Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection:an international, multi-centre, prospective audit

Introduction: The optimal bowel preparation strategy to minimise the risk of anastomotic leak is yet to be determined. This study aimed to determine whether oral antibiotics combined with mechanical bowel preparation (MBP+Abx) was associated with a reduced risk of anastomotic leak when compared to mechanical bowel preparation alone (MBP) or no bowel preparation (NBP). Methods: A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 Left Sided Colorectal Resection audit was performed. Patients undergoing elective left sided colonic or rectal resection with primary anastomosis between 1 January 2017 and 15 March 2017 by any operative approach were included. The primary outcome measure was anastomotic leak. Results: Of 3676 patients across 343 centres in 47 countries, 618 (16.8%) received MBP+ABx, 1945 MBP (52.9%) and 1099 patients NBP (29.9%). Patients undergoing MBP+ABx had the lowest overall rate of anastomotic leak (6.1%, 9.2%, 8.7% respectively) in unadjusted analysis. After case-mix adjustment using a mixed-effects multivariable regression model, MBP+Abx was associated with a lower risk of anastomotic leak (OR 0.52, 0.30–0.92, P = 0.02) but MBP was not (OR 0.92, 0.63–1.36, P = 0.69) compared to NBP. Conclusion: This non-randomised study adds ‘real-world’, contemporaneous, and prospective evidence of the beneficial effects of combined mechanical bowel preparation and oral antibiotics in the prevention of anastomotic leak following left sided colorectal resection across diverse settings. We have also demonstrated limited uptake of this strategy in current international colorectal practice

Regulation of the transcriptional activity of c-Fos by ERK. A novel role for the prolyl isomerase PIN1

The activation of the activating protein-1 (AP-1) family of transcription factors, including c-Fos and c-Jun family members, is one of the earliest nuclear events induced by growth factors that stimulate extracellular signal-regulated kinases (ERKs). In the case of c-Fos, the activation of ERK leads to an increased expression of c-fos mRNA. In turn, we have recently shown that ERK phosphorylates multiple residues within the carboxylterminal transactivation domain (TAD) of c-Fos, thus resulting in its increased transcriptional activity. However, how ERK-dependent phosphorylation regulates c-Fos function is still poorly understood. In this regard, it has been recently observed that the prolyl isomerase Pin1 can interact with proteins phosphorylated on serine or threonine residues that precede prolines (pS/T-P), such as the transcription factors p53 and c-Jun, thereby controlling their activity by promoting the cis-trans isomerization of these pS/T-P bonds. Here, we found that Pin1 binds c-Fos through specific pS/T-P sites within the c-Fos TAD, and that this interaction results in an enhanced transcriptional response of c-Fos to polypeptide growth factors that stimulate ERK. Our findings suggest that c-Fos represents a novel target for the isomerizing activity of Pin1 and support a role for Pin1 in the mechanism by which c-Jun and c-Fos can cooperate to regulate AP-1-dependent gene transcription upon phosphorylation by mitogen-activated kinase (MAPK) family members

FRI0446 VIRAL ARTHRITIS: DESCRIPTIVE ANALYSIS OF A SERIES OF 131 PATIENTS

Background:Arthritis of viral aetiology is considered the most frequent cause of acute arthritis. The most common etiologic agent is parvovirus B19 (B19). Besides, other viruses can lead to inflammatory joint disease, such as Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Human immunodeficiency virus (HIV), Rubella, Mumps, Hepatitis B and C virus (HBV and HCV) and Chikungunya (in transcontinental travellers or immigrants).Objectives:To describe the epidemiological characteristics, clinical and analytical course, evolution and treatment of a series of patients with a confirmed diagnosis of viral arthritis.Methods:A descriptive study was performed, considering a series of cases of viral arthritis collected between 2000 and 2019. Epidemiological (sex, age, the season of the year, year of diagnosis, children of pediatric age), clinics (joint pattern, prodromes, accompanying clinic) and analytical (CRP, ESR, ANA, RF) variables were collected. Statistical analysis was performed with the SPSS 22.0 program.Results:The data of 131 patients (109 women, 22 men), with a mean age of 39.7 years (SD 11.9) were collected. 93.9% of the cases were produced by B19, 3.8% by EBV, and only 3 by other viruses (1 by CMV, 1 by HBV, 1 by Mumps). The highest incidence years were 2005(55 cases), 2000(10 cases) and 2016(8 cases). Almost half of the cases (46.6%) occurred in spring, while 32.8% in summer, 15.3% in winter and 5.3% in autumn. Contrary to the expectations, only 20% of the patients had children in pediatric age.The most frequent clinical picture was acute polyarthritis (53.4%), followed by inflammatory polyarthralgias (19.1%). Moreover, acute oligoarthritis was present in 10.7% of cases, and acute monoarthritis in 3.1% of cases. More than half of the patients (54.2%) had prodromes, most frequently respiratory symptoms, and the joint clinic was accompanied by a skin rash in 35.1% and fever in 29% of cases. Analytically, 33.6% presented high CRP, 39.7% high ESR, 19.8% transient anemia, 9.9% positive ANA (4.6% transiently), 9.1% anti dc-DNA (7.6% transiently), and 10.7% positive RF (3.1% transiently). In 79.4% of cases, the clinic picture was limited, with a mean duration of 36 days (SD 47.7), but 12.3% had recurrences. The 69.5% of the patients needed treatment with acetaminophen and/or NSAIDs (6.7% did not need treatment), but corticotherapy was needed in 21.4% of cases. 4.6% of the cases evolved to chronicity, which made DMARD necessary in 3 patients (two of them with a final diagnosis of rheumatoid arthritis, being treated with Methotrexate and Leflunomide, and the third one had a diagnosis of undifferentiated connective disease, treated with Hydroxychloroquine).Conclusion:B19 remains the most common cause of viral arthritis in our population. It appears with a sporadic, occasionally epidemic, pattern of presentation, predominantly in warm seasons. A clinical presentation as an oligoarthritis or an acute monoarthritis or even the positivity of autoimmunity markers, should not make us rule out this possible aetiology. One out of 20 cases can evolve to chronicity and even make necessary the addition of DMARD.Disclosure of Interests:Ana V Orenes Vera: None declared, I Vázquez-Gómez: None declared, L Montolio-Chiva: None declared, Eduardo Flores: None declared, Desamparados Ybañez: None declared, Elia Valls-Pascual Grant/research support from: Roche, Novartis, and AbbVie, Speakers bureau: AbbVie, Lilly, Pfizer, MSD, Novartis, Janssen, Bristol Myers Squibb, UCB Pharma, À Martínez-Ferrer: None declared, A Sendra-García: None declared, V Núñez-Monje: None declared, Inmaculada Torner Hernández: None declared, Juanjo J Alegre-Sancho Consultant of: UCB, Roche, Sanofi, Boehringer, Celltrion, Paid instructor for: GSK, Speakers bureau: MSD, GSK, Lilly, Sanofi, Roche, UCB, Actelion, Pfizer, Abbvie, Novartis, Nagore Fernandez-Llanio: None declared</jats:sec

AB0595 EFFECTIVENESS OF TOPICAL SODIUM TIOSULFATE FOR THE TREATMENT OF CALCINOSIS-ASSOCIATED CUTANEOUS ULCERS IN PATIENTS WITH SYSTEMIC SCLEROSIS

Background:Treatment of calcinosis associated with systemic sclerosis (SSc) mainly involves the use of systemic therapies, which often have limited efficacy. However, little attention has been paid to local treatment, which is especially useful when associated with skin ulcers.Objectives:To show our experience with topical sodium thiosulfate (TST) for the treatment of calcinosis-associated cutaneous ulcers in patients with SSc.Methods:Descriptive analysis of a case series of patients with SSc and calcinosis-associated skin ulcers treated with TST.Wound management procedure: wounds and perilesional skin cleaning and disinfection is performed and, if needed, additional debridement. TST is compounded at 25% as w/o emulsion, for extensive calcinosis, or as beeler-base or cold-cream ointment, for limited calcinosis. Wounds are then covered with a polymeric foam dressing. This cure in moist healing environment shows some advantages over the dry cure (exudate control without damaging the periulceral skin, protection against contamination, and reduction of the needed cures, healing time and pain).Results:Nine patients (7 women) with calcinosis-associated skin ulcers and SSc were included: 2 patients with diffuse SSc (DcSSc), 6 with limited SSc (LcSSc) and 1 with overlap syndrome. Median age was 60 years (IQR 20). 6 patients had localized wounds and 3 had extensive involvement and/or tumoral calcinosis which had been refractory to systemic treatment with diltiazem, colchicine, zoledronate, rituximab, and/or acenocoumarol and had suffered recurrent superinfections. Follow-up results of more than 3 months are available for 8 patients, who have been on TST a median time of 9 months (IQR 8.25). They have shown clinical improvement (disappearing of many calcinosis foci and partial or complete healing of the ulcers together with an improvement in pain, function, quality of life and satisfaction of the patients). Radiological improvement was also observed in 1 case. No TST related adverse effect has been detected, except for slight maceration of the wound edges due to the ointment preparation, which was resolved by protecting these with zinc oxide creamConclusion:In our experience, treatment with TST for calcinosis-associated skin ulcers in patients with SSc is an effective, safe and easily implementable therapeutic alternative in clinical practice.Disclosure of Interests:Inmaculada Torner Hernández: None declared, A Sendra-García: None declared, V Núñez-Monje: None declared, L Montolio-Chiva: None declared, Ana V Orenes Vera: None declared, I Vázquez-Gómez: None declared, Eduardo Flores Fernandez: None declared, À Martínez-Ferrer: None declared, Elia Valls-Pascual Grant/research support from: Roche, Novartis, and AbbVie, Speakers bureau: AbbVie, Lilly, Pfizer, MSD, Novartis, Janssen, Bristol Myers Squibb, UCB Pharma, D Ybáñez-García Speakers bureau: Lilly, Roche, Sanofi, Juanjo J Alegre-Sancho Consultant of: UCB, Roche, Sanofi, Boehringer, Celltrion, Paid instructor for: GSK, Speakers bureau: MSD, GSK, Lilly, Sanofi, Roche, UCB, Actelion, Pfizer, Abbvie, Novartis</jats:sec

AB0620 EFFECTIVENESS OF RITUXIMAB IN PATIENTS WITH EARLY DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS. A MULTICENTER ANALYSIS.

Background:Rituximab (RTX) is effective in improving skin affection in patients with diffuse cutaneous systemic sclerosis (DcSSc). However, there are few data on early use of this drug.Objectives:To evaluate RTX effectiveness for skin disease in patients with DcSSc of less than 3 years of evolution.Methods:Multicenter, observational and retrospective study. Patients with DcSSc starting RTX within 3 years since first non-Raynaud symptom were recruited. Demographic variables, time of disease duration at the beginning of RTX, immune pattern and time on RTX treatment were collected. Effectiveness was defined as modified Rodnan skin score (mRSS) improvement. Evaluations were done by the same experienced rheumatologist. Patients subjective perception of skin hardening and/or tightness was evaluated. mRSS changes from baseline to 6 and 12 months after RTX beginning and, later on, to the last available observation were analysed using Wilcoxon test. Statistical analysis was performed with SPSS 20.0.Results:11 patients (8 women) were recruited from 2 university hospitals. Median age was 48 years (IQR 22). Median time since diagnosis to RTX beginning was 12 months (IQR 8). 5, 3 and 2 patients presented ATA +, RNPIII + and Ro-52 +, respectively. Median duration of RTX treatment was 12 months (IQR 68). Median baseline mRSS was 15.5 (IQR 18). Median mRSS after 6 and 12 months of RTX treatment and at last available mRSS evaluation was 15 (IQR 13), 14.5 (IQR 13) and 11 (IQR 16), respectively. mRSS showed statistically significant improvement at 6 (29%, IQR 37) and 12 months of RTX treatment (35%, IQR 34) and, thereafter, at last available observation (39%, IQR 51), compared to basal mRSS. Most patients reported subjective improvement at 6 (9 of 10 patients) and 12 months (6 of 7), and at last available evaluation (6 of 8); all other patients reported stability.Conclusion:In our experience, patients with DcSSc seem to benefit of early RTX treatment. Improvement may be seen as early as 6 months and seems to reach a plateau at 12 months.Disclosure of Interests:I Vázquez-Gómez: None declared, J. Narváez: None declared, J Lluch Pons: None declared, Marta Aguilar-Zamora: None declared, L Montolio-Chiva: None declared, Ana V Orenes Vera: None declared, Eduardo Flores: None declared, Elia Valls-Pascual Grant/research support from: Roche, Novartis, and AbbVie, Speakers bureau: AbbVie, Lilly, Pfizer, MSD, Novartis, Janssen, Bristol Myers Squibb, UCB Pharma, Desamparados Ybañez: None declared, À Martínez-Ferrer: None declared, A Sendra-García: None declared, Inmaculada Torner Hernández: None declared, V Núñez-Monje: None declared, Juanjo J Alegre-Sancho Consultant of: UCB, Roche, Sanofi, Boehringer, Celltrion, Paid instructor for: GSK, Speakers bureau: MSD, GSK, Lilly, Sanofi, Roche, UCB, Actelion, Pfizer, Abbvie, Novartis</jats:sec