Abstract Background The ESC/ERS 2015 guidelines presented a comprehensive risk assessment model with three risk categories based on different clinical and biomarkers data. Low, intermediate and high risk were defined with one-year mortality of <5%, 5–10% and >10%. Different groups suggested different methods of risk assessment based on this model. Purpose We applied three different methods to validate the ESC/ERS risk prediction model for one-year survival in SSc-PAH. Methods 309 patients with SSc-PAH have been diagnosed and managed in our institution from 2006 to 2017. We used three different risk assessment models that have been previously suggested. 1. Suggested by the Swedish group 1: Having a score of 1 (low risk), 2 (intermediate risk) or 3 (high risk) resulting from the average of the sum obtained after grading each of the variables (whichever available) from 1 to 3 according to ESC/ERS guidelines cut-offs for WHO-functional class (FC), 6-minute walking distance (6MWD), NT-Pro BNP, right atrial pressure (RAP) and cardiac index (CI). 2. Suggested by the French group 2: Having none, 1, 2, 3 or 4 of the following low-risk criteria of; FC, 6MWD, RAP and CI. 3. Instead of the invasive data, The French group also suggested the use of a non-invasive model including NT-Pro BNP. Patients were divided into different risk groups according to data obtained at baseline and at their 6-month follow-up. Survival analysis over a 5-year period was performed using Kaplan-Meier analysis. Results Overall median follow-up was 33.3 months. One year survival was significantly different between the risk groups (p<0.001) using either baseline or follow-up data. Applying the French group non-invasive model, almost two thirds of the population ended up in the higher risk group. Whilst applying the Swedish model, two thirds of the population ended up in the intermediate risk group. In all the models used, there were significantly less number of patients in the lower risk groups at onset with improvement of risk profile at follow up. An important advantage of the Swedish model, that it can be calculated even in the presence of missing data, a problem commonly encountered. The French models are easier to calculate but they cannot be applied when there is missing data. 5-year survival with different models Conclusion All models used were valuable in risk prediction of SSc-PAH both at onset and at follow up. However, each model has some caveats which should be considered. In all the methods used, the prevalence of high risk criteria is higher amongst the SSc-PAH population which indicates the higher risk profile at the time of diagnosis in comparison to other PAH populations, which could explain the poorer outcome.

Background: Accidental hypothermic cardiac arrest is associated with unfortunate prognosis and large studies are rare. We therefore have performed an outcome analysis in patients that were admitted to Vienna University Hospital with the diagnosis of accidental hypothermic cardiac arrest.Methods: This study employed a retrospective outcome analysis of prospectively collected data in a selected cohort of hypothermic cardiac arrest patients. We screened 3800 cardiac arrest patients, treated at our department between 1991 and 2010, for eligibility. Inclusion criteria were cardiac arrest with a body core temperature <= 28 degrees C and return of spontaneous circulation.Results: A total of 18 patients who achieved return of spontaneous circulation were analysed. Nine patients (50%) achieved survival in good neurologic condition (defined as cerebral performance category CPC 1 or 2). Accidental hypothermia with consecutive cardiac arrest was caused by intoxication in most cases (67%). These patients had a better outcome than patients with other causes of accidental hypothermic cardiac arrest (OR = 28; 95%KI 2-37.9; p < 0.01). Hypothermia associated typical ECG changes after return of spontaneous circulation (Osborne waves) were more frequent in the surviving population (OR 16; 95%KI 1.3-19.5; p = 0.05).Conclusions: Accidental hypothermic cardiac arrest in a central European urban area is rare. Prognosis was excellent in patients where hypothermic cardiac arrest was caused by intoxication. (C) 2014 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.

Background Primary Sjögren Syndrome (pSS) has an estimated prevalence of 0.2%. Connective tissue disorders are known risk factors for causing pulmonary arterial hypertension (PAH). The association of PAH and pSS is rare. Objectives To examine the incidence of PAH in pSS and to review the clinical, hemodynamic parameters and medical management of each case. Methods We included 1,036 patients followed in a specialist Pulmonary Hypertension Centre between 1996-2010. History of appetite suppressant intake, thyroid hormone level and human immunodeficiency virus (HIV) serology were collected to rule out other causes of PAH. Cardiac echo-doppler excluded congenital heart disease. A ventilation/perfusion lung scan, a spiral computed tomography of the chest, and a pulmonary angiography if necessary were performed to exclude chronic thromboembolic pulmonary hypertension. Of 1036 patients, 79% had systemic sclerosis, 7% had SLE, 5% had mixed connective tissue disease, 2.5% had undifferentiated connective tissue disease, 2% had myositis and the remainder had overlap diseases. Seven patients (<1%) fulfilled the 2002 revised criteria for pSS proposed by the American-European Concensus group. All patients with secondary SS were excluded. In 7 patients with pSS who underwent a right heart catherisation (RHC), 4 patients had PAH (mean pulmonary arterial pressure ≥25mmHg and pulmonary capillary wedge pressure <15mmHg), 1 patient had post capillary pulmonary hypertension (mean pulmonary arterial pressure ≥25mmHg and pulmonary capillary wedge pressure >15mmHg) and 2 patients did not have pulmonary hypertension. Results All patients with pSS and PAH were female with a mean age at PAH diagnosis of 61.8 ± 10.8 years. Clinical presentation of PAH was severe in all cases: WHO functional class (FC) was III in patients 1-3 and IV in patient 4. Mean 6-minute walk distance was 310 ± 105m (range, 152-448m). Overall, PAH was severe with a mean mPAP of 51 ± 12mmHg. Among the 4 patients, patients 1 and 2 received Bosentan therapy alone, patient 3 received a combination of Bosentan and Sildenafil and patient 4 received inhaled Iloprost alone. Patient 4 did not have a repeat RHC at 3-4 months. The remaining three patients showed a reduction in mPAP with no change in WHO FC at 3-4 months (Table 1). Two patients died from PAH at 35 (patient 2) and 26 (patient 4) months after diagnosis. Conclusions PAH in pSS is rare and to our knowledge, there are less than 50 published case reports in the English literature. We report a case series of four patients with pSS and PAH over 14 years in a specialist pulmonary hypertension centre. Standard PAH therapies (endothelin receptor antagonists, phosphodiesterase type 5 inhibitors or prostanoids) were initially effective but the best treatment strategy remains to be defined. Disclosure of Interest None Declared

Background Pulmonary hypertension (PH) is a severe complication of systemic sclerosis (SSc), affecting 5-12% of patients. Despite recent progress in treatment, prognosis remains poor. Early therapeutic management and goal-oriented approach can improve long-term prognosis. Response to therapy is usually assessed by functional and hemodynamic parameters between 3-6 months after initiation of treatment. Objectives To compare the changes in NT-proBNP with functional and hemodynamic parameters between baseline and 3-6 months after initiation of therapy. Methods A retrospective study, undertaken in a National Pulmonary Hypertension Centre, identified patients diagnosed with pre-capillary PH on right heart catheterisation (RHC) (mean pulmonary arterial pressure (mPAP) ≥ 25mmHg and pulmonary capillary wedge pressure (PCWP) ≤ 15mmHg) between January 2006 and August 2012. Patients were included if they had a second RHC between 3 and 6 months after the initial RHC diagnosing PH and if NT-proBNP results were available within 30 days prior to each RHC. 48 patients were identified. 2 patients with glomerular filtration rate < 30 mL/min/1.73m2 were excluded. Changes in variables (Δ) between baseline and 3-6 months were calculated in absolute value, percentage of variation and logarithm of each value. Pearson or Spearman methods were used to estimate correlation coefficient, where appropriate. Patients were divided into two groups: D=“NT-proBNP decreasing” and I/S=“NT-proBNP increasing or stable” according to the difference in NT-proBNP levels between baseline and repeat RHC. Survival analyses were performed using Kaplan-Meier method and log-rank test. Results 46 patients (40 female and 6 male) were included. 78% had limited cutaneous SSc and 51% were anti-centromere antibody positive. The mean age at diagnosis of PAH was 62.1 ± 11.5 years; the mean time between both RHCs was 3.6 ± 1.0 months and the mean follow-up after first RHC was 28.0 ± 15.4 months. Mean mPAP and PVR (pulmonary vascular resistances) significantly decreased with therapy (ΔmPAP: -3.2mmHg, p<0.001; ΔPVR: -75dynes.s.cm-5, p<0.001), even in the group I/S. PCWP tended to increase in the group I/S (9.9 ± 3.7mmHg at baseline vs 10.9 ± 4.0 after 3-6 months, p=0.072). In the total population, ΔNT-proBNP in absolute value was negatively correlated with Δ6MWD (six minute walking distance) in absolute value (R= -0.362, p=0.017) or percentage (R= -0.525, p<0.001) and with ΔmPAP in percentage (R= -0.327, p=0.027). No correlation was found between ΔNT-proBNP in percentage or in log with PVR, mPAP, cardiac output, cardiac index, venous oxygen saturation, right arterial pressure, PCWP and 6MWD. At 28 months, no difference in survival was found between the two groups (73% in group D and 67% in group I/S). Conclusions A significant improvement occurred in both hemodynamic parameters and NT-proBNP levels at 3-6 months. However, no strong or clinically relevant correlation was found between RHC or 6MWD and ΔNT-proBNP. Changes in NT-proBNP levels do not seem to be associated with response to therapy or prognosis. Acknowledgements Dr Vincent Sobanski has received research grants from Association des Sclérodermiques de France, Société Nationale Française de Médecine Interne, Groupe Pasteur-Mutualité, GSK and Institut Servier. Disclosure of Interest None Declared

Anti-aquaporin-4 autoantibodies are specific for the neuromyelitis optica spectrum disorders (NMOSD) and they have also been described in patients with systemic lupus erythematosus (SLE) with neurological signs consistent with NMOSD. Our objective was to test for the presence and pathogenicity of anti-AQP4 antibodies in SLE patients without neurological disease.Sera from 89 non-CNS-SLE patients were screened for anti-AQP4 autoantibodies. Two of the 89 patients were positive. Archived samples dating back 11 years were also positive. A brain and spinal cord MRI did not reveal any NMOSD-compatible lesions. An in vitro cytotoxicity assay showed that either sera or purified IgG from these patients induced a complement-mediated damage in cultured astrocytes comparable to antibodies obtained from typical NMO patients.We conclude that AQP4-antibodies can be present in SLE patients and persist for many years, without concurrent clinical or radiological NMOSD signs. It is unclear why the anti-AQP4 antibodies did not induce CNS disease.

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception (“I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire (“it’s not cosmetic surgery; it’s something that’s more important than that, you know?”). Clinician opinion: Surgeons’ post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients’ lasting impression irrespective of how the outcome compared to their initial goals (“when he’d done it … he said that hasn’t worked as good as he’d wanted to … but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously (“in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons’ appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interest.

Background: B cell depletion therapy (BCDT) using rituximab, a monoclonal antibody targeting CD20, was first used for systemic lupus erythematosus (SLE) in 2000 for patients refractory to conventional immunosuppressants. Although the successful use of BCDT has been reported in open label studies randomized controlled trials in SLE have not met their endpoints. SLE is a heterogeneous disease and it is possible that variation in response to BCDT might be due to differences in the rate of B cell repopulation and/or serological and cellular factors in treated patients. The aim of this study was to correlate the repopulation of B cells with disease relapse after BCDT and to identify any differences in B cell numbers and phenotype between patients with active disease according to other disease parameters. Methods: Fifty-nine patients with refractory SLE treated with BCDT using a combination of rituximab, cyclophosphamide and methylprednisolone were followed up for a minimum of 18 months or until relapse if this occurred within 18 months. Patients were assessed with the ‘classic' British Isles Lupus Assessment Group (BILAG) activity index. Relapse was defined as a new BILAG ‘A’ or two new ‘B’s in any organ system. Anti-dsDNA antibody titres, complement and leukocyte numbers were measured at baseline and relapse. B cell phenotypes were measured at relapse by flow cytometry using the markers CD19, IgD and CD27. Results: The median time to relapse following BCDT was 16 months. During repopulation B cell numbers remained below baseline numbers for up to 9 months (p < 0.01). B cell numbers (normal range 0.11-0.50 x109 cells/L) increased more rapidly in patients that relapsed (within 18 months) compared to those that remained in remission (p < 0.01). At relapse, B cell numbers were lower than at baseline (p < 0.05). Patients that relapsed with very low B cell numbers (<0.01x109 cells/L) had the lowest B cell numbers at baseline (P < 0.05) and the highest anti-dsDNA antibody titres (normal range 0-50 IU/mL) at relapse (P < 0.05). Relapse with high anti-dsDNA antibody titres (>100 IU/mL) was associated with an increased percentage of IgD-CD27hi switched plasmablasts (p < 0.05) whereas relapse with low anti-dsDNA antibody titres was associated with an increased percentage of IgD-CD27- memory B cells (p < 0.05). Conclusions: Whilst clinical trials have not confirmed the reported benefit of BCDT in SLE this study shows that early relapse was associated with faster rates of B cell repopulation despite similar levels of depletion. The number of B cells and the B cell phenotype found at relapse differed according to the anti-dsDNA antibody titres. This data suggest that different pathologies might exist in patients with low anti-dsDNA antibody titres compared to those with high titres, possibly governed by specific B cell subsets. Future clinical trials in SLE should take into account serological and cellular variation between patients. Disclosure statement: D.I. has received honoraria from Roche, Vifor, GlaxoSmithKline, Teva and Merck Serono; these were donated to a local arthritis charity. All other authors have declared no conflicts of interest.

9545 Background: The combination of ifosfamide, carboplatin, and etoposide (ICE) has previously been demonstrated to be an effective regimen in children with recurrent or refractory solid tumors (Cairo et al JPHO, 2001). Substituting topotecan (a Topoisomerase I inhibitor) for etoposide (a Topoisomerase II inhibitor) may be a more efficacious regimen due to the cytotoxic activity of topotecan in pediatric solid tumor xenografts, as well as its in vitro synergistic activity with platinum and alkylating agents (Houghton et al CCP, 1992). Methods: In this limited institution study, we evaluated the addition of escalating doses of topotecan with fixed doses of ifosfamide and carboplatin. Patients initially received ifosfamide 3,000 mg/m2/day × 3 days, carboplatin dosed to an AUC of 3 mg/ml/min (equivalent to 250 mg/m2/dose) × 3 days, and topotecan × 3 days. 6 patients were enrolled at dose level #1 (topotecan: 0.5 mg/m2/day), with 2 patients having ifosfamide related neurotoxicity (related to the dosing schedule). The schedule was amended to 1,800 mg/m2/day × 5 days with 6 further patients enrolled at dose level #1 and no further reports of neurotoxicity. 3 patients were enrolled at dose level #2 (topotecan: 0.75 mg/m2/day). Results: 14 patients (3-18 yrs) with relapsed/refractory disease and histological verification of their disease at the time of initial diagnosis or relapse were enrolled on this study (Wilms 2; osteosarcoma 2; germ cell tumor 2; high grade glioma 1; rhabdomyosarcoma 1; sarcoma 1; non-Hodgkin's lymphoma 1; neuroblastoma 1; medulloblastoma 1; hepatoblastoma 1; neurocytoma 1). Overall, 2 DLT's (dose level #1: hematologic; dose level #2: hematologic and infection) were observed with a median of 3 cycles being administered (range: 1-3). Disease response showed 4/14 with CR, 2/14 with PR, and 1/14 with SD for an overall response rate (ORR) of 43%. Conclusions: These preliminary results demonstrate that the combination of topotecan, ifosfamide, and carboplatin (TIC) is feasible, induces a ≥40% ORR in relapsed/refractory patients, and warrants further study in children with CNS and solid tumors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline