The impact of gastroesophageal reflux disease and its treatment on interstitial lung disease outcomes.

BACKGROUND: To determine the relationship between gastroesophageal reflux disease (GORD) and its treatment and interstitial lung disease in patients with systemic sclerosis (SSc). METHODS: SSc patients from the Australian Scleroderma Cohort Study (ASCS) were included. GORD was defined as self-reported GORD symptoms, therapy with a proton pump inhibitor (PPI) or histamine 2 receptor antagonist (H2RA) and/or the presence of reflux oesophagitis diagnosed endoscopically. The impact of GORD and its treatment on ILD features (including severity and time to ILD development) and survival was evaluated. RESULTS: GORD was a common manifestation affecting 1539/1632 (94%) of SSc patients. GORD affected 450/469 (96%) of those with SSc-ILD cohort. In SSc-ILD, there was no relationship between the presence of GORD or its treatment and time to ILD development or ILD severity. However, GORD treatment was associated with improved survival in those with ILD (p = 0.002). Combination therapy with both a PPI and a H2RA was associated with a greater survival benefit than single agent therapy with PPI alone (HR 0.3 vs 0.5 p < 0.050 respectively). CONCLUSION: GORD is a common SSc disease manifestation. While the presence or treatment of GORD does not influence the development or severity of ILD, aggressive GORD treatment, in particular with a combination of PPI and H2RA, is associated with improved survival in those with SSc-ILD.

Anti-Ro52/TRIM21 is independently associated with pulmonary arterial hypertension and mortality in a cohort of systemic sclerosis patients.

Objective: We undertook a comprehensive cross-sectional analysis of a multicentred Australian cohort of systemic sclerosis (SSc) patients to evaluate the associations of anti-Ro52/TRIM21 with SSc pulmonary involvement.Method: The study included 596 patients from the Australian Scleroderma Cohort Study database whose anti-Ro52/TRIM21 status was known. Anti-Ro52/TRIM21 was measured via line immunoassay. Data on demographic variables, autoantibody profiles, presence of interstitial lung disease (ILD), presence of pulmonary arterial hypertension (PAH), oxygen saturation, Six-Minute Walk Test distance, Borg dyspnoea score, and lung function tests were extracted. SPSS software was used to examine associations using univariate and multivariate analyses.Results: Anti-Ro52/TRIM21 was present in 34.4% of SSc patients. In the cross-sectional analysis, anti-Ro52/TRIM21 was independently associated with PAH [odds ratio 1.75, 95% confidence interval (CI) 1.05-2.90], but not ILD or other surrogate measures of pulmonary involvement such as average patient oxygen saturation. The antibody, however, was also associated with a higher forced vital capacity/diffusing capacity of the lung for carbon monoxide ratio. Prospectively, anti-Ro52/TRIM21 was also associated with an increased risk of death in patients with SSc (hazard ratio 1.62, 95% CI 1.11-2.35), independent of confounding factors. The primary cause of death appeared to be related to PAH and/or ILD, and anti-Ro52/TRIM21 was associated with PAH-related complications.Conclusion: Anti-Ro52/TRIM21 was independently associated with PAH and mortality in SSc patients. Future longitudinal studies are recommended to investigate the timing and pathogenic mechanisms of this autoantibody in PAH.

Management of inflammatory neurologic and psychiatric manifestations of systemic lupus erythematosus: A systematic review.

BACKGROUND: The neurological and psychiatric manifestations of systemic lupus erythematosus (NPSLE) are a heterogeneous group of conditions with variable clinical presentation and significant morbidity and mortality. OBJECTIVES: Our aim was to comprehensively assess and present the evidence for treatments used in the management of inflammatory NPSLE. METHODS: Medline, Embase, CINHAL and Cochrane CENTRAL were searched from 1990 to end of March 2019 using key words that related to NPSLE and treatment. Included studies comprised clinical trials, observational studies or case series with ≥5 patients and sufficient data related to treatment and outcome in NPSLE patients. RESULTS: There were 7222 studies identified in the search, of which 90 were included in the review. There was a notable paucity of clinical trials, with only two randomised controlled trials and one pilot study. Treatment categories included corticosteroids (14 studies), cyclophosphamide (18 studies), synthetic DMARDs (7 studies), biologic therapies (14 studies), therapeutic plasma exchange (6 studies), intravenous immunoglobulin (2 studies), autologous stem cell transplant (3 studies), other therapies (8 studies), combination therapies (6 studies), studies with grouped outcome data (5 studies) and observational studies with therapy-specific associations (7 studies). Corticosteroids are accepted as first line treatment in NPSLE and there is low-moderate evidence supporting their benefit. Moderate evidence, based on consistent data in numerous studies and some trial data, supports the use of cyclophosphamide in the treatment of NPSLE. Limited data support some synthetic DMARDs such as mycophenolate, azathioprine and intrathecal methotrexate. In refractory disease, low-moderate evidence supports rituximab therapy and limited evidence supports benefit following autologous stem cell transplant. Regarding adjuvant treatments, limited evidence favours addition of plasma exchange, intravenous immunoglobulin and hydroxychloroquine. There exists very limited data for other therapies. CONCLUSION: There are multiple therapeutic options for the management of inflammatory NPSLE including systemic, biologic and interventional therapies; however, currently there is a paucity of high-quality trial data to guide firm recommendations. In order to better understand the optimal treatment of NPSLE and its different subtypes, further well-designed clinical trials are needed.

Management of cutaneous manifestations of lupus erythematosus: A systematic review.

BACKGROUND: Cutaneous lupus erythematosus (CLE), occurring with or without systemic lupus erythematosus (SLE), is a group of inflammatory skin diseases that can be very debilitating, causing significant psychological distress, and sometimes scarring. OBJECTIVES: We sought to comprehensively present the evidence for different treatment modalities in patients with cutaneous manifestations of lupus erythematosus (LE). METHODS: Medline, Embase, Scopus and Cochrane CENTRAL were searched electronically from 1990 to March 2019, using keywords related to cutaneous lupus and synonyms and treatment. Articles retrieved were screened for relevance, including reference lists of retrieved reviews. We included clinical trials, observational studies or case series with ≥5 patients focussing on treatment of CLE, with or without SLE. RESULTS: The search identified 6637 studies, of which 107 were included. Each study commonly included a heterogeneous mixture of CLE subtypes, with or without SLE. The 107 included studies investigated 11 different categories of treatment in 7343 patients. Treatments included topical calcineurin inhibitors (13 studies), sun protection (5 studies), R-salbutamol cream (2 studies), antimalarials (22 studies), synthetic DMARDs (10 studies), retinoids (2 studies), thalidomide/lenalidomide (22 studies), biologic therapies (15 studies), intravenous immune globulin (3 studies), laser (6 studies) and other therapies (7 studies). General measures to be considered include smoking cessation, sun protection measures and optimisation of vitamin D levels. Moderate evidence exists for benefit with topical CNIs, particularly as a steroid sparing agent in areas at high risk of steroid complications (e.g. facial skin). There is moderate evidence for hydroxychloroquine, which is first-line in SLE patients, limited evidence to support other synthetic DMARDs, and moderate evidence supporting thalidomide but with significant risk of toxicity. Of biologic therapies, there are moderate data to support belimumab. Limited evidence exists for other therapies. CONCLUSION: Many management options are available for CLE, including topical, systemic and biologic therapies, with a variable balance of efficacy and toxicity. There is a paucity of high-quality clinical trial data. Further trials are required to better understand optimal management of CLE, particularly in specific subgroups.

Longitudinal associations of active renal disease with irreversible organ damage accrual in systemic lupus erythematosus.

OBJECTIVE: To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate <50%/proteinuria >3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. RESULTS: Patients (N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p < 0.02). Active lupus nephritis was strongly associated with damage accrual in renal but not in non-renal organ domains (hazard ratios = 13.0 (95% CI: 6.58, 25.5) p < 0.001 and 0.96 (95% CI: 0.69, 1.32) p = 0.8, respectively). There was no effect of ethnicity on renal damage accrual, but Asian ethnicity was significantly associated with reduced non-renal damage accrual. CONCLUSION: Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated with renal, but not non-renal, damage accrual in SLE.

Damage indices in rheumatic diseases: A systematic review of the literature.

OBJECTIVE: To review the current literature, and evaluate the psychometric properties of disease damage indices in rheumatic diseases. METHODS: A search of Medline, EMBASE, and Cochrane Library databases was performed to June 2018 to identify damage indices in all systemic rheumatic diseases. Articles were included in a systematic review if indices were composite (multi-organ) in nature and if adequate detail on methodology was described. Articles pertaining to the validation of these indices were also reviewed in order to assess the psychometric properties of the indices using the Outcome Measures in Rheumatology Arthritis Clinical Trials (OMERACT) filter as a guide. RESULTS: Of the 2659 articles retrieved through the search, we identified 7 damage indices in five diseases: idiopathic inflammatory myopathy, systemic lupus erythematosus, systemic vasculitis, SjÓ§gren's syndrome and antiphospholipid syndrome. A further 48 articles were identified pertaining to the validation of these damage indices. The methodological process for the development of these indices included expert consensus, item reduction and item weighting methods. The level of validation that these indices have achieved is variable, with only 2 damage indices fulfilling all criteria of the OMERACT filter. CONCLUSIONS: To date, there have been 7 composite disease damage indices created in a variety of rheumatic diseases, with the exception of systemic sclerosis (SSc). This review has informed methodology for the development of a disease damage index in SSc.

Longitudinal association of type 1 interferon-induced chemokines with disease activity in systemic lupus erythematosus.

Type I interferon (IFN) pathways are significant in SLE pathogenesis. Less is known about the utility of measuring markers of IFN activity in patients, or whether patient subsets with different profiles exist. We explored the longitudinal associations of IFN-induced chemokines with disease activity in a cohort of SLE patients. We calculated a validated composite score (IFN-CK) of three type I IFN-inducible chemokines (CCL2/CXCL10/CCL19) measured in 109 SLE patients (median 7 occasions over 3.2 years). Longitudinal associations of IFN-CK score with disease activity (SLEDAI-2K) and other variables were assessed using general estimating equation (GEE) methods. IFN-CK was detectable in all patients. SLEDAI-2K was significantly associated with IFN-CK, damage score and prednisolone dose. SLEDAI-2K remained significantly associated with IFN-CK over time after adjustment of covariates. Patients with high time-adjusted mean IFN-CK had lower complement and higher time-adjusted disease activity. Concordance between IFN-CK and SLEDAI-2K varied widely among patients, with some individuals having none, others weak, and a subset very high concordance. In summary in our cohort of SLE patients, serum IFN-CK varied over time with disease activity, but with wide variation in concordance. Differing relationships between IFN pathway activation and disease activity may be valuable in assigning patients to emerging IFN-pathway targeting treatments.

Single-specificity anti-Ku antibodies in an international cohort of 2140 systemic sclerosis subjects: clinical associations.

Autoantibodies directed against the Ku autoantigen are present in systemic sclerosis (SSc) and have been associated with myositis overlap and interstitial lung disease (ILD). However, there is a paucity of data on the clinical correlates of anti-Ku antibodies in the absence of other SSc-specific antibodies. The aim of this study was to assess the clinical correlates of single-specificity anti-Ku in SSc.An international (Canada, Australia, USA, Mexico) cohort of 2140 SSc subjects was formed, demographic and clinical variables were harmonized, and sera were tested for anti-Ku using a line immunoassay. Associations between single-specificity anti-Ku antibodies (i.e., in isolation of other SSc-specific antibodies) and outcomes of interest, including myositis, ILD, and survival, were investigated.Twenty-four (1.1%) subjects had antibodies against Ku, and 13 (0.6%) had single-specificity anti-Ku antibodies. Subjects with single-specificity anti-Ku antibodies were more likely to have ILD (58% vs 34%), and to have increased creatine kinase levels (>3× normal) at baseline (11% vs 1%) and during follow-up (10% vs 2%). No difference in survival was noted in subjects with and without single-specificity anti-Ku antibodies.This is the largest cohort to date focusing on the prevalence and disease characteristics of single-specificity anti-Ku antibodies in subjects with SSc. These results need to be interpreted with caution in light of the small sample. International collaboration is key to understanding the clinical correlates of uncommon serological profiles in SSc.

The Impact of Turmeric Cream on Healing of Caesarean Scar.

OBJECTIVE: The aim of this study was to assess the impact of turmeric cream on the healing of Caesarean wound. METHODS: This study was done as a randomized double blind trial in three groups on women who had a Caesarean operation. The redness, oedema, ecchymosis, drainage, approximation (REEDA) scale was used to evaluate the wound healing process. The χ², analysis of variance (ANOVA) and Tukey tests were used for statistical analysis. RESULTS: Seven days after the surgery, the averages of REEDA score in the intervention, placebo and control groups were respectively, 0.46, 0.88, and 1.17 (p < 0.001), while on day 14, it was 0.03, 0.22 and 0.36 (p < 0.001), showing a significant statistical difference. Similarly, there was a difference between the intervention and placebo groups in the amount of oedema on the 7th and 14th days after the surgery (respectively, p = 0.066 and p < 0.001). The observed difference between the intervention and control groups in the amount of oedema was statistically significant on the 7th and 14th days after the surgery (p < 0.001). CONCLUSION: Turmeric was effective in faster healing of wounds of Caesarean operation. The use of turmeric is suggested to reduce the complications of the wounds from Caesarean section.

The Effectiveness of Prenatal Intervention on Pain and Anxiety during the Process of Childbirth-Northern Iran: Clinical Trial Study.

BACKGROUND: Due to the painful nature of childbirth and its maternal and neonatal complications, the woman needs support in this phase of their life. Increased knowledge and skills during pregnancy prepares pregnant mothers for labor and leads to promoted health. AIM: This study was designed to evaluate the effectiveness of "prenatal education" on the process of childbirth. SUBJECTS AND METHODS: This clinical trial was conducted on 195 pregnant women, that is, control group (N = 132) and case group (N = 63) attending health centers in Amol-Iran from 20 weeks of gestation age during 2012. Case group members attended in "prenatal education" class and the control group only received routine care. Data were collected through demographic questionnaire, standard hospital anxiety questionnaire, and a checklist related to childbirth information, and intensity of pain based on visual analogue scale and McGill scales. The data were analyzed by Statistical Package for the Social Sciences software using t-test and Chi-square test. RESULTS: The result of this study showed that the parent with a high level of education was more interested to participant in prenatal classes. The anxiety level in case group (who received education) was 14.47 (4.69) and in control group it was 16 (4.86), (P < 0.001) the pain intensity in case group was 85.68 (1.85) and in control group was 90.99 (14.72) (P = 0.03), intervention on labor such episiotomy was 39 %66.1 (39/63) in case group and 80 %72.8 (80/132) in control group (P = 0.01) and cesarean section was 13 %17.1 (13/63) in case group and 58 %32.2 (58/132) in control group (P = 0.01). CONCLUSIONS: According to findings of this study, the prenatal education and psychological support are beneficial for mothers during pregnancy and labor. Therefore, it is recommended for educating all the pregnant women.

Intravenous cyclophosphamide as a therapeutic option for severe refractory gastric antral vascular ectasia in systemic sclerosis.

Gastric antral vascular ectasia (GAVE) is a rare but important cause of upper gastrointestinal bleeding. It is commonly associated with autoimmune conditions such as systemic sclerosis, and standard treatment involves both supportive measures, as well as endoscopic interventional therapies. While the current therapies are effective for most patients, a few patients develop severe and refractory bleeding. Herein we report two cases of refractory GAVE in patients with diffuse scleroderma, which improved significantly after the administration of intravenous cyclophosphamide. One of these cases is, to our knowledge, the first reported case of cyclophosphamide being used specifically for the treatment of refractory GAVE.

Cost savings with a new screening algorithm for pulmonary arterial hypertension in systemic sclerosis.

BACKGROUND: Screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) is now standard care in this disease. The existing Australian Scleroderma Interest Group algorithm (ASIGSTANDARD ) is based on transthoracic echocardiography (TTE) and pulmonary function tests (PFT). Recently, ASIG has derived and validated a new screening algorithm (ASIGPROPOSED ) that incorporates N-terminal pro-B-type natriuretic peptide level together with PFT in order to decrease reliance on TTE, which has some limitations. Right heart catheterisation (RHC) remains the gold standard for the diagnosis of PAH in patients who screen 'positive'. AIM: To compare the cost of PAH screening in SSc with ASIGSTANDARD and ASIGPROPOSED algorithms. METHODS: We applied both ASIGSTANDARD and ASIGPROPOSED algorithms to 643 screen-naïve SSc patients from the Australian Scleroderma Cohort Study (ASCS), assuming a PAH prevalence of 10%. We compared the costs of screening, the number of TTE required and both the total number of RHC required and the number of RHC needed to diagnose one case of PAH, and costs, according to each algorithm. We then extrapolated the costs to the estimated total Australian SSc population. RESULTS: In screen-naïve patients from the ASCS, ASIGPROPOSED resulted in 64% fewer TTE and 10% fewer RHC compared with ASIGSTANDARD , with $1936 (15%) saved for each case of PAH diagnosed. When the costs were extrapolated to the entire Australian SSc population, there was an estimated screening cost saving of $946 000 per annum with ASIGPROPOSED , with a cost saving of $851 400 in each subsequent year of screening. CONCLUSIONS: ASIGPROPOSED substantially reduces the number of TTE and RHC required and results in substantial cost savings in SSc-PAH screening compared with ASIGSTANDARD .

Interpretation of an Extended Autoantibody Profile in a Well-Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis.

OBJECTIVE: To determine the relationships between systemic sclerosis (SSc)-related autoantibodies, as well as their clinical associations, in a well-characterized Australian patient cohort. METHODS: Serum from 505 Australian SSc patients were analyzed with a commercial line immunoassay (EuroLine; Euroimmun) for autoantibodies to centromere proteins CENP-A and CENP-B, RNA polymerase III (RNAP III; epitopes 11 and 155), the 90-kd nucleolar protein NOR-90, fibrillarin, Th/To, PM/Scl-75, PM/Scl-100, Ku, topoisomerase I (topo I), tripartite motif-containing protein 21/Ro 52, and platelet-derived growth factor receptor. Patient subgroups were identified by hierarchical clustering of the first 2 dimensions of a principal components analysis of quantitative autoantibody scores. Results were compared with detailed clinical data. RESULTS: A total of 449 of the 505 patients were positive for at least 1 autoantibody by immunoblotting. Heatmap visualization of autoantibody scores, along with principal components analysis clustering, demonstrated strong, mutually exclusive relationships between CENP, RNAP III, and topo I. Five patient clusters were identified: CENP, RNAP III strong, RNAP III weak, topo I, and other. Clinical features associated with CENP, RNAP III, and topo I were consistent with previously published reports concerning limited cutaneous and diffuse cutaneous SSc. A novel finding was the statistical separation of RNAP III into 2 clusters. Patients in the RNAP III strong cluster had an increased risk of gastric antral vascular ectasia, but a lower risk of esophageal dysmotility. Patients in the other cluster were more likely to be male and to have a history of smoking and a history of malignancy, but were less likely to have telangiectasia, Raynaud's phenomenon, and joint contractures. CONCLUSION: Five major autoantibody clusters with specific clinical and serologic associations were identified in Australian SSc patients. Subclassification and disease stratification using autoantibodies may have clinical utility, particularly in early disease.

Association of low vitamin D with high disease activity in an Australian systemic lupus erythematosus cohort.

BACKGROUND: Vitamin D status varies with geographic location and no studies of vitamin D in systemic lupus erythematosus (SLE) have been reported in the Southern Hemisphere. OBJECTIVES: To assess the prevalence of vitamin D deficiency in an Australian SLE cohort, and its relationship with disease activity. METHODS: Data were collected prospectively on 119 consecutive patients with SLE in the Monash Lupus Clinic in Melbourne, Australia, between January 2007 and January 2013. Patients had simultaneous serum 25-hydroxyvitamin D concentration and disease activity (SLEDAI-2K) recorded. Statistical methods were used to determine the correlation of serum vitamin D level and disease activity both at baseline and at a subsequent time point. Adjustments were made for the use of glucocorticoids, immunosuppressants and vitamin D supplementation. RESULTS: Vitamin D deficiency (<40 nmol/L) was detected in 27.7% of patients at baseline. Multiple regression analysis showed a significant inverse correlation of SLEDAI-2K with baseline vitamin D level and with vitamin D supplementation. Over a 12-month period of observation, among the 119 patients, there were 464 serial vitamin D measurements with corresponding SLEDAI-2K, representing 266 time intervals. The median change in vitamin D level was an increase of 25 nmol/L and this corresponded with a decline in SLEDAI-2K of 2 units. In regression analysis, there was a significant association between low vitamin D at a prior time point and a rise in SLEDAI-2K at the subsequent time point (univariable OR 3.3, 95% CI 1.5 to 7.7, p=0.005) or having a high disease activity (SLEDAI-2k>10) at the subsequent time point (univariable OR 3.1, 95% CI 1.4 to 6.8, p=0.004). CONCLUSIONS: In Australian patients with SLE, low vitamin D was associated with a higher disease activity and an increase in serum vitamin D was associated with reduced disease activity over time. The therapeutic effect of vitamin D in SLE should be further assessed in interventional studies.

Prospects for improving outcomes in systemic sclerosis-related pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a leading cause of morbidity and mortality in patients with systemic sclerosis (SSc). Approximately one in 10 will develop PAH during their lifetime. These patients have a worse prognosis than those with PAH due to other causes. The most common clinical feature of SSc-PAH in the early stages is non-specific exercise intolerance that can be erroneously attributed to other manifestations of SSc. Screening provides an opportunity for early identification of SSc-PAH and prompt initiation of therapies with the potential to improve quality of life and survival. International guidelines recommend annual transthoracic Doppler echocardiography (TTE), but TTE has limitations. The tricuspid regurgitant jet required for estimating the systolic pulmonary artery pressure is absent in up to 39% of patients, including a proportion with PAH. This has prompted a move to new screening algorithms that are less dependent on TTE. Not all pulmonary hypertension (PH) in patients with SSc is PAH. Other causes include PH secondary to left heart disease, interstitial lung disease-related PH, chronic thromboembolic PH and pulmonary veno-occlusive disease. With the advent of evidence-based therapies, including newer agents such as macitentan, riociguat and selexipag, the establishment of centres with expertise in PAH and the focus on early detection, there has been considerable improvement in survival. The role of anti-coagulation for SSc-PAH has been the subject of a recent meta-analysis of nine observational studies that suggests it may confer a survival benefit, but to date, there have been no randomised controlled trials to confirm this.

Shb deficiency in endothelium but not in leucocytes is responsible for impaired vascular performance during hindlimb ischaemia.

AIM: Myeloid cells have been suggested to participate in angiogenesis and regulation of vascular function. Shb-deficient mice display both vascular and myeloid cell abnormalities with possible consequences for recovery after hindlimb ischaemia. This study was conducted in order to assess the contribution of Shb deficiency in myeloid cells to impaired vascular function in ischaemia. METHODS: Wild type and Shb-deficient mice were subjected to peritoneal vascular endothelial growth factor A (VEGFA) followed by intraperitoneal lavage, after which blood and peritoneal cells were stained for myeloid markers. VEGFA-induced leucocyte recruitment to cremaster muscle was investigated using intravital microscopy of both mouse strains. Blood flow after femoral artery ligation was determined on chimeric mice after bone marrow transplantation. RESULTS: No differences in neutrophil numbers or cell surface phenotypes were detected. Moreover, neutrophil extravasation in VEGFA-activated cremaster muscle was unaffected by Shb deficiency. However, blood and peritoneal CXCR4+ monocytes/macrophages were reduced in response to intraperitoneal VEGFA but not lipopolysaccharide (LPS) in the absence of Shb. Furthermore, the macrophage population in ischaemic muscle was unaffected by Shb deficiency after 2 days but reduced 7 days after injury. The bone marrow transplantation experiments revealed that mice with wild type vasculature showed better blood flow than those with Shb-deficient vasculature irrespective of leucocyte genotype. CONCLUSION: The observed aberrations in myeloid cell properties in Shb-deficient mice are likely consequences of an abnormal vascular compartment and are not responsible for reduced muscle blood flow. Structural vascular abnormalities seem to be the primary cause of poor vascular performance under provoked vascular stress in this genetic model.

A systematic review of prevalence, disease characteristics and management of systemic lupus erythematosus in Australia: identifying areas of unmet need.

BACKGROUND: Few epidemiological studies of systemic lupus erythematosus (SLE) have been conducted in Australia, and current management practice and levels of unmet need in this country are not well characterised. AIM: To perform a systematic literature review to identify Australia-specific information on SLE, particularly areas of unmet need. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched (1 January 1990 to 29 November 2013). All articles on prevalence, disease characteristics, management and outcomes of SLE in Australia were included. RESULTS: There is limited published information on SLE in Australia. Of 24 articles included, 18 described results from observational studies, three were narrative reviews, one was a clinical update, and two were medical education articles. In remote regions, SLE was reported to be more prevalent in Aboriginal Australians than non-Aboriginal Australians; information in urban populations is lacking. Asian Australians may be more affected by SLE than non-Asian Australians. Pregnancy outcomes may also be adversely affected. Many Australians with SLE may experience high levels of unmet need, including delayed diagnosis, ongoing symptoms, flares, depression/anxiety, sleeping difficulty and decreased quality of life. Published guidance on the SLE management in Australia is limited and dated. CONCLUSIONS: Published information on SLE in Australia is limited, but suggests that ethnicity may affect the prevalence and disease characteristics and that many Australians with SLE have unmet needs. Improvements in diagnosis, treatment and management are needed to alleviate these needs. Up-to-date guidance on the management of SLE would benefit healthcare professionals and patients.

A prospective study of acute inpatient gout diagnoses and management in a tertiary hospital: the determinants and outcome of a rheumatology consultation.

BACKGROUND: Despite acute gout frequently complicating hospital admissions, diagnosis and management are variable. Rheumatology input may improve patient outcomes. AIM: To examine acute episodes of inpatient gout in a tertiary hospital to determine (i) factors that may lead to rheumatology input being sought and (ii) the differences in outcomes when rheumatology input occurs. METHODS: Data collection occurred between February and October 2012 for inpatients in a tertiary Australian hospital. Data were prospectively collected for all rheumatology consultations with a diagnosis of gout. Subjects who had an inpatient admission complicated by acute gout and who did not have rheumatology input were identified through health information coding from discharge summaries. RESULTS: Fifty-eight patients (41% with rheumatology input) were included in the study. Rheumatology input was significantly more likely when the patient was younger (68.9 years vs 78.4 years; P = 0.04) with knee joint involvement (41.7% vs 3.0%; P < 0.001). When rheumatology input occurred, subjects were more likely to have had a serum urate measured (83% vs 50%; P = 0.009), joint aspiration performed (54.2% vs 0%; P < 0.001), been prescribed acute gout medications at discharge (95.8% vs 61.3%; P = 0.001), a documented discharge plan (91.7% vs 23.5%; P < 0.001) and outpatient follow up (41.7% vs 0%; P < 0.001). CONCLUSION: Among inpatients with acute gout, rheumatology input was more likely to be sought in younger patients with knee joint disease. When rheumatology input occurred, patients were more likely to have a synovial fluid confirmed diagnosis of gout with appropriate acute management and a follow-up plan.

The association of antiphospholipid antibodies with cardiopulmonary manifestations of systemic sclerosis.

OBJECTIVES: To determine the prevalence and correlates of antiphospholipid antibodies (APLA) in systemic sclerosis (SSc). METHODS: Nine hundred and forty SSc patients were tested for APLA using an ELISA assay at recruitment. Clinical manifestations were defined as present, if ever present from SSc diagnosis. Logistic regression analysis was used to determine the associations of APLA. RESULTS: One or more types of APLA were present in 226 (24.0%) patients. Anticardiolipin (ACA) IgG (ACA-IgG) antibodies were associated with right heart catheter-diagnosed pulmonary arterial hypertension (PAH), with higher titres corresponding with a higher likelihood of PAH (moderate titre (20-39 U/ml) ACA-IgG odds ratio [OR] 1.70, 95% CI: 1.01-2.93, p=0.047; high titre (>40 U/ml) ACA-IgG OR 4.60, 95% CI:1.02-20.8, p=0.047). Both ACA-IgM (OR 2.04, 95% CI: 1.4-3.0, p<0.0001) and ACA-IgG (OR 1.84, 95% CI: 1.2-2.8, p=0.005) were associated with interstitial lung disease (ILD). Increasing ACA-IgM and IgG titres were associated with increased likelihood of ILD. ACA-IgG was a marker of coexistent pulmonary hypertension and ILD (ILD-PH) (OR 2.10, 95% CI: 1.1-4.2, p=0.036). We also found an association between ACA-IgG and digital ulcers (OR 1.76, 95% CI: 1.16-2.67, p=0.008) and ACA-IgM and Raynaud's phenomenon (OR 2.39, 95% CI: 1.08-5.27, p=0.031). There was no association between APLA and SSc disease subtype, peak skin score, presence of other autoantibodies, mortality or other disease manifestations. CONCLUSIONS: The association of APLA with PAH, ILD, ILD-PH, Raynaud's phenomenon and digital ulcers suggests that endothelial abnormalities and small vessel thrombosis may be important in the pathogenesis of these disease features.