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Objectives To characterise the prevalence and associations of metabolic syndrome (MetS) in a multiethnic cohort of patients with SLE. Methods Using a standardised protocol, baseline demographics, per visit disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K) and treatment data, and annual recording of organ damage accrual (Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC-ACR) Damage Index) were captured on patients with SLE from a single tertiary centre. The presence of MetS, defined using modified updated joint consensus criteria, was assessed at the final visit from patient records. Serum concentrations of adipocytokines were measured by Quantibody. Results 116 patients, with median (Q1, Q3) age at enrolment of 39.5 (31.4-51.1) years and disease duration of 6.1 (1.4-12) years, were followed for a median of 6.7 (4.1-8.1) years. The prevalence of MetS was 29% (34/116), while the prevalence of MetS components varied: hypertension (59%), low high-density lipoproteins (HDLs) (51%), hypertriglyceridaemia (32%), obesity (16%) and hyperglycaemia (22%). In univariable analysis, MetS was associated with baseline organ damage (OR 4.34; 95% CI 1.80 to 10.48; p<0.01) and organ damage accrual (OR 2.34; 95% CI 1.02 to 5.36; p=0.04) but not with disease activity. In multivariable analysis, baseline organ damage remained significantly associated with MetS (adjusted OR 3.36; 95% CI 1.32 to 8.59; p=0.01). Glucocorticoid use was not associated with MetS or any of its five components. High serum concentrations of resistin were significantly negatively associated with MetS (OR 0.17; 95% CI 0.04 to 0.70; p=0.014). Conclusion MetS was common in a multiethnic cohort of patients with SLE, with the most frequent components being hypertension and low HDL. An independent association was found between MetS and organ damage but not glucocorticoid exposure or disease activity.Copyright ©

Objectives To characterise the prevalence and associations of metabolic syndrome (MetS) in a multiethnic cohort of patients with SLE. Methods Using a standardised protocol, baseline demographics, per visit disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K) and treatment data, and annual recording of organ damage accrual (Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC-ACR) Damage Index) were captured on patients with SLE from a single tertiary centre. The presence of MetS, defined using modified updated joint consensus criteria, was assessed at the final visit from patient records. Serum concentrations of adipocytokines were measured by Quantibody. Results 116 patients, with median (Q1, Q3) age at enrolment of 39.5 (31.4-51.1) years and disease duration of 6.1 (1.4-12) years, were followed for a median of 6.7 (4.1-8.1) years. The prevalence of MetS was 29% (34/116), while the prevalence of MetS components varied: hypertension (59%), low high-density lipoproteins (HDLs) (51%), hypertriglyceridaemia (32%), obesity (16%) and hyperglycaemia (22%). In univariable analysis, MetS was associated with baseline organ damage (OR 4.34; 95% CI 1.80 to 10.48; p<0.01) and organ damage accrual (OR 2.34; 95% CI 1.02 to 5.36; p=0.04) but not with disease activity. In multivariable analysis, baseline organ damage remained significantly associated with MetS (adjusted OR 3.36; 95% CI 1.32 to 8.59; p=0.01). Glucocorticoid use was not associated with MetS or any of its five components. High serum concentrations of resistin were significantly negatively associated with MetS (OR 0.17; 95% CI 0.04 to 0.70; p=0.014). Conclusion MetS was common in a multiethnic cohort of patients with SLE, with the most frequent components being hypertension and low HDL. An independent association was found between MetS and organ damage but not glucocorticoid exposure or disease activity.Copyright ©

Objectives: To determine the presence and clinical associations of the soluble receptors of B cell-activating factor from the tumor necrosis factor family (BAFF) in serum of patients with systemic lupus erythematosus (SLE). Method(s): Serum BAFF and soluble BAFF receptor (sBAFF-R) were quantified using ELISA, and soluble B cell maturation antigen (sBCMA) and transmembrane activator and cyclophilin ligand interactor (sTACI) by Luminex, in 87 SLE patients and 17 healthy controls (HC). Disease activity and organ damage were assessed using SLE Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics (SLICC) SLE Damage Index (SDI), respectively. Result(s): BAFF and all receptors were detectable in all serum samples. Serum sBCMA and sTACI, but not sBAFF-R, were significantly higher in SLE than in HC. Serum BAFF was also increased in SLE, but this association was attenuated after adjusting for age and ethnicity. Increased serum BAFF was associated with flare and organ damage. Increased serum sBCMA was associated with the presence of anti-dsDNA, but not with overall or organ-specific disease activity, flare or organ damage. Neither sTACI nor sBAFF-R was associated with any SLE clinical parameters in multivariable analysis. While serum BAFF correlated negatively with sBAFF-R in HC, no statistically significant correlations were observed between BAFF and its receptors in SLE patients. Conclusion(s): Serum BAFF was associated with flare and organ damage independent of the presence of its soluble receptors. While sBCMA was associated with anti-dsDNA positivity, other soluble BAFF receptors were not associated with SLE clinical indicators.Copyright © 2019 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology Inc.

Bacterial infection a leading cause of death among patients with stroke, with elderly patients often presenting with more debilitating outcomes. The findings from our retrospective study, supported by previous clinical reports, showed that increasing age is an early predictor for developing fatal infectious complications after stroke. However, exactly how and why older individuals are more susceptible to infection after stroke remains unclear. Using a mouse model of transient ischaemic stroke, we demonstrate that older mice (>12 months) present with greater spontaneous bacterial lung infections compared to their younger counterparts (7-10 weeks) after stroke. Importantly, we provide evidence that older poststroke mice exhibited elevated intestinal inflammation and disruption in gut barriers critical in maintaining colonic integrity following stroke, including reduced expression of mucin and tight junction proteins. In addition, our data support the notion that the localized pro-inflammatory microenvironment driven by increased tumour necrosis factor-alpha production in the colon of older mice facilitates the translocation and dissemination of orally inoculated bacteria to the lung following stroke onset. Therefore, findings of this study demonstrate that exacerbated dysfunction of the intestinal barrier in advanced age promotes translocation of gut-derived bacteria and contributes to the increased risk to poststroke bacterial infection.Copyright © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Objectives: To determine the presence and clinical associations of the soluble receptors of B cell-activating factor from the tumor necrosis factor family (BAFF) in serum of patients with systemic lupus erythematosus (SLE). Method(s): Serum BAFF and soluble BAFF receptor (sBAFF-R) were quantified using ELISA, and soluble B cell maturation antigen (sBCMA) and transmembrane activator and cyclophilin ligand interactor (sTACI) by Luminex, in 87 SLE patients and 17 healthy controls (HC). Disease activity and organ damage were assessed using SLE Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics (SLICC) SLE Damage Index (SDI), respectively. Result(s): BAFF and all receptors were detectable in all serum samples. Serum sBCMA and sTACI, but not sBAFF-R, were significantly higher in SLE than in HC. Serum BAFF was also increased in SLE, but this association was attenuated after adjusting for age and ethnicity. Increased serum BAFF was associated with flare and organ damage. Increased serum sBCMA was associated with the presence of anti-dsDNA, but not with overall or organ-specific disease activity, flare or organ damage. Neither sTACI nor sBAFF-R was associated with any SLE clinical parameters in multivariable analysis. While serum BAFF correlated negatively with sBAFF-R in HC, no statistically significant correlations were observed between BAFF and its receptors in SLE patients. Conclusion(s): Serum BAFF was associated with flare and organ damage independent of the presence of its soluble receptors. While sBCMA was associated with anti-dsDNA positivity, other soluble BAFF receptors were not associated with SLE clinical indicators.Copyright © 2019 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology Inc.

Bacterial infection a leading cause of death among patients with stroke, with elderly patients often presenting with more debilitating outcomes. The findings from our retrospective study, supported by previous clinical reports, showed that increasing age is an early predictor for developing fatal infectious complications after stroke. However, exactly how and why older individuals are more susceptible to infection after stroke remains unclear. Using a mouse model of transient ischaemic stroke, we demonstrate that older mice (>12 months) present with greater spontaneous bacterial lung infections compared to their younger counterparts (7-10 weeks) after stroke. Importantly, we provide evidence that older poststroke mice exhibited elevated intestinal inflammation and disruption in gut barriers critical in maintaining colonic integrity following stroke, including reduced expression of mucin and tight junction proteins. In addition, our data support the notion that the localized pro-inflammatory microenvironment driven by increased tumour necrosis factor-alpha production in the colon of older mice facilitates the translocation and dissemination of orally inoculated bacteria to the lung following stroke onset. Therefore, findings of this study demonstrate that exacerbated dysfunction of the intestinal barrier in advanced age promotes translocation of gut-derived bacteria and contributes to the increased risk to poststroke bacterial infection.Copyright © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The primary objective of this review is to assess the feasibility and safety of discontinuing immunosuppressant or biologic drugs, administered alone or in combination, in patients with quiescent CD.Copyright © 2017 The Cochrane Collaboration.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The primary objective of this review is to assess the feasibility and safety of discontinuing immunosuppressant or biologic drugs, administered alone or in combination, in patients with quiescent CD.Copyright © 2017 The Cochrane Collaboration.

Aims Treating to low disease activity is routine in rheumatoid arthritis, but no comparable goal has been defined for systemic lupus erythematosus (SLE). We sought to define and validate a Lupus Low Disease Activity State (LLDAS). Methods A consensus definition of LLDAS was generated using Delphi and nominal group techniques. Criterion validity was determined by measuring the ability of LLDAS attainment, in a single-centre SLE cohort, to predict non-accrual of irreversible organ damage, measured using the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Results Consensus methodology led to the following definition of LLDAS: (1) SLE Disease Activity Index (SLEDAI)-2K <=4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0-3) <=1; (4) a current prednisolone (or equivalent) dose <=7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents. Achievement of LLDAS was determined in 191 patients followed for a mean of 3.9 years. Patients who spent greater than 50% of their observed time in LLDAS had significantly reduced organ damage accrual compared with patients who spent less than 50% of their time in LLDAS (p=0.0007) and were significantly less likely to have an increase in SDI of >=1 (relative risk 0.47, 95% CI 0.28 to 0.79, p=0.005). Conclusions A definition of LLDAS has been generated, and preliminary validation demonstrates its attainment to be associated with improved outcomes in SLE.Copyright © 2016 Published by the BMJ Publishing Group Limited.

Aims Treating to low disease activity is routine in rheumatoid arthritis, but no comparable goal has been defined for systemic lupus erythematosus (SLE). We sought to define and validate a Lupus Low Disease Activity State (LLDAS). Methods A consensus definition of LLDAS was generated using Delphi and nominal group techniques. Criterion validity was determined by measuring the ability of LLDAS attainment, in a single-centre SLE cohort, to predict non-accrual of irreversible organ damage, measured using the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Results Consensus methodology led to the following definition of LLDAS: (1) SLE Disease Activity Index (SLEDAI)-2K <=4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0-3) <=1; (4) a current prednisolone (or equivalent) dose <=7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents. Achievement of LLDAS was determined in 191 patients followed for a mean of 3.9 years. Patients who spent greater than 50% of their observed time in LLDAS had significantly reduced organ damage accrual compared with patients who spent less than 50% of their time in LLDAS (p=0.0007) and were significantly less likely to have an increase in SDI of >=1 (relative risk 0.47, 95% CI 0.28 to 0.79, p=0.005). Conclusions A definition of LLDAS has been generated, and preliminary validation demonstrates its attainment to be associated with improved outcomes in SLE.Copyright © 2016 Published by the BMJ Publishing Group Limited.

Quality issue: Omitting time-critical medications leads to delays in treatment and may result in patient harm. Initial assessment: Published studies show that omission of prescribed medication doses is common. Although most are inconsequential, up to 86% of omitted medications place patients at some risk of harm. Solution: Funding was obtained to develop a medication safety package to facilitate decreasing omitted dose incidents by audit, education and feedback. Implementation: A panel of nursing and pharmacy hospital staff in Victoria, Australia, reviewed existing audit tools and published studies to develop a critical medication list and audit tool. The tool, definitions and instructions were tested in 11 rural, urban and teaching hospitals. Qualitative feedback was sought to refine the tool using a Plan-Do-Study-Act model. An educational presentation was developed using reported incidents. Evaluation: Staff in 11 hospitals tested the audit tool in 321 patients receiving 17 361 doses of medication. Feedback indicated audit data were useful for informing improvements in practice and for accreditation. The educational material consists of the User Guide, plus a presentation for nursing staff illustrated by six cases with questions, with instructions on how to decrease harm from omitted doses by ensuring correct documentation and prioritising time-critical medications. Lessons learned: A medication safety package using standard definitions and a critical medication list was successfully tested. It is now used by nursing and pharmacy staff across the state. Several interstate hospitals are using the tools as part of their hospital medication safety programmes.Copyright © The Author 2014.

Quality issue: Omitting time-critical medications leads to delays in treatment and may result in patient harm. Initial assessment: Published studies show that omission of prescribed medication doses is common. Although most are inconsequential, up to 86% of omitted medications place patients at some risk of harm. Solution: Funding was obtained to develop a medication safety package to facilitate decreasing omitted dose incidents by audit, education and feedback. Implementation: A panel of nursing and pharmacy hospital staff in Victoria, Australia, reviewed existing audit tools and published studies to develop a critical medication list and audit tool. The tool, definitions and instructions were tested in 11 rural, urban and teaching hospitals. Qualitative feedback was sought to refine the tool using a Plan-Do-Study-Act model. An educational presentation was developed using reported incidents. Evaluation: Staff in 11 hospitals tested the audit tool in 321 patients receiving 17 361 doses of medication. Feedback indicated audit data were useful for informing improvements in practice and for accreditation. The educational material consists of the User Guide, plus a presentation for nursing staff illustrated by six cases with questions, with instructions on how to decrease harm from omitted doses by ensuring correct documentation and prioritising time-critical medications. Lessons learned: A medication safety package using standard definitions and a critical medication list was successfully tested. It is now used by nursing and pharmacy staff across the state. Several interstate hospitals are using the tools as part of their hospital medication safety programmes.Copyright © The Author 2014.

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease that has a relapsing and remitting course. It has a wide range of non-specific symptoms with various organ manifestations. In 1982, the American College of Rheumatology (ACR) published the revised criteria for the classification of SLE. The diagnosis of SLE may be made if four or more of the 11 ACR criteria are present, either serially or simultaneously, during any interval of observation. Whilst the diagnosis of SLE is based on clinical and laboratory features, with no universally accepted radiological diagnostic criteria, imaging is nonetheless useful for diagnosing specific organ manifestations, monitoring disease progression, and identifying complications secondary to immunosuppressive therapy. In this review, we describe the spectrum of radiological findings of SLE in various organ systems and compile a list of organ manifestations including the most frequently occurring diseases as well as the rare but not-to-be-missed diseases. This review aims to serve as a concise reference tool in an endeavour to assist clinicians and radiologists in the diagnosis and monitoring of this disease. This pictorial review presents the various radiological findings of CNS, cardiovascular and thoracic manifestation of SLE. The gastrointestinal, renal and musculoskeletal systems will be covered in part II. © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease that has a relapsing and remitting course. It has a wide range of non-specific symptoms with various organ manifestations. In 1982, the American College of Rheumatology (ACR) published the revised criteria for the classification of SLE. The diagnosis of SLE may be made if four or more of the 11 ACR criteria are present, either serially or simultaneously, during any interval of observation. Whilst the diagnosis of SLE is based on clinical and laboratory features, with no universally accepted radiological diagnostic criteria, imaging is nonetheless useful for diagnosing specific organ manifestations, monitoring disease progression, and identifying complications secondary to immunosuppressive therapy. In this review, we describe the spectrum of radiological findings of SLE in various organ systems and compile a list of organ manifestations including the most frequently occurring diseases as well as the rare but not-to-be-missed diseases. This review aims to serve as a concise reference tool in an endeavour to assist clinicians and radiologists in the diagnosis and monitoring of this disease. This pictorial review presents the various radiological findings of CNS, cardiovascular and thoracic manifestation of SLE. The gastrointestinal, renal and musculoskeletal systems will be covered in part II. © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

This article analyzes the current recommended practices and evidence in the immunization of pediatric ''special risk groups'. Special risk group patients are at higher risk of vaccine-preventable diseases and hence require additional strategies to maximize protection against these diseases. The special risk groups include those with an underlying chronic disease, some of whom are on immunosuppressive therapy to treat that condition. The article uses four special risk groups (acute lymphoblastic leukemia; preterm birth; juvenile idiopathic arthritis; and inflammatory bowel disease), to highlight the management considerations and potential vaccination strategies. The risks, benefits and timing of vaccination in the setting of immunosuppression require detailed discussion with treating clinicians, in particular the use of live-attenuated vaccines. The immunogenicity of vaccines in these special risk groups helps provide the evidence base for their immunization guidelines. Protection can include ''cocooning' (i.e., ensuring appropriate immunizations within the immediate family; e.g., varicella, influenza and pertussis vaccination). Improving timeliness and minimizing missed opportunities to vaccinate individuals with these special risk conditions will also optimize protection from vaccine-preventable diseases. © 2011 Expert Reviews Ltd.

This article analyzes the current recommended practices and evidence in the immunization of pediatric ''special risk groups'. Special risk group patients are at higher risk of vaccine-preventable diseases and hence require additional strategies to maximize protection against these diseases. The special risk groups include those with an underlying chronic disease, some of whom are on immunosuppressive therapy to treat that condition. The article uses four special risk groups (acute lymphoblastic leukemia; preterm birth; juvenile idiopathic arthritis; and inflammatory bowel disease), to highlight the management considerations and potential vaccination strategies. The risks, benefits and timing of vaccination in the setting of immunosuppression require detailed discussion with treating clinicians, in particular the use of live-attenuated vaccines. The immunogenicity of vaccines in these special risk groups helps provide the evidence base for their immunization guidelines. Protection can include ''cocooning' (i.e., ensuring appropriate immunizations within the immediate family; e.g., varicella, influenza and pertussis vaccination). Improving timeliness and minimizing missed opportunities to vaccinate individuals with these special risk conditions will also optimize protection from vaccine-preventable diseases. © 2011 Expert Reviews Ltd.