ANCA-Associated Vasculitides and Hematologic Malignancies: Lessons from the Past and Future Perspectives

The purpose of this paper is to collect and summarize all evidences relating to an association between ANCA-associated vasculitides (AAVs) and hematologic malignancies, in the form of either a paraneoplastic vasculitis or leukemias and lymphomas developing on a preexisting vasculitis. Additionally, the role of cyclophosphamide in vasculitis treatment has been assessed and compared to rituximab. Paraneoplastic AAV seems to be an uncommon presentation of hemopathies. Hematologic malignancy risk in AAV is more likely to be increased by cyclophosphamide, although not yet definitely proven. Furthermore, the pathogenesis of ANCA-associated vasculitis has been reviewed with particular emphasis on the role of proteinase 3 (PR3) in fuelling granulomatosis with polyangiitis (GPA) inflammation. PR3 is a bactericidal protein expressed by neutrophilic granules and on their plasma membrane. Derangements in its expression and function have been linked to leukemias and GPA alike. PR3-derived PR1 peptide is being studied as an immunotherapy target in leukemia and multiple myeloma. This study is aimed at bringing together various evidences from the field of immunological and hematological research, at exposing contradictions, and at revealing novel insights on the association between ANCA-associated vasculitis and hematologic malignancies

Word2vec Word Embedding-Based Artificial Intelligence Model in the Triage of Patients with Suspected Diagnosis of Major Ischemic Stroke: A Feasibility Study

Background: The possible benefits of using semantic language models in the early diagnosis of major ischemic stroke (MIS) based on artificial intelligence (AI) are still underestimated. The present study strives to assay the feasibility of the word2vec word embedding-based model in decreasing the risk of false negatives during the triage of patients with suspected MIS in the emergency department (ED). Methods: The main ICD-9 codes related to MIS were used for the 7-year retrospective data collection of patients managed at the ED with a suspected diagnosis of stroke. The data underwent “tokenization” and “lemmatization”. The word2vec word-embedding algorithm was used for text data vectorization. Results: Out of 648 MIS, the word2vec algorithm successfully identified 83.9% of them, with an area under the curve of 93.1%. Conclusions: Natural language processing (NLP)-based models in triage have the potential to improve the early detection of MIS and to actively support the clinical staff

FRI0199\u2005EFFECTIVENESS AND SAFETY OF BELIMUMAB IN PATIENTSWITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS FROM A LARGE, NATIONWIDE, MULTICENTRIC STUDY

Background: Belimumab is the unique biologic therapy available for patients with SLE. Objectives: To investigate effectiveness and safety of belimumab in SLE patients in clinical practice. Methods: 458 active SLE patients (ACR criteria) from 24 Italian Centers, mean±SD age 43.5±11.3 years; mean±SD disease duration 12.3±8.7 years, were treated with belimumab (10 mg/kg day 0, 14, 28 and then every 28 days), as add-on therapy. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24H proteinuria, CLASI, PGA, Fatigue (VAS 0-10) were recorded at baseline and every 6 months. Flares were defined according to SFI. Response was evaluated according to SRI-4. Statistics were performed by pairs Ttest, chi-square test and multiple logistic regression (SPSS, version 22.0). Results: Mean±SD follow-up was 21.2±15.3 months (range 3-60). Most common features treated with belimumab were articular in 67%, mucocutaneous in 55%, and renal in 17% of cases. Improvement of clinical and serological variables, including daily prednisone dosage, was observed (Table). SRI-4 is summarized in the Figure. At the end of follow-up 293 patients (66%) were still on belimumab. Most common cause of discontinuation were inadequate response (36%), AEs (31%), and pregnancy (8%). Mean number of flare during belimumab treatment compared with the corresponding period before belimumab initiation decreased (p<0.001). SLEDAI-2K 10 was an independent predictor of response by logistic regression at month 12 and 24 (p=0.003 and p=0.025). 9,998 infusions were analyzed. 784 AEs were observed in 330 patients, SAEs were 43 in 36 patients. No severe infusion reactions were observed; 16 patients had infective SAEs, and 22 non infective SAEs. Conclusion: We confirmed the effectiveness, the steroid sparing effect and good safety profile of belimumab in our cohort

Effectiveness and safety of belimumab in patients with active systemic lupus erythematosus: results from a large, nationwide, multicentric study.

Background: Belimumab is the unique biologic therapy available for patients with SLE. Objectives: To investigate effectiveness and safety of belimumab in SLE patients in clinical practice. Methods: 458 active SLE patients (ACR criteria) from 24 Italian Centers, mean±SD age 43.5±11.3 years; mean±SD disease duration 12.3±8.7 years, were treated with belimumab (10 mg/kg day 0, 14, 28 and then every 28 days), as add-on therapy. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24H proteinuria, CLASI, PGA, Fatigue (VAS 0-10) were recorded at baseline and every 6 months. Flares were defined according to SFI. Response was evaluated according to SRI-4. Statistics were performed by pairs Ttest, chi-square test and multiple logistic regression (SPSS, version 22.0). Results: Mean±SD follow-up was 21.2±15.3 months (range 3-60). Most common features treated with belimumab were articular in 67%, mucocutaneous in 55%, and renal in 17% of cases. Improvement of clinical and serological variables, including daily prednisone dosage, was observed (Table). SRI-4 is summarized in the Figure. At the end of follow-up 293 patients (66%) were still on belimumab. Most common cause of discontinuation were inadequate response (36%), AEs (31%), and pregnancy (8%). Mean number of flare during belimumab treatment compared with the corresponding period before belimumab initiation decreased (p<0.001). SLEDAI-2K 10 was an independent predictor of response by logistic regression at month 12 and 24 (p=0.003 and p=0.025). 9,998 infusions were analyzed. 784 AEs were observed in 330 patients, SAEs were 43 in 36 patients. No severe infusion reactions were observed; 16 patients had infective SAEs, and 22 non infective SAEs. Conclusion: We confirmed the effectiveness, the steroid sparing effect and good safety profile of belimumab in our cohort