No abstract

Human colon sialidase has been characterized, and its activity levels in normal mucosa and colonic adenocarcinoma have been determined. Sialidase activity was maximal at pH 5.5. and was unstable with storage at 4 and -20 °C. The bulk of activity was pelletassociated. and could not be released with triton X-100 or 3-([3-cholamidopropyl]- dimethylammonio)-l-propanesulfonate. Using 2’-(4-methylumbelliferyl)α-D-N-acelylneuraminic acid as substrate, the K(m) and V(max) values were estimated to be 0.140 mmol/1 and 63 mU/g. respectively. Furthermore, an inhibition by substrate concentrations above 1.5 mmol/1 was detected. Neuraminic acid caused a competitive inhibition with a K(1) of 3.5 mmol/1. A statistically significant increase (p< 0.001) in the sialidase specific activity was found in primary colonic adenocarcinoma (104.20±8.00 mU/g) compared to that of the normal mucosa (72.50±7.67 mU/g).

ObjectivesTo characterize the main features at presentation of sarcoidosis associated with the development of end-stage organ failure in a large multicenter cohort of patients from Southern Europe.MethodsIn January 2017, the Spanish National Registry of Sarcoidosis (SARCOGEAS-SEMI) included 1082 consecutive patients diagnosed with sarcoidosis according to the ATS/ERS/WASOG 1999 statement and extrathoracic involvement to the 2014 WASOG instrument. The development of end-stage organ failure was assessed at the last visit.ResultsThe cohort consisted of 618 (57%) women and 464 (43%) men, with a mean age at diagnosis of 47yrs. After a mean follow-up of 82 months, 90 (8%) patients developed end-stage organ failure, including respiratory failure (n=56), chronic renal failure (n=13), cardiac failure/permanent cardiac device (n=8) and liver cirrhosis (n=3). The following baseline features were associated with end-stage organ failure in the univariate analysis: patients born in Spain (p=0.008), a higher mean age at diagnosis (p<0.001) and a radiological stage III/IV (p<0.001) With respect to extrathoracic involvement, spleen (p=0.015), renal (p=0.001), cardiac (p=0.028) and bone marrow (p=0.003) involvements, hypercalcemia (p=0.018) and use of corticosteroids (p<0.001) were associated with end-stage organ failure, while patients with cutaneous sarcoidosis had a lower risk (p=0.029). Multivariate analysis identified age at diagnosis (OR 1.05), radiological stages III/IV (OR 3.12) and use of corticosteroids (OR 4.55) as independent variables associated with the development of end-stage organ failure.ConclusionsNearly 10% of patients with sarcoidosis developed end-stage organ failure. Respiratory failure represented two thirds of cases of sarcoidosis-related organ failure, followed by renal (15% of cases) and cardiac (9%). Older patients, as well as those presenting with advanced radiological stages, had an enhanced risk of developing end-stage organ failure.Disclosure of InterestNone declared

ObjectivesTo characterize the main features at presentation of sarcoidosis in a large multicenter cohort from Southern Europe.MethodsIn January 2016, the Autoimmune Diseases Study Group (GEAS-SEMI) created a national registry (SARCOGEAS) of patients with sarcoidosis. Sarcoidosis was diagnosed in agreement with the criteria proposed by the ATS/ERS/WASOG 1999 statement, and extrathoracic disease was classified with the 2014 WASOG instrument.ResultsThe cohort consisted of 1082 patients (82% biopsy-proven), including 618 (57%) women and 464 (43%) men, with a mean age at diagnosis of 47yrs; 140 (13%) patients were born outside Spain, 965 (89%) were White, 69 (6%) Hispanic, 30 (3%) Black/African American and 18 (2%) Asian. Thoracic involvement was present at diagnosis in 979 (90%) patients, including 437 (40%) patients with stage I, 374 (35%) with stage II, 123 (11%) with stage III and 26 (2%) with stage IV. The most frequently reported extrathoracic involvements at diagnosis were cutaneous in 385 (36%) patients, extrathoracic lymph nodes in 218 (20%), liver involvement in 151 (14%) and ocular involvement in 118 (11%). Potentially life-threatening WASOG involvements were reported in frequencies less than 10%, including neurological involvement in 77 (7%) patients, kidney involvement in 59 (5%) or cardiac involvement in 21 (2%). Therapeutic approaches at diagnosis included the use of oral glucocorticosteroids in 637 (59%) patients, immunosuppressive agents in 84 (8%, mainly methotrexate in 63 patients) and biological agents in 15 (1%, mainly infliximab in 10 cases).ConclusionsIn this large series of sarcoidosis from Southern Europe, clinical presentation is dominated by adenopathies (both thoracic and extrathoracic) and cutaneous involvement (erythema nodosum), with lower frequencies in the main extrathoracic involvements than that reported in US and Japanese series.Disclosure of InterestNone declared

ObjectivesTo analyse the clinical features and outcomes of patients presenting with life-threatening systemic disease in a large cohort of Spanish patients with primary Sjogren syndrome (SjS).MethodsThe GEAS-SS multicenter registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS. By January 2018, the database included 1535 consecutive patients fulfilling the 2002/2016 criteria. Life-threatening systemic disease was defined as an activity level scored as “High” in at least one ESSDAI domain.Results209 (14%) were classified as presenting with a life-threatening systemic disease: 194 presented one ESSDAI domain classified as high, 14 two domains and only one presented three high activity domains. The high-ESSDAI domains included lymphadenopathy in 78 (37%) cases, CNS in 28 (13%), PNS in 25 (12%), pulmonary in 25 (12%), renal in 22 (10%), cutaneous in 18 (9%), articular in 18 (9%), haematological in 7 (3%) and muscular in 4 (2%); the most frequent clinical presentations in each domain were, respectively, parotid lymphoma (n=41), focal neurological deficit (n=20), ganglionopathy (n=11), usual interstitial pneumonitis (n=9), renal failure (n=11), ulcerated cutaneous vasculitis (n=9), symmetric polyarthritis (m=17), severe thrombocytopenia (n=3) and severe myositis (n=3). With respect to therapeutic approach, 144 (69%) required glucocorticoids, 65 (31%) immunosuppressive agents and 42 (20%) biological therapies. During the follow-up, 36 (17%) patients died, mainly due to lymphoma (n=16), pulmonary fibrosis (n=5), end-stage renal failure (n=4), CNS progressive disease (n=3) and systemic vasculitis (n=3).ConclusionsA 14% of patients with primary SjS develop a potentially life-threatening systemic disease (mainly lymphoma, but also severe internal organ involvements including nervous system, the lungs and the kidneys). This subset of patients requires intensive therapeutic management with a mortality rate of nearly 20% of cases.Disclosure of InterestNone declared