tbuckley/cabot-search huggingface dataset:
FRI0477 STUDY OF CORTICAL AND TRABECULAR COMPARTMENTS THROUGH 3D-SHAPER IN LUNG TRANSPLANTED PATIENTS
Authors: Mireia Barceló-Bru, Alba Erra, Carina Espinet
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Osteoporosis in lung transplant (LT) patients is a frequent complication. Glucocorticoid treatment (GC) is a prominent risk factor (RF) that alters both bone mass and architecture. Studying the volumetric BMD using 3D-SHAPER software would help the study of architecture. <h3>Objectives</h3> To study the change in cortical surface density, volumetric trabecular density and integral volumetric density measured by 3D-SHAPER before and after LT as well as changes in bone mineral density (BMD) measured by densitometry (DXA). <h3>Methods</h3> LT patients assessed in Rheumatology are included. The demographic characteristics, diagnosis of lung disease and RF of low bone mass prior to LT are collected. Patients were grouped into 3 groups according to the type of disease, these being: Chronic Obstructive Pulmonary Disease (COPD), Interstitial Lung Diseases (ILD) and OTHER pathologies. Bone mass was evaluated by DXA (GE-LUNAR) before and 6 months after LT and 3D-SHAPER software (v2.7, Galgo Medical) was applied in all DXAs. <h3>Results</h3> 49 LT patients were included (46.9% women), with an average age of 56.9 ± 8.7 years. In the ILD group, a higher proportion of patients with a low calcium intake (p = 0.027) and with high doses of GC (p = 0.001) was observed. COPD group presented the highest proportion of smokers (p = 0.027). Prevalence of osteoporosis prior to LT was 24.5%, higher in COPD (p=0.007). Values of BMD and 3D-SHAPER as well as the percentage of post-transplant variation are shown in Table 1. Of the 47 patients, 19 (38.8%) started osteoactive treatment before LT, with a higher percentage of patients treated in the COPD group (p = 0.007). Of 42 patients, we have DXA at 6 months post-transplant, with a prevalence of osteoporosis of 23.8%. 27/42 patients underwent post-transplant osteoactive treatment, with an average treatment time until DXA was 19.2 ± 26.1 months, with no differences between groups. <h3>Conclusion</h3> Prevalence of low bone mass is high both before and after the transplant. Prevalence of some osteoporosis RFs was different between the lung disease groups. COPD group presented a worse bone mass before LT. Subsequently, they experienced a significant improvement in BMD and volumetric measurements with respect to the other two groups, which showed losses of these parameters. COPD was the group most treated for osteoporosis and with a lower proportion of patients with GC at high doses. Trabecular BMDv was the most altered measure of 3D-SHAPER, with greater decrease in patients with GC at high doses and lower in those with osteoactive treatment. <h3>Disclosure of Interests</h3> None declared
Comment on Barbour and Feig. Metformin for Gestational Diabetes Mellitus: Progeny, Perspective, and a Personalized Approach. Diabetes Care 2019;42:396–399
Authors: Janet A. Rowan
Journal: Diabetes Care (2019)

Barbour and Feig (1) have presented a clear discussion of metformin use in women with gestational diabetes mellitus and outline potential effects on the offspring, which require ongoing study. However, some of the relevant findings from the 7- to 9-year-old participants in the Metformin in Gestational Diabetes: The Offspring Follow-Up (MiG TOFU) study were not included (2). Also, Barbour and Feig have focused on potential adverse effects of metformin on the offspring and have not discussed data that suggest metformin may be beneficial in specific situations.

With respect to the MiG TOFU data, Barbour and Feig note that the 9-year-old offspring in the Auckland subgroup ( n = 99) exposed to metformin, …
PB1897 MANAGEMENT OF AUTOIMMUNE CYTOPENIA COMPLICATING CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: O. Vyhovska, Y. Yevstakhevych, Z. Maslyak, I. Yevstakhevych, N. Pelenyo, M. Semerak, Y. Vyhovska
Journal: HemaSphere (2019)

Background: Chronic lymphocytic leukemia (CLL) in 4.3‐9.7% of patients is complicated with immune cytopenia (IC). Timely diagnostics of IC is important, as the therapeutic tactics in patients with IC is significantly different from standards of treatment of patients with CLL without immune complications. Aims: Determination of the peculiarities of the course of IC in patients with CLL and assessment of different treatment regimens. Methods: Under our observation, there were 83 patients with CLL complicated with IC: 38 patients with autoimmune hemolytic anemia (AIHA), 26 patients with immune thrombocytopenia (ITP), 15 patients with Fischer‐Evans syndrome, 3 patients with partial red cell aplasia, one patient with immune neutropenia. The prognostic markers of the disease were determined: expression of CD38, ZAP70, β2 MG level, Coombs’ test, FISH analysis (del11q 22.3 and del17p 13.1). 58 patients received drug therapy (the first line ‐ steroid hormones, further: the schemes of COP, CHOP or RCOP, RCHOP or monotherapy with rituximab (rituximab at a dose of 375 mg / m2 / day, 4 injections with a weekly break), 25 patients underwent splenectomy. Results: The most severe course of the disease was observed in patients complicated with Fischer‐Evans syndrome (the median overall survival of 75 months). Insignificantly better results were observed in patients with AIHA (the median overall survival of 78 months). In patients with ITP, the median overall survival has not been achieved (observation time 12‐133 months). In case of steroid hormones use, as the first line of treatment, most patients experienced short‐term remissions.When using monotherapy with rituximab, the median progression‐free was 20 months. Conducted course therapy, based on RCOP or RCHOP regimens, was effective in 82% of patients. The median progression‐free survival has not been achieved in patients of this group (observation time 12‐57 months). The median of overall survival for CLL with ITP after splenectomy was 135.0 months, for CLL with AIHA it was 69.6 months, and for CLL complicated with Fischer‐Evans syndrome it was only 49.5 months. Summary/Conclusion: Treatment of patients with CLL complicated with immune cytopenias should be individualized: 1. For patients with CLL that runs without significant enlargement of lymph nodes and spleen, low lymphocytosis, in case of occurrence of AIHA or ITP the use of monotherapy with rituximabis is optimal. 2. In case of occurrence of AIHA, ITP or Fisher‐Evans syndrome in patients with CLL that runs with enlargement of lymph nodes, spleen, significant lymphocytosis, the use of R‐COP or R‐CHOP schemes, 4‐6 courses, is the most effective. 3. In case of resistance to drug therapy and the presence of splenomegaly in patients with CLL, complicated with IC, splenectomy is indicated.
Preexisting Autoimmune Disease: Implications for Immune Checkpoint Inhibitor Therapy in Solid Tumors
Authors: Laura C. Kennedy, Shailender Bhatia, John A. Thompson, Petros Grivas
Journal: Journal of the National Comprehensive Cancer Network (2019)

The use of immune checkpoint inhibitors (ICIs) is rapidly expanding to the treatment of many cancer types, both in the metastatic setting and as an adjuvant to other therapies. Clinical trials using ICIs have largely excluded patients with preexisting autoimmune diseases due to concerns for increased toxicity. However, emerging evidence shows that ICIs may be considered in some patients with autoimmunity. This review discusses the commonalities between clinical autoimmune diseases and ICI-induced immunotherapy-related adverse events, and summarizes the existing case series that describes patients with solid tumors who have a preexisting autoimmune disease. This review also discusses which patients with autoimmunity could be considered reasonable candidates for ICI therapy.
OP0012 EFFECTIVENESS OF TNFI AFTER A FIRST SWITCH IS LOWER IN PATIENTS WITH EARLY AXIAL SPONDYLOARTHRITIS: A LONGITUDINAL ANALYSIS OF THE DESIR COHORT
Authors: Marion Pons, Sylvie Chevret, Karine Briot, Maria-Antonietta D’agostino, Christian Roux, Maxime Dougados, Anna Moltó
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Some contradictory data has been reported on the effectiveness of a second and third line of TNFi in early axial spondyloarthritis (axSpA). <h3>Objectives</h3> To evaluate the effectiveness after a first and second TNFi switch, in real life conditions, over 5 years of follow-up in an early axSpa population. <h3>Methods</h3> Observational prospective French cohort (DESIR) with 5 years of follow-up, including 708 TNFi-naïve early axSpA patients. Study visits were scheduled every 6 months in the first two years of follow up then yearly up to 5 years. Treatment (TNFi or other) was at the discretion of the treating rheumatologist's. The characteristics of patients who received a second and a third TNFi were compared to those who never switched. Effectiveness was defined by the drug survival of the first, second and third TNFi were estimated by the Kaplan-Meier method, and compared using the log-rank test. <h3>Results</h3> Of the 708 patients included in the analysis, 258 (36.4%) patients initiated a first TNFi during the 5 years of follow up. Of these, 127/258 (49.2%) switched to a second TNFi, and among them 59/127(46.5%) switched to a third TNFi. Patients who switched to a second or a third TNFi were more frequently older, predominantly females, HLA-B27 negative, with MRI and radiographic sacroiliitis negative, without history of peripheral arthritis, and with higher BASFI and BASDAI scores at baseline of the DESIR cohort (see table). Estimated median drug survival for the first, second and third TNFi was 21.7 months [95%CI 17.6-33.6], 18.8 months [95%CI 15.1-24.4] and 25.0 months [95%CI 11.8-NA] respectively. Drug survival was significantly extended for the first TNFi compared to the second one (<i>p</i>=0.04), but no differences were observed between the 2<sup>nd</sup> and the 3<sup>rd</sup> TNFi. <h3>Conclusion</h3> Our study suggests a poorer TNFi effectiveness after a first switch in real-life conditions in early axial spondyloarthritis. <h3>Disclosure of Interests</h3> Marion Pons: None declared, Sylvie Chevret: None declared, Karine Briot Consultant for: Karine Briot has received consultancy honoraria and conference fees from UCB, Amgen, Lilly and MSD, Maria-Antonietta d'Agostino: None declared, Christian Roux Grant/research support from: Alexion, Amgen, UCB, maxime dougados Grant/research support from: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma, Consultant for: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma, Anna Moltó: None declared
PS951 MORE OR LESS? IMPACT OF DOSE NUMBER ON OUTCOMES OF PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH INOTUZUMAB OZOGAMICIN
Authors: D.I. Marks, D.J. DeAngelo, E. Jabbour, A. Advani, S. O’Brien, T. Wang, A. Neuhof, E. Vandendries, H. Kantarjian, W. Stock, M. Stelljes, R. Cassaday
Journal: HemaSphere (2019)

Background: In INO‐VATE (NCT01564784), patients with relapsed/refractory acute lymphoblastic leukemia who were treated with inotuzumab ozogamicin (InO) vs standard chemotherapy had significantly greater remission rates and longer overall survival (OS), with more patients proceeding to stem‐cell transplant (SCT). Aims: Here we report outcomes by number of InO cycles (Cyc) received. Methods: Methods are detailed in Kantarjian, NEJM 2016. Outcomes are reported based on number of InO Cyc received (≤3 or &gt;3 Cyc with no SCT and ≤2 or &gt;2 with SCT [consistent with current recommendations]) in patients who achieved complete remission (CR)/CR with incomplete hematologic recovery. Data cutoff: Jan 4, 2017. Results: Among patients who responded but did not proceed to SCT, MRD‐negativity was achieved by 88% of 32 patients receiving &gt;3 Cyc vs 61% of 18 patients receiving ≤3 Cyc ( P = 0.037). Patients who had &gt;3 Cyc had a longer duration of remission (HR 0.35, P = 0.0005) and improved survival outcomes vs those who had ≤3 Cyc ( Table ). The rate of serious adverse events (AE) and the percentage of patients discontinuing treatment due to AEs was numerically lower with &gt;3 Cyc vs ≤3 Cyc. Among patients who responded and proceeded to SCT, the percentage achieving MRD‐negativity (81% vs 69%, P = 0.123) and the duration of remission (HR 1.37, P = 0.848) were similar for those who had &gt;2 Cyc (36 patients) vs ≤2 Cyc (35 patients). Patients with ≤2 Cyc had improved survival outcomes and non‐relapse mortality (NRM) vs those with &gt;2 Cyc ( Table ). 17.1% of patients receiving ≤2 Cyc and 33.3% of patients receiving &gt;2 Cyc developed veno‐occlusive disease ( Table ). Summary/Conclusion: These results are in agreement with current recommendations that patients proceeding to SCT should receive ≤2 Cyc, whereas those not proceeding to SCT may benefit from receiving up to 6 cycles of therapy. image
FRI0561 COMPARISON OF INITIAL PRESENTATIONS BETWEEN JUVENILE IDIOPATHIC ARTHRITIS CHILDREN WITH SYSTEMIC ONSET WITH NON-BIOLOGIC MONOCYCLIC AND PERSISTENT COURSES
Authors: Mikhail Kostik, Maria Rumyantseva, Eugenia Isupova, Irina Chikova, Margarita Dubko, Vera Masalova, Ludmila Snegireva, Tatiana Kornishina, Tatiana Likhacheva, Ekaterina Gaidar, Andrey Santimov, Olga Kalashnikova
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Juvenile idiopathic arthritis with systemic onset (soJIA) may have monocycling, polycycling or relapsed course [1]. There were not known soJIA course predictors. <h3>Objectives</h3> The aim of our study was to evaluate initial clinical or laboratory features of the patients with soJIA who had monocyclic course without biologics. <h3>Methods</h3> In the present study were included data about 130 soJIA patients. After selection we identified a subgroup of the soJIA patients (n=22) who successfully achieved remission without any biologic medication and were stable in the remission off-medication at least two years. The second group consisted of the patients with chronic persistent course (n=83). The remained 25 patients were excluded due to missing data or who did not meet the selection criteria. We evaluated routine clinical (fever, rash, hepatosplenomegaly, serositis, lymphadenopathy, MAS, joint involvement) and laboratorial (WBC, PLT, Hb, ferritin, ALS, AST, LDH, GGTP, ALP, albumin, Na, triglycerids, ESR, CRP, prothrombin, fibrinogen) soJIA features in the onset of the disease. <h3>Results</h3> Patient with monocycling course have no any differences except the ferritin level: 275 (133; 698) ng/ml vs 950 (150; 3240) ng/ml, (p=0.04), time to achievement remission 17.7 (8.2; 38.0) months vs 60.2 (36.0; 99.0) months (p=0.00002) and rare elbow involvement 4.6% vs 30.9% (p=0.01). The parameters, associated with possible monocycling course are in the table. <h3>Conclusion</h3> Patients with soJIA initially have quit similar clinical presentations independently the further clinical course. The prediction of possible course of soJIA is a difficult problem. Patients with soJIA with monocycling course were younger and had less impressive laboratory activity. Further investigations required. <h3>Reference:</h3> [1] Cimaz R. Systemic-onset juvenile idiopathic arthritis. Autoimmun Rev. 2016;15(9):931-4. <h3>Disclosure of Interests</h3> None declared
PF628 O-12-M1: AN EVALUATION OF TIME TO NEXT TREATMENT IN MELFLUFEN AND DEXAMETHASONE-TREATED PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
Authors: S. Bringhen, P.G. Richardson, P. Voorhees, T. Plesner, U.-H. Mellqvist, J.A. Zonder, B. Reeves, S. Zavisic, J. Harmenberg, J. Obermüller, P. Sonneveld
Journal: HemaSphere (2019)

Background: Melflufen is a novel peptide-conjugated alkylator potentiated by intracellular aminopeptidases, which are markedly overexpressed in multiple myeloma. Melflufen plus dexamethasone had encouraging activity in patients with relapsed/refractory multiple myeloma and ≥2 prior lines of therapy in the phase 1/2 O-12-M1 study (overall response rate, 31%; median overall survival, 20.7 months; Richardson et al. ASH 2017. Abs. 3150). Time to next treatment is used in real world evidence to assist treatment decisions and support economic reimbursement modeling. Aims: To present a time to next treatment analysis of melflufen plus low-dose dexamethasone in relapsed/refractory multiple myeloma patients exposed to bortezomib and lenalidomide in O-12-M1 (NCT01897714) and how it compares to recently reported relapsed/refractory multiple myeloma studies. Methods: Patients with relapsed/refractory multiple myeloma and ≥2 prior lines of therapy, including bortezomib and lenalidomide received 40 mg melflufen intravenously on day 1 of each 28-day cycle plus 40 mg weekly dexamethasone until progressive disease or unacceptable toxicity. Patients were followed up for 2 years after PD, and time to next treatment was retrospectively reviewed for subsequent therapy. Results: As of 9 Nov 2017, 45 patients were treated: median age, 66 years (range, 47–78 years); International Staging System stage II/III, 60%; high-risk cytogenetics, 44%. Patients had 4 median prior lines of therapy; 87% were refractory to last line of therapy including alkylators (24%), proteasome inhibitors (27%), IMiDs (56%), and monoclonal antibodies (9%); 11% were last-line double refractory. At data cutoff, 44 patients (98%) discontinued melflufen plus dexamethasone, mainly due to adverse events (40%) and progressive disease (29%). Twenty-six patients received subsequent therapy. Median time from start of melflufen plus dexamethasone to first subsequent therapy or death, whichever occurred first, (time to next treatment) was 7.9 months (95% CI, 5.7–11.0); next therapy included alkylators (27%), proteasome inhibitors (38%), IMiDs (58%), and monoclonal antibodies (8%).Summary/Conclusion: Types of subsequent salvage therapy used after melflufen plus dexamethasone were similar to studies of approved agents in relapsed/refractory multiple myeloma; time to next treatment was also similar (Table). Further trials are ongoing, including a phase 3 study of melflufen plus dexamethasone vs pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma refractory to lenalidomide (NCT03151811).
SAT0258 SEXUAL HEALTH IMPAIRMENT IN WOMEN WITH SYSTEMIC SCLEROSIS
Authors: Barbora Heřmánková, Maja Špiritović, Hana Smucrova, Sabina Oreska, Hana Štorkánová, Kristyna Bubova, Karel Pavelka, Jiří Vencovský, Ladislav Šenolt, Radim Bečvář, Michal Tomčík
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic sclerosis (SSc) is a chronic autoimmune disease that may affect all aspects of life including sexual function. <h3>Objectives:</h3> To assess sexual function, pelvic floor function and sexual quality of life women with SSc compared to age-/sex-matched healthy controls (HC). To subanalyze sexual function in sexually active individuals. <h3>Methods:</h3> In total 47 women with SSc (mean age: 50.5, disease duration: 5.6 years, lcSSc/dcSSc: 27/20, mRSS: 12.7, ESSG activity index: 2.5), who fulfilled the ACR/EULAR 2013 criteria, and 47 healthy women (mean age: 50.5) filled in 11 well-established and validated questionnaires assessing sexual function, pelvic floor function, quality of life, fatigue, physical activity and depression. Data are presented as mean±SEM. <h3>Results:</h3> Compared to HC, patients with SSc had significantly higher prevalence and greater severity of sexual impairment (FSFI, BISF-W), pelvic floor dysfunction (PISQ-12, PFIQ7), and worse sexual quality of life (SQol-F) (table 1). There were no significant differences in sexual function between limited and diffuse SSc. Even sexually active SSc patients reported significantly greater sexual health impairment compared to sexually active HC. Sexual health impairment in SSc was associated with disease activity/duration, health status, physical activity, fatigue and depression (table 2). <h3>Conclusion:</h3> Women with SSc reported significantly impaired sexual function, sexual quality of life and pelvic floor function than age-matched HC. Worse scores in SSc were associated with disease activity/duration/health status, physical activity, fatigue, and depression. Acknowledgements: Supported by AZV-16-33574A, MHCR 023728. <h3>Disclosure of Interests:</h3> Barbora Heřmánková: None declared, Maja Špiritović: None declared, Hana Smucrova: None declared, Sabina Oreska: None declared, Hana Štorkánová: None declared, Kristyna Bubova: None declared, Karel Pavelka: None declared, Jiří Vencovský Consultant for: Samsung, Speakers bureau: AbbVie, Novartis, Pfizer, Sanofi, Eli Lilly, Biogen, UCB, MSD, Werfen, Roche, Ladislav Šenolt Grant/research support from: AbbVie, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene Corporation, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Amgen, Takeda, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Radim Bečvář Consultant for: consultancy Actelion, Michal Tomčík: None declared
Interspecific Plastome Recombination Reflects Ancient Reticulate Evolution in Picea (Pinaceae)
Authors: Alexis R. Sullivan, Bastian Schiffthaler, Stacey Lee Thompson, Nathaniel R. Street, Xiao-Ru Wang
Journal: Molecular Biology and Evolution (2017)

Plastid sequences are a cornerstone in plant systematic studies and key aspects of their evolution, such as uniparental inheritance and absent recombination, are often treated as axioms. While exceptions to these assumptions can profoundly influence evolutionary inference, detecting them can require extensive sampling, abundant sequence data, and detailed testing. Using advancements in high-throughput sequencing, we analyzed the whole plastomes of 65 accessions of Picea, a genus of ∼35 coniferous forest tree species, to test for deviations from canonical plastome evolution. Using complementary hypothesis and data-driven tests, we found evidence for chimeric plastomes generated by interspecific hybridization and recombination in the clade comprising Norway spruce (P. abies) and 10 other species. Support for interspecific recombination remained after controlling for sequence saturation, positive selection, and potential alignment artifacts. These results reconcile previous conflicting plastid-based phylogenies and strengthen the mounting evidence of reticulate evolution in Picea. Given the relatively high frequency of hybridization and biparental plastid inheritance in plants, we suggest interspecific plastome recombination may be more widespread than currently appreciated and could underlie reported cases of discordant plastid phylogenies.