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Objective: To describe the frequency of progressive pulmonary fibrosis (PPF) in an incident cohort of systemic sclerosis (SSc)-related interstitial lung disease (ILD) and its impact on survival., Methods: Incident ILD was defined as the new development of characteristic fibrotic changes on chest HRCT scan. PPF was defined as per the 2022 American Thoracic Society. Determinants of PPF were identified using generalised estimating equations. Impact on survival was analysed using accelerated failure time regression modelling., Results: Of our incident SSc-ILD cases, 38.8% (n = 180) experienced PPF within a 12-month period after ILD diagnosis. Determinants of PPF included older age (OR 1.02, 95%CI 1.00-1.03, P = 0.011), dcSSc (OR 1.54, 95% CI 1.06-2.25, P = 0.024) and SSc-specific antibodies (anticentomere antibody OR 0.51, 95%CI 0.29-0.91, P = 0.021 and anti-Scl-70 antibody OR 1.46, 95%CI 1.01-2.09, P = 0.043). Raised CRP was numerically associated with PPF but did not reach statistical significance (OR 1.29, 95%CI 0.99-1.68, P = 0.064) nor did GORD or dysphagia (OR 1.18, 95%CI 0.57-2.42, P = 0.658 and OR 1.17, 95%CI 0.57-2.40, P = 0.664, respectively). The presence of PPF significantly impacted survival in SSc-ILD (hazard ratio 2.66, 95%CI 1.59-4.41, P < 0.001)., Conclusions: PPF occurred in a third of our incident SSc-ILD cohort; however, its occurrence was significantly associated with mortality indicating an at-risk group who may be suitable for earlier introduction of immunosuppressive and/or antifibrotic therapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To determine long-term (20 year) survival in RA patients enrolled in the Australian Rheumatology Association Database (ARAD)., Methods: ARAD patients with RA and data linkage consent who were diagnosed from 1995 onwards were included. Death data were obtained through linkage to the Australian National Death Index. Results were compared with age-, gender- and calendar year-matched Australian population mortality rates. Analysis included both the standardized mortality ratio (SMR) and relative survival models. Restricted mean survival time (RMST) at 20 years was calculated as a measure of life lost. Cause-specific SMRs (CS-SMRs) were estimated for International Classification of Diseases, Tenth Revision cause of death classifications., Results: A total of 1895 RA patients were included; 74% were female, baseline median age 50 years (interquartile range 41-58), with 204 deaths. There was no increase in mortality over the first 10 years of follow up, but at 20 years the SMR was 1.49 (95% CI 1.30, 1.71) and the relative survival was 94% (95% CI 91, 97). The difference between observed (18.41 years) and expected (18.68 years) RMST was 4 months. Respiratory conditions were an important underlying cause of death in RA, primarily attributable to pneumonia [CS-SMR 5.2 (95% CI 2.3, 10.3)] and interstitial lung disease [CS-SMR 7.6 (95% CI 3.0, 14.7)], however, coronary heart disease [CS-SMR 0.82 (95% CI 0.42, 1.4)] and neoplasms [CS-SMR 1.2 (95% CI 0.89, 1.5)] were not., Conclusion: Mortality risk in this RA cohort accrues over time and is moderately increased at 20 years of follow-up. Respiratory diseases may have supplanted cardiovascular diseases as a major contributor to this mortality gap., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: Jaw symptoms can be a vital clue to the diagnosis of GCA. Guidelines recommend more intensive treatment if jaw claudication is present. We sought to explore how patients with GCA described their jaw symptoms., Methods: We carried out a secondary, qualitative analysis of interview data from 36 participants from the UK ( n  = 25) and Australia ( n  = 11), originally collected in order to develop a patient-reported outcome measure for GCA. In all cases, GCA had been confirmed by biopsy/imaging. Interview transcripts were organized within QSR NVivo 12 software and analysed using template analysis. Themes were refined through discussion among the research team, including a patient partner., Results: Twenty of 36 participants reported jaw symptoms associated with GCA. The median age of these 20 participants was 76.5 years; 60% were female. Five themes were identified: physical sensations; impact on function; impact on diet; symptom response with CSs; and attribution to other causes. Physical sensations included ache, cramp, stiffness and 'lockjaw'. Functional impacts included difficulty in eating/chewing, cleaning teeth, speaking or opening the mouth. Dietary impacts included switching to softer food. Response to CSs was not always immediate. Jaw symptoms were initially mis-attributed by some participants to arthritis, age or viral illnesses; or by health-care professionals to a dental cavity, ear infection or teeth-grinding., Conclusion: Jaw symptoms in GCA are diverse and can lead to diagnostic confusion with primary temporomandibular joint disorder, potentially contributing to delay in GCA diagnosis. Further research is needed to determine the relationship of jaw stiffness to jaw claudication., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: People with rheumatic diseases are frequent, long-term attenders of health-care services. Their care experiences are central to improving services. The aim of this study was to explore real-world experiences and priorities of people attending outpatient rheumatology care and those of health-care professionals (HCPs) providing care., Methods: This qualitative study consisted of five semi-structured focus groups. Participants included rheumatology outpatients ( n  = 16) of two tertiary teaching hospitals and HCPs ( n  = 14; rheumatologists, rheumatology trainees, physiotherapists, a specialty nurse and a pharmacist). Participants explored priorities when attending outpatient services, real experiences and aspirations for improving future care. Transcripts were coded using inductive and deductive thematic analysis., Results: Seven key themes were identified: smooth flow of technical processes, care coordination, individualized care, information sharing, clinical excellence, patient empowerment and comprehensive care. The findings were aligned conceptually with quality standards in Australia and worldwide. Different sub-themes and prioritization of concerns emerged from patient and HCP subgroups. Highly prioritized themes for patients pertained to processes and technical aspects of care. HCPs focused on themes relating to non-technical aspects of service provision: information sharing, individualization of care, patient advocacy and empowerment., Conclusion: This study captured valuable insights into the current experience of outpatient rheumatology care from the perspective of patients and HCPs. It informs a collective understanding of differing and shared priorities, positives of current care and areas requiring change. Themes derived from the study data can be conceptualized in terms of the process, content and impact of care. Such domains can be measured longitudinally by routine implementation of validated patient-reported experience measures in rheumatology., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: There is increasing evidence for the involvement of vascular disease in the pathogenesis of knee OA. Popliteal artery wall thickness can be used as a surrogate marker of atherosclerosis. We examined the association between popliteal artery wall thickness and knee cartilage volume in individuals with symptomatic knee OA., Methods: This prospective cohort study analysed 176 participants from a randomized placebo-controlled trial examining the effect of atorvastatin on structural progression in knee OA. The participants underwent MRI of the study knee at baseline and 2-year follow-up. Popliteal artery wall thickness and tibial cartilage volume were measured from MRI using validated methods. The top quartile of the rate of tibial cartilage volume loss was defined as rapid progression., Results: At baseline, every 10% increase in popliteal artery wall thickness was associated with 120.8 mm3 (95% CI 5.4, 236.2, P = 0.04) lower of medial tibial cartilage volume and 151.9 mm3 (95% CI 12.1, 291.7, P = 0.03) lower of lateral tibial cartilage volume. Longitudinally, for every 10% increase in popliteal artery wall thickness, the annual rate of medial tibial cartilage volume loss was increased by 1.14% (95% CI 0.09%, 2.20%, P = 0.03), and there was a 2.28-fold (95% CI 1.07, 4.83, P = 0.03) risk of rapid progression of medial tibial cartilage loss, adjusted for age, sex, BMI, tibial bone area, smoking, vigorous physical activity, and intervention group allocation., Conclusion: The findings support a role for vascular pathology in the progression of knee OA. Targeting atherosclerosis has the potential to improve outcomes in knee OA., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To determine COVID-19 vaccine hesitancy rates in inflammatory arthritis patients and identify factors associated with changing vaccine hesitancy over time., Methods: This investigation was a prospective cohort study of inflammatory arthritis patients from community and public hospital outpatient rheumatology clinics enrolled in the Australian Rheumatology Association Database (ARAD). Two surveys were conducted, one immediately prior to (pre-pandemic) and another approximately 1 year after the start of the pandemic (follow-up). Coronavirus disease 2019 (COVID-19) vaccine hesitancy was measured at follow-up, and general vaccine hesitancy was inferred pre-pandemic; these were used to identify factors associated with fixed and changing vaccine beliefs, including sources of information and broader beliefs about medication., Results: Of the 594 participants who completed both surveys, 74 (12%) were COVID-19 vaccine hesitant. This was associated with pre-pandemic beliefs about medications being harmful (P < 0.001) and overused (P = 0.002), with stronger beliefs resulting in vaccine hesitancy persistent over two time points (P = 0.008, P = 0.005). For those not vaccine hesitant pre-pandemic, the development of COVID-19 vaccine hesitancy was associated with a lower likelihood of seeking out vaccine information from health-care professionals (P < 0.001). COVID-19 vaccine hesitancy was not associated with new influenza vaccine hesitancy (P = 0.138)., Conclusion: In this study of vaccine beliefs before and during the COVID-19 pandemic, factors associated with COVID-19 vaccine hesitancy in inflammatory arthritis patients varied, depending on vaccine attitudes immediately prior to the start of the pandemic. Fixed beliefs reflected broader views about medications, while fluid beliefs were highly influenced by whether they sought out information from health-care professionals, including rheumatologists., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study aimed to explore gender equity in rheumatology leadership in the Asia-Pacific region as represented by the member national organizations (MNOs) of the Asia-Pacific League of Associations for Rheumatology (APLAR)., Methods: We conducted a retrospective cross-sectional review of gender representation among the presidents of MNOs of APLAR in April 2022. We used the official website of each organization to acquire names and terms in the office of current and past presidents of each organization. The binary gender of each president was estimated using the name-to-gender inference platform Gender API (https://gender-api.com/). Proportions of male and female presidents were estimated for each organization. Data were compared for presidencies commencing before and in/after the year 2000., Results: We found a significant gap in gender parity, with most presidents in the region being men (210 of 252, 83%). More than one-third (7 of 19, 36.8%) of the MNOs had all male presidents, although the proportion of women improved from 7 to 25% in/after 2000 ( P  = 0.0002). A statistically significant increase in female representation was observed in Australia ( P  = 0.0268, from 7 to 39%) and New Zealand ( P  = 0.0011, where the proportion of female presidents increased from 0 to 45%), but not in other countries., Conclusion: A significant gap in gender parity exists in rheumatology leadership in the MNOs of APLAR. Trends suggest improvement over the last two decades, although statistically significant improvement is limited to a small number of countries., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: The impact of the US Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock: Management Bundle (SEP-1) core measure on overall antibacterial utilization is unknown., Methods: We performed a retrospective multicenter longitudinal cohort study with interrupted time-series analysis to determine the impact of SEP-1 implementation on antibacterial utilization and patient outcomes. All adult patients admitted to 26 hospitals between 1 October 2014 and 30 September 2015 (SEP-1 preparation period) and between 1 November 2015 and 31 October 2016 (SEP-1 implementation period) were evaluated for inclusion. The primary outcome was total antibacterial utilization, measured as days of therapy (DOT) per 1000 patient-days., Results: The study cohort included 701 055 eligible patient admissions and 4.2 million patient-days. Overall antibacterial utilization increased 2% each month during SEP-1 preparation (relative rate [RR], 1.02 per month [95% confidence interval {CI}, 1.00-1.04]; P = .02). Cumulatively, the mean monthly DOT per 1000 patient-days increased 24.4% (95% CI, 18.0%-38.8%) over the entire study period (October 2014-October 2016). The rate of sepsis diagnosis/1000 patients increased 2% each month during SEP-1 preparation (RR, 1.02 per month [95% CI, 1.00-1.04]; P = .04). The rate of all-cause mortality rate per 1000 patients decreased during the study period (RR for SEP-1 preparation, 0.95 [95% CI, .92-.98; P = .001]; RR for SEP-1 implementation, .98 [.97-1.00; P = .01]). Cumulatively, the monthly mean all-cause mortality rate/1000 patients declined 38.5% (95% CI, 25.9%-48.0%) over the study period., Conclusions: Announcement and implementation of the CMS SEP-1 process measure was associated with increased diagnosis of sepsis and antibacterial utilization and decreased mortality rate among hospitalized patients., Competing Interests: Potential conflicts of interest. D. J. A reports receiving additional grant funding from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Agency for Healthcare Research and Quality for grants unrelated to this study and receiving royalties for authorship from UpToDate Online. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: We compared survival and causes of death in Western Australian (WA) ANCA-associated vasculitis (AAV) and PAN patients with controls and the WA population., Methods: In this data linkage study, we identified patients with incident AAV/PAN and age, sex and temporally matched controls 1980-2014 from the WA Rheumatic Disease Epidemiological Registry. Survival analyses and time-varying analyses were performed., Results: Six hundred and fourteen patients with incident AAV/PAN were compared with 6672 controls; 229 AAV/PAN patients died over 5277 person-years of follow-up and 1009 controls died over 73835 person-years. Survival was reduced in patients with AAV/PAN compared with matched controls [hazard ratio (HR) 3.5 (95% CI: 3.1, 4.1)], and matched WA population rates [standardized mortality ratio 3.3 (95% CI: 2.9, 3.8)]. Greatest excess mortality in AAV/PAN patients was observed in the first year after diagnosis and remained higher than controls throughout follow-up. Greater excess mortality was observed in patients >60 years at diagnosis. In cause-specific analyses, mortality HR for vasculitis, infection and non-infective respiratory disease were greatest early after diagnosis and remained persistently elevated. The HRs for malignancy and cerebrovascular disease related deaths increased during follow-up, and were constant for ischaemic heart disease related deaths., Conclusion: Mortality was increased in AAV/PAN patients compared with controls, with patients older at diagnosis at greater risk. These findings provide mortality risk for AAV/PAN in an Australian population, highlighting key contributors to mortality at different time periods over follow-up and potential areas of focus for reducing mortality., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Chronic lung disease has been attributed to stem cell aging and/or exhaustion. We investigated these mechanisms using mouse and human tracheobronchial tissue-specific stem cells (TSC). In mouse, chromatin labeling and flow cytometry demonstrated that naphthalene (NA) injury activated a subset of TSC. These activated TSC continued to proliferate after the epithelium was repaired and a clone study demonstrated that ~96% of activated TSC underwent terminal differentiation. Despite TSC attrition, epithelial repair after a second NA injury was normal. The second injury accelerated proliferation of previously activated TSC and a nucleotide-label retention study indicated that the second injury recruited TSC that were quiescent during the first injury. These mouse studies indicate that (a) injury causes selective activation of the TSC pool; (b) activated TSC are predisposed to further proliferation; and (c) the activated state leads to terminal differentiation. In human TSC, repeated proliferation also led to terminal differentiation and depleted the TSC pool. A clone study identified long- and short-lived TSC and showed that short-lived TSC clones had significantly shorter telomeres than their long-lived counterparts. The TSC pool was significantly depleted in dyskeratosis congenita donors, who harbor mutations in telomere biology genes. The remaining TSC had short telomeres and short lifespans. Collectively, the mouse and human studies support a model in which epithelial injury increases the biological age of the responding TSC. When applied to chronic lung disease, this model suggests that repeated injury accelerates the biological aging process resulting in abnormal repair and disease initiation., (© 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Objectives: There is a growing acceptance of the need for routine implementation of patient-reported experience measures (PREMs) in health care. Rheumatology patients, as frequent and long-term users of care, stand to benefit from collection of experience-related data. The aim of this study was to perform a systematic review to identify and critically appraise the development and psychometric validation of PREMs in rheumatology., Methods: Six databases were searched systematically from inception to 14 December 2020: MEDLINE, EMBASE, PsycINFO, SCOPUS, Cochrane and Google Scholar. We included articles in English that described the use or development of PREMs, with results of psychometric testing, in an adult outpatient rheumatology context. This study is registered with PROSPERO (CRD42021233819). Articles were appraised using the COnsensus Based Standards for the selection of health status Measurement Instruments (COSMIN) (i) Risk of Bias checklist and (ii) criteria for good measurement properties., Results: The search yielded 3809 publications, and six studies met inclusion criteria. All the included studies on PREM development fulfilled COSMIN standards for 'doubtful' or 'inadequate' quality of instrument development. One study fulfilled a 'sufficient' rating for content validity, and the remainder fulfilled 'inconsistent' ratings. During validity testing, studies fulfilled between one and four of the eight COSMIN checklist criteria for good measurement properties., Conclusion: Methodological concerns regarding instrument development and validation limit the generalizability of the existing six validated PREMs in use in rheumatology contexts. There is a need for further well-designed studies to validate existing and new PREMs in this area., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To quantify the burden of interstitial lung disease (ILD) in SSc., Methods: Clinical data for SSc patients enrolled in the Australian Scleroderma Cohort Study were linked with healthcare databases for the period 2008-2015. ILD was defined by characteristic fibrotic changes on high-resolution CT (HRCT) lung, while severity was defined by the extent lung involvement on HRCT (mild <10%, moderate 10-30%, severe >30%). Determinants of healthcare cost were estimated using logistic regression., Results: SSc-ILD patients utilized more healthcare resources, including hospitalization, emergency department presentation and ambulatory care services, than those without ILD with a total cost per patient of AUD$48 368 (26 230-93 615) vs AUD$33 657 (15 144-66 905), P<0.001) between 2008-2015. Healthcare utilization was associated with an annual median (25th-75th) excess cost per SSc-ILD patient compared with those without ILD of AUD$1192 (807-1212), P<0.001. Increasing ILD severity was associated with significantly more healthcare utilization and costs with an annual excess cost per patient with severe ILD compared with mild ILD of AUD$2321 (645-1846), P<0.001. ILD severity and the presence of coexistent PAH were the main determinants of overall healthcare cost above median for this SSc-ILD cohort (OR 5.1, P<0.001, and OR 2.6, P=0.01, respectively). Furthermore, SSc-ILD patients reported worse physical HRQoL compared with those without ILD [34.3 (10.5) vs 39.1 (10.8), P<0.001], with a progressive decline with increasing ILD severity (P=0.002)., Conclusion: SSc-ILD places a large burden on the healthcare system and the patient through poor HRQoL in addition to incremental healthcare resource utilization and associated direct cost., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The human airway epithelium is regenerated by basal cells. Thus, basal cell therapy has the potential to cure cystic fibrosis (CF) lung disease. We previously reported that the human basal cells repopulated the mouse airway epithelium after transplantation, and we estimated that 60 million cells would be needed to treat a human patient. To further develop cell therapy, we compared the proliferation potential of non-CF and CF tissue-derived bronchial basal cells. Three methods were used: regenerative cell frequency, burst size, and cell division frequency. Second, we used a serial passage strategy to determine if CF basal cells could be amplified to the estimated therapeutic dose. These studies evaluated that tissue-derived bronchial basal cells and the basal cells that were recovered by brushing bronchial airways or the nasal respiratory epithelium. Finally, we used the limiting dilution method to isolate non-CF and CF basal cell clones. The proliferation assays and the air-liquid-interface differentiation method were used to determine if cell amplification altered the proliferation and/or differentiation potential of clonal isolates. We demonstrate that: (a) non-CF and CF basal cell proliferation is similar, (b) CF basal cells can be amplified to a therapeutic cell dose, and (c) amplified non-CF and CF basal cell clones differentiate normally. Despite these encouraging findings, we also find that the cell amplification process depletes the regenerative basal cell pool. Analysis of basal cell clones indicates that serial passage selects for long-lived basal cells and raise the possibility that prospective isolation of these stem-like cells will improve the efficacy of cell replacement therapy. Stem Cells Translational Medicine 2019;8:225&235., (© 2018 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

The wingless/integrase-1 (WNT)/β-catenin signaling pathway is active in several chronic lung diseases including idiopathic pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease. Although this WNT/β-catenin pathway activity is associated with an increase in mucus cell frequency and a decrease in ciliated cell frequency, a cause and consequence relationship between signaling and cell frequency has not been established. We previously demonstrated that genetic stabilization of β-catenin inhibited differentiation of mouse bronchiolar tissue stem cells (TSC). This study determined the effect of β-catenin and its co-factors P300 (E1A-binding protein, 300 kDa) and cAMP response element binding (CREB)-binding protein (CBP) on human bronchial epithelial TSC differentiation to mucus and ciliated cells. We developed a modified air-liquid interface (ALI) culture system in which mucus and ciliated cell frequency is similar. These cultures were treated with the β-catenin agonist CHIR99021 (CHIR) and antagonists to β-catenin (XAV939), P300 (IQ1), and CBP (ICG001). We report that human TSC differentiation to mucus and ciliated cells can be divided into two stages, specification and commitment. CHIR treatment inhibited mucus and ciliated cell commitment while XAV939 treatment demonstrated that β-catenin was necessary for mucus and ciliated cell specification. Additional studies demonstrate that a β-catenin/P300 complex promotes mucus cell specification and that β-catenin interacts with either P300 or CBP to inhibit ciliated cell commitment. These data indicate that activation of β-catenin-dependent signaling in chronic lung disease leads to changes in mucus and ciliated cell frequency and that P300 and CBP tune the β-catenin signal to favor mucus cell differentiation. Stem Cells 2018;36:1905-12., (©AlphaMed Press 2018.)

Background: Shoulder pain is a common problem that can impact on work. Leisure time physical activity (LTPA) has the potential to reduce the impact of shoulder pain through its physiological, psychological and social benefits., Aims: To determine whether LTPA reduces the prevalence of shoulder pain in a working population., Methods: Participants were selected from a longitudinal population-based cohort study, the North West Adelaide Health Study. Information was gathered by questionnaire on LTPA, smoking, depression and socio-economic factors. Body mass index was measured in a clinic setting. Occupational physical activity (OPA) estimated by job title and shoulder pain was measured using the Shoulder Pain and Disability Index. Workers with and without shoulder pain were compared using logistic regression analysis., Results: Of the 1502 working participants, 16% reported having current shoulder pain. Shoulder pain was associated with older age (OR 1.98, 95% CI: 1.31-2.99) (age >50 years), smoking (OR 1.44, CI: 1.02-2.04), secondary-level educational attainment (OR 1.68, 95% CI: 1.07-2.65), high body mass index (BMI) (OR 1.54, 95% CI: 1.14-2.08) and depression (OR 2.42, 95% CI: 1.60-3.64). There was no effect of LTPA on shoulder pain., Conclusions: In this community-based cohort, there was no statistically significant association seen between LTPA, OPA and shoulder pain. There was, however, an association between smoking, BMI, secondary-level education, depression and shoulder pain. These modifiable factors may be better targets for preventive efforts than LTPA to reduce the risk of shoulder pain.

Objective: Results of previous studies investigating the association between GCA and malignancy are conflicting. We performed a study of the risk of cancer in patients with biopsy-proven GCA., Methods: Patients with biopsy-proven GCA were identified from pathology reports of temporal artery biopsies from the major pathology laboratories in South Australia (SA). All subjects with biopsy-proven GCA were linked to the SA Cancer Registry to identify cases of cancer until 31 December 2006. Standardized incidence ratios (SIRs) for cancer were determined using the age- and gender-specific rates for SA., Results: There were 226 cases of biopsy-proven GCA (163 females and 63 males). Thirty-one cases were diagnosed with cancer, following the diagnosis of biopsy-proven GCA. There was no increased risk of cancer among those with biopsy-proven GCA, following the diagnosis of GCA compared with the general population (SIR 1.2; 95% CI 0.8, 1.6)., Conclusion: This cohort study did not demonstrate any increased risk for malignancy in subjects with biopsy-proven GCA.

Nonluteal ovarian tissue extracts were tested for their ability to stimulate migration and proliferation of cultured bovine capillary endothelial cells. Stimulation of migratory and proliferative activity was found in the 105,000 X g supernatant of homogenates of either whole nonluteal porcine ovaries or isolated theca (follicular walls). Maximal proliferative and migratory activity was obtained with 1-10 micrograms homogenate protein. Neither follicular fluid nor extracts of granulosa cells showed significant activity when tested over a broad concentration range. The proliferative and migratory activities were associated with a heat-labile, nondialyzable, protease-sensitive fraction that was soluble in 40%, but not 60% (NH4)2SO4. The tissue extracts that effectively stimulated growth and migration of capillary endothelial cells in vitro also stimulated the formation of new capillary blood vessels in an angiogenesis assay performed on chick chorioallantoic membranes.