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  1. Article ; Online: Systemic lupus erythematosus.

    Hoi, Alberta / Igel, Talia / Mok, Chi Chiu / Arnaud, Laurent

    Lancet (London, England)

    2024  

    Abstract: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterised by the presence of autoantibodies towards nuclear antigens, immune complex deposition, and chronic inflammation at classic target organs such as skin, joints, and ... ...

    Abstract Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterised by the presence of autoantibodies towards nuclear antigens, immune complex deposition, and chronic inflammation at classic target organs such as skin, joints, and kidneys. Despite substantial advances in the diagnosis and management of SLE, the burden of disease remains high. It is important to appreciate the typical presentations and the diagnostic process to facilitate early referral and diagnosis for patients. In most patients, constitutional, mucocutaneous, and musculoskeletal symptoms represent the earliest complaints; these symptoms can include fatigue, lupus-specific rash, mouth ulcers, alopecia, joint pain, and myalgia. In this Seminar we will discuss a diagnostic approach to symptoms in light of the latest classification criteria, which include a systematic evaluation of clinical manifestations (weighted within each domain) and autoantibody profiles (such as anti-double-stranded DNA, anti-Sm, hypocomplementaemia, or antiphospholipid antibodies). Non-pharmacotherapy management is tailored to the individual, with specific lifestyle interventions and patient education to improve quality of life and medication (such as hydroxychloroquine or immunosuppressant) adherence. In the last decade, there have been a few major breakthroughs in approved treatments for SLE and lupus nephritis, such as belimumab, anifrolumab, and voclosporin. However the disease course remains variable and mortality unacceptably high. Access to these expensive medications has also been restricted across different regions of the world. Nonetheless, understanding of treatment goals and strategies has improved. We recognise that the main goal of treatment is the achievement of remission or low disease activity. Comorbidities due to both disease activity and treatment adverse effects, especially infections, osteoporosis, and cardiovascular disease, necessitate vigilant prevention and management strategies. Tailoring treatment options to achieve remission, while balancing treatment-related comorbidities, are priority areas of SLE management.
    Language English
    Publishing date 2024-04-17
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(24)00398-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Recent advances in understanding and managing gout.

    Igel, Talia F / Krasnokutsky, Svetlana / Pillinger, Michael H

    F1000Research

    2017  Volume 6, Page(s) 247

    Abstract: Gout is the most common crystal arthropathy and the leading cause of inflammatory arthritis. It is associated with functional impairment and, for many, a diminished health-related quality of life. Numerous studies have demonstrated the impact of gout and ...

    Abstract Gout is the most common crystal arthropathy and the leading cause of inflammatory arthritis. It is associated with functional impairment and, for many, a diminished health-related quality of life. Numerous studies have demonstrated the impact of gout and its associated conditions on patient morbidity and mortality. Unfortunately, gout remains under-diagnosed and under-treated in the general community. Despite major advances in treatment strategies, as many as 90% of patients with gout are poorly controlled or improperly managed and their hyperuricemia and recurrent flares continue. The introduction of novel urate-lowering therapies, new imaging modalities, and a deeper understanding of the pathogenesis of gout raise the possibility of better gout care and improved patient outcomes. Here, we spotlight recent advances in the diagnosis and management of gout and discuss novel therapeutics in gout treatment.
    Language English
    Publishing date 2017
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2699932-8
    ISSN 2046-1402
    ISSN 2046-1402
    DOI 10.12688/f1000research.9402.1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Initiating guideline-concordant gout treatment improves arterial endothelial function and reduces intercritical inflammation: a prospective observational study.

    Toprover, Michael / Shah, Binita / Oh, Cheongeun / Igel, Talia F / Romero, Aaron Garza / Pike, Virginia C / Curovic, Fatmira / Bang, Daisy / Lazaro, Deana / Krasnokutsky, Svetlana / Katz, Stuart D / Pillinger, Michael H

    Arthritis research & therapy

    2020  Volume 22, Issue 1, Page(s) 169

    Abstract: Background: Patients with gout have arterial dysfunction and systemic inflammation, even during intercritical episodes, which may be markers of future adverse cardiovascular outcomes. We conducted a prospective observational study to assess whether ... ...

    Abstract Background: Patients with gout have arterial dysfunction and systemic inflammation, even during intercritical episodes, which may be markers of future adverse cardiovascular outcomes. We conducted a prospective observational study to assess whether initiating guideline-concordant gout therapy with colchicine and a urate-lowering xanthine oxidase inhibitor (XOI) improves arterial function and reduces inflammation.
    Methods: Thirty-eight untreated gout patients meeting American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for gout and ACR guidelines for initiating urate-lowering therapy (ULT) received colchicine (0.6 mg twice daily, or once daily for tolerance) and an XOI (allopurinol or febuxostat) titrated to ACR guideline-defined serum urate (sU) target. Treatment was begun during intercritical periods. The initiation of colchicine and XOI was staggered to permit assessment of a potential independent effect of colchicine. Brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent (smooth muscle) arterial responsiveness, respectively. High-sensitivity C-reactive protein (hsCRP), IL-1β, IL-6, myeloperoxidase (MPO) concentrations, and erythrocyte sedimentation rate (ESR) assessed systemic inflammation.
    Results: Four weeks after achieving target sU concentration on colchicine plus an XOI, FMD was significantly improved (58% increase, p = 0.03). hsCRP, ESR, IL-1β, and IL-6 also all significantly improved (30%, 27%, 19.5%, and 18.8% decrease respectively; all p ≤ 0.03). Prior to addition of XOI, treatment with colchicine alone resulted in smaller numerical improvements in FMD, hsCRP, and ESR (20.7%, 8.9%, 13% reductions, respectively; all non-significant), but not IL-1β or IL-6. MPO and NMD did not change with therapy. We observed a moderate inverse correlation between hsCRP concentration and FMD responsiveness (R = - 0.41, p = 0.01). Subgroup analyses demonstrated improvement in FMD after achieving target sU concentration in patients without but not with established cardiovascular risk factors and comorbidities, particularly hypertension and hyperlipidemia.
    Conclusions: Initiating guideline-concordant gout treatment reduces intercritical systemic inflammation and improves endothelial-dependent arterial function, particularly in patients without established cardiovascular comorbidities.
    MeSH term(s) Allopurinol/therapeutic use ; Febuxostat/therapeutic use ; Gout/drug therapy ; Gout Suppressants/therapeutic use ; Humans ; Hyperuricemia/drug therapy ; Inflammation/drug therapy
    Chemical Substances Gout Suppressants ; Febuxostat (101V0R1N2E) ; Allopurinol (63CZ7GJN5I)
    Language English
    Publishing date 2020-07-11
    Publishing country England
    Document type Journal Article ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2107602-9
    ISSN 1478-6362 ; 1478-6354
    ISSN (online) 1478-6362
    ISSN 1478-6354
    DOI 10.1186/s13075-020-02260-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Impaired arterial responsiveness in untreated gout patients compared with healthy non-gout controls: association with serum urate and C-reactive protein.

    Krasnokutsky, Svetlana / Romero, Aaron Garza / Bang, Daisy / Pike, Virginia C / Shah, Binita / Igel, Talia F / Dektiarev, Irina / Guo, Yu / Zhong, Judy / Katz, Stuart D / Pillinger, Michael H

    Clinical rheumatology

    2018  Volume 37, Issue 7, Page(s) 1903–1911

    Abstract: To determine whether arterial responsiveness is impaired among patients with gout, and whether arterial responsiveness inversely correlates with serum urate and inflammatory measures. This is a cross-sectional study of untreated gout subjects (n = 34) ... ...

    Abstract To determine whether arterial responsiveness is impaired among patients with gout, and whether arterial responsiveness inversely correlates with serum urate and inflammatory measures. This is a cross-sectional study of untreated gout subjects (n = 34) and non-gout healthy controls (n = 64). High-resolution dynamic ultrasound-measured flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent arterial responsiveness respectively. Serum urate (sUA) and high-sensitivity C-reactive protein (hsCRP) were measured in the gout group, and correlated with FMD and NMD responses. Both FMD (2.20 ± 0.53 vs 3.56 ± 0.31, p = 0.021) and NMD (16.69 ± 1.54 vs 24.51 ± 0.90, p = 0.00002) were impaired in the gout versus control group. Stratification for individual comorbidities suggested that no single risk factor accounted for impaired FMD/NMD in the gout subjects. However, the degree of association between gout and FMD, but not NMD impairment, was dampened after multivariable adjustment (FMD unadjusted beta = - 1.36 (SE 0.58), p = 0.02; adjusted beta = - 1.16 (SE 0.78), p = 0.14 and NMD unadjusted beta = - 7.68 (SE 1.78), p < 0.0001; adjusted beta = - 5.33 (SE 2.46), p = 0.03). Within the gout group, there was an inverse correlation between FMD and sUA (R = - 0.5, p = 0.003), and between FMD and hsCRP (R = - 0.42, p = 0.017), but not between NMD and sUA or hsCRP. Compared with healthy controls, subjects with gout have reduced arterial function. Individual comorbidities are insufficient to account for differences between gout and control groups, but multiple comorbidities may collectively contribute to impairment in endothelium-dependent arterial responsiveness. Endothelial impairment is also related to sUA and hsCRP, markers of gout severity and inflammation respectively. Studies to determine whether gout therapy may improve arterial responsiveness are warranted.
    MeSH term(s) Adult ; Aged ; Brachial Artery ; C-Reactive Protein/analysis ; Case-Control Studies ; Cross-Sectional Studies ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/physiopathology ; Europe ; Gout/blood ; Gout/physiopathology ; Humans ; Male ; Middle Aged ; Nitroglycerin ; Prospective Studies ; Regional Blood Flow/drug effects ; Regional Blood Flow/physiology ; Uric Acid/blood ; Vasodilation/physiology ; Vasodilator Agents ; Young Adult
    Chemical Substances Vasodilator Agents ; Uric Acid (268B43MJ25) ; C-Reactive Protein (9007-41-4) ; Nitroglycerin (G59M7S0WS3)
    Language English
    Publishing date 2018-02-15
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 604755-5
    ISSN 1434-9949 ; 0770-3198
    ISSN (online) 1434-9949
    ISSN 0770-3198
    DOI 10.1007/s10067-018-4029-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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