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BACKGROUND: Adverse pregnancy outcomes (APO) contribute to higher risk of maternal cerebrovascular disease, but longitudinal data that include APO and stroke timing are lacking. We hypothesized that APO are associated with younger age at first stroke, with a stronger relationship in those with >1 pregnancy with APO. METHODS: We analyzed longitudinal Finnish nationwide health registry data from the FinnGen Study. We included women who gave birth after 1969 when the hospital discharge registry was established. We defined APO as a pregnancy affected by gestational hypertension, preeclampsia, eclampsia, preterm birth, small for gestational age infant, or placental abruption. We defined stroke as first hospital admission for ischemic stroke or nontraumatic intracerebral or subarachnoid hemorrhage, excluding stroke during pregnancy or within 1 year postpartum. We used Kaplan-Meier survival curves and multivariable-adjusted Cox and generalized linear models to assess the relationship between APO and future stroke. RESULTS: We included 144 306 women with a total of 316 789 births in the analysis sample, of whom 17.9% had at least 1 pregnancy with an APO and 2.9% experienced an APO in ≥2 pregnancies. Women with APO had more comorbidities including obesity, hypertension, heart disease, and migraine. Median age at first stroke was 58.3 years in those with no APO, 54.8 years in those with 1 APO, and 51.6 years in those with recurrent APO. In models adjusted for sociodemographic characteristics and stroke risk factors, risk of stroke was greater in women with 1 APO (adjusted hazard ratio, 1.3 [95% CI, 1.2–1.4]) and recurrent APO (adjusted hazard ratio, 1.4 [95% CI, 1.2–1.7]) compared with those with no APO. Women with recurrent APO had more than twice the stroke risk before age 45 (adjusted odds ratio, 2.1 [95% CI, 1.5–3.1]) compared with those without APO. CONCLUSIONS: Women who experience APO have earlier onset of cerebrovascular disease, with the earliest onset in those with more than 1 affected pregnancy.

25 páginas, 6 figuras, 2 tablas, Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele., This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not

(68)Ga-citrate has one of the simplest chemical structures of all (68)Ga-radiopharmaceuticals, and its clinical use is justified by the proven medical applications using its isotope-labeled compound (67)Ga-citrate. To support broader application of (68)Ga-citrate in medical diagnosis, further research is needed to gain clinical data from healthy volunteers. In this work, we studied the biodistribution of (68)Ga-citrate and subsequent radiation exposure from it in healthy men. Methods: (68)Ga-citrate was prepared with an acetone-based radiolabeling procedure compliant with good manufacturing practices. Six healthy men (age 41 ± 12 y, mean ± SD) underwent sequential whole-body PET/CT scans after an injection of 204 ± 8 MBq of (68)Ga-citrate. Serial arterialized venous blood samples were collected during PET imaging, and the radioactivity concentration was measured with a γ-counter. Urinary voids were collected and measured. The MIRD bladder-voiding model with a 3.5-h voiding interval was used. A model using a 70-kg adult man and the MIRD schema was used to estimate absorbed doses in target organs and effective doses. Calculations were performed using OLINDA/EXM software, version 2.0. Results: Radioactivity clearance from the blood was slow, and relatively high radioactivity concentrations were observed over the whole of the 3-h measuring period. Although radioactivity excretion via urine was rather slow (biologic half-time, 69 ± 24 h), the highest decay-corrected concentrations in urinary bladder contents were measured at the 90- and 180-min time points. Moderate concentrations were also seen in kidneys, liver, and spleen. The source organs showing the largest residence times were muscle, liver, lung, and heart contents. The heart wall received the highest absorbed dose, 0.077 ± 0.008 mSv/MBq. The mean effective dose (International Commission on Radiological Protection publication 103) was 0.021 ± 0.001 mSv/MBq. Conclusion: PET imaging with (68)Ga-citrate is associated with modest radiation exposure. A 200-MBq injection of (68)Ga-citrate results in an effective radiation dose of 4.2 mSv, which is in the same range as other (68)Ga-labeled tracers. This suggests the feasibility of clinical studies using (68)Ga-citrate imaging in humans and the possibility of performing multiple scans in the same subjects across the course of a year.

Objective: The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks. Method: We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland. A rheumatologist reviewed the medical records to assess whether each patients’ diagnosis was correct. The diagnosis was compared with the diagnostic codes in the Finnish Care Register for Health Care (CRHC) and special reimbursement data of the Social Insurance Institution of Finland. Results: The positive predictive value (PPV) of CRHC diagnosis of RA (for seropositive and seronegative RA combined) was 0.82. For patients with a special reimbursement for anti-rheumatic medications for RA, the PPV was 0.89. The PPV was higher in patients with more than one visit. For one, two, five, and 10 visits, the PPV was 0.82, 0.85, 0.89, and 0.90, respectively, and for patients who also had the special reimbursement, the PPV was 0.89, 0.91, 0.93, and 0.94 for one, two, five, and 10 visits, respectively. In patients positive for anti-citrullinated protein antibodies, the PPV was 0.98. Conclusion: These results demonstrate that the validity of RA diagnoses in Finnish biobanks was good and can be further improved by including data on special reimbursement for medication, number of visits, and serological data. publishedVersion

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Objectives: In patients with axial spondyloarthritis (axSpA) initiating their first tumor necrosis factor alpha-inhibitor (TNFi), we aimed to identify common baseline predictors of Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) inactive disease (primary objective) and clinically important improvement (CII) at 6 months, and drug retention at 12-months across 15 European registries. Methods: Baseline demographic and clinical characteristics were collected. Outcomes were investigated per registry and in pooled data using logistic regression analyses on multiply imputed data. Results: The consistency of baseline predictors in individual registries justified pooling the data. In the pooled dataset (n = 21,196), the 6-month rates for ASDAS inactive disease and ASDAS CII were 26% and 51%, and the 12-month drug retention rate 65% in patients with available data (n = 9,845, n = 6,948 and n = 21,196, respectively). Nine common baseline predictors of ASDAS inactive disease, ASDAS CII and 12-month drug retention were identified, and the odds ratios (95%-confidence interval) for ASDAS inactive disease were: age, per year: 0.97 (0.97–0.98), men vs. women: 1.88 (1.60–2.22), current vs. non-smoking: 0.76 (0.63–0.91), HLA-B27 positive vs. negative: 1.51 (1.20–1.91), TNF start year 2015–2018 vs. 2009–2014: 1.24 (1.06–1.45), CRP>10 vs. ≤10 mg/l: 1.49 (1.25–1.77), one unit increase in health assessment questionnaire (HAQ): 0.77 (0.58–1.03), one-millimeter (mm) increase in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) fatigue and spinal pain: 0.99 (0.99–1.00) and 0.99 (0.99–1.99), respectively Conclusion: Common baseline predictors of treatment response and adherence to TNFi could be identified across data from 15 European registries, indicating that they may be universal across different axSpA populations.

Introduction The diagnosis of systemic vasculitis is a challenge because of the heterogeneity of clinical manifestations. The aim of this study is to analyze the diagnostic delay in systemic vasculitis, the total costs during the first year of care, and how the diagnostic delay affects the costs in a tertiary health care facility. Methods Patients with a new diagnosis of systemic vasculitis between 2010 and 2018 were identified from hospital records. The diagnostic delay and health care costs were evaluated during the diagnostic period and within 12 months after the first contact with tertiary health care. Vasculitis-related costs were recorded as true costs charged. A total of 317 patients fulfilled the study criteria. The diagnoses were grouped into three clinically relevant groups: IgA vasculitis and other small-vessel vasculitis (n = 64), ANCA-associated vasculitis (AAV) (n = 112), and large-vessel vasculitis (LVV) (n = 141). Results The diagnostic delay from the first referral to tertiary-level clinic was shortest in the LVV group and longest in the AAV group. Total costs during the diagnostic period were the highest in the AAV group (median = €6754 [IQR €8812]) and lowest in the LVV group (median = €3123 [IQR €4517]), p

Sialic acid-binding immunoglubulin-like lectin 9 (Siglec-9) is a ligand of vascular adhesion protein 1 (VAP-1). A gallium 68-labeled peptide of Siglec-9, 68Ga-DOTA-Siglec-9, holds promise as a novel PET tracer for imaging of inflammation. This first-in-human study investigated the safety, tolerability, biodistribution, and radiation dosimetry of this radiopharmaceutical. Methods: Six healthy males underwent dynamic whole-body PET/CT. Serial venous blood samples were drawn from 1–240 min after intravenous injection of 162 ± 4 MBq of 68Ga-DOTA-Siglec-9. In addition to gamma counting, the plasma samples were analyzed by high-performance liquid chromatography to detect intact tracer and radioactive metabolites. Radiation doses were calculated using the OLINDA/EXM 2.2 software. In addition, a patient with early rheumatoid arthritis was studied with both 68Ga-DOTA-Siglec-9 and 18F-FDG PET/CT to determine the ability of the new tracer to detect arthritis. Results:68Ga-DOTA-Siglec-9 was well tolerated by all subjects. 68Ga-DOTA-Siglec-9 was rapidly cleared from blood circulation and several radioactive metabolites were detected. The organs with the highest absorbed doses were the urinary bladder wall (0.38 mSv/MBq) and kidneys (0.054 mSv/MBq). The mean effective dose was 0.022 mSv/MBq (range 0.020–0.024 mSv/MBq). Most importantly, however, 68Ga-DOTA-Siglec-9 was able to detect arthritis comparable to 18F-FDG. Conclusion: Intravenous injection of 68Ga-DOTA-Siglec-9 was safe and biodistribution is favorable for testing of the tracer in larger group of patients with rheumatoid arthritis planned in the next phase of clinical trials. The effective radiation dose of 68Ga-DOTA-Siglec-9 was within the same range as those of other 68Ga-labeled tracers. Injection of 150 MBq of 68Ga-DOTA-Siglec-9 would expose a subject to 3.3 mSv. These findings support the possible repeated clinical use of 68Ga-DOTA-Siglec-9, e.g., in trials aiming to elucidate the treatment efficacy of novel drug candidates.

Background The diagnosis of cardiac implantable electronic device (CIED) infection is challenging because of its variable presentations. We studied the value of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the detection of CIED infection. Methods and results Thirty patients with suspected CIED infection underwent 18F-FDG-PET/CT. The control group was ten patients with asymptomatic CIED who underwent cancer-related 18F-FDG-PET/CT. 18F-FDG-PET/CT was evaluated visually, semiquantitatively as maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). Final diagnosis of CIED infection was based on clinical and bacteriological data. 18F-FDG-PET/CT was visually positive in all 9 patients with recent (≤ 8 weeks) implantation of CIED, but only 4 had confirmed CIED infection. 18F-FDG-PET/CT was true positive in 9 out of 21 cases with remote implantation of CIED and false positive in 3 (14.3%) cases. 18F-FDG-PET/CT was also false positive in 3 (30%) cases of control group. The SUVmax of the pocket area was significantly higher in patients with CIED infection than in the control group (4.8 ± 2.4 vs 2.0 ± .8, P 18F-FDG-PET/CT for the diagnosis of CIED infection in patients with remote implantation was 90% and specificity 73%, PPV 75%, and NPV 89%. Conclusions 18F-FDG-PET/CT is a sensitive but nonspecific method in the diagnosis of CIED infection.

Objective Frequent monitoring of patients with early rheumatoid arthritis (RA) is required for achieving good outcomes. This study was undertaken to investigate the influence of text message (SMS)-enhanced monitoring on early RA outcomes. Methods We randomized 166 patients with early, disease-modifying antirheumatic drug-naive RA to receive SMS-enhanced follow-up or routine care. All patients attended visits at 0, 3, and 6 months, and a follow-up visit at 12 months. Treatment was at the physicians' discretion. The intervention included 13 SMSs during weeks 0-24 with questions concerning medication problems (yes/no) and disease activity (patient global assessment [PtGA], scale 0-10). Patients were contacted if response SMSs indicated medication problems or PtGA exceeded predefined thresholds. Primary outcome was 6-month Boolean remission (no swollen or tender joints and normal C-reactive protein levels). Quality of life (QoL; measured by the Short Form 36 survey) and Disease Activity Score in 28 joints (DAS28) were assessed. Results Six and 12-month follow-up data were available for 162 and 157 patients, respectively. In the intervention group, 46% of the patients (38 of 82) reported medication problems and 49% (40 of 82) reported text message PtGAs above the alarm limit. Remission rates at 6 months (P = 0.34) were 51% in the intervention group and 42% in the control group. These rates were 57% and 43% at 12 months (P = 0.17) in the intervention and control groups, respectively. The respective mean ± SD DAS28 scores for the intervention and control groups were 1.92 ± 1.12 and 2.22 ± 1.11 at 6 months (P = 0.09); and 1.79 ± 0.91 and 2.08 ± 1.22 at 12 months (P = 0.28). No differences in QoL were observed. Conclusion The study did not meet the primary outcome despite a trend favoring the intervention group. This may be explained by the notably high overall remission rates.

Diagnosis of Candida spp. infective endocarditis (IE) is challenging, and diagnostic delays are common. We describe two patients with Candida spp. prosthetic valve endocarditis (PVE) and 18fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) as a part of diagnostic workup. We also refer to 5 other cases we found from the published literature. These cases highlight that 18F-FDG-PET/CT can improve diagnostic accuracy in prosthetic valve Candida endocarditis.

Visual Abstract, Sialic acid–binding immunoglubulinlike lectin 9 (Siglec-9) is a ligand of vascular adhesion protein 1. A 68Ga-labeled peptide of Siglec-9, 68Ga-DOTA-Siglec-9, holds promise as a novel PET tracer for imaging of inflammation. This first-in-humans study investigated the safety, tolerability, biodistribution, and radiation dosimetry of this radiopharmaceutical. Methods: Six healthy men underwent dynamic whole-body PET/CT. Serial venous blood samples were drawn from 1 to 240 min after intravenous injection of 162 ± 4 MBq of 68Ga-DOTA-Siglec-9. In addition to γ-counting, the plasma samples were analyzed by high-performance liquid chromatography to detect intact tracer and radioactive metabolites. Radiation doses were calculated using the OLINDA/EXM software, version 2.2. In addition, a patient with early rheumatoid arthritis was studied with both 68Ga-DOTA-Siglec-9 and 18F-FDG PET/CT to determine the ability of the new tracer to detect arthritis. Results: 68Ga-DOTA-Siglec-9 was well tolerated by all subjects. 68Ga-DOTA-Siglec-9 was rapidly cleared from the blood circulation, and several radioactive metabolites were detected. The organs with the highest absorbed doses were the urinary bladder wall (0.38 mSv/MBq) and kidneys (0.054 mSv/MBq). The mean effective dose was 0.022 mSv/MBq (range, 0.020–0.024 mSv/MBq). Most importantly, however, 68Ga-DOTA-Siglec-9 was comparable to 18F-FDG in detecting arthritis. Conclusion: Intravenous injection of 68Ga-DOTA-Siglec-9 was safe and biodistribution was favorable for testing of the tracer in larger group of patients with rheumatoid arthritis, as is planned for the next phase of clinical trials. The effective radiation dose of 68Ga-DOTA-Siglec-9 was within the same range as the effective radiation doses of other 68Ga-labeled tracers. Injection of 150 MBq of 68Ga-DOTA-Siglec-9 would expose a subject to 3.3 mSv. These findings support the possible repeated clinical use of 68Ga-DOTA-Siglec-9, such as in trials to elucidate the treatment efficacy of novel drug candidates.

Objective Patients receiving chemotherapy are prone to neutropoenic infections, presenting with non-specific symptoms such as a high fever and elevated inflammatory parameters. Large-vessel vasculitis (LVV) may have a similar clinical presentation and should be included in differential diagnostics. A few published case reports and adverse event reports suggest a causal association between LVV and the use of granulocyte colony-stimulating factor (G-CSF) and chemotherapy. Our objective was to evaluate the relationship between LVV, G-CSF and chemotherapy. Methods Between 2016 and 2018, we identified six patients in Finland with probable drug-induced LVV associated with G-CSF and chemotherapy. All six patients had breast cancer. A systematic literature review was performed according to PRISMA guidelines using comprehensive search terms for cancer, chemotherapy, G-CSF and LVV. Results The literature search identified 18 similar published case reports, of which most were published after 2014. In all patients combined (n = 24), the time delay from the last drug administration to the LVV symptoms was on average 5 days with G-CSF (range = 1–8 days) and 9 days with chemotherapy (range = 1–21 days). Common symptoms were fever (88%), neck pain (50%) and chest pain (42%). Based on imaging, 17/24 (71%) had vascular inflammation in the thoracic aorta and supra-aortic vessels, but 5/24 (21%) reportedly had inflammation limited to the carotid area. Conclusion This review suggests that LVV may be a possible serious adverse event associated with G-CSF and chemotherapy. Successful management of drug-induced LVV requires early identification, through diagnostic imaging, and discontinuation of the drug.

To assess what proportion of patients with disease-modifying anti-rheumatic drug (DMARD)-naïve early rheumatoid arthritis (ERA) reach 28-joint Disease Activity Score (DAS28) remission over 1 year, and remission variability across clinics in Finland.Patients with DMARD-naïve newly diagnosed inflammatory arthritis were recruited. The proportion of patients in 28-joint Disease Activity Score with three variables (DAS28-3) remission was compared across sites. Repeated measures were analysed using a mixed models approach with appropriate distribution and link function.In total, 611 patients were recruited at five sites: 67% were female; the mean (sd) age was 57 (16) years; 71% and 68% were positive for rheumatoid factor and anti-cyclic citrullinated peptides, respectively; and 23% had radiographic erosions. A total of 506 (83%) fulfilled the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for rheumatoid arthritis for further analyses. DAS28-3 remission was met by 68% and 75% at 3 and 12 months, respectively. The clinical site had no effect on remission when adjusted for confounders. At baseline, 68% used methotrexate-based combination therapy, and 31% used triple therapy with methotrexate, hydroxychloroquine, and sulphasalazine (the Fin-RACo regimen). In multivariate analysis, the only independent predictors of DAS28-3 remission at 12 months were lower baseline DAS28-3 and triple therapy as the initial treatment.Three out of four DMARD-naïve ERA patients in Finland are in remission during the first year from the diagnosis. High remission rates were achieved for most patients with the use of conventional synthetic DMARDs in combination. Treatment of DMARD-naïve ERA patients with the FIN-RACo regimen is a predictor of DAS28-3 remission in real-life rheumatology settings.

Purpose. This study evaluated the potential of68Ga-citrate positron emission tomography/computed tomography (PET/CT) for the detection of infectious foci in patients withStaphylococcus aureusbacteraemia by comparing it with 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT.Methods.Four patients admitted to hospital due toS. aureusbacteraemia underwent both18F-FDG and68Ga-citrate whole-body PET/CT scans to detect infectious foci.Results.The time from hospital admission and the initiation of antibiotic treatment to the first PET/CT was 4–10 days. The time interval between18F-FDG and68Ga-citrate PET/CT was 1–4 days. Three patients had vertebral osteomyelitis (spondylodiscitis) and one had osteomyelitis in the toe; these were detected by both18F-FDG (maximum standardised uptake value [SUVmax]6.0±1.0) and68Ga-citrate (SUVmax 6.8±3.5,P=0.61). Three patients had soft tissue infectious foci, with more intense18F-FDG uptake (SUVmax 6.5±2.5) than68Ga-citrate uptake (SUVmax 3.9±1.2,P=0.0033).Conclusions.Our small cohort of patients withS. aureusbacteraemia revealed that68Ga-citrate PET/CT is comparable to18F-FDG PET/CT for detection of osteomyelitis, whereas18F-FDG resulted in a higher signal for the detection of soft tissue infectious foci.

Background Large vessel vasculitis (LVV) and neutropenic infection in patients receiving chemotherapy present similar clinical symptoms with fever and high inflammation parameters. Infection is more frequent but LVV should be kept in mind as differential diagnosis. LVV is a serious condition which may lead to vessel wall damage. Published few case reports and adverse event reports suggest causal association between LVV and use of granulocyte colony-stimulating factor (G-CSF) and/or chemotherapy (1). Objectives To evaluate the rare connection of LVV and anticancer therapy by describing our six patient cases and a systematic review of the literature. Methods Between 2016-2018 we identified six patients with probable drug induced LVV associated with chemotherapy and G-CSF. All patients had breast cancer. Systematic literature review was performed according to PRISMA guidelines using comprehensive search terms for breast cancer, chemotherapy, LVV and G-CSF. Results In our case series, 5/6 patients developed LVV symptoms within two weeks after administration of docetaxel and G-CSF. Vasculitis symptoms disappeared after drug cessation or drug change. Literature search identified 16 published case reports with association of LVV and chemotherapy fulfilling our study criteria. Altogether 22 cases were analyzed. Mean age was 59 years (range 40-77 years). In 14/22 cases data from G-CSF administration was available. Time delay from drug administration to LVV symptoms was average 10 days (range 1-42 days) with G-CSF and median 12 days (range 2-310 days) with chemotherapy. Most prevalent cancer types were breast cancer (8/22), hematological malignancies (7/22) and lung cancer (3/22). Most common clinical LVV symptom were fever (18/22), neck pain (11/22) and chest pain (8/22). Diagnosis was confirmed with imaging studies showing vasculitis in various large vessels in upper body. Notably, four cases had vascular inflammation only in carotid region and this was recognized by radiologist as carotidynia/transient perivascular inflammation of the carotid artery (TIPIC) syndrome. Conclusion Large vessel vasculitis is a possible serious rare adverse event associated with chemotherapy (possibly docetaxel) and G-CSF. Since signs and symptoms are non-specific, we assume this condition is underdiagnosed and should be kept in mind when treating oncological patients. Successful management requires early identification and cessation of the drug. When diagnosed and treated properly, the recovery is usually fast. Reference: [1] Lardieri, A., McCulley, L., Christopher Jones, S. & Woronow, D. Granulocyte colony-stimulating factors and aortitis: A rare adverse event. Am. J. Hematol. 93, E333–E336 (2018). Disclosure of Interests Kirsi Taimen Speakers bureau: Pfizer, Novartis, Abbvie, Roche (lectures), Samu Heino: None declared, Ia Kohonen: None declared, Heikki Relas Speakers bureau: Pfizer, Riikka Huovinen Consultant for: Roche, Amgen, Novartis, Pfizer, Speakers bureau: Roche, Amgen, Novartis, Pfizer, Arno Hanninen Speakers bureau: Roche, Laura Pirila Consultant for: Abbvie, Novartis, Eli Lilly, MSD Finland, Pfizer, UCB, Roche, Jansen- Cilag, Sandoz, Speakers bureau: Pfizer

Background The current biomarkers for the diagnosis and monitoring of diseased and injured skeletal muscles, such as creatine kinase (CK), have limited tissue specificity and incapability to differentiate between pathological and physiological changes. Thus, new biomarkers with improved diagnostic certainty are needed. Skeletal troponin I (skTnI) is a promising new biomarker for injured and diseased skeletal muscle tissue. Although studies have reported that circulating skTnI levels are elevated in response to trauma, exercise and various muscular diseases (1), its clinical utility to serve as a diagnostic indicator has largely been unexplored. Objectives Our aim was to develop and validate a novel assay for skTnI, and to assess its clinical performance with idiopathic inflammatory myopathy (IIM) patients. Methods A two-step fluoroimmunoassay was used to analyze the levels of skTnI in samples from healthy reference individuals (n=125), trauma patients (n=151), and patients with IIM (n=94). Later, skTnI and CK levels in patients with IIM were compared according to their disease activity status (active, pre-active or stable). Results The limit of detection was 1.2 ng/ml, and the upper reference limit (90th percentile) was 5.4 ng/ml. The median skTnI concentrations were Conclusion With the developed skTnI assay, IIM patients were identified from healthy individuals and from patients with traumatic muscular injuries. Also, skTnI was shown to outperform CK in detecting IIM patients in different disease activity statuses. Reference [1] Kiely PDW, Bruckner FE. Serum skeletal troponin I in inflammatory muscle disease: Relation to creatine kinase, CKMB and cardiac troponin I. Ann Rheum Dis 2000;59:750–1. Disclosure of Interests Katriina Bamberg: None declared, Laura Mehtala: None declared, Olli Arola: None declared, Seppo Laitinen: None declared, Pauliina Nordling: None declared, Marjatta Strandberg: None declared, Niko Strandberg: None declared, Johanna Paltta: None declared, Markku Mali: None declared, Fabricio Espinosa-Ortega: None declared, Laura Pirila Consultant for: Abbvie, Novartis, Eli Lilly, MSD Finland, Pfizer, UCB, Roche, Jansen- Cilag, Sandoz, Speakers bureau: Pfizer, Ingrid E. Lundberg Grant/research support from: Dr. Lundberg has received honoraria from Bristol Myers Squibb and MedImmune and is currently receiving a research grant from Bristol Myers Squibb and from Astra Zeneca., Consultant for: She is a scientific advisor for Bristol Myers Squibb, and aTyr, Tanja Savukoski: None declared, Kim Pettersson: None declared

Background The current biomarkers for diagnosis and monitoring of injured and diseased skeletal muscles, such as creatine kinase (CK), have limited tissue specificity and incapability to differentiate between pathological and physiological changes. Thus, new biomarkers with improved diagnostic accuracy are needed. Our aim was to develop and validate a novel assay for skeletal troponin I (skTnI), and to assess its clinical performance in patients with idiopathic inflammatory myopathies (IIM). Methods A two-step fluoroimmunoassay was used to analyze samples from healthy reference individuals (n = 140), patients with trauma (n = 151), and patients with IIM (n = 61). Results The limit of detection was 1.2 ng/mL, and the upper reference limit (90th percentile) was 5.2 ng/mL. The median skTnI concentrations were Conclusions With the skTnI assay, patients with IIM were identified from healthy individuals and from patients with traumatic muscular injuries. When compared to CK, skTnI appeared to be more accurate in managing patients with low-grade IIM disease activities. The developed assay serves as a reliable analytical tool for the assessment of diagnostic accuracy of skTnI in the diagnosis and monitoring of myopathies.

18F-Fluorodeoxyglucose positron-emission tomography (18F-FDG-PET) with computed tomography (CT) is effective for diagnosing large vessel vasculitis, but its usefulness in accurately diagnosing suspected, unselected vasculitis remains unknown. We evaluated the feasibility of 18F-FDG-PET/CT in real-life cohort of patients with suspicion of vasculitis. The effect of the dose and the timing of glucocorticoid (GC) medication on imaging findings were in special interest. 82 patients with suspected vasculitis were evaluated by whole-body 18F-FDG-PET/CT. GC treatment as prednisolone equivalent doses at the scanning moment and before imaging was evaluated. 38/82 patients were diagnosed with vasculitis. Twenty-one out of 38 patients had increased 18F-FDG accumulation in blood vessel walls indicating vasculitis in various sized vessels. Vasculitis patients with a positive vasculitis finding in 18F-FDG-PET/CT had a significantly shorter duration of GC use (median = 4.0 vs 7.0 days, P=0.034), and they used lower GC dose during the PET scan (median dose = 15.0 mg/day vs 40.0 mg/day, p=0.004) compared to 18F-FDG-PET/CT-negative patients. Vasculitis patients with a positive 18F-FDG-PET/CT result had significantly higher C-reactive protein (CRP) than patients with a negative 18F-FDG-PET/CT finding (mean value = 154.5 vs 90.4 mg/L, p=0.018). We found that 18F-FDG-PET/CT positivity was significantly associated with a lower dose and shorter duration of GC medication and higher CRP level in vasculitis patients. 18F-FDG-PET/CT revealed clinically significant information in over half of the patients and was effective in confirming the final diagnosis.

In inflammatory arthritis peptidyl arginine deiminase (PAD) enzymes can citrullinate arginine residues in extracellular matrix (ECM) proteins, such as collagens and fibronectin. This may lead to the generation of anti-citrullinated protein antibodies, important diagnostic markers in rheumatoid arthritis. In addition, the citrullination may directly affect protein function. Based on structural analysis, we found that most ECM-associated growth factors (GFs) have arginine residues in their receptor recognition sites. Thus, they are potential functional targets of extracellular citrullination. To examine this further, we focused on the citrullination of transforming growth factor-βs (TGF-β), well-known ECM-associated GFs. PAD-treatment of CHO-LTBP1 cell derived matrix, rich with TGF-β, decreased the level of TGF-β activity as detected by HaCaT and MLEC-PAI-1/Lu reporter cells. Additional experiments indicated that PAD-treatment inhibits the integrin-mediated TGF-β activation since PAD-treatment decreased the binding of integrin αVβ6 ectodomain as well as integrin-mediated spreading of MG-63 and HaCaT cells to β1-latency associated peptide (TGF-β1 LAP). The citrullination of the RGD site, an important integrin recognition motif, was confirmed by mass spectrometry. Furthermore, the citrullination of active TGF-β1 inhibited its binding to recombinant TGF-β receptor II, and prevented its ability to activate TGF-β signaling. Thus, extracellular PAD activity can affect the function of ECM-associated growth factors by different mechanisms. Importantly, the citrullination of both latent and active TGF-β has the potency to regulate the inflammatory process.

Background:Finnish healthcare registers are used in medical research, but there is little data about the validity of these registers in rheumatology.Objectives:The aim of our study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in the Finnish Biobanks.Methods:We reviewed the electronic patient charts of 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA and 250 age-and-sex matched controls. Patients were randomly selected from Finnish biobank participants. We evaluated whether the patients’ diagnosis of RA recorded in the hospital discharge registry at the participating hospital was correct according to chart review and expert opinion. In the control group it was investigated whether the diagnosis of RA was written in the patients’ chart, but the diagnosis code was not recorded.Results:The positive predictive value (PPV) of a single hospital registry diagnosis of seropositive RA was 0.74 but rose to 0.98 in patients with a special reimbursement for seropositive RA and 0.98 in anti-citrullinated protein antibody positive patients. For seronegative RA, the PPV of a diagnosis was 0.72 and in patients with a special reimbursement for seronegative RA 0.89. The PPV was higher in patients with more than one visit with the diagnosis: 0.92 if the patients had at least 5 visits with seropositive RA and 0.88 with at least 5 visits with seronegative RA. Negative predictive value for RA diagnosis was 0.99.Conclusion:These results demonstrate that the validity of RA diagnoses in healthcare registers can be markedly improved with data about special reimbursement for medication, number of visits and serological data.Disclosure of Interests:Antti Palomäki Consultant of: Pfizer, Speakers bureau: Pfizer, Sanofi, MSD, Johanna Paltta Consultant of: Lilly, Abbvie, Laura Pirilä Consultant of: Novartis, MSD Finland, Roche, Bristol-Myers-Squibb, Pfizer, Sanofi, Abbvie, Oy Eli LIlly Finland Ab, UCB Pharma Oy Finland, Jansen-Cilag, Mylan, Sandoz, Boehringer-Ingelheim, Paid instructor for: Boehringer -Ingelheim, MSD Finland, Speakers bureau: Boehringer-Ingelheim, Pfizer Finland, Hanna-Kaisa Heikkilä: None declared, Pia Isomäki Consultant of: Abbvie, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Johanna Huhtakangas Consultant of: Boehringer Ingelheim, Tuulikki Sokka-Isler: None declared, Oili Kaipiainen-Seppänen Speakers bureau: Boehringer Ingelheim, Kari Eklund Consultant of: Celgene, Lilly, Speakers bureau: Pfizer, Roche

Background:Routine laboratory testing is recommended for early identification of toxicity during conventional synthetic disease modifying antirheumatic drug (csDMARD) treatment. Based on expert consensus, testing is recommended every 2–4 weeks for the first 3 moths and quarterly thereafter (1).Objectives:In addition to evaluating the incidence of alanine transaminase (ALT) elevations in rheumatoid arthritis (RA) patients initiated on 1–2 csDMARDs, we aimed to distinguish patterns in ALT levels to develop a model for identifying patients at high risk for liver toxicity.Methods:We identified RA patients who were initiated a new csDMARD course at the rheumatology clinic of Turku University Hospital in 2013–2019. Baseline and follow-up safety monitoring results were drawn from the electronic health record (EHR) data. Data on diagnoses and csDMARD initiation/cessation dates were manually confirmed from the EHR.As the primary endpoint, we used ALT-elevations of more than twice the upper limit of reference range (women ≥ 70 U/l, men ≥ 100 U/l) within 6 months after treatment initiation. Intergroup differences were tested using Mann-Whitney test for continuous variables and the chi-square test or Fisher’s exact test (nResults:We identified 2851 RA patients of whom 1017 initiated a new csDMARD course requiring laboratory monitoring. Of these, 860 patients (58.9 years, 68% women, 65% seropositive) were included in the analyses after excluding patients with missing laboratory results (n=148) or elevated ALT at baseline (n=9). Of the 860 patients, 220 initiated two csDMARDs simultaneously [99% sulfasalazine (SSZ) and methotrexate (MTX)]. Primary endpoint was reached in 55 of 860 (6.4%) patients, including 10 who initiated two csDMARDS. Of these 55 patients, primary endpoint was reached in 40 of 55 (73%) patients during first three follow-up tests. In 31 of 55 (56%) patients, including 3 initiators of 2 csDMARDs, elevated ALT led to csDMARD cessation during the first 6 months. In Cox proportional hazards model with age, sex, seropositivity, baseline ALT, and csDMARDs as the explanatory variables, only baseline ALT level [hazard ratio 1.56 per 1 SD increase, 95% confidence interval (CI) 1.30–1.88, pTable.Multivariable Cox proportional hazards model including the results of the first follow-up laboratory test. Only values before occurrence of primary endpoint were used (n=843).CharacteristicHazard ratio (95% CI)P ValueAge (per year)1.00 (0.98-1.02)0.78Sex (male)0.50 (0.21-1.15)0.10Seronegativity0.88 (0.44-1.75)0.71Baseline ALT*1.72 (1.32-2.25)ALT / t (per 1 SD increase / 30 days)§1.33 (1.17-1.52)Methotrexate0.58 (0.22-1.52)0.27Sulfasalazine0.95 (0.38-2.35)0.91Azathioprine2.30 (0.48-11.13)0.30Leflunomide1.08 (0.23-5.16)0.92*Normalized ALT according to sex-specific reference range;§Rate of change from baseline to 1stfollow-up testConclusion:Most incident ALT elevations can be predicted before the first csDMARD dose. Patients with elevated ALT at baseline or a rising trend at first follow-up are at high risk for liver toxicity and benefit from frequent testing.References:[1]Saag KG et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008;59:762-84.Disclosure of Interests:Laura Kuusalo Consultant of: Gilead, Pfizer Finland, Speakers bureau: Abbvie, Orion, Pfizer Finland, Novartis, Sanofi, Mikko Venäläinen: None declared, Sofia Saranpää: None declared, Heidi Kirjala: None declared, Laura Elo: None declared, Laura Pirilä Consultant of: Novartis, MSD Finland, Roche, Bristol-Myers-Squibb, Pfizer Finland, Sanofi, Abbvie, Eli Lilly Finland, UCB Pharma, Janssen-Cilag, Mylan, Sandoz, Boerhinger-Ingelheim, Paid instructor for: Boehringer-Ingelheim, MSD Finland, Speakers bureau: Boehringer-Ingelheim, Pfizer Finland

Background Finnish on-line Health village environment, so-called HUS-MAP©, was used to develop on-line information for rheumatic patients. Objectives To face the challenge of increasing demand for rheumatological care without additional resources a new virtual client-orientated service was developed. Methods In Finland, an on-line Health village environment, so-called HUS-MAP©, has been developed to offer virtual digital information to citizens, patients, and healthcare professionals. By using this HUS-MAP© environment, we provide information and support to citizens and patients who need information on different rheumatic diseases and various unspecified aches and musculoskeletal pains. The study group consisted of participants from every university hospital in Finland, from local authorities; rheumatologists, other specialists, general practitioners, nurses, special professionals such as physical therapists, and patients. Information provided was based on updated international and Finnish guidelines on rheumatic diseases. After the information was reviewed and accepted by our study group, it was fed into a special program and published on-line in the Health village environment. Results E-service for citizens and patients was opened in March 2017. Detailed description of symptoms, diagnosis and therapy of various rheumatic diseases, such as rheumatoid arthritis, spondyloarthritis, connective tissue diseases and vasculitis are available. Early diagnosis and treatment to remission when possible is emphasised. The service aids to identify, by using symptom navigator and questionnaires for back pain, as well as swollen and painful joints those who may have a rheumatic disease and guide patients to find medical services without delay. Already 60 500 persons have visited our website. Conclusions Finnish e-service, rheumaticdiseases.fi, offers an easy way to reach people and increase citizen’s awareness on their own health. By guiding people to search for care the service may reduce delays in diagnosis of rheumatic diseases and the onset of therapy Acknowledgements To patients and healthcare professionals workin in Finnish Helathvillage.fi-rheumaticdisease.fi Disclosure of Interest None declared

Background Mooren ulcer has been considered as an idiopathic autoimmune keratitis. However, it has been in some cases suggested to be associated with hepatitis C, although the evidence is very vague. Case presentation We present a case of a man who was diagnosed with a primary Mooren ulcer in his right eye. The eye became blind despite of intensive treatment with local medications and extensive surgical procedures. After 10 years, the patient was diagnosed with the same disease, now in his left, previously healthy eye. There was no history that would suggest a secondary Mooren ulcer, but a chronic hepatitis C infection was detected. Treatment was targeted against hepatitis C (ribavirin and interferon) in addition to immunosuppressive medical and surgical treatment which resulted in a full and more than 6 years lasting remission of the disease. Conclusions Whether the immunomodulatory and immunosuppressive medication against hepatitis C was the key reason for the good results in the treatment of the second eye, remains elusive. The causality of hepatitis C with respect to the pathogenesis of Mooren ulcer on this patient remains open, but should be considered as one of the possible etiological factors of the disease.

Objective.Because of the role of tumor necrosis factor (TNF) in host defense, it was hypothesized that its inhibition might lead to an increased risk of malignancies and infections. The objective of our study was to assess the incidence of serious infections leading to hospitalization and malignancies among patients with rheumatoid arthritis (RA) receiving either TNF inhibitor or rituximab (RTX) therapy.Methods.The study population was identified from the National Register for Biologic Treatment in Finland and the hospital records of Central Finland Central Hospital for conventional disease-modifying antirheumatic drug (cDMARD) users. Data on infections and malignancies were acquired from national healthcare registers. A Poisson model was used to calculate the adjusted incidence rate ratios (aIRR) and was composed of age, sex, time from diagnosis, year of the beginning of the followup, rheumatoid factor status, Disease Activity Score at 28 joints, Health Assessment Questionnaire, prior malignancy, prior serious infection, prior biologic use, and time-updated use of methotrexate, sulfasalazine, hydroxychloroquine, and oral corticosteroids as confounders.Results.In total, during the followup of 10,994 patient-years, 92 malignancies and 341 serious infections were included in the analyses. The aIRR of infections compared to cDMARD users were 1.2 (95% CI 0.63–2.3), 0.84 (95% CI 0.53–1.3), 0.98 (95% CI 0.60–1.6), and 1.1 (95% CI 0.59–1.9) for the patients treated with infliximab (IFX), etanercept, adalimumab, and RTX, respectively. The crude rates of malignancies were highest among the users of cDMARD and RTX, and lowest among patients treated with IFX with no differences in aIRR.Conclusion.Our results provide some reassurance of the safety of biologic treatments in the treatment of RA.

Purpose This study evaluated the potential of 68Ga-citrate positron emission tomography/computed tomography (PET/CT) for the detection of infectious foci in patients with Staphylococcus aureus bacteraemia by comparing it with 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT. Methods Four patients admitted to hospital due to S. aureus bacteraemia underwent both 18F-FDG and 68Ga-citrate whole-body PET/CT scans to detect infectious foci. Results The time from hospital admission and the initiation of antibiotic treatment to the first PET/CT was 4–10 days. The time interval between 18F-FDG and 68Ga-citrate PET/CT was 1–4 days. Three patients had vertebral osteomyelitis (spondylodiscitis) and one had osteomyelitis in the toe; these were detected by both 18F-FDG (maximum standardised uptake value [SUVmax] 6.0 ± 1.0) and 68Ga-citrate (SUVmax 6.8 ± 3.5, P = 0.61). Three patients had soft tissue infectious foci, with more intense 18F-FDG uptake (SUVmax 6.5 ± 2.5) than 68Ga-citrate uptake (SUVmax 3.9 ± 1.2, P = 0.0033). Conclusions Our small cohort of patients with S. aureus bacteraemia revealed that 68Ga-citrate PET/CT is comparable to 18F-FDG PET/CT for detection of osteomyelitis, whereas 18F-FDG resulted in a higher signal for the detection of soft tissue infectious foci.

Background Immunization to biological drugs can reduce the treatment efficacy and increase the risk of adverse events. Objectives To determine the drug trough concentrations and anti-drug antibody (ADAb) levels of self-injected TNF-inhibitors, in non-selected patients with ankylosing spondylitis (AS) attending the rheumatological outpatient clinic, and to study the patient related factors affecting the immunization to antiTNF drugs. Methods A total of 313 patients with AS were recruited. A blood sample, taken 1–2 days prior to next drug injection, was obtained from 273 patients. Trough concentration of the anti-TNF drugs were measured with capture-ELISA (Promonitor EIA, Progenica), the levels of ADAb with radioimmunoassay (Sanquin Laboratories, The Netherlands), and the serum TNF-blocking capacity by using an in-house reporter gene assay. The clinical activity of AS was assessed using the Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI), and the Maastricht AS Entheses Score (MASES). Results ADAbs were observed in 21% of patients on adalimumab (n=99), in 0% of those on etanercept (n=83), in 3% of those on golimumab (n=79) and in 50% of those on certolizumab pegol (n=12). The BASDAI in ADAb positive patients was 1.4 (sd 1.4) and in the ADAb negative patients 2.0 (sd 1.8 p=0.060). Factors affecting the immunization to biological drug could be further analyzed in patients using adalimumab. Trough drug concentrations of adalimumab correlated with the presence of ADAb (r=-0.54, rp Conclusions The disease activity of AS patients using self injected antiTNF drugs was low. The immunization to adalimumab was relatively common in nonselected AS patient population. However, no clear association was observed between the presense of ADAb and the disease activity. Acknowledgements The study was financially supported by Pfizer Disclosure of Interest J. Hiltunen: None declared, P. Parmanne: None declared, T. Sokka-Isler: None declared, T. Lamberg: None declared, O. Kaipiainen-Seppanen: None declared, P. Isomaki: None declared, M. Kauppi: None declared, L. Pirila: None declared, T. Uutela: None declared, R. Tuompo: None declared, H. Relas: None declared, T. Yli-Kerttula: None declared, H. Valleala: None declared, M. Romu: None declared, T. Rannio: None declared, K. Paalanen: None declared, A. Juha: None declared, P. Ekman: None declared, K. Tadesse: None declared, J. Borodina: None declared, P. Elfving: None declared, R. Peltomaa: None declared, M. Leirisalo-repo: None declared, H. Kautiainen: None declared, S. Jokiranta: None declared, K. Eklund Grant/research support from: Pfizer has supported the study financially, Consultant for: Advisory board meetings BMS, MSD, Pfizer, Abbvie, Speakers bureau: Lectures: BMS, Roche, Pfizer, Novartis

The diagnosis of infective endocarditis (IE), especially the diagnosis of prosthetic valve endocarditis (PVE) is challenging since echocardiographic findings are often scarce in the early phase of the disease. We studied the use of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in IE. Sixteen patients with suspected PVE and 7 patients with NVE underwent visual evaluation of 18F-FDG-PET/CT. 18F-FDG uptake was measured also semiquantitatively as maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). The modified Duke criteria were used as a reference. There was strong, focal 18F-FDG uptake in the area of the affected valve in all 6 cases of definite PVE, in 3 of 5 possible PVE cases, and in 2 of 5 rejected cases. In all patients with definite PVE, SUVmax of the affected valve was higher than 4 and TBR higher than 1.8. In contrast to PVE, only 1 of 7 patients with NVE had uptake of 18F-FDG by PET/CT in the valve area. Embolic infectious foci were detected in 58% of the patients with definite IE. 18F-FDG-PET/CT appears to be a sensitive method for the detection of paravalvular infection associated with PVE. Instead, the sensitivity of PET/CT is limited in NVE.

Objective: A systematic review found that an average of 27% of rheumatoid arthritis (RA) patients using tumour necrosis factor (TNF) inhibitors discontinue their treatment within 1year. The aim of this study was to assess drug survival on TNF inhibitors among patients with RA.Methods: Patients were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is a longitudinal cohort study established to monitor the effectiveness and safety of biologic drugs in rheumatic diseases. Inclusion was limited to TNF-inhibitor treatments started as the patient's first, second, or third biologic treatment between 2004 and 2014. Follow-up was truncated at 36months. The results of a time-dependent Cox proportional hazards model were reported as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs).Results: Of the 4200 TNF-inhibitor treatment periods identified from ROB-FIN, 3443 periods from 2687 patients met the inclusion criteria. Twenty-seven per cent of the patients discontinued their treatment within 12months. Infliximab (HR 1.8, 95% CI 1.3-2.5) and certolizumab pegol (HR 1.7, 95% CI 1.2-2.3) had lower drug survival compared to golimumab. A similar trend was seen with adalimumab (HR 1.2, 95% CI 0.90-1.7) and etanercept (HR 1.2, 95% CI 0.87-1.6). Concomitant use of methotrexate (MTX) was associated with improved drug survival (HR 0.76, 95% CI 0.64-0.90) in comparison with TNF-inhibitor monotherapy.Conclusions: Golimumab was better in terms of drug survival than infliximab or certolizumab pegol and at least as good as adalimumab and etanercept. Concomitant use of MTX improved drug survival on TNF inhibitors.

Objective Efficacy of TNF inhibitors in the treatment of RA assessed in randomized controlled trials (RCTs) may not be fully comparable to routine care owing to the stringent inclusion criteria. The objective of this study was to observe the effectiveness of TNF inhibitors in real-world patients and assess the patients' potential eligibility for the RCTs. Methods RA patients starting a TNF-inhibitor treatment between 2004 and 2014 were identified from the National Register for Biologic Treatment in Finland, which is a longitudinal observational cohort study. Effectiveness was measured using the ACR and EULAR response criteria and by studying the proportion of patients reaching DAS28 remission. The patients' baseline characteristics were compared against the inclusion criteria of 27 RCTs. Results EULAR moderate and good treatment responses at 6 months were achieved by 69 and 40% of the users of the first TNF inhibitor, respectively. ACR20, ACR50 and ACR70 responses were reached by 48, 27 and 13%, respectively. DAS28 remission was reached by 47%. Only 7.6-44% of the patients would have been potentially eligible for the RCTs. The eligible patients had better treatment responses compared with the non-eligible patients. Different TNF inhibitors were mostly equipotent, but the usage of MTX co-therapy had a major influence on treatment response. Conclusion Only a small proportion of patients would have been eligible for RCTs, and the efficacy of TNF inhibitors assessed in them cannot be generalized directly into Finnish routine health care.

OBJECTIVE Increased atherosclerosis in RA is not fully explained by the ordinary risk factors, but it may be related to vascular inflammation. The aim of this study was to investigate the degree of carotid artery inflammation in drug-naive patients with early RA before and after DMARD triple therapy. METHODS Fifteen non-diabetic patients with recently diagnosed RA [age 51 (16) years, 6 males] were examined before and at 2 and 4 weeks after the initiation of combination therapy with MTX, SSZ, HCQ and ⩽10 mg/day oral prednisolone. Eight healthy males aged 49 (6) years were examined once as controls. Inflammation in the carotid artery was quantified, using [(18)F]fluorodeoxyglucose ((18)F-FDG)-PET/CT, as the maximum standardized uptake value (SUVmax) and the maximum target-to-background ratio (TBRmax). RESULTS Before the treatment, patients with RA had significantly higher carotid artery (18)F-FDG uptake, as compared with healthy controls [TBRmax 1.78 (0.07) vs 1.51 (0.08), P = 0.03]. The 4-week DMARD therapy reduced the TBRmax to the level of healthy controls [1.53 (0.05), P = 0.84]. Compared with the baseline, the TBRmax decreased by 12.4 (16.8)% (P = 0.01) during 4-week DMARD therapy. At baseline, the SUVmax correlated with ESR (r = 0.52, P = 0.02) and CRP (r = 0.65, P = 0.01). Change in SUVmax correlated with changes in ESR and CRP after 4 weeks of treatment, as did the changes in TBRmax and SUVmax with DAS at 12 weeks of treatment. CONCLUSION (18)F-FDG-PET/CT revealed that drug-naive patients with early RA show carotid artery inflammation that can be efficiently reduced by 1-month DMARD triple therapy.

The aim of the study was to determine household chores and leisure-time activities most affected by rheumatoid arthritis (RA) and to evaluate the perceived impact on performing these activities. Also, our aim was to estimate the required and received assistance for household chores. In an interview study via telephone, 124 patients with moderate-to-severe RA, visiting a tertiary-level dermatological clinic, listed spontaneously without predefined list the household chores and leisure-time activities that they considered were particularly affected by the RA. Ability to perform household chores and leisure-time activities were asked. The need for outside assistance with household chores and help received were also determined. Rheumatoid arthritis affected wide range of everyday household activities, with tasks related to cleaning of the house mentioned most often. Eleven of the categories out of 16 were similar to those included in the HAQ index. The majority of the patients (84.6 %) reported disadvantage in performing household chores because of RA. More than half of the patients (55.7 %) received assistance with household chores, women significantly more often than men (69.0 vs. 26.3 %, p < 0.01). Most of the household chores mentioned were physically demanding. Leisure-time activities listed by respondents as affected by RA were mostly related to sport. The majority of patients (77.2 %) had either reduced or completely given up at least one leisure-time activity. When estimating the total burden of the disease, the impact on both household chores and leisure-time activities should be taken into account.

Mice heterozygous for the Del1 transgene locus with a short deletion mutation in the type II collagen gene develop early-onset degenerative changes in the knee joints that progress to end-stage osteoarthritis by the age of 12-15 months. This study focuses on the expression and distribution of syndecan-1, a cell-surface heparan sulfate proteoglycan, during the development of osteoarthritic cartilage degeneration, to better understand its role in this disease.Northern analyses of total RNA extracted from knee joints of transgenic Del1 mice and their nontransgenic controls were used to monitor changes in syndecan-1 mRNA levels during development, growth, ageing, and cartilage degeneration. Immunohistochemistry was used to study the distribution of syndecan-1 in the knee joints at different stages of cartilage degeneration.Syndecan-1 mRNA was present in knee joints throughout life, with the highest mRNA levels in ageing knee joints. In Del1 mice, a transient upregulation of syndecan-1 mRNA synthesis was observed at the age of 6 months coinciding with early stages of cartilage degeneration and a period of attempted repair. Immunostaining for syndecan-1 was most intense in chondrocytes of superficial and intermediate zones of articular cartilage adjacent to defect areas. Chondrocyte clusters also stained strongly for syndecan-1.The present temporospatial expression data on upregulation of syndecan-1 in articular cartilage during early stages of cartilage degeneration suggest that this molecule is involved in the attempted repair of cartilage fibrillations. Combined with the known role of syndecan-1 during skeletal development and wound healing, this interesting finding warrants further validation.

This letter is inspired by the ‘EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update’.1 There is no question that we are in full agreement with the overarching principles of the EULAR recommendations. What goes against our principles, however, is the tone of the bullet points. …

A 47-year-old man had fever, fatigue, abdominal pain, and claudication due to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Whole-body [18 F] FDG PET/CT scan was performed as a diagnostic procedure, and it revealed abnormal [18 F] FDG accumulation in smalland medium-sized vessels of the upper extremities and in the lower extremities appearing as a tree-root-like [18 F] FDG uptake pattern (Panel A). Increased [18 F] FDG uptake in vertebral bone marrow and the spleen was observed due to hematopoietic stimulation. For comparison, two different [18 F] FDG PET/CT scans are presented. A 76-year-old woman had an atypical [18 F] FDG uptake pattern in the larger arteries, which indicated giant cell vasculitis (Panel B). A 39-year-old man had Staphylococcus aureus septicaemia. He had no [18 F] FDG metabolic activity in vessel walls, but the activation of axillary lymph nodes and metastatic infectious foci in the left leg and spleen was observed (Panel C). [F] FDG PET/CT is a useful tool for evaluating the distribution of inflammation and infection, as in our case. It can detect the affected organs and also show unexpected localizations of ANCA-associated vasculitis [1].

A 42-year-old woman developed a rapidly progressing fatal heart failure. At the autopsy extensive necrosis of the myocardium was seen, with an almost complete absence of inflammatory cells and the presence of bacterial structures identified as Staphylococcus lugdunensis by PCR. In addition, the cytomegalovirus genome was found to be located inside the cardiomyocytes.

Background Previous studies have found that 26 to 34% of Rheumatoid Arthritis (RA) patients using Tumor Necrosis Factor (TNF)-inhibitors discontinue their treatment within one year [1,2]. Infliximab has been associated with poorer drug survival as compared to adalimumab and etanercept. Objectives The aim of this study was to assess the drug survival on TNF-inhibitors including golimumab and certolizumab pegol among patients with RA and the effect of co-medication on drug survival. Methods Patients were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is a longitudinal cohort study established in 1999 to monitor the effectiveness and safety of Biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in rheumatic diseases. Inclusion was limited to TNF-inhibitor treatments started as the patients9 first, second or third biologic treatment between 2004 and 2014. Missing baseline data was imputed by multiple imputation. Follow-up data was available until the end of 2015; however follow-up of individual treatment periods was truncated at 36 months. A Cox proportional hazards model with age as well as conventional synthetic DMARD (csDMARD) and glucocorticoid use as time-dependent confounders was carried out to compare the survival of individual TNF-inhibitors and to study the effect of co-medication. The results were reported as adjusted Hazard Ratios (HRs) with 95% Confidence Intervals (CI). Results Of the 4,067 TNF-inhibitor treatment periods identified from ROB-FIN, 3,345 periods from 2,641 patients met the inclusion criteria, accumulating a total of 5,620 patient years. Median baseline age and DAS28 score were 55 and 3.8, respectively while 74% of the included patients were women. Etanercept, adalimumab, infliximab, golimumab and certolizumab Pegol were used by 1320 (39%), 1306 (39%), 333 (10%), 195 (5.8%) and 191 (5.7%) patients, respectively. Infliximab (34%) and golimumab (20%) were associated with the highest and the lowest percentages of patients discontinuing their treatment within one year, respectively while the overall percentage was 23%. Infliximab (HR 2.2, 95% CI 1.6–3.1) and certolizumab pegol (HR 1.8, 95% CI 1.3–2.6) had lower drug survival when compared to golimumab. Similar although statistically non-significant trend was seen with adalimumab (HR 1.3, 95% CI 0.99–1.8) and etanercept (HR 1.4, 95% CI 0.99–1.8) as well. Concomitant use of methotrexate (MTX) with or without any additional csDMARDs was associated with improved drug survival (HR 0.78, 95% CI 0.66–0.92) in comparison with TNF-inhibitor monotherapy. Conclusions We found that golimumab was better in terms of drug survival than infliximab or certolizumab pegol and at least as good adalimumab and etanercept. Concomitant use of MTX improves drug survival on TNF-inhibitors. References Neovius M et al. Ann Rheum Dis 2015;74:354–60. Flouri I et al. Semin Arthritis Rheum 2014;43:447–57. Acknowledgement This study was sponsored by MSD. In addition, ROB-FIN has received financial support from the following pharmaceutical companies: Abbvie, Pfizer and Roche. Disclosure of Interest None declared

Background Finnish national combination treatment trials [1,2] have demonstrated excellent outcomes in patients with early rheumatoid arthritis (RA) including 90% of patients reaching 28-joint Disease Activity Score (DAS28) remission. Whether similar results are reached in clinical praxis is not known. Objectives To assess what proportion of patients with dmard-naive early rheumatoid artritis (RA) reach DAS28 remission over one year and remission variability across clinics in Finland Methods Patients with dmard-naive inflammatory arthritis diagnosed as new early RA were recruited. Comparison among sites were made in proportion of patients in 28-joint Disease Activity Score with 3 variables (DAS28–3) remission. Repeated measures were analyzed using mixed models approach with appropriate distribution and link function. Results 611 patients were recruited at 5 sites: 67% female; the mean age (SD) at diagnosis was 57 (16) years; respective 71% and 68% were RF and AntiCCP positive; 23% had radiographic erosions. A total of 506 (83%) fulfilled the ACR/EULAR 2010 classification criteria for RA for further analyses. DAS28–3 remission was met by 68% and 75% at 3 and 12 mo, respectively. Clinic had no effect in remission when adjusted for confounders (Figure 1). At baseline, a total of 68% used MTX based combination therapy, and 31% used triple therapy with methotrexate, hydroxychloroquine and sulphasalazine. In multivariate analysis, the only independent predictors of DAS28–3 remission at 12 mo were lower baseline DAS28–3 (odds ratio 0.6, 95% confidence interval 0.4–0.7, P P =0.048). Conclusions Three out of every four dmard-naive early RA patients are in remission in Finland after 1 year of diagnosis. High remission rates were achieved with use of csDMARDs in combinations for majority of patients. Treatment with triple therapy is a predictor of DAS28–3 remission also in real-life rheumatology settings. References Mottonen T, Hannonen P, Leirisalo-Repo M, Nissila M, Kautiainen H, Korpela M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: A randomised trial. FIN-RACo trial group. Lancet 1999; 353:1568–73 Leirisalo-Repo M, Kautiainen H, Laasonen L, Korpela M, Kauppi MJ, Kaipiainen-Seppanen O, et al. Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study). Ann Rheum Dis 2013;72:851–7 Acknowledgement We would like to thank study nurses. This study was supported by Pfizer. Disclosure of Interest None declared

Background Efficacy of Tumor Necrosis Factor (TNF)-inhibitors in treatment of rheumatoid arthritis (RA) measured in randomized controlled trials (RCTs) may not be fully generalizable to routine care owing to the stringent inclusion criteria [1]. Objectives The objective of this study was to observe the effectiveness of TNF-inhibitors in Finland and to assess the real-world patients9 potential eligibility for the RCTs. Methods RA patients starting a TNF-inhibitor as their first, second or third biologic treatment between 2004 and 2014 were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is an observational cohort study. Effectiveness was measured using the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria and as the proportion of patients reaching Disease Activity Score 28 (DAS28) remission. Logistic regression was employed to identify any predictors of achieving EULAR response. The patients9 baseline characteristics were compared against the inclusion criteria of 28 RCTs identified from two systematic reviews [2,3]. Treatment responses measured in the RCTs were compared to those achieved by routine care patients either eligible or not eligible for the same RCTs. Results Of the 4067 TNF-inhibitor treatment periods, 2259 periods from 1899 patients with valid baseline visit were included in this study. The included patients were predominantly female (73%) with a median age of 55. Adalimumab, etanercept infliximab, golimumab and certolizumab pegol accounted for 41%, 40%, 9.7%, 5.1% and 4.6% of the medication periods, respectively. Moderate and good EULAR responses at 6 months were achieved by 69% and 40% of the users of the first biologic drug, respectively. ACR20, ACR50 and ACR70 responses were reached by 47%, 25% and 13%, respectively. DAS28 remission was reached by 45%. Concomitant use of methotrexate (MTX) was associated with higher odds of achieving at least moderate EULAR response (odds ratio 1.8, 95% confidence interval 1.1– 3.0) as compared to TNF-inhibitor monotherapy. Golimumab and certolizumab pegol were possibly more effective than infliximab, depending on whether the discontinuers were included in the analysis or not. Only 3.8% to 50% of the patients would have been eligible for the included RCTs. The eligible patients had generally better ACR50 responses as compared to the non-eligible ones. Conclusions Different TNF-inhibitors were mostly equipotent in routine clinical practice, but the use of MTX co-therapy had a major influence on treatment response. The efficacy of TNF-inhibitors measured in RCTs cannot be directly generalized into Finnish routine healthcare. References Zink A et al. Arthritis Rheum 2006;54:3399–407. Nam JL et al. Ann Rheum Dis 2010;69:976–86. Nam JL et al. Ann Rheum Dis 2014;73:516–28. Acknowledgement ROB-FIN has received financial support from the following pharmaceutical companies: Abbvie, MSD, Pfizer and Roche Disclosure of Interest None declared

We describe a patient with the m.3243AG mitochondrial DNA mutation who developed sepsis caused by Streptococcus constellatus. In the acute phase of illness, abnormally high uptake of (18)F-FDG was observed in both adrenal glands that appeared anatomically normal. In repeated imaging six months later the adrenal uptake had diminished but remained clearly elevated. We did not observe high adrenal FDG uptake as in the patient described here among 30 patients with Staphylococcus aureus sepsis that were investigated with identical imaging protocol. In sepsis, oxygen consumption and metabolic rate are increased compared to normal metabolism. The observed high adrenal FDG uptake during sepsis in this patient probably reflects the acute metabolic stress induced by the infection. Interestingly, in repeated imaging six months later, the adrenal SUVs had diminished but were still abnormally high: this suggests constant high levels of metabolic stress associated with the mitochondrial disorder.

Objective.To evaluate the performance of biological drugs in psoriatic arthritis (PsA) in a routine care setting, using the Finnish national register of biological treatment (ROB-FIN).Methods.Patients with PsA who started therapy with infliximab or etanercept between June 2000 and February 2006 (n = 127) were followed for up to 24 months. Response was evaluated using American College of Rheumatology response criteria including individual measures.Results.Significantly diminished values for swollen and tender joints, patient’s global and pain assessments, doctor’s global assessment of disease activity, erythrocyte sedimentation rate, C-reactive protein, and Health Assessment Questionnaire score were observed within 3 months after commencement of both infliximab and etanercept. Values remained significantly lower throughout the 24 months of followup. ACR20 response at 3 months was 79% (n = 22/28) for infliximab and 76% (n = 34/45) for etanercept. The first biological drug was discontinued in 16% due to lack of effectiveness and in 6% due to adverse events.Conclusion.Anti-tumor necrosis factor-α therapy, often combined with conventional disease-modifying antirheumatic drugs, appeared to have limited toxicity and persistent effectiveness for up to 2 years in a cohort of Finnish patients with severe peripheral PsA.

Background Finnish national combination treatment trials [1, 2] have demonstrated excellent outcomes in patients with (ERA) including 90% of patients reaching DAS28 remission at 6 months. Whether similar results are reached in clinical praxis is not known. Objectives We describe characteristics, disease activity, and DAS28-remission rates at 3 months in ERA patients treated in 5 Finnish outpatient clinics. Methods FIN-ERA is the first national multicenter observational cohort of adult patients with early inflammatory arthritis clinically diagnosed as RA between Oct 2011 and Sep 2014. Data comprising demographic, clinical and treatment characteristics were collected as a part of routine care. Treatment decisions were made by treating rheumatologists with cooperation with the patient at each clinic. Finnish treatment recommendations emphasize early and active therapy with csDMARDs and prednisolone starting at the diagnosis, and unlimited glucocorticoid injections to all swollen joints. Results Out of 605 recruited patients, 586 completed baseline and 3 months visit and had full data for disease activity score (DAS28-3) with ESR. In the entire cohort, the mean age was 56±16 yrs, the median (IQR) duration of symptoms was 6 (3,11) mo, rheumatoid factor (RF) and anti cyclic-citrullinated peptide antibodies (anti-CCP) were positive in 68% (data for N=569) and 69% (data for N=584), respectively. Twenty three percent of patients had radiographic erosions at baseline. A total of 498 (85%) fulfilled the ACR/EULAR 2010 classification criteria for RA. Figure 1 represents the mean DAS28-3 at baseline and at 3 mo at FIN-ERA clinics A-E. The respective mean HAQ and DAS28 (with ESR, 4 variables,DAS28-4) were 0.4±0.5 (data for N=431) and 2.2±1.0 (data for N=457). A total of 68% (data for N=457) met DAS28-4 remission at 3 mo. Remission rates were similar in patients classified as undifferentiated arthritis (15% of the cohort).DAS28-4 remission rates at sites A-E were 75% (data for N=188), 64% (data for N=78), 70% (Data for N=54), 61% (Data for N=54) and 60% (data for N=83). Conclusions Two thirds of ERA patients reach early DAS28 remission in Finland at 3 months. References Mottonen T, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: A randomised trial. FIN-RACo trial group. Lancet 1999 Leirisalo-Repo M, et al. Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study). Ann Rheum Dis 2012. Acknowledgements We would like to thank study nurses L. Miina, S. Sarakari, M.Lemmetty, K.Arvola, and T.Reini. This study was supported by Pfizer. Disclosure of Interest None declared