Abstract Aim This audit aims to assess the conformity of operative notes to the guidelines established by the Royal College of Surgeons England (RCSEng). Method We prospectively collected and analysed the date over a two-week period before we introduced the intervention. We created a poster featuring the guidelines and placed it in the vascular operating theatres. We also introduced an electronic operative note system in vascular surgery. The reaudit commenced two weeks after the intervention. Result: All operative notes contained the date and time, names of surgeons, details of the operative procedure, descriptions of tissue removed, identification of prosthetics, and the surgeon's signature. Some areas saw significant improvement with the intervention, such as incision (26% to 89%), operative diagnosis (58% to 93%), closure technique (92% to 100%), and post-operative instructions (83% to 93%). However, there was a lack of documentation on DVT prophylaxis and antibiotic prophylaxis in both loops, resulting in a decrease from 63% to 50% for DVT prophylaxis and from 38% to 14% for antibiotic prophylaxis. Only two electronic operative notes were recorded in the second loop. Conclusions Some areas showed improvement, but not all achieved full compliance. The majority of vascular surgeons continued to utilize handwritten operative notes due to logistical and technological challenges. It is recommended that a future re-audit be conducted over a longer period of time, during which a greater number of cases should be reviewed.

Abstract Background Primary prevention of cardiovascular events in people with Type 2 diabetes mellitus (T2DM) needs to improve due to risk of cardiovascular events. A major problem in T2DM is the high incidence of silent yet potentially lethal cardiac abnormalities, namely myocardial ischaemia (MI), left ventricular hypertrophy (LVH), left ventricular systolic dysfunction (LVSD), left ventricular diastolic dysfunction (LVDD), and left atrial enlargement (LAE). All these independently predict cardiovascular events and mortality. There is not a single study with comprehensive enough cardiac phenotyping to document the prevalence of all the aforementioned 5 cardiac abnormalities. To improve primary prevention of cardiovascular disease in diabetes, we need to first identify the type of silent cardiac abnormality and treat accordingly. However cardiac phenotyping in all people with T2DM would be prohibitively expensive. Purpose Our study examines the prevalence of all 5 cardiac abnormalities, and the accuracy of biomarkers in identifying them in a cohort of patients with well-controlled T2DM and blood pressure (BP) with no known cardiovascular symptom or disease. Methods This is a cross-sectional study of randomly selected patients with T2DM with no known cardiovascular symptom or disease, clinic BP or average 24-hour BP ≤140/80mmHg, and HbA1c ≤64mmol/mol. Patients with renal impairment, atrial fibrillation, moderate to severe valvular heart disease were excluded. All participants underwent transthoracic echocardiogram, electrocardiogram and dobutamine stress echocardiogram (DSE). Those who did not tolerate DSE or whose DSE was inconclusive, a myocardial perfusion scan or computed tomography coronary angiogram was done. Biomarkers such as BNP, NT-proBNP, high-sensitivity cardiac Troponin I (hs-cTnI), and high sensitivity cardiac Troponin T (hs-cTnT) were measured. Results Of 246 participants (mean age 66 years, 63% male), 141 (57.3%) had silent cardiac abnormalities. 90 (36.6%) had 1 cardiac abnormality, 44 (17.9%) had 2 cardiac abnormalities and 7 (2.8%) had 3 cardiac abnormalities. The most prevalent abnormality was LAE, n=106 (43.1%); followed by LVH, n=71 (28.9%); LVDD, n=13 (5.3%); MI, n=8 (3.3%); LVSD, n=1 (0.4%). Both NT-proBNP and hs-cTnI performed best in detecting silent cardiac abnormalities with p-values of 0.02 and 0.0004, and AUC 0.66 and 0.68 respectively. Increasing NT-proBNP (p=0.002) and hs-cTnI (p=0.002) levels correlated to increasing number of concomitant cardiac abnormalities. Our key new finding is that biomarkers identify those with multiple silent cardiac abnormalities. Conclusion BNP and high-sensitivity cardiac Troponin appear to identify those with multiple silent cardiac abnormalities which may make them useful screening tests so that cardiac investigations are focused on this high-risk subset, with a view to intensifying potential therapies on this subset to reduce the cardiotoxic effect of diabetes. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Chief Scientist Office

Background: Given the unmet clinical needs in systemic lupus erythematosus (SLE), including poor disease control and drug toxicities, new therapies are needed. In a phase 2, randomized, placebo-controlled, double-blind study (JAHH), once-daily baricitinib (bari) resulted in significant clinical improvement in patients (pts) with active SLE versus PBO. Bari inhibits JAK1 and JAK2 signalling, and in turn may affect STAT1, STAT2, STAT4 pathways. Therefore, bari has the potential to simultaneously impact several pro-inflammatory immune cytokines implicated in the pathogenesis of SLE, including IFN-α, IFN-γ, IL-6, IL-12, and IL-23. Objectives: The objectives of the current study were: 1) to examine baseline serum cytokines in the JAHH phase 2 clinical trial for correlations with clinical or immunologic assessments; 2) to determine if changes in serum cytokine levels were associated with bari treatment. Methods: Pts enrolled in the JAHH phase 2 trial received daily treatment with PBO, bari 2 mg, or bari 4 mg through week 24. Serum samples were collected at baseline (week [wk] 0), wk 12, and wk 24) from SLE pts (n=270) and 50 sex- and age-matched controls. Samples were analyzed for: IL-2, IL-3, IL-5, IL-6, IL-10, IL-17A, IL-21, IL-12/23p40, IL-12p70, GM-CSF, IFN-α and IFN-γ using ultrasensitive quantitative assays. IFN gene signature, autoantibodies, C3 and C4 were measured as previously described [1]. Results: At wk 0, serum IL-17A, IL-12/23p40, IL-6, IFN-γ and IFN-α were readily detectable. IL-12/23p40 was detectable in 100% of pts vs. 100% of controls, IFN-γ in 89% of pts vs. 66% of controls, IL-6 in 53% of pts vs. 12% of controls and in IFN-α 41% of pts vs. 2% of controls; detection of serum IL-2, GM-CSF, IL-5, IL-10 and IL-17A was variable (Fig 1). At baseline (wk 0), IL-12/23p40 was positively correlated with SLEDAI and IFN gene signature and negatively correlated with serum C4. IL-6 was positively correlated with joint swelling, joint tenderness, IFN-γ and C3. Serum IFN-α was positively correlated with serum IFN-γ, anti-Sm and anti-RNP, and the IFN gene signature (Fig 2). Treatment with bari 4 mg (Fig 1B) significantly decreased serum IL12/23p40 and IL-6 cytokine levels at wk 12 (p<0.05) but not serum IFN-α or IFN-γ levels (Fig 1B). Figure 1. * p = 0.015; ** p = 0.001; Abbreviations: LLOQ, Lower limit of quantification. Figure 2. Abbreviations: Anti-dsDNA, Anti-double stranded DNA; Anti-RNP, Anti-ribonucleoprotein; CLASI, Cutaneous lupus erythematosus disease area and severity index; SLEDAI, SLE disease activity index. Conclusion: Bari 4 mg treatment was associated with statistically significant decreases of serum IL-12/23p40 and IL-6 at week 12 which continued through week 24. Serum IFN-α or IFN-γ were not reduced with bari treatment. Thus, bari 4 mg simultaneously impacted multiple pro-inflammatory cytokines implicated in the pathogenesis of SLE. References: [1]Hoffman RW, et al. Arthritis Rheumatol. 2017;69(3):643-654. Disclosure of Interests: Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Michelle A Petri Grant/research support from: GSK, Eli Lilly and Company, Consultant of: Eli Lilly and Company, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Daniel Wallace Consultant of: Amgen, Eli Lilly and Company, EMD Merck Serono, and Pfizer, Brenda Crowe Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ernst Dow Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Richard E Higgs Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Guilherme Rocha Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Robert Benschop Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Maria Silk Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Stephanie de Bono Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Robert Hoffman Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Damiano Fantini Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company

Triterpene saponins include bioactive compounds with structures consisting of triterpene aglycones (sapogenins) and one or more sugar moieties linked through acetal or ester glycosidic linkages at one or more sites. Centella asiatica (L.) Urban is a medicinal plant that contains bioactive ursane-type saponins, such as madecassoside and asiaticoside. In this work, glucosylation of triterpenoids in C. asiatica was investigated starting with plant extracts. An enzyme capable of glucosylating asiatic and madecassic acids was partially purified. Proteomics methods and cDNA sequence data were employed as tools to obtain a full-length cDNA clone encoding a glucosyltransferase. The recombinant gene product, UGT73AD1, was functionally expressed in Escherichia coli and purified by immobilized metal-affinity chromatography. Purified recombinant UGT73AD1 was found to have a narrow specificity, glucosylating asiatic and madecassic acids at the C28 carboxyl. mRNA accumulated in all tissues tested (leaves, stems, roots and flowers), with highest expression in leaves. Thus, UGT73AD1 was identified as a triterpenoid carboxylic acid: UDP-glucose 28-O-glucosyltransferase that appears to be involved in saponin biosynthesis in C. asiatica.

Background: AGEN1884 is a novel anti–cytotoxic T-lymphocyte-associated antigen (CTLA)-4 fully human immunoglobulin (IgG)-1 monoclonal antibody. Objective: Assess safety, maximum tolerated dose, and pharmacokinetics (PK)/pharmacodynamics of AGEN1884 in patients (pts) with advanced/refractory malignancies and in pts refractory to recent anti–programmed death 1 (PD-1)/PD-L1 therapy. Methods: Adult pts with relapsed/refractory lymphoma or solid tumors received AGEN1884 at 0.1, 0.3, 1, 3, or 6 mg/kg (3 + 3 design). 10 more pts each were enrolled in 1 and 3 mg/kg expansion cohorts. 10 pts with disease progression after prior treatment with approved or investigational PD-1/PD-L1 inhibitor as most recent therapy (2–5 weeks [wks] before first study drug) will be enrolled at 1 mg/kg. AGEN1884 was administered intravenously Q3 wks for 4 doses, then Q3, 6, or 12 wks at investigator's discretion. Results: 33 pts enrolled as of 03Jan2018: 0.1 mg/kg (n = 5; 2 not evaluable [NE] for dose-limiting toxicity [DLT]); 0.3 mg/kg (n = 3); 1 mg/kg (n = 10); 3 mg/kg (n = 12; 2 NE for DLT); 6 mg/kg (n = 3). Median age: 61 y (range 26–88); baseline ECOG scores: 0 (n = 4), 1 (n = 25), unknown (n = 4); median 10 (range 3–26) prior therapies. No DLTs reported as of 31Jan2018. Immune-related adverse events (AEs) reported in 10 (30.3%) pts: 0.1 mg/kg (1, 20.0%), 0.3 mg/kg (1, 33.3%), 1 mg/kg (1, 10%), 3 mg/kg (6, 50%); included hypophysitis, colitis, diarrhea, rash, pruritus. Most were mild-moderate, consistent with other CTLA-4 inhibitors. 6 (18.2%) pts came off study due to disease progression or AEs, none treatment-related. Of 11 pts evaluable for response, 1 had complete response (angiosarcoma, 0.1 mg/kg). Stable disease (SD) in 3 pts: 1 with adenoid cystic carcinoma (0.3 mg/kg, 53 wks of SD) and 2 with breast cancer (3 mg/kg, SD at wks 6 and 12, respectively). Conclusions: AGEN1884 was well tolerated at 0.1, 0.3, 1, and 3-mg/kg dose levels. Enrollment is ongoing at 6 mg/kg. Updated safety, PK, and results for the anti–PD-1/PD-L1 refractory expansion cohort will be presented. A starting dose of 1 mg/kg is being evaluated in ongoing trials in combination with PD-1 blockade. Clinical trial identification: NCT02694822. Editorial acknowledgement: Editorial support was provided by The Medicine Group, LLC (New Hope, PA, USA) and funded by Agenus Inc. (Lexington, MA). Legal entity responsible for the study: The licensed antibody AGEN1884 was originally developed under a Collaborative Research and Development Agreement between Ludwig Cancer Research, 4-Antibody AG (now Agenus Switzerland Inc.) and Recepta Biopharma S.A. This antibody is partnered with Recepta Biopharma S.A. for certain South American rights. Funding: This analysis was funded by Agenus Inc. (Lexington, MA, USA). Disclosure: B.A. Wilky: Employment: Novartis, Janssen Oncology, Lilly; Travel, accommodations, expenses: Novartis, Lilly, Advenchen Laboratories; Research funding: Novartis, Merck Sharp & Dohmn, Daiichi Sankyo, ArQule, Agenus. R. Wesolowski: Consulting or advisory role: Novartis, Agenus, Pfizer; Research funding: Acerta Pharma. J.J. Hwang: Consulting or advisory role: Genentech/Roche, Amgen, Bayer, Taiho Pharmaceutical, Bristol-Myers Squibb, Boehringer Ingelheim, Ipsen; Speakers bureau: Genentech/Roche, Amgen, Celgene, Ipsen, Bristol-Myers Squibb. G. Yuan, M. Lim, J-M. Cuillerot, J.J. Raizer, E. Drouin, N. Wilson, A.M. Gonzalez, J.M. Goldberg, J.S. Buell, R.B. Stein, H. Youssoufian: Employee: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA. C.D. Dupont: Employee: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA; An immediate family member: Employee: Vertex; An immediate family member: Employee: Rochester Eye Associates; Travel, accommodations, expenses: Agenus; Research funding: Agenus; An immediate family member: Vertex, Pfizer, Sanofi. Stock and other ownership: Agenus; An immediate family member: Vertex. O. Shebanova: Employee: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA; Travel, accommodations, expenses: Agenus; Stock and other ownership: Agenus. E. Dow: Employee: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA; Employment: Baxalta/Shire; Foundation Medicine stock and other ownership: Baxalta/Shire, Foundation Medicine. W. Ortuzar: Full time contracted consultant: Agenus Bio, Inc. All other authors have declared no conflicts of interest.

Background: Cytotoxic T-lymphocyte-associated antigen (CTLA)-4 and programmed death 1 (PD-1) pathways have important, distinct roles in T-cell modulation; blockade of both has been synergistic in vitro and in the clinic. This study will assess safety and tolerability of AGEN1884 (anti–CTLA-4 human immunoglobulin [IgG]-1 monoclonal antibody [mAb]) in combination with AGEN2034 (anti–PD-1 human IgG4 mAb) in patients (pts) with advanced/refractory solid tumors, with expansion into select solid tumors. Methods: A dose-escalation phase and expansion focusing on adult female pts with recurrent/metastatic cervical cancer that has relapsed after platinum-containing doublet treatment. Phase 1 (Ph1) pts (n = 20) will be enrolled to 2 dose regimens of AGEN1884 + AGEN2034 (starting: 1 mg/kg AGEN1884 Q6w + 1 mg/kg AGEN2034 Q2w; escalating: 1 mg/kg AGEN1884 Q6w + 3 mg/kg AGEN2034 Q2w). Escalation phase primary endpoints: safety, determination of recommended Ph2 dose (RP2D); Ph2 (n = 40) also includes best overall response assessment by Independent Endpoint Review Committee per RECIST 1.1. Secondary endpoints: AGEN1884 and AGEN2034 pharmacokinetic (PK)/pharmacodynamic (PD) profiles, objective response rate, duration of response, progression-free and overall survival. Results: 0 pts were enrolled 01Dec2017–10Apr2018 in 3 Australia centers: 7 pts at starting dose, 3 pts at escalating dose. No dose-limiting toxicity has been observed; most common toxicities observed were expected for therapeutic class. 8 pts experienced toxicity, mostly grade 1 or 2. Most common toxicities: diarrhea/nausea/vomiting, n = 6; rash/pruritus, n = 2; transaminases elevated, n = 1; fever/flu-like, n = 3; fatigue, n = 2. There was 1 serious adverse event and grade 3 toxicity unrelated to study drug. No discontinuation due to study drug, no deaths observed. Median dose administered was 1 for AGEN1884, 3 for AGEN2034. Dose level 2 was determined for RP2D. Updated safety, efficacy, and PK/PD of AGEN1884 + AGEN2034 will be presented. Conclusions: AGEN1884 (1 mg/kg Q6w) + AGEN2034 (3 mg/kg Q2w) is well tolerated and being evaluated in Ph2 combination in 2L cervical cancer and other solid tumors. Clinical trial identification: ACTRN12618000003279. Editorial acknowledgement: The Medicine Group, LLC (New Hope, PA, USA) and funded by Agenus Inc. (Lexington, MA). Legal entity responsible for the study: The licensed antibodies AGEN1884 and AGEN2034 were originally developed under a Collaborative Research and Development Agreement between Ludwig Cancer Research, 4-Antibody AG (now Agenus Switzerland Inc.) and Recepta Biopharma S.A. These antibodies are partnered with Recepta Biopharma S.A. for certain South American rights. Funding: Agenus Inc. (Lexington, MA, USA). Disclosure: J. Coward: Amgen: ESMO conference 2018 sponsorship MSD: Tumour agnostic advisory board Dec 2017. C.D. Dupont: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA Vertex-An Immediate Family Member Rochester Eye Associates- An Immediate Family Member; Travel, accommodations, expenses: Agenus Research Funding: Agenus; Vertex-family member Pfizer Sanofi Stock and other ownership: Agenus Vertex-family member. A.M. Gonzalez, M. Lim, D. Savitsky, M. Carini, S. Hu, H. Youssoufian: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA. O. Shebanova: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA Travel, Accommodations, Expenses Agenus Stock and other ownership: Agenus. E. Dow: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA employment: Baxalta/Shire; Foundation Medicine Stock and other ownership: Baxalta/Shire; Foundation ;Medicine W. Ortuzar: Full time contracted consultant for Agenus Bio, Inc. J.S. Buell: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA Travel, Accommodations, Expenses: Agenus. R.B. Stein: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA Stock and other ownership: Agenus. All other authors have declared no conflicts of interest.

Background: AGEN2034 is a fully-human immunoglobulin (IgG)-4 monoclonal antibody antagonist targeting programmed death protein 1 (PD-1). The objective was to assess safety, maximum tolerated dose, preliminary efficacy, and pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of AGEN2034 in patients (pts) with advanced malignancies. Methods: 30 pts were enrolled at dose cohorts of 1, 3, and 10 mg/kg. AGEN2034 is given intravenously Q2w for ≤2 years with cohorts at Q3w dosing at 6 and 10 mg/kg. A phase 2 expansion of AGEN2034 3 mg/kg Q2w in pts with relapsed/refractory cervical cancer is under way. Results: 10 pts were enrolled at each dose level. Median age was 58 y, with ECOG scores 0–1. No dose-limiting toxicities were observed. Immune-related adverse events (AEs) consistent with this drug class were observed, including pneumonitis, colitis, diarrhea, rash, and pruritus. 21 of 30 pts had treatment-related AEs (TRAEs). 13 (43%) subjects discontinued (d/c) due to disease progression and 1 patient each d/c due to TRAEs of hepatitis and pneumonitis. At the time of data cutoff, in 25 evaluable heavily pretreated pts, 3 partial responses (2 confirmed) were noted in pts with cervical, ovarian, and breast cancers in the 1 and 3 mg/kg cohorts. 13 patients had stable disease, including 5 of 5 patients with ovarian cancer. AGEN2034 demonstrates a dose-proportional Cmax of 19.6 µg/mL at 1 mg/kg and 73.6 µg/mL at 3 mg/kg in 12 pt samples analyzed in the first 2 cohorts. Average PD-1 receptor occupancy (RO) on circulating CD8+ and CD4+ effector memory T lymphocytes (n = 18) demonstrated >59% saturation at all dose levels at day 15 post infusion. Conclusions: AGEN2034 is pharmacologically active, well-tolerated PD-1 antagonist antibody, demonstrating early signals of clinical activity in cervical and ovarian cancers. PK and RO results are comparable to commercial PD-1 antagonists. Updated safety and efficacy results for the dose escalation and the relapsed cervical cancer cohorts will be presented. (NCT03104699). A phase 2 combination study of AGEN2034 and AGEN1884 (CTLA-4) is under way. Clinical trial identification: NCT03104699. Editorial acknowledgement: Editorial support was provided by The Medicine Group, LLC (New Hope, PA, USA) and funded by Agenus Inc. (Lexington, MA, USA). Legal entity responsible for the study: The licensed antibody AGEN2034 was originally developed under a Collaborative Research and Development Agreement between Ludwig Cancer Research, 4-Antibody AG (now Agenus Switzerland Inc.) and Recepta Biopharma S.A. This antibody is partnered with Recepta Biopharma S.A. for certain South American rights. Funding: Agenus Inc. (Lexington, MA, USA). Disclosure: K.N. Moore: Consulting or advisory role: Genentech/Roche, Immunogen, Advaxis, AstraZeneca, Clovis Oncology, Tesaro, VBL Therapeutics, Janssen Oncology; Travel, accomodations, expenses: Genentech/Roche; Research funding: PTC Therapeutics Lilly. J.F. Liu: Consulting or advisory role: Tesaro, AstraZeneca; Research funding: Genentech/Roche, AstraZeneca, Merrimack, Boston Biomedical, Atara Biotherapeutics, Acetylon Pharmaceuticals, Bristol-Myers Squibb, Agenus, CytomX Therapeutics. D.M. O’Malley: Consulting or advisory role: Janssen Oncology, AstraZeneca, Clovis Oncology, Amgen, Tesaro, Novocure, Myriad Genetics; Research funding: Amgen, VentiRx, AstraZeneca, Genentech/Roche, Regeneron, Immunogen,Janssen Research & Development, Clovis Oncology, EMD Serono, Ergomed, Ajinomoto, Immunogen, Cerulean Pharma, PharmaMar, Array BioPharma, Bristol-Myers Squib, Agenus, Tesaro, Tracon Pharma, Stem CentRx; Honoraria: Clovis Oncology. J.S.-Z. Wang: Speakers’ bureau: AstraZeneca/MedImmune. V. Subbiah: Consulting or advisory role: MedImmune; Travel, accomodations, expenses: PharmaMar, Bayer; Research funding: Novartis, GlaxoSmithKline, NanoCarrier, Northwest, Biotherapeutics, Genentech/Roche, Berg Pharma, Bayer, Incyte, Fujufilm, PharmaMar, D3 Oncology Solutions, Pfizer, Amgen, Abbvie, Multivir, Blueprint Medicines, Loxo, Vegenics, Takeda, Alfasigma, Agensys, Idera, Boston Biomedical. B.A. Wilky: Consulting or advisory role: Novartis, Janssen Oncology, Lilly; Travel, accomodations, expenses: Novartis, Lilly, Advenchen Laboratories; Research Funding: Novartis, Merck Sharp & Dohme, Daiichi Sankyo, ArQule, Agenus. G. Yuan, A.M. Gonzalez, D. Savitsky, S. Coulter, E. Dow, H. Youssoufian: Agenus Inc. or subsidiary there of (current or former employee). C.D. Dupont: Agenus Inc. or subsidiary there of (current or former employee); Vertex -An Immediate Family Member Rochester Eye Associates- An Immediate Family Member Travel, Accomodations, Expenses: Agenus Research Funding: Agenus; Vertex; Pfizer; Sanofi Stock and other ownership: Agenus O. Shebanova: Agenus Inc. or subsidiary there of (current or former employee); Travel, Accomodations, Expenses: Agenus; Stock and other ownership: Agenus. W. Ortuzar: Full time contracted consultant: Agenus Bio, Inc. J.S. Buell: Agenus Inc. or subsidiary there of (current or former employee); Travel, Accommodations, Expenses: Agenus. R.B. Stein: Agenus Inc. or subsidiary there of (current or former employee); Stock and other ownership: Agenus. All other authors have declared no conflicts of interest.

Objectives The PRECISESADS project aims at using OMICs, and bioinformatics to identify new classifications for systemic autoimmune diseases (SADs) known to share common pathophysiological mechanisms in view of personalised treatments. Multi OMICs parameters collected in addition to routine clinical data in a cross-sectional study involving patients suffering from systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren’s syndrome (Sjs), rheumatoid arthritis (RA), primary antiphospholipid syndrome (PAPs), mixed connective tissue disease (MCTD), undifferentiated connective tissue disease (UCTD) and healthy controls (HC) will be analysed to identify clinically relevant clusters. Methods A European multi centre, non-randomised, cross-sectional clinical study was conducted in 18 sites and 9 countries. Collection of OMIC data including genetic, epigenomic, transcriptomic (from peripheral blood and from isolated cells), flow cytometry, metabolomics and proteomic in plasma and urine, exosome analysis and classical serology (antibodies and autoantibodies) was organised. Novel and innovative methodologies including fine flow cytometry were conducted. Quality procedures were established to ensure standardisation of samples collection, processing, transportation and storage. Techniques were validated to ensure reproducibility of analyses. Unsupervised bioinformatics and biostatistics approaches will be applied. Results Recruitment started in December 2014 and ended in October 2017. A total of 2656 participants were recruited: 377 RA, 470 SLE, 402 SSc, 385 SjS, 99 MTCD, 106 PAPs, 166 UCTD patients and 651 HCs. Median age was between 46 and 59 years and was consistent with each disease onset peak. 97% of the population was Caucasian. Most of the patients were treated with standard of care therapies and less than 10% were on biologics. OMICs and bioinformatics analyses are on-going. Conclusions We have established one of the largest collaborative multi-OMICs studies from patients with SADs. The most important challenge is now the integration of all these novel data to support hypothesis-free, machine learning-led analytical protocols. It is expected that the integration of data from affected patients, in comparison with well-matched controls, will provide new biomarker-led descriptions of clusters of potentially etiologically distinct disease entities. Acknowledgements This work has received support from the EU/EFPIA/Innovative Medicines Initiative Joint Undertaking PRECISESADS grant n° 1 15 565 Disclosure of Interest None declared

Background and Aims Randomised controlled trials in SLE have shown that response to treatment is influenced by baseline disease activity. The current investigation used objective molecular and biochemical baseline parameters to characterise SLE patients in two large multinational trials (n=2262 patients). Methods Patients were categorised with four dichotomous baseline parameters. SLE(+) was defined by any of the following: IFN signature (high), anti-dsDNA (+), C3 (low) and/or C4 (low). SLE(-) required all of the following: IFN signature (normal), anti-dsDNA (-), C3 (normal) and C4 (normal). Results Baseline RNA transcript data were available for 1747 of 2262 patients. When IFN status was combined with the serology criteria, 1500 (86%) were classified as SLE(+) and 247 (14%) were classified as SLE(-). At baseline, SLE(-) patients had significantly lower mean SLEDAI scores (8.3) compared to SLE(+) (10.7). Baseline SLEDAI <10 was observed in 72% of SLE(-) compared to 38% of SLE(+). The proportion on corticosteroids at baseline was 49% in SLE(-) compared to 78% in SLE(+); the proportion on immunosuppressants at baseline was 31% in SLE(-) compared to 44% in SLE(+). In the US, 22% were SLE(-) compared to 10% for Latin America, 7% for Europe, and 5% for ROW. Conclusions A subset of clinical trial patients was identified using biochemical and molecular markers with high sensitivity for SLE. Seronegative SLE patients with normal IFN gene signature had lower disease activity and were taking less background medication at baseline, two factors which have been negatively associated with response to treatment in some previous trials.

Liver function tests are widely used by GPs in UK. Abnormal results from these tests(ALFTs) are common, and are either left uninvestigated further– potentially overlooking curable liver disease which would otherwise be fatal, or associated with a lengthy process of retesting, referral, costing both the patient and the health services time and resources. iLFT is a semi-automated liver test cascading system with a structured diagnostic algorithm to maximise the efficiency of requesting LFTs. This study undertook a cost-effectiveness analysis of the iLFT decision tool compared to routine practice in Scotland, UK. An economic evaluation alongside the trial, and lifetime model undertaken from the perspective of NHS of Scotland. A step wedge design trial was carried out which compared effect before and after intervention. Within trial outcomes are reported as incremental cost per correct diagnosis at six months follow up, while a Markov model was used to extrapolate out to a life-time analysis of costs and quality adjusted life years gained in each arm, to account for early detection of Alcoholic Liver Disease(ALD) and Non-Alcoholic Liver Fatty liver Disease(NAFLD). The within trial analysis found costs to be £ 198.99 (95%CI 180.05, 217.94) and £260.14 (95%CI 190.93, 329.35) in routine practice and iLFT arms respectively. Probability of correct liver diagnosis was 0.41 (95%CI 0.37,0.46) in routine and 0.94 (95%CI 0.88,0.99) in iLFT, resulting in an ICER of £117.59 (95%CI 88,126) . The lifetime model found an incremental QALY gain of 0.99(95%CI .0843, .115) and a decreased cost of -31227.6(95%CI -31655.38, -30957.55at) , resulting in an ICER of £-312872. iLFT has a higher correct diagnosis rate and cost in short-term, in life-time model it dominates.

Dr. Hoffman is a full-time employee and stockholder of Eli Lilly and Company. Dr. Merrill has received consulting fees, speaking fees, and/or honoraria from Eli Lilly and Company (less than $10,000 each). Dr. Alarcón-Riquelme has received consulting fees, speaking fees, and/or honoraria from Eli Lilly and Company (less than $10,000 each). Dr. Petri has received consulting fees from Eli Lilly (less than $10,000 each). Dr. Dow is a full-time employee and stockholder of Eli Lilly and Company. Dr. Nisenbaum is a fulltime employee and stockholder of Eli Lilly and Company. Dr. Schroeder is a full-time employee and stockholder of Eli Lilly and Company. Ms. Komocsar is a full-time employee and stockholder of Eli Lilly and Company. Dr. Perumal is a full-time employee and stockholder of Eli Lilly and Company. Dr. Linnik is a full-time employee and stockholder of Eli Lilly and Company. Dr. Airey is a full-time employee of Eli Lilly and Company. Dr. Liu is a full-time employee and stockholder of Eli Lilly and Company. Dr. Rocha is a full-time employee and stockholder of Eli Lilly and Company. Dr. Higgs is a full-time employee and stockholder of Eli Lilly and Company.

Recently, our understanding of psoriasis has expanded from a superficial skin disease to a systemic inflammatory process that affects multiple organs. It has been postulated that circulating high levels of pro-inflammatory cytokines may predispose psoriasis patients to serious comorbid conditions such as atherosclerosis, psoriatic arthritis, obesity, and diabetes (Davidovici et al., 2010). However, the mechanistic link between increased circulating cytokine levels and these comorbid conditions remains to be established.

Introduction Detectable levels of cardiac troponin-T by high sensitivity assay (hs-TnT) are elevated by both ischaemia and LV systolic dysfunction (LVSD) but it is unknown whether hs-TnT could be a useful biomarker to identify ischaemia either in the presence or the absence of LVSD. Methods 500 consecutive patients undergoing a clinically indicated dipyridamole myocardial perfusion scintigraphy were studied. Those with impaired renal functions and history of atrial fibrillation or valvular disease were excluded. The troponin-T levels were measured in serum using a highly sensitive assay on an automated platform (Elecsys E170, Roche Diagnostics, lower limit of detection 3 ng/l). All scans were interpreted by a trained physician blinded to the biomarker data. Patients were divided into four groups based on reversible ischaemia and stress ejection fraction (EF) on gated SPECT imaging. Results Data were available for 453 patients and 97/453 had a reversible ischaemic defect. hsTnT levels were significantly higher in patients with a reversible ischaemia (Median (IQR) 7.2 (3.3–10.9) vs 4.2 (3.0–7.5) pg/ml p<0.001) compared to those without. When analysed according to four groups based on LV function and reversible ischaemia, hsTnT levels were highest in patients with ischaemia and a low EF and lowest in patients with no ischaemia and normal EF (pTREND <0.001) as shown in the table 1. In a multivariate model which included age, gender, cardiovascular co-morbidities, eGFR, haemoglobin, BNP, and LV ejection fraction, hs-TnT remained an independent predictor of reversible perfusion defect (p=0.026). Conclusions Baseline hs-cTnT levels are an independent predictor of reversible myocardial ischaemia and this is still the case in the presence of LVSD.