tbuckley/cabot-search huggingface dataset:
OP0329 DEVELOPMENT OF SALIVARY GLAND ORGANOIDS TO STUDY SJÖGREN’S DISEASE
Authors: L. Meudec, N. Goudarzi, J. Pascaud, F. Jaulin, Q. Pascal, T. Lazure, L. Amazit, O. Dellis, X. Mariette, G. Nocturne
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Salivary gland epithelial cells (SGEC) play a pathogenic role in Sjögren's disease (Sjo), mainly through their interaction with immune cells. Actual 2D culture models of SGEC do not recapitulate the complexity of cellular interactions within salivary glands and lack epithelial readouts, highlighting the necessity to develop new relevant models. <h3>Objectives:</h3> To develop and characterize differentiated organoids (DO) of SGEC derived from minor salivary gland biopsies (MSGB) of Sjo patients and controls. <h3>Methods:</h3> We included Sjo patients fulfilling the ACR/EULAR 2016 criteria and controls with sicca syndrome without autoimmune disease. MSGB were firstly dissociated enzymatically, encapsulated in extracellular matrix (ECM), and then cultured in Growth Expansion Medium (GEM) containing growth factors, until organoids formation. Organoids were passaged every 7-12 days for self-renewal and cultured in a Differentiation Medium (DM) to develop DO. Proliferation was measured by cell counting and SGEC markers were investigated by RT-qPCR, immunohistochemistry and immunofluorescence. The calcium influx was assessed by fluorescence spectroscopy. <h3>Results:</h3> We included 7 Sjo and 13 controls. Organoids were forming and differentiating in both Sjo and controls (<b>Figure 1A-B</b>). The mean culture duration was respectively 3.7 ± 1.5 and 2.7 ± 1.1 months in Sjo and controls. The self-renewal capacity of organoids for long-term culture was comparable between the two groups (<b>Figure 1C</b>). We then characterized DO and found that they highly express the ductal markers CK7/CK18 and to a lesser degree, the acinar markers AQP5 and α-amylase in both groups (<b>Figure 1D-E</b>). DO also expressed BAFF, CXCL10 and IL-7 when exposed to PolyIC and IFNα supporting a capacity of response to inflammation (<b>Figure 1F</b>). Exposure of DO to pilocarpine induced an increase of calcium levels, suggesting a capacity to secrete saliva in response to a cholinergic stimulation. Of note, the effect was reduced in Sjo-derived DO compared to control-derived DO (<b>Figure 1G</b>). Last, we performed preliminary experiments to develop immuno-organoids (IOSG) by adding PBMC to the DO (<b>Figure 1H).</b> Additional experiments are currently underway to develop and characterize IOSG. <h3>Conclusion:</h3> We established a culture system of SG organoids from MSGB from Sjo patients and controls with long term expansion, maturation markers expression and functionality. Additional investigations are ongoing to further characterize the organoids and to develop IOSG that will be used to study the crosstalk between epithelial cells and immune cells and to test the effect of drugs on this crosstalk. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1161 RETROSPECTIVE ANALYSIS OF HERPES ZOSTER INFECTION IN A LARGE COHORT OF SLE PATIENTS: RISK AND PROTECTIVE FACTORS
Authors: F. Arru, F. Vesentini, I. Gennaio, C. Cruciani, Z. Rahme, G. Hulej, M. Zen, A. Doria
Journal: Annals of the Rheumatic Diseases (2024)
A phase 1 single-arm, open-label study of emavusertib (CA-4948) in combination with azacitidine and venetoclax in patients (pts) with acute myeloid leukemia (AML) in complete response (CR) with measurable residual disease (MRD).
Authors: Adolfo de la Fuente Burguera, Claudio Cerchione, Sebastian Scholl, Jan Moritz Middeke, Nitika Nitika, Maureen E Lane, Wanying Zhao, Steven Angelides, Reinhard von Roemeling, Uwe Platzbecker
Journal: Journal of Clinical Oncology (2024)

TPS6587 Background: Emavusertib is a novel potent oral inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4) with additional inhibitory activity against FMS-like tyrosine kinase 3 (FLT3) and CDC-like kinases (CLK1/2/4). Inhibition of these 3 onco-proteins by emavusertib may address the unmet need for novel therapies in AML. Clinical studies with emavusertib monotherapy have demonstrated a significant reduction in AML blasts with clinical and molecular responses in pts with relapsed or refractory AML (Metzeler 2022). Azacitidine + venetoclax (aza+ven) is an approved therapy for newly diagnosed pts with AML, unfit for intensive chemotherapy. Pre-clinical studies have demonstrated that emavusertib in combination with aza+ven has synergistic and antileukemic effects. In the VIALE-A study, composite CR (CRc) (CR, CRh, or CRi) in the absence of MRD of &lt;1 residual blast/1000 leukocytes (MRD negative [MRD−]) resulted in longer duration of response (DOR), event-free survival, and overall survival (OS) compared with AML pts who achieved CRc but were MRD+ (Pratz, 2022). Therefore, adding emavusertib to aza+ven in CR or CRh, MRD+ pts may convert MRD status without significant toxicity and become a potential new regimen in front-line therapy. Methods: This is a single-arm, open-label Phase 1 study of emavusertib in combination with first line aza+ven in AML pts ≥60 years of age who achieved CR or CRh with MRD+ status based on local testing. The primary objective is to determine a safe and tolerable dosing schedule for the triple combination. Secondary objectives include determining the MRD conversion rate, pharmacokinetics, DOR, and OS. The study will enroll approximately 24 pts at 5 to 10 sites globally. Pts will have received aza+ven as first line therapy and achieved CR or CRh after 1-6 cycles of aza+ven. If MRD status remains positive, emavusertib will be added to the existing aza+ven regimen. Key exclusion criteria include residual toxicities and significant comorbidities. In the first cohort, the starting emavusertib dose is 200 mg BID for 7 days per cycle of 28 days. The duration of emavusertib treatment will extend to 14 and 21 days, in subsequent cohorts. The pts will continue triple treatment (emavusertib+aza+ven) until consent withdrawal, disease progression, intolerable toxicity, or not achieving MRD- after 6 cycles of treatment. Enrollment to cohort 1 began in December 2023. (EU CT Number 2023-505828-58). Clinical trial information: 2023-505828-58.
POS0922 COMPARATIVE STUDY OF TWO CLASSIFICATION CRITERIA SETS IN REAL CLINICAL PRACTICE IN BEHÇET’S DISEASE
Authors: R. Gálvez-Sánchez, J. L. Martín-Varillas, I. Ferraz-Amaro, C. Lasa Teja, E. Aurrecoechea, R. Blanco
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Behçet's disease (BD) is a variable-vessel vasculitis with a high variability of clinical manifestations. Diagnosis of BD was traditionally performed according to the International Study Group (ISG) [1]. Recently, criteria proposed by the International Team for the Revision of the International Criteria for BD (ITR-ICBD) have demonstrated a higher sensitivity [2]. <h3>Objectives:</h3> The aim of study was to assess a) the concordance and differences between ISG and ICDB criteria b) sensitivity in diagnosing severe manifestations (ocular, vascular and neurological). <h3>Methods:</h3> The study included 142 patients diagnosed with definitive or possible BD by expert rheumatologists. They were diagnosed at a well-defined population in Northern Spain between January 1980 and November 2023. The ISG and ICBD diagnostic criteria for BD were applied to all patients and compared among them. To assess how the observed agreement proportion behaved between both diagnostic criteria, one of the criteria was added for all subjects, reassessing those who met ISG and ICBD criteria to recalculate Kappa once again. Same was done removing one of the criteria to all subjects. <h3>Results:</h3> 142 patients (73 men/ 69 women) were studied. Mean age at diagnosis was 36.4 + 13.9 years. 80 (56.3%) patients fulfilled ISG criteria and 117 (82.4%) ICBD criteria (<b>Table 1</b>). Concordance between both criteria was moderate (Kappa 0.43 IC 95% 0.29-0.57) with a 74% of subjects classified consistently. The highest Kappa size was observed when vascular involvement was excluded from all patients (Kappa 0.52 IC 95% 0.38-0.67), and the smallest Kappa size was observed when vascular involvement was included across all patients (Kappa 0.21 IC 95% 0.07-0.34) (<b>Graph 1</b>). <h3>Conclusion:</h3> ICBD criteria are more likely to diagnose BD and classify more patients with severe manifestations of the disease. The greatest changes in agreement between both diagnostic criteria for the disease were found when modifying the vascular involvement variable. <h3>REFERENCES:</h3> [1] Lancet 1990; 335:1078-80. [2] J Eur Acad Dermatology Venereol 2014;28:338-47. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
Phase 2 study evaluating selinexor monotherapy in patients with JAKi-naïve myelofibrosis and moderate thrombocytopenia.
Authors: Joseph Scandura, Aaron Thomas Gerds, Ellen K. Ritchie, Xulong Wang, Steve Kye, Raajit Rampal
Journal: Journal of Clinical Oncology (2024)

TPS6593 Background: While multiple JAKi therapies are approved in myelofibrosis, thrombocytopenia, which commonly occurs in myelofibrosis and is associated with poor outcomes, is an on-target side effect; use of suboptimal ruxolitinib doses used to manage adverse effects leads to reduced efficacy. In a Phase 1 study (NCT04562389) of selinexor, an investigational XPO1 inhibitor, plus the JAKi ruxolitinib in JAKi-naïve myelofibrosis the most common AEs in the 60 mg cohort were nausea (79%), anemia (64%), thrombocytopenia (64%), and fatigue (57%). Nausea events were predominantly Grade 1 and transient in nature. Among patients who received at least one prophylactic antiemetic (64% of 60 mg cohort), nausea (Grade 1 only) was experienced by 67% of patients compared with 100% of those who did not receive prophylactic antiemetics (Grades 1-3). In the selinexor 60 mg cohort, 79% of the intent-to-treat population achieved SVR35 and 58% achieved TSS50 at Week 24. Response rates were consistent across subgroups, including sex and regardless of ruxolitinib dose. In a Phase 2 study, selinexor monotherapy in patients with myelofibrosis refractory or intolerant to JAKi therapy (NCT03627403; ESSENTIAL) was generally tolerable and preliminary signs of efficacy were observed with single-agent selinexor. These results provide rationale to explore selinexor monotherapy in myelofibrosis subpopulations with high unmet need such as those with thrombocytopenia. Methods: XPORT-MF-044 (NCT05980806) is a two arm, sequential, multicenter, open-label, Phase 2 study evaluating the efficacy of selinexor (40 mg or 60 mg QW; N=29 per arm) in patients with JAKi-naïve MF and moderate thrombocytopenia (platelet count: 50-100x10 9 /L) with optional expansion arms (n=30 per arm). Optional ruxolitinib or pacritinib, or momelotinib treatment (based on platelet count) may be added for patients whose SVR from baseline is &lt;10% at week 12 or &lt;35% at week 24. Inclusion criteria include ≥18 years of age, spleen volume ≥450 cm 3 by MRI or CT scan, DIPSS intermediate-1 with symptoms, intermediate-2, or high-risk, ECOG ≤2, platelet counts of 50-100x10 9 /L, and not eligible for stem cell transplantation. Select exclusion criteria include &gt;10% blast in peripheral blood or bone marrow and previous treatment with JAKi for myelofibrosis. Primary endpoint is SVR35 at week 24. Key secondary endpoints are safety, TSS50 at week 24, anemia response at week 24, overall survival, and overall response rate. Clinical trial information: NCT05980806 .
Evolving patterns of transplant strategies for mantle cell lymphoma in the era of BTK inhibitors and CAR-T therapy.
Authors: Ashok Maddukuri, Yoshitaka Inoue, Kevin Rakszawski, David Claxton, Christopher Ehmann, Hong Zheng, Kentaro Minagawa, Shin Mineishi, Seema Naik
Journal: Journal of Clinical Oncology (2024)

e19012 Background: Mantle cell lymphoma is an aggressive lymphoma with poor survival after chemotherapy alone. Both autologous (auto) and allogeneic (allo) transplants have improved outcomes over the years, but transplant strategies most beneficial for MCL are not clearly defined. Recently, BTK inhibitors and chimeric antigen therapies (CAR T) therapy approach has changed the landscape of Mantle cell Lymphoma. Methods: Patient Population:A total of 71 patients underwent transplant for diagnosis of MCL at Penn State Cancer Institute, between March 1993 and March 2023. Median follow up was 3.1 years (32 days-9883 days) after transplant. Patient Characteristics: A total of 71 patients (62 M: 9 F) underwent transplants, including autologous (n=30), allogeneic (n=32), and CAR T (n=9). Since 2020, 19 transplants were performed: CAR T (n=9) auto transplants (n=9) and allogeneic transplants (n=1). Relapsed and refractory MCL (n=4) patients received CAR T whereas patients achieving CR 1 (n=8) and PR1 (n=1) received auto transplants. Most patients were Caucasian (n= 68), with few Hispanic (1), African American (1), or Asian (1). Results: Median age at the time of transplant was 61 (37-70) years for autologous, 56 (33-67) years for allogenic and 63 (55 -75) years for CAR T respectively. Disease status at transplant was CR 52.1% (n=37), primary induction failure or relapsed/refractory 36.6% (n=26), PR 11.3% (n=8). High LDH was seen at the time of transplant in 16.9% (n=12) patients and normal in 83.1%(n=59) patients. Blastoid morphology was seen in only 13.8% (n=4) autologous, 37.9% (n=11) allogenic and 33.3% (n=3) CAR T patients. Outcomes: Overall survival (OS) at 1 year and 3 years was 93.3% and 85.9% for autologous (auto) transplants, 62.5% and 52.9% for Allogeneic (allo) transplants, 88.9% and 76.2% for CAR-T therapy respectively (P = 0.007). Progression free survival at 1 year and 3 years was 86.3% and 75.0% for auto transplants; 50.0% and 43.3% for allo Transplants; 66.7% and 66.7% for CART Therapy (P = 0.03). Primary cause of death was Treatment Related Mortality (TRM) (n= 9) (GVHD=4; Pulmonary=3; MOF=2) and disease progression (n=10); unknown (n=4); other (n=1). Primary cause of death for CAR T therapy was grade IV ICANS and disease progression. Conclusions: Recently CAR T therapies have changed the landscape of MCL treatment algorithm in both Blastoid and non-Blastoid histology MCL patients. But in the era of CAR T therapy and BTK inhibitors for MCL, achieving CR at the time of transplant predicts improved long-term outcomes. Randomized studies or larger retrospective CIBMTR data analysis may be important to answer best transplant strategy for MCL patients. [Table: see text]
POS0572 FACTORS ASSOCIATED WITH VACCINE RESPONSE AFTER COVID VACCINE BOOSTER IN PATIENTS WITH AUTOIMMUNE DISEASES: DATA FROM MULTICENTRIC PROSPECTIVE PHASE IV SAFER STUDY
Authors: K. Lysie Libardi Lira Machado, S. T. Miyamoto, A. P. Neves Burian, K. Rosemarie Lallemand Tapia, J. Geraldo Mill, Y. Gurtler Pinheiro de Oliveira, A. C. Simões Moulin, L. Gonçalves Rodrigues Aguiar, B. Oliveira Souza, G. Smith Sobral Vieira, L. Lorenzoni Grillo, M. Deorce de Lima, I. Ribeiro Moulaz, M. De Oliveira Macabú, P. Dias Cardoso Ribeiro, V. De Oliveira Magalhães, M. Freitas de Aguiar, E. Biegelmeyer, F. M. Matos Melo Campos Peixoto, C. Kayser, A. Wagner Silva de Souza, C. Heldan de Moura Castro, S. Lúcia Euzébio Ribeiro, C. Maria Paiva França Telles, J. Buhring, R. Lima, S. H. Dos Santos, S. Elias Basualto Dias, N. Seixas de Melo, R. Holanda Da Silva Sanches, A. Luiz Boechat, N. Sartori, V. Hax, L. Denardi Dória, R. Poubel Vieira de Rezende, K. Lino Baptista, N. Rodrigues Querido Fortes, A. K. Melo, T. Santos Melo, V. Cruz, J. Rêgo, R. Maria Rodrigues Vieira, A. Sophia Rodrigues Vieira, A. M. Kakehasi, A. C. Faria Moreira Gomes Tavares, A. Teixeira de Landa, P. Costa, V. F. Azevedo, O. Assis Martins-Filho, V. Peruhype-Magalhães, M. Pinheiro, O. A. Monticielo, E. Torres Dos Reis Neto, G. A. Ferreira, V. Angelina de Souza, A. Teixeira-Carvalho, R. Machado Xavier, E. I. Sato, G. Salviato Pileggi, V. Valim
Journal: Annals of the Rheumatic Diseases (2024)
POS1374 (DIS)ASSOCIATION BETWEEN PHYSICAL EXAMINATION AND ULTRASOUND FINDINGS IN RHEUMATOID AND PSORIATIC ARTHRITIS
Authors: S. Aydin, O. Bayindir Tsechelidis, R. Sabido-Sauri, U. Gazel, S. B. Açikgöz, S. Sangwa, C. Ivory, E. Hepworth
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Ultrasound (US) has emerged as a sensitive method, especially when compared to clinical examination, for evaluating disease activity and damage in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Several studies have shown discrepancies between the physical examination and US to detect inflammation. <h3>Objectives:</h3> This study investigates and compares the frequencies of PE and US findings on a joint level, using heat map analysis and agreement between the PE and US based on the joint and disease. <h3>Methods:</h3> The <b>O</b>ttawa <b>R</b>heumatology <b>C</b>ompre<b>HE</b>n<b>S</b>ive <b>TR</b>eatment and <b>A</b>ssessment Clinic (ORCHESTRA) is a prospective cohort that includes all patients with inflammatory arthritis starting a new advanced therapy at the Ottawa Hospital Rheumatology Division. A standardized protocol is followed, including a comprehensive US scan. We analyzed the results of the PE and US of RA and PsA patients. The B-mode and Doppler findings were scored according to the OMERACT definitions on a scale between 0-3 per joint and ≥2 was used as a threshold of positivity for this analysis. In addition to the heat map analysis, we have also tested the agreement between the PE and US using kappa testing. <h3>Results:</h3> There were 98 RA and 46 PsA patients with 3518 and 2020 joints being analyzed, respectively. The mean (SD) age was 55.6(15.2), with a median (IQR) disease duration of 7 (17.8) years. Sixty RA patients (61.2%) and 20 PsA patients (43.5%) were bio-naive at baseline. Overall, on the heatmap, same joints had higher degrees of involvement, regardless of the modality (Figure 1). The joint distribution for the physical exam seemed comparable for RA and PsA, whereas the Bmode findings were less prevalent for PsA than RA. US positivity was present more often in swollen joints, than tender joints. The agreement between PE and US was none-to-slight for most of the joints, only with a few joints having fair agreement (data not given). <h3>Conclusion:</h3> The agreement between the US and PE is not consistent in all joints and only slight to fair in half of the comparisons. The large discrepancy between the US and PE needs further research to understand the role of each modality on the patients' care. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Sibel Aydin Abbvie, Jannsen, Novartis, Pfizer, and UCB, Abbvie, Celgene, Eli Lilly, Novartis, Pfizer, Sanofi, and UCB, Abbvie, Celgene, Eli Lilly, Jannsen, Novartis, Pfizer, Sanofi, Novartis and UCB, Ozun Bayindir Tsechelidis: None declared, Ricardo Sabido-Sauri: None declared, Ummugulsum Gazel: None declared, Seyyid Bilal Açikgöz: None declared, Sylvia Sangwa: None declared, Catherine Ivory: None declared, Elliott Hepworth: None declared
OP0084 THE ROLE OF MECHANICAL STRAIN-INDUCED HOTAIR LNCRNA DOWNREGULATION IN THE PATHOPHYSIOLOGY OF RHEUMATOID ARTHRITIS
Authors: F. Meier, T. Janczi, Y. Fehrl, B. Böhm, F. Behrens, H. Burkhardt, R. Kinne
Journal: Annals of the Rheumatic Diseases (2024)
POS1166 PURSUING THE BEST TYPE I INTERFERON-STIMULATED GENE SIGNATURE SUITABLE FOR EVALUATING SYSTEMIC LUPUS ERYTHEMATOSUS ACTIVITY
Authors: S. Sumitomo, H. Oka, H. Shimizu, T. Iwasaki, M. Kanamori, H. Nishioka, K. Ohmura
Journal: Annals of the Rheumatic Diseases (2024)
POS0562 THE DIAGNOSTIC PERFORMANCE OF RAMAN SPECTROSCOPY FOR DIAGNOSING CPPD WITH RESPECT TO THE 2023 ACR/EULAR CPPD CLASSIFICATION CRITERIA
Authors: T. Niessink, M. Janssen, C. Otto, T. Jansen
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Due to a lack of reliable detection methods, diagnosing CPP associated arthritis (CPPD) is plagued by flaws. Frequently used diagnostic modalities such as polarized light microscopy, conventional radiology, and ultrasonography suffer from sensitivity issues, poor interrater reliability, and subjectivity. The newly developed 2023 ACR/EULAR CPPD classification criteria provides a well-defined description of the disease for clinicians but is not a diagnostic instrument. There is an urgent need for objective and specific methods to diagnose CPPD. We have integrated a Raman spectroscope with an ordinary polarized light microscope (iRPolM) to increase the specificity and objectivity of synovial fluid analysis. <h3>Objectives:</h3> In this study, we evaluate the performance of iRPolM analysis of synovial fluids for the diagnosis of CPPD using the criteria set. <h3>Methods:</h3> We collected 400 unselected synovial fluid samples from patients visiting our outpatient clinic in Venlo, the Netherlands, and analyzed these with Raman spectroscopy for the presence of CPP crystals. The results of Raman spectroscopy were compared to the outcome of the 2023 ACR/EULAR CPPD classification criteria set. This set includes conventional polarized light microscopy (PLM), clinical presentation, and conventional radiology; patients are classified as positive if CPP crystals are identified in synovial fluid using PLM or when over 56 classification criteria points can be awarded. <h3>Results:</h3> A total of 50 patients were classified as CPPD according to the 2023 ACR/EULAR criteria set. The interrater reliability between iRPolM and the 2023 ACR/EULAR criteria set for CPPD was strong (k = 0.88). The sensitivity was 86.0% (95% CI 73.3 - 94.2), specificity was 99.1% (95% CI 97.5 - 99.8), positive likelihood ratio was 100.3 (95% CI 32.3 - 311.3), negative likelihood ratio was 0.14 (95% CI 0.07 - 0.28), positive predictive value was 93.5% (95% CI 82.2 - 97.8), negative predictive value was 98.0% (95% CI 86.8 - 99.9), and the accuracy was 97.5% (95% CI 95.5 - 98.8). <h3>Conclusion:</h3> We here demonstrated that Raman spectroscopy can be used to diagnose CPPD with improved performance. Due to a high specificity, we propose that Raman spectroscopic identification of CPP crystals can be applied as the new gold standard in diagnosing CPPD. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Tom Niessink: None declared, Matthijs Janssen Crystalytics B.V. (Start-up), Cees Otto Hybriscan technologies B.V., Tim Jansen Crystallytics B.V.