings question the mechanism proposed by the Impaired Integration theory and pave the way for future research to advance our understanding of psychopathic trait etiology by assessing specific and falsifiable mechanisms thought to bring about the observed cognitive and behavioral deficits. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Introduction: Rapid outpatient diagnostic programs (RODP) expedite lung cancer evaluation, but their impact on racial disparities in the timeliness of evaluation is less clear., Materials and Methods: This was a retrospective analysis of the impact of an internally developed application-supported RODP on racial disparities in timely referral completion rates for patients with potential lung cancer at a safety-net healthcare system. An application screened referrals to pulmonology for indications of lung mass or nodule and presented relevant clinical information that enabled dedicated pulmonologists to efficiently review and triage cases according to urgency. Subsequent care coordination was overseen by a dedicated nurse coordinator. To determine the program's impact, we conducted an interrupted time series analysis of the monthly fraction of referrals completed within 30 days, stratified by those identified as White, non-Hispanic and those that were not (racial and ethnic minorities)., Results: There were 902 patients referred in the 2 years preintervention and 913 in the 2 years postintervention. Overall, the median age was 63 years, and 44.7% of referred patients were female. 44.2% were White, non-Hispanic while racial and ethnic minorities constituted 54.3%. After the intervention, there was a significant improvement in the proportion of referrals completed within 30 days (62.4% vs. 48.2%, P <.01). The interrupted time series revealed a significant immediate improvement in timely completion among racial and ethnic minorities (23%, P < .01) that was not reflected in the majority White, non-Hispanic subgroup (11%, not significant)., Conclusion: A thoughtfully designed and implemented RODP reduced racial disparities in the timely evaluation of potential lung cancer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To determine whether SLE patients with inflammatory joint symptoms and US synovitis/tenosyovitis achieve better clinical responses to glucocorticoids compared with patients with normal scans. Secondary objectives included identification of clinical features predicting US synovitis/tenosynovitis., Methods: In a longitudinal multicentre study, SLE patients with physician-diagnosed inflammatory joint pain received intramuscular methylprednisolone 120 mg once. Clinical assessments, patient-reported outcomes and bilateral hand/wrist USs were collected at 0, 2 and 6 weeks. The primary outcome (determined via internal pilot) was the early morning stiffness visual analogue scale (EMS-VAS) at 2 weeks, adjusted for baseline, comparing patients with positive (greyscale ≥2 and/or power Doppler ≥1) and negative US. Post hoc analyses excluded FM., Results: Of 133 patients, 78 had a positive US. Only 53 (68%) of these had one or more swollen joint. Of 66 patients with one or more swollen joint, 20% had a negative US. A positive US was associated with joint swelling, symmetrical small joint distribution and serology. The primary endpoint was not met: in the full analysis set (N = 133) there was no difference in baseline-adjusted EMS-VAS at week 2 [-7.7 mm (95% CI -19.0, 3.5); P = 0.178]. After excluding 32 patients with FM, response was significantly better in patients with a positive US at baseline [baseline-adjusted EMS-VAS at 2 weeks -12.1 mm (95% CI -22.2, -0.1); P = 0.049]. This difference was greater when adjusted for treatment [-12.8 mm (95% CI -22, -3); P = 0.007]. BILAG and SLEDAI responses were higher in US-positive patients., Conclusion: In SLE patients without FM, those with a positive US had a better clinical response to therapy. Imaging-detected synovitis/tenosynovitis may be considered to decide on therapy and enrich clinical trials., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: Type I interferon (IFN) responses are broadly associated with autoimmune diseases, including systemic lupus erythematosus (SLE). Given the cardinal role of autoantibodies in SLE, this study was undertaken to investigate whether the findings of a B cell-specific IFN assay correlate with SLE activity., Methods: B cells and peripheral blood mononuclear cells (PBMCs) were stimulated with type I IFN and type II IFN. Gene expression was analyzed, and the expression of pathway-related membrane proteins was determined. A flow cytometry assay for tetherin (CD317), an IFN-induced protein ubiquitously expressed on leukocytes, was validated in vitro and then clinically against SLE diagnosis, plasmablast expansion, and the British Isles Lupus Assessment Group (BILAG) 2004 score in a discovery cohort (n = 156 SLE patients, 30 rheumatoid arthritis [RA] patients, and 25 healthy controls). A second, longitudinal validation cohort of 80 SLE patients was also evaluated for flare prediction., Results: In vitro, a close cell-specific and dose-response relationship between type I IFN-responsive genes and cell surface tetherin was observed in all immune cell subsets. Tetherin expression on multiple cell subsets was selectively responsive to stimulation with type I IFN compared to types II and III IFNs. In patient samples from the discovery cohort, memory B cell tetherin showed the strongest associations with diagnosis (SLE:healthy control effect size 0.11 [P = 0.003]; SLE:RA effect size 0.17 [P < 0.001]), plasmablast numbers in rituximab-treated patients (R = 0.38, P = 0.047), and BILAG 2004. These associations were equivalent to or stronger than those for IFN score or monocyte tetherin. Memory B cell tetherin was found to be predictive of future clinical flares in the validation cohort (hazard ratio 2.29 [95% confidence interval 1.01-4.64]; P = 0.022)., Conclusion: Our findings indicate that memory B cell surface tetherin, a B cell-specific IFN assay, is associated with SLE diagnosis and disease activity, and predicts flares better than tetherin on other cell subsets or whole blood assays, as determined in an independent validation cohort., (© 2019 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

We report an interesting case of hepatitis C virus-negative type II cryoglobulinaemic vasculitis (CV) in a patient with a background history of systemic lupus erythematosus. The type II CV became less responsive to traditional treatments over time and culminated in an intensive care unit admission with critical multiorgan failure. A detailed flow cytometric evaluation of the bone marrow proved to be helpful in treatment. It demonstrated that bortezomib was a viable alternative treatment option for the type II CV. The patient received bortezomib and has made a full and durable recovery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate clinical, interferon and imaging predictors of progression from 'At Risk' to autoimmune connective tissue diseases (AI-CTDs)., Methods: A prospective observational study was conducted in At-Risk of AI-CTD (defined as antinuclear antibody (ANA) positive; ≤1 clinical systemic lupus erythematosus (SLE) criterion; symptom duration <12 months and treatment-naïve). Bloods and skin biopsy (non-lesional) were analysed for two interferon-stimulated gene expression scores previously described (IFN-Score-A and IFN-Score-B). Forty-nine healthy controls (HCs) and 114 SLE were used as negative and positive controls. Musculoskeletal ultrasound was performed. Progression was defined by meeting classification criteria for AI-CTDs at 12 months., Results: 118 individuals with 12-month follow-up were included. Of these, 19/118 (16%) progressed to AI-CTD (SLE=14, primary Sjogren's=5). At baseline, both IFN scores differed among At-Risk, HCs and SLE groups (p<0.001) and both were elevated in At-Risk who progressed to AI-CTD at 12 months versus non-progressors, to a greater extent for IFN-Score-B (fold difference (95% CI) 3.22 (1.74 to 5.95), p<0.001) than IFN-Score-A (2.94 (1.14 to 7.54); p=0.018). Progressors did not have significantly greater baseline clinical characteristics or ultrasound findings. Fold difference between At-Risk and HCs for IFN-Score-A was markedly greater in skin than blood. In multivariable logistic regression, only family history of autoimmune rheumatic disease, OR 8.2 (95% CI 1.58 to 42.53) and IFN-Score-B, 3.79 (1.50-9.58) increased the odds of progression., Conclusion: A two-factor interferon score and family history predict progression from ANA positivity to AI-CTD. These interferon scores may allow stratification of individuals At-Risk of AI-CTD permitting early intervention for disease prevention and avoid irreversible organ damage., Competing Interests: Competing interests: EMV is an NIHR Clinician Scientist. He has received honoraria and research grant support from Roche, GSK and AstraZeneca. PE has received consultant fees from BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB. He has received research grants paid to his employer from Abbott, BMS, Pfizer, MSD and Roche. MW has received honoraria for educational activity and consultancy from Novartis, Janssen, Abbvie and Cellgene. ASZ has received honoraria from Roche/Chugai, BMS, Biogen and Menarini., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The international literature advocates for cancer screening in newly diagnosed patients with autoimmune myositis; however, there is no widely accepted consensus or guideline to outline the optimal cancer screening strategy and the evidence is currently insufficient to support any recommendation., Aim: Our study aimed to establish the current trends in practice in malignancy screening in autoimmune myositis among Australian rheumatologists., Methods: All rheumatologists who were full members of the Australian Rheumatology Association in 2016 (386) were invited to complete an online questionnaire. Respondent demographics and information on screening approach and concerns were collected using multiple choice and open-response questions. There were 60 respondents (16% response rate). All available quantitative data were analysed and reported using statistical software. Qualitative data were analysed and grouped according to themes., Results: Most respondents (93%) performed cancer screening. Significant variation was found in terms of approach to patient selection, choice of screening test, delegation of screening and repeat screening. A lack of clinical practice consensus and guideline (77%), test selection knowledge (37%), knowledge on repeated screening (53%) and the potential for harm (62%) were identified challenges in this area., Conclusion: Malignancy screening in autoimmune myositis was variable among this small cohort of Australian rheumatologists. The observed differences were driven by patient factors and clinician preferences. The group identified several challenges in the cancer screening process. Further research is warranted to address these challenges, close the evidence gap and develop workable guidelines., (© 2017 Royal Australasian College of Physicians.)

It is well established that the autoantibodies that characterize both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are present systemically years before patients develop disease. In both these autoimmune rheumatic diseases, evidence is growing that local autoimmune processes occur at epithelial surfaces potentially initiating localized autoimmunity. For RA, these are mucosal surfaces including the oral mucosa, lung, and gut. At the oral mucosa and lung, risk factors such as periodontal disease and smoking may contribute to autoimmunity by driving the local generation of citrullinated autoantigens. For SLE, the skin may be integral in pathogenesis. It is proposed that defective clearance of apoptotic debris leads to initial innate immune responses preceding autoimmunity. Many tissues may be implicated but the frequency of skin disease, even without autoantibodies, and the role of UV light as a trigger suggest that keratinocytes may be a key site of initiation. In both diseases, a local break in immune tolerance could lead to systemic autoimmunity, and, in the gut, bacterial organisms that colonize the intestine may influence the localized gut immune response through T-cells and promote the development of systemic autoimmunity. In this review, we discuss the evidence for localized epithelial autoimmunity in those at risk of RA and SLE and early disease. Localized autoimmunity at the oral mucosa, lung, gut, and skin will be considered as potential initiating sites of ARD-related autoimmunity.

I was one of more than 40 nursing students who travelled to Berlin in June for a five-day trip focusing on the health and care of refugees and asylum seekers - an area I previously knew little about.

A well-established literature has identified different selective attentional orienting mechanisms underlying anxiety-related attentional bias, such as engagement and disengagement of attention. These mechanisms are thought to contribute to the onset and maintenance of anxiety disorders. However, conclusions to date have relied heavily on experimental work from subclinical samples. We therefore investigated individuals with diagnosed generalized anxiety disorder (GAD), healthy volunteers, and individuals with high trait anxiety (but not meeting GAD diagnostic criteria). Across two experiments we found faster disengagement from negative (angry and fearful) faces in GAD groups, an effect opposite to that expected on the basis of the subclinical literature. Together these data challenge current assumptions that we can generalize, to those with GAD, the pattern of selective attentional orienting to threat found in subclinical groups. We suggest a decisive two-stage experiment identifying stimuli of primary salience in GAD, then using these to reexamine orienting mechanisms across groups.

Adaptive behavior relies on the ability to effectively and efficiently ignore irrelevant information, an important component of attentional control. The current research found that fundamental difficulties in ignoring irrelevant material are related to dispositional differences in trait propensity to worry, suggesting a core deficit in attentional control in high worriers. The degree of deficit in attentional control correlated with the degree of difficulty in suppressing negative thought intrusions in a worry assessment task. A cognitive training procedure utilizing a flanker task was used in an attempt to improve attentional control. Although the cognitive training was largely ineffective, improvements in attentional control were associated with improvements in the ability to suppress worry-related thought intrusions. Across two studies, the findings indicate that the inability to control worry-related negative thought intrusions is associated with a general deficiency in attentional control.