tbuckley/cabot-search huggingface dataset:
POS1245 MORTALITY OF COVID-19 IN PATIENTS WITH RHEUMATIC DISEASES: COMPARISON TO THE GENERAL POPULATION IN MÉXICO
Authors: M. U. Martínez-Martínez, F. Irazoque-Palazuelos, T. S. Rodriguez-Reyne, E. Zamora, A. Castillo Ortiz, B. E. Zazueta, S. Duran Barragan, M. Rull-Gabayet, J. F. Moctezuma-Ríos, X. Jimenez Jimenez, E. Martin-Nares, D. Cervantes-Rosete, D. Vega-Morales, D. X. Xibille Friedmann, A. Barragán-Garfías, E. Alvarez Hernandez, M. Vázquez-Del Mercado Espinosa, C. F. Pacheco Tena, D. Alpizar-Rodriguez
Journal: Annals of the Rheumatic Diseases (2021)

Background: COVID-19 outcomes in Mexican patients with rheumatic diseases (RDs) in comparison to general population patients are unknown. Objectives: To compare mortality and hospitalization of COVID-19 patients with RDs and those without. Methods: We included for this study all the Mexican patients with RDs and COVID-19 registered from April 17 th to October 30 th , 2020 in the COVID-19 Global Rheumatology Alliance registry. We compare clinical and demographic characteristics of patients with RDs and COVID-19 to patients with COVID-19 that were selected randomly from the Mexican Epidemiology database (1:3). A logistic regression analysis was performed to adjust for confusion variables. Results: We included 322 patients with COVID-19 and RDs and 969 controls without RDs. Table 1 shows the demographic characteristics and comorbidities of both groups. Bivariate analysis showed that patients with RDs had higher mortality, were older, and were more frequently hospitalized. Comorbidities, such as diabetes, hypertension, cardiovascular and renal diseases were also more frequent in patients with RDs. In the multivariate analysis, having a RD was no longer associated with mortality (Figure 1). Figure 1. Multivariate analysis of mortality Conclusion: Patients with RDs had higher comorbidities, hospitalizations, and mortality than the general population in the bivariate analysis. However, adjusted multivariate analysis showed that the odds for mortality were not increased because of having a RD. These findings suggest that the increased mortality of Mexican patients with RDs may be explained by the higher frequency of comorbidities in this population. Table 1. Comparison of patients with COVID-19 with and without RDs COVID-19 patients without RDs COVID-19 patients with RDs p-value N 969 323 Age (mean (SD)) 42.6 (17.4) 51.2 (13.9) &lt;0.001 Sex = Male (%) 455 (47.0) 55 (17.0) &lt;0.001 Deceased = Yes (%) 55 (5.7) 43 (13.3) &lt;0.001 Hospitalization = Hospitalized (%) 164 (16.9) 152 (47.1) &lt;0.001 Intubation = Yes (%) 27 (2.8) 32 (11.8) &lt;0.001 COPD_Asthma = Yes (%) 37 (3.8) 15 (4.6) 0.522 Diabetes = Yes (%) 114 (11.8) 49 (15.2) 0.116 Obesity = Yes (%) 128 (13.3) 21 (6.5) 0.001 Hypertension = Yes (%) 152 (15.8) 88 (27.2) &lt;0.001 Cardiovascular disease = Yes (%) 19 (2.0) 14 (4.3) 0.02 CRF = Yes (%) 22 (2.3) 17 (5.3) 0.007 Pregnancy = Yes (%) 5 (0.5) 2 (0.6) 0.827 Smoker = Yes (%) 86 (8.9) 10 (3.1) 0.001 Abbreviations: RDs, rheumatic diseases; COPD, chronic obstructive pulmonary disease; CRF, chronic renal failure. Disclosure of Interests: None declared
Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT
Authors: Jaime Sanz, Jacques-Emmanuel Galimard, Myriam Labopin, Boris Afanasyev, Moiseev Ivan Sergeevich, Emanuele Angelucci, Nicolaus Kröger, Yener Koc, Fabio Ciceri, J. L. Diez-Martin, Mutlu Arat, Simona Sica, Montserrat Rovira, Mahmoud Aljurf, Johanna Tischer, Bipin Savani, Annalisa Ruggeri, Arnon Nagler, Mohamad Mohty
Journal: Journal of Hematology & Oncology (2021)

Abstract Background There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) ( n = 78), matched unrelated (MUD) ( n = 94) and haploidentical family (Haplo) ( n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% ( p = 0.4); 13%, 15%, and 15% ( p = 0.8); 35%, 50%, and 42% ( p = 0.01); and 11%, 17%, and 21% ( p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% ( p = 0.8); and 21%, 18%, and 21% ( p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% ( p = 0.8); 66%, 69%, and 62% ( p = 0.8); and 46%, 44%, and 35% ( p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.
Letter regarding “Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients—a report of the PET/RANO group”: 18F-fluciclovine and target volume delineation
Authors: Rupesh Kotecha, Mariam Aboian, Seyed Ali Nabavizadeh, Ephraim E Parent, Daniel M Trifiletti, Samuel T Chao
Journal: Neuro-Oncology (2021)
Incidentally Detected Hypermetabolism in Pons Suggestive of Pontine Myelinolysis on 18F-FDG PET/CT Scan
Authors: Anand Zade, Amol Ingule, Chintan Trivedi, Smriti Jha, Anup Agrwal
Journal: Clinical Nuclear Medicine (2021)

Abstract Central pontine myelinolysis (CPM) is demyelinating condition of pons caused by osmotic stress due to rapid correction of hyponatremia. We present a case where CPM was an incidental finding on FDG PET/CT scan. To the best of our knowledge, only 3 case reports have been published till date describing CPM on 18 F-FDG PET/CT scans.
Base-edited CAR T cells for combinational therapy against T cell malignancies
Authors: Christos Georgiadis, Jane Rasaiyaah, Soragia Athina Gkazi, Roland Preece, Aniekan Etuk, Abraham Christi, Waseem Qasim
Journal: Leukemia (2021)

Abstract Targeting T cell malignancies using chimeric antigen receptor (CAR) T cells is hindered by ‘T v T’ fratricide against shared antigens such as CD3 and CD7. Base editing offers the possibility of seamless disruption of gene expression of problematic antigens through creation of stop codons or elimination of splice sites. We describe the generation of fratricide-resistant T cells by orderly removal of TCR/CD3 and CD7 ahead of lentiviral-mediated expression of CARs specific for CD3 or CD7. Molecular interrogation of base-edited cells confirmed elimination of chromosomal translocations detected in conventional Cas9 treated cells. Interestingly, 3CAR/7CAR co-culture resulted in ‘self-enrichment’ yielding populations 99.6% TCR−/CD3−/CD7−. 3CAR or 7CAR cells were able to exert specific cytotoxicity against leukaemia lines with defined CD3 and/or CD7 expression as well as primary T-ALL cells. Co-cultured 3CAR/7CAR cells exhibited highest cytotoxicity against CD3 + CD7 + T-ALL targets in vitro and an in vivo human:murine chimeric model. While APOBEC editors can reportedly exhibit guide-independent deamination of both DNA and RNA, we found no problematic ‘off-target’ activity or promiscuous base conversion affecting CAR antigen-specific binding regions, which may otherwise redirect T cell specificity. Combinational infusion of fratricide-resistant anti-T CAR T cells may enable enhanced molecular remission ahead of allo-HSCT for T cell malignancies.
Long-term Predictions of Incident Coronary Artery Calcium to 85 Years of Age for Asymptomatic Individuals With and Without Type 2 Diabetes
Authors: Bart S. Ferket, M.G. Myriam Hunink, Umesh Masharani, Wendy Max, Joseph Yeboah, Kirsten E. Fleischmann
Journal: Diabetes Care (2021)

To examine the utility of repeated computed tomography (CT) coronary artery calcium (CAC) testing, we assessed risks of detectable CAC and its cardiovascular consequences in individuals with and without type 2 diabetes ages 45-85 years.We included 5,836 individuals (618 with type 2 diabetes, 2,972 without baseline CAC) from the Multi-Ethnic Study of Atherosclerosis. With logistic and Cox regression we evaluated the impact of type 2 diabetes, diabetes treatment duration, and other predictors on prevalent and incident CAC. We used time-dependent Cox modeling of follow-up data (median 15.9 years) for two repeat CT exams and cardiovascular events to assess the association of CAC at follow-up CT with cardiovascular events.For 45 year olds with type 2 diabetes, the likelihood of CAC at baseline was 23% vs. 17% for those without. Median age at incident CAC was 52.2 vs. 62.3 years for those with and without diabetes, respectively. Each 5 years of diabetes treatment increased the odds and hazard rate of CAC by 19% (95% CI 8-33) and 22% (95% CI 6-41). Male sex, White ethnicity/race, hypertension, hypercholesterolemia, obesity, and low serum creatinine also increased CAC. CAC at follow-up CT independently increased coronary heart disease rates.We estimated cumulative CAC incidence to age 85 years. Patients with type 2 diabetes develop CAC at a younger age than those without diabetes. Because incident CAC is associated with increased coronary heart disease risk, the value of periodic CAC-based risk assessment in type 2 diabetes should be evaluated.
Efficacy of Combining Varenicline and Naltrexone for Smoking Cessation and Drinking Reduction: A Randomized Clinical Trial
Authors: Lara A. Ray, ReJoyce Green, Craig Enders, Adam M. Leventhal, Erica N. Grodin, Gang Li, Aaron Lim, Emily Hartwell, Alex Venegas, Lindsay Meredith, Steven J. Nieto, Steven Shoptaw, Diana Ho, Karen Miotto
Journal: American Journal of Psychiatry (2021)

Pharmacological treatments that can concomitantly address cigarette smoking and heavy drinking stand to improve health care delivery for these highly prevalent co-occurring conditions. This superiority trial compared the combination of varenicline and naltrexone against varenicline alone for smoking cessation and drinking reduction among heavy-drinking smokers.This was a phase 2 randomized double-blind clinical trial. Participants (N=165) who were daily smokers and drank heavily received either 2 mg/day of varenicline plus 50 mg/day of naltrexone or 2 mg/day of varenicline plus matched placebo pills for 12 weeks. Primary outcomes were 7-day point prevalence of nicotine abstinence (bioverified by a breath CO reading ≤5 ppm) at the 26-week follow-up and number of drinks per drinking day during the 12-week treatment phase.Smoking abstinence at week 26 was significantly higher in the varenicline plus placebo condition than in the varenicline plus naltrexone condition (N=37 [45.1%] compared with N=22 [26.5%]). For drinks per drinking day, there was a medication effect favoring the combination of varenicline and naltrexone over varenicline alone across the 12-week treatment phase, although it did not meet the significance threshold.These findings suggest that smoking cessation and drinking reduction can be concomitantly targeted with pharmacotherapy and that while varenicline alone may be sufficient as a smoking cessation aid in heavy-drinking smokers, the combination of varenicline and naltrexone may confer benefits with regard to drinking outcomes, particularly during the 12-week period of active medication treatment.
POS0389 NEUTROPHIL AND MONOCYTE EXTRACELLULAR TRAPS IN RHEUMATOID ARTHRITIS: POTENTIAL SOURCE OF DIAGNOSTIC BIOMARKERS
Authors: A. Trofimenko, S. Bedina, M. Mamus, E. Mozgovaya, S. Spitsina
Journal: Annals of the Rheumatic Diseases (2021)

Background: Up-to date quite high rheumatoid arthritis (RA) prevalence has also a trend towards steady increase for several decades. Earliest possible diagnosis and personalized treatment of RA are commonly believed to be principal way to prevent or diminish joint destruction. Emerging biomarkers retrieval has therefore critical importance for improvement of RA treatment outcomes, especially for its biological treatment. One of upcoming sources of new biomarkers is newly discovered phenomenon of neutrophil extracellular traps (NET) and monocyte extracellular traps (MET) formation, specifically in RA. Objectives: Evaluation of peripheral blood neutrophils and monocytes ability to generate NET and MET spontaneously and after induction in vitro in RA. Methods: The research was carried out in agreement with the WMA Declaration of Helsinki principles. 30 patients with verified RA according to the ACR/EULAR 2010 criteria were included in the study. 30 healthy volunteers were enrolled as a reference group. RA disease activity was assessed using DAS28 score did not exceeded 2.6 in every patient at the inclusion timepoint. Neutrophils and monocytes were isolated with one-step centrifugation procedure using three-layer ficoll-amidotrizoate density gradient with density of upper, intermediate and lower layers 1068 kg/m 3 , 1080 kg/m 3 , and 1090 kg/m 3 , respectively. The cell types in the resulting fractions were identified histochemically, and the extent of cell activation was assessed using common nitro-blue tetrazolium test. Generation of NETs was stimulated by phorbol-12-myristate-13-acetate (PMA). Generation of METs was stimulated using bacterial LPS. The shape and size of NETs and ETs were assessed using fluorescence microscopy with SYBR green. Results: Mean contamination fraction of neutrophils and monocytes in the reference group did not exceeded 3% and 2%, respectively. Mean purity of neutrophil fraction in RA group was 93.1±6.1%, and cell viability in every sample was above 95.4±5.1%. Mean purity of monocyte fraction in RA group was 98.4±6.4%, cell viability in every sample was above 93.4±4.8%. Spontaneous NET and MET formation was observed in neutrophils and monocytes isolated from both RA patients and, significantly less, in healthy controls. Neutrophils from ACPA-positive RA patients were found to reveal increased spontaneous and induced NETs formation compared to ACPA- negative RA patients. Monocytes did not demonstrate any difference between these subgroups. Conclusion: NETs could probably be considered as a candidate source of citrulline autoantigen participating in autoantibody production, whereas METs may play less important role in this phenomenon. NETs and ETs can be considered as potential diagnostic biomarkers of RA. Further studies of NETosis and ETosis in RA patients can promote emerging researches for targeted therapy of RA. Disclosure of Interests: None declared
AB0124 STRUCTURAL DAMAGE IN THE FOOT IN RHEUMATOID ARTHRITIS: DON’T MISS THE OTHER METATARSOPHALANGEAL JOINTS
Authors: M. Yasmine, H. Ferjani, D. Kaffel, K. Maatallah, S. Rahmouni, W. Hamdi
Journal: Annals of the Rheumatic Diseases (2021)

Background: The foot involvement in rheumatoid arthritis (RA) affects the functionality and the quality of life in patients. Despite this, the clinicians do not give enough care to the foot in RA patients, especially if asymptomatic, resulting in joint damage, deformity, and disability. The distribution of erosions of the other MTP joints (excluding the 5th) has not previously been studied. Objectives: This study aimed to investigate the distribution of erosions in MTP joints and their clinical implications. Methods: We conducted a retrospective study including patients with RA according to the American college of rheumatology/ the European league against rheumatism classification criteria. Sociodemographic data, as well as disease activity related characteristics, were recorded. Posterior–anterior radiographs of the hands and feet of each patient were assessed for erosions. All patients were assessed by Ultrasonography (US) of the hands. US erosions were scored 0-3 according to Szkudlarek [1]. We divided patients into two groups (G1 without MTPs erosions and G2 with MTPs erosions). Results: We enrolled forty-two females and eleven males in our studies. The mean age was 58.6 years ±12.7 [23-77], and the mean disease duration was 8.4 years [1-47]. Rheumatoid factor or cyclic citrullinated peptide antibodies (Anti-CCP) were positive in 62.3% of cases. The mean DAS28ESR score was 5.1±1.16 [2.5-7.7]. Half of the patients had the active disease (52.8%). Hand erosions evaluated with plain radiographs and the US were found in 43.1% and 50.9% of cases, respectively. The distribution of foot erosions (15.1%) was at follows: 5th right MTP (7.5%), the 5th right IPP (2%), the 1st left MTP (2%), 3th left MTP (3.8%), 4th left MTP (5.7%) and the 5th left MTP (9.4%). Erosions on MTPs with the exclusion of the 5th MTP were present in 9.4% of cases. The presence of MTPs erosion was more frequent in males (p=0.01) but was not associated with age (p=0.6) or disease duration (p=0.2). Seropositivity was similar between the two groups (p=0.06). Similarly, the inflammatory markers (ESR and CRP), as well as DAS28 ESR, did not differ between the two groups (p&gt;0.05). MTPs erosion was not associated with the presence of hand erosions on a plain radiograph (p=0.445). However, MTPs erosion was significantly more frequent in patients with less erosive hands-on US (p=0.034). Conclusion: Our study showed that screening of other MTPs (excluding the 5th) is mandatory in RA diagnosis. Interestingly, in our result, MTPs erosion is more frequent in males with less erosive hands. Disclosure of Interests: None declared
AB0060 INCREASED AGE/AUTOIMMUNE-ASSOCIATED B CELLS IN RA AND CLINICAL IMPLICATIONS
Authors: Y. Qin, Z. Chen
Journal: Annals of the Rheumatic Diseases (2021)

Background: Age/Autoimmune-associated B cells (ABCs) are an emerging B cell subset that accumulate in aged and autoimmune-prone mice. Expansion of human ABCs has been observed in patients with autoimmune diseases like SLE and correlated with disease activity. However, it is less known whether ABCs contribute to the pathogenesis of RA. Objectives: The aim of this work was to explore the role of ABCs in RA. Methods: 83 RA patients who met the 2010 ACR classification criteria for RA, 42 sex and age matched healthy control (HC), 35 Spondyloarthritis (SpA) and 31 Osteoarthritis (OA) patients were enrolled and blood samples were collected. The proportion of circulating ABCs was detected by flow cytometry and association with clinical and laboratory parameters were analyzed. Expression of characteristic proteins and inflammatory cytokines on ABCs were examined by quantitative real-time PCR. Results: The proportion of ABCs, defined as CD19 + CD27 - IgD - CD21 - CD11c + , was significantly elevated in RA patients, compared with HC, SpA and OA patients. The frequency of ABCs was higher in patients with high disease activity (DAS28&gt;3.2) compared with remission and low disease activity (DAS28&lt;3.2). There was a positive correlation of ABCs with SJC, TJC, DAS28 whereas no association with RF and anti-CCP titer were observed. In addition, increased mRNA expression levels of T-bet, IL-21, MAF and IL-17 were noted on ABCs compared with CD19 + CD27 - CD11c - B cells. Conclusion: ABCs were expanded in RA patients and associated with active disease status. It might contribute to RA development by production of IL-17. References: [1]Cancro, M.P., Age-Associated B Cells. Annu Rev Immunol, 2020. 38(315-340). [2]F. Zhang, K. Wei, K. Slowikowski et al., Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol 2019, 20, 928-942. Disclosure of Interests: None declared
An immune-competent, replication-permissive Syrian Hamster glioma model for evaluating Delta-24-RGD oncolytic adenovirus
Authors: Lynette M Phillips, Shoudong Li, Joy Gumin, Marc Daou, Daniel Ledbetter, Jing Yang, Sanjay Singh, Brittany C Parker Kerrigan, Anwar Hossain, Ying Yuan, Candelaria Gomez-Manzano, Juan Fueyo, Frederick F Lang
Journal: Neuro-Oncology (2021)

Oncolytic adenoviruses are promising new treatments against solid tumors, particularly for glioblastoma (GBM), and preclinical models are required to evaluate the mechanisms of efficacy. However, due to the species selectivity of adenovirus, there is currently no single animal model that supports viral replication, tumor oncolysis, and a virus-mediated immune response. To address this gap, we took advantage of the Syrian hamster to develop the first intracranial glioma model that is both adenovirus replication-permissive and immunocompetent.We generated hamster glioma stem-like cells (hamGSCs) by transforming hamster neural stem cells with hTERT, simian virus 40 large T antigen, and h-RasV12. Using a guide-screw system, we generated an intracranial tumor model in the hamster. The efficacy of the oncolytic adenovirus Delta-24-RGD was assessed by survival studies, and tumor-infiltrating lymphocytes (TILs) were evaluated by flow cytometry.In vitro, hamGSCs supported viral replication and were susceptible to Delta-24-RGD mediated cell death. In vivo, hamGSCs consistently developed into highly proliferative tumors resembling high-grade glioma. Flow cytometric analysis of hamster gliomas revealed significantly increased T-cell infiltration in Delta-24-RGD infected tumors, indicative of immune activation. Treating tumor-bearing hamsters with Delta-24-RGD led to significantly increased survival compared to hamsters treated with phosphate buffered saline (PBS).This adenovirus-permissive, immunocompetent hamster glioma model overcomes the limitations of previous model systems and provides a novel platform to study the interactions between tumor cells, the host immune system, and oncolytic adenoviral therapy; understanding of which will be critical to implementing oncolytic adenovirus in the clinic.
Final results of a phase 1b study of isatuximab short-duration fixed-volume infusion combination therapy for relapsed/refractory multiple myeloma
Authors: Saad Z. Usmani, Chatchada Karanes, William I. Bensinger, Anita D’Souza, Noopur Raje, Sascha A. Tuchman, Douglas Sborov, Jacob P. Laubach, Giada Bianchi, Dheepak Kanagavel, Rao Saleem, Franck Dubin, Frank Campana, Paul G. Richardson
Journal: Leukemia (2021)

Part B of this phase 1b study (ClinicalTrials.gov number, NCT02283775) evaluated safety and efficacy of a fixed-volume infusion of isatuximab, an anti-CD38 monoclonal antibody, in combination with pomalidomide and dexamethasone (Pd) in relapsed/refractory multiple myeloma patients. Isatuximab (10 mg/kg weekly for 4 weeks, then every other week) was administered as a fixed-volume infusion of 250 mL (mL/h infusion rate) with standard doses of Pd on 28-day cycles. Patients (N = 47) had a median of three prior treatment lines (range, 1-8). Median duration of exposure was 36.9 weeks and median duration of first, second, and 3+ infusions were 3.7, 1.8, and 1.2 h, respectively. The most common non-hematologic treatment-emergent adverse events were fatigue (63.8%), infusion reactions (IRs), cough, and upper respiratory tract infection (40.4% each). IRs were all grade 2 and occurred only during the first infusion. The overall response rate was 53.2% in all patients (55.5% in response-evaluable population, 60.0% in daratumumab-naïve patients). Efficacy and safety findings were consistent with data from the isatuximab plus Pd infusion schedule in Part A of this study and also from the phase 3 ICARIA-MM study, and these new data confirm the safety, efficacy, and feasibility of fixed-volume infusion of isatuximab.