tbuckley/cabot-search huggingface dataset:
AB0507 ASSESSMENT OF FIBRINOGEN TO ALBUMIN RATIO IN RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: CORRELATION WITH DISEASE ACTIVITY
Authors: M. Slouma, S. Bouzid, K. Lahmar, R. Dhahri, I. Gharsallah, L. Metoui, B. Louzir
Journal: Annals of the Rheumatic Diseases (2021)

Background: Radiographic axial spondyloarthritis is a chronic inflammatory disease that involves the spine and the sacroiliac joints. No specific biomarker that reflects disease activity is yet available. Objectives: This study aimed to assess the relationship between fibrinogen (Fib) to albumin (ALB) ratio (FAR) and disease activity in radiographic axial spondyloarthritis. Methods: We performed a cross-sectional study including 51 patients with radiographic axial spondyloarthritis. Disease activity was assessed using Ankylosing Spondylitis Disease Activity Score (ASDAS). C-reactive protein (CRP), fibrinogen (Normal value: 2 -4g/L), erythrocyte sedimentation rate (ESR) and albumin levels (Normal value: 35 -50 g/L) were measured. The fibrinogen to albumin ratio (FAR) was calculated. We excluded patients with infectious disease, hematological disease, and those with malabsorption syndrome Statistical analysis was performed using SPSS 26. Results: The study included 43 males and 8 females with a mean age of 41.25 ± 10.97 years. The mean disease duration was 117.92 (85.4 months). The mean fibrinogen and albumin levels were 3.94 ± 1.24 g/L and 36.94 ± 5.89 g/L, respectively. Fibrinogen level was elevated in 45% patients and albumin levels was decreased in 51% cases. Mean FAR was 0.11 ± 0.44. ESR levels were elevated in 67% with a mean of 40.22 ± 34.64 mm. CRP levels were high in 61% with a mean of 28.57 ± 33.25 mg/L. Mean ASDAS was 3.32 ± 1. 27 patients had very high disease activity (ASDAS&gt;3.5). Significant correlation was found between FAR and following parameters: ESR (r = 0.836, p&lt; 0.001), CRP (r = 0.785, p &lt; 0.001), and ASDAS (r = 0.463, P &lt; 0.001). The ability of FAR to distinguish patients with very high disease activity from those without very high disease activity was excellent, with Aire under the curve of 0.819. The optimal FAR cutoff value with the highest accuracy was 0,1065 with a sensitivity of 0,792 and specificity of 0,852. Conclusion: Our study showed that fibrinogen to albumin ratio correlate with ESR, CRP and ASDAS. This finding suggests that this ratio may be a used to assess disease activity in radiographic axial spondyloarthritis (1). References: [1]Liu M, Huang Y, Huang Z, Zhong Z, Deng W, Huang Z, et al. The role of fibrinogen to albumin ratio in ankylosing spondylitis: Correlation with disease activity. Clin Chim Acta. juin 2020;505:136-40. Disclosure of Interests: None declared.
Rubella vaccine–induced granulomas are a novel phenotype with incomplete penetrance of genetic defects in cytotoxicity
Authors: Miriam Groß, Carsten Speckmann, Annette May, Tania Gajardo-Carrasco, Katharina Wustrau, Sarah Lena Maier, Marcus Panning, Daniela Huzly, Abbas Agaimy, Yenan T. Bryceson, Sharon Choo, C.W. Chow, Gregor Dückers, Anders Fasth, Sylvie Fraitag, Katja Gräwe, Sabine Haxelmans, Dirk Holzinger, Ole Hudowenz, Judith M. Hübschen, Claudia Khurana, Korbinian Kienle, Roman Klifa, Klaus Korn, Heinz Kutzner, Tim Lämmermann, Svea Ledig, Dan Lipsker, Marie Meeths, Nora Naumann-Bartsch, Jelena Rascon, Anne Schänzer, Maximilian Seidl, Bianca Tesi, Christelle Vauloup-Fellous, Beate Vollmer-Kary, Klaus Warnatz, Claudia Wehr, Bénédicte Neven, Pablo Vargas, Fernando E. Sepulveda, Kai Lehmberg, Annette Schmitt-Graeff, Stephan Ehl
Journal: Journal of Allergy and Clinical Immunology (2021)
A modified IFN-γ ELISPOT assay to detect specific responses to human primary tumor cells
Authors: Susan L. Strobl, Sattva Neelapu, Kimberly Shafer-Weaver, Tracy Ulderich, Michael Baseler, Larry Kwak, Anatoli Malyguine
Journal: Cancer Research (2004)

1235  The interferon-γ (IFN-γ) ELISPOT assay is one of the most useful techniques for immunological monitoring of patient responses to cancer vaccines but has mainly been used to measure reactivity to the vaccine components. This reactivity, however, does not necessarily equate to recognition and elimination of tumor cells. We have developed a novel autologous tumor IFN-γ ELISPOT assay that directly measures immune responsiveness against tumor cells in vaccinated cancer patients with lymphoma. We utilized autologous follicular or mantle cell lymphoma tumor cells from patients vaccinated with immunoglobulin idiotype (Id) protein as targets and patients’ peripheral blood mononuclear cells (PBMC) as effector cells. Our ELISPOT protocol was optimized for variables including plate type, appropriate medium, target stimulation time, PBMC culture condition, assay incubation time, effector to target cell ratio and color development system. Using our optimized ELISPOT protocol, we have shown that pre-activation of the tumor cells with recombinant human soluble CD40 ligand (sCD40L, Immunex) markedly enhanced IFN-γ secretion by effector cells in vitro when activated tumor cells were incubated with autologous PBMC. IFN-γ secretion was specific, as the reactivity against sCD40L activated normal B-cells was negligible compared to reactivity against similarly activated tumor cells from the same patients. Using different patients, significant effect of vaccination on IFN-γ secretion was detected. These results were highly reproducible. Based on our findings, the modified tumor ELISPOT assay directly measures vaccination-induced activity against autologous lymphoma tumor cells and therefore may provide important immunological insight into patient responses to cancer vaccines that may then be directly assessed against clinical outcome.
Abstract 11507: High Clinical False-Negative Rate of Direct-to-Consumer Genetic Screening for Familial Hypercholesterolemia
Authors: Tom E Callis, Edward D Esplin, Eden Haverfield, Rebecca Truty, Matteo Vatta, Robert L Nussbaum
Journal: Circulation (2019)

Genetic screening for familial hypercholesterolemia (FH) is a growing opportunity to institute precision medicine interventions to prevent early heart disease and stroke. The FDA has authorized dir...
POS1329 A COHORT STUDY ON THE RISK OF DEVELOPING OBSTRUCTIVE SLEEP APNEA, TEMPOROMANDIBULAR JOINT DISORDERS AND CRANIOFACIAL DEFORMITIES IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS
Authors: K. S. K. MA, L. T. Wang
Journal: Annals of the Rheumatic Diseases (2021)

Background: Juvenile Idiopathic Arthritis (JIA), an autoimmune disease, has been proposed to be comorbid with obstructive sleep apnea (OSA). Objectives: We aimed at identifying the relationship between JIA and OSA. Methods: We performed a cohort study including JIA and OSA patients from 1999 to 2013. A total of 2791 patients diagnosed with OSA after JIA onset were recruited, which 11,164 eligible individuals without JIA history were selected as matched-controls. A Cox proportional hazard model was developed to estimate the risk of OSA in JIA patients. A cumulative probability model was adopted to assess the time-dependent effect of JIA on OSA development, implying the casual link of the association. To identify whether JIA patients have higher risks for developing temporomandibular joint (TMJ) disorders, craniofacial anomalies and deformities than non-JIA individuals, subgroup analyses was conducted. Finally, Ingenuity Systems Pathway Analysis (IPA) was conducted to identify underlying mechanisms of the above disease correlation among peripheral blood mononuclear cells (PBMCs) from rheumatic factor (RF)-positive and RF-negative JIA patients, and subcutaneous fat tissues from OSA patients, using p-value visualization for RNA-seq analyses. Results: The Cox proportional hazard model showed that JIA patients were more likely to have OSA than non-JIA individuals (adjusted hazard ratio =1.949, 95% CI =1.264–3.005). The incidence of developing OSA was particularly high among patients who developed JIA aged 18-30 years old (aHR= 2.034, 95% CI=1.305-3.169) and males (aHR=1.82, 95% CI=1.121-2.954). The risk of developing OSA increased within 0-36 months (aHR = 2.216, 95% CI = 1.001 – 4.907) and over 60 months (aHR = 2.558, 95% CI = 1.346 – 4.860) of follow-up duration after JIA onset. Subgroup analyses showed that JIA patients were more likely to have TMJ disorders (relative risk = 2.047, 95% CI = 1.446-2.898) and to receive treatment for craniofacial deformities (RR = 1.722, 95% CI = 1.38-2.148) than non-JIA controls. IPA analyses suggested that the underlying mechanisms involved activation of antigen presentation pathway followed by antigen presentation to CD4+ and CD8+ T lymphocytes, as well as B cell development. Conclusion: Our findings identified high risks of developing OSA, TMJ disorders, and craniofacial deformities following JIA onset, which the underlying mechanisms may involve both cellular and humoral immunity. Disclosure of Interests: None declared
The promise and challenges of cell therapy for psoriasis*
Authors: S.M. Lwin, J.A. Snowden, C.E.M. Griffiths
Journal: British Journal of Dermatology (2021)

The management of moderate-to-severe psoriasis has been transformed by the introduction of biological therapies. These medicines, particularly those targeting interleukin (IL)-17 and IL-23p19, can offer clear or nearly clear skin for the majority of patients with psoriasis, with good long-term drug survival. However, as currently used, none of these therapies is curative and disconcertingly there is a small but increasing number of patients with severe psoriasis who have failed all currently available therapeutic modalities. A similar scenario has occurred in other immune-mediated inflammatory diseases (IMIDs) where treatment options are limited in severely affected patients. In these cases, cell therapy, including haematopoietic stem cell transplantation (HSCT) and mesenchymal stromal cells (MSC), has been utilized. This review discusses the various forms of cell therapy currently available, their utility in the management of IMIDs and emerging evidence for efficacy in severe psoriasis that is unresponsive to biological therapy. Balancing the risks and benefits of treatment vs. the underlying disease is key; cell therapy carries significant risks, costs, regulation and other complexities, which must be justified by outcomes. Although HSCT has anecdotally been reported to benefit severe psoriasis, sometimes with apparent cure, this has mainly been in the setting of other coincidental 'routine' indications. In psoriasis, cell therapies, such as MSC and regulatory T cells, with a lower risk of complications are likely to be more appropriate. Well-designed controlled trials coupled with mechanistic studies are warranted if advanced cell therapies are to be developed and delivered as a realistic option for severe psoriasis.
POS1358 THE EFFECTS AND SAFETY OF APREMILAST AND CYTOKINE EXPRESSION IN BEHCET’S DISEASE PATIENTS
Authors: Y. Ushio, R. Wakiya, K. Ueeda, T. Kameda, S. Nakashima, H. Shimada, M. Mahmoud Fahmy Mansour, M. Kato, T. Miyagi, K. Sugihara, R. Senba, M. Mizusaki, H. Dobashi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Apremilast, the small-molecule phosphodiesterase (PDE) -4 inhibitor, was approved for the treatment of recurrent oral ulcers associated with Behcet’s disease (BD) in Japan from September 2019, following the success of the phase 3 RELIEF study (1). However, the efficacy of apremilast on domains other than oral ulcers in BD patients is unclear. On the other hand, it has been reported that apremilast may decrease the production of proinflammatory cytokine and increase the production of anti-inflammatory mediators in psoriasis (PS) and psoriatic arthritis (PsA) (2). Objectives: To evaluate the effects and safty of apremilast on clinical symptoms and the changing of serum cytokine expression. Methods: BD patients who had treated with apremilast for active oral ulcers were included in the study. We investigated the improvement rate of oral and genital ulcers, skin lesions, arthritis. In addition, serum cytokines (IFN-γ, IL-10, IL-8, and TNF-α) before and after apremilast treatment were measured using a multiplex immunoassay (Luminex Assay, R&amp;D Systems). Results: Fourteen patients (3 males and 11 females) were enrolled in this study. The mean age was 46.6 ± 13.0 years and the mean duration of disease was 10.2 ± 8.8 years. All patients had active oral ulcers, five had genital ulcers, six had skin lesions, and four had arthritis. Three months after the treatment with apremilast, oral ulcers improved in 13 patients (92.9%). The improvement rates of genital ulcers, skin lesions and arthritis were 60%, 25% and 25%, respectively. Changes in serum cytokines were different from those previously reported in PS. Adverse events were gastrointestinal symptoms such as nausea and diarrhea in 6 patients and sensorineural deafness in 1 patient. Medication was reduced in 2 patients, and discontinued in 1 patient due to nausea and diarrhea. Conclusion: Apremilast is useful not only for oral ulcers, but also for other lesions in BD patients. The effect of apremilast for other domain such as genital ulcers, skin lesions, arthritis was not comparable to that of active oral ulcers. Additionally, BD may have different cytokine profile from PS and PsA. References: [1]Hatemi G, Mahr A, Ishigatsubo Y, et al. Trial of Apremilast for Oral Ulcers in Behcet’s Syndrome. N Engl J Med. 2019;381(20):1918-28 [2]Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83(12):1583-1590 Disclosure of Interests: None declared
Improving the Assessment of COVID-19–Associated Posttraumatic Stress Disorder—Reply
Authors: Delfina Janiri, Georgios D. Kotzalidis, Gabriele Sani
Journal: JAMA Psychiatry (2021)

Delfina Janiri, MD; Angelo Carfì, MD; Georgios D. Kotzalidis, MD, PhD; Roberto Bernabei, MD; Francesco Landi, MD, PhD; Gabriele Sani, MD; Gemelli Against COVID-19 Post-Acute Care Study Group
68Ga-FAPI PET/CT Versus 18F-FDG PET/CT for the Evaluation of Disease Activity in Takayasu Arteritis
Authors: Simin Wu, Yizhen Pang, Liang Zhao, Long Zhao, Haojun Chen
Journal: Clinical Nuclear Medicine (2021)

Abstract Evaluation of disease activity in Takayasu arteritis (TA) is challenging because clinical, biological, and imaging data do not always correlate. In this case, a 19-year-old woman with TA underwent 18 F-FDG PET/CT for evaluating disease activity. However, no abnormal 18 F-FDG uptake was observed in the large arteries. Follow-up with 68 Ga-FAPI PET/CT showed intense activity in the mildly thickened walls of bilateral carotid, subclavian arteries, and thoracic and abdominal aorta. This case presented an example where 68 Ga-FAPI outperformed 18 F-FDG for detecting active inflammation of TA. Therefore, 68 Ga-FAPI PET/CT may allow monitoring of disease activity and facilitate selecting the optimal therapy for TA patients.
AB0154 USAGE OF THE SARC-F QUESTIONNAIRE FOR SARCOPENIA SCREENING IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: O. Dobrovolskaya, N. Toroptsova, O. Nikitinskaya, A. Efremova, N. Demin
Journal: Annals of the Rheumatic Diseases (2021)

Background: Sarcopenia, characterized by low muscle strength and low muscle quantity or quality and associated with increased risks of falling and mortality. The prevalence of sarcopenia is 37% among patients with RA [1]. However, in clinical practice settings, sarcopenia among RA patients remains underdiagnosed. The SARC-F questionnaire [2] was recommended by the European Working Group on Sarcopenia in Older People (EWGSOP) before performing muscle strength tests and assessment muscle mass. Objectives: To evaluate the diagnostic value of the SARC-F questionnaire for the screening of sarcopenia (SP) in women with rheumatoid arthritis (RA). Methods: 83 women (average age 59±8 years) with RA without aseptic bone necrosis, joint replacement and severe comorbidities were recruited. All patients were interviewed with the SARC-F questionnaire. The summation score ≥ 4 corresponded to cut-off for suspected sarcopenia. Sarcopenia was evaluated using the European Working Group on Sarcopenia in Older People (EWGSOP2), which included dual-energy X-ray absorptiometry (DXA), handgrip strength or chair stand test, and gait speed. The sensitivity, specificity, positive and negative prognostic values of the SARC-F questionnaire were estimated. Results: Confirmed SP was diagnosed in 20 (24%) RA patients, who had low muscle strength and mass. When conventional cut-off point (≥4) for SARC-F questionnaire was applied, only 30% of the patients with SP met this condition (sensitivity 30%, 95% confidence interval [95% CI] 13% to 54%), and 41% of the patients without SP did not meet this condition (specificity 41%, 95% CI 29% to 54%). Positive and negative prognostic values were 14% (95% CI 6% to 29%) and 65% (95% CI 48% to 79%), respectively. Conclusion: The SARC-F questionnaire alone is not adequate for screening of SP in RA patient. It is necessary to develop other simple screening methods that can easily be carried out in real clinical practice to identify individuals with possible SP for further diagnostic tests. References: [1]Torii M, Hashimoto M, Hanai A, et al. Prevalence and factors associated with sarcopenia in patients with rheumatoid arthritis. Modern Rheumatology, 2018;29(4):589-595. doi:10.1080/14397595.2018.1510565. [2]Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16-31. doi:10.1093/ageing/afy169. Disclosure of Interests: None declared
Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk
Authors: Shambavi Richard, Ajai Chari, Sosana Delimpasi, Maryana Simonova, Ivan Spicka, Ludek Pour, Iryna Kriachok, Meletios A. Dimopoulos, Halyna Pylypenko, Holger W. Auner, Xavier Leleu, Ganna Usenko, Roman Hajek, Reuben Benjamin, Tuphan Kanti Dolai, Dinesh Kumar Sinha, Christopher P. Venner, Mamta Garg, Don Ambrose Stevens, Hang Quach, Sundar Jagannath, Phillipe Moreau, Moshe Levy, Ashraf Badros, Larry D. Anderson, Nizar J. Bahlis, Thierry Facon, Maria Victoria Mateos, Michele Cavo, Hua Chang, Yosef Landesman, Yi Chai, Melina Arazy, Jatin Shah, Sharon Shacham, Michael G. Kauffman, Sebastian Grosicki, Paul G. Richardson
Journal: American Journal of Hematology (2021)

In the phase 3 BOSTON study, patients with multiple myeloma (MM) after 1-3 prior regimens were randomized to once-weekly selinexor (an oral inhibitor of exportin 1 [XPO1]) plus bortezomib-dexamethasone (XVd) or twice-weekly bortezomib-dexamethasone (Vd). Compared with Vd, XVd was associated with significant improvements in median progression-free survival (PFS), overall response rate (ORR), and lower rates of peripheral neuropathy, with trends in overall survival (OS) favoring XVd. In BOSTON, 141 (35.1%) patients had MM with high-risk (presence of del[17p], t[4;14], t[14;16], or ≥4 copies of amp1q21) cytogenetics (XVd, n = 70; Vd, n = 71), and 261 (64.9%) exhibited standard-risk cytogenetics (XVd, n = 125; Vd, n = 136). Among patients with high-risk MM, median PFS was 12.91 months for XVd and 8.61 months for Vd (HR, 0.73 [95% CI, (0.4673, 1.1406)], p = 0.082), and ORRs were 78.6% and 57.7%, respectively (OR 2.68; p = 0.004). In the standard-risk subgroup, median PFS was 16.62 months for XVd and 9.46 months for Vd (HR 0.61; p = 0.004), and ORRs were 75.2% and 64.7%, respectively (OR 1.65; p = 0.033). The safety profiles of XVd and Vd in both subgroups were consistent with the overall population. These data suggest that selinexor can confer benefits to patients with MM regardless of cytogenetic risk. ClinicalTrials.gov identifier: NCT03110562.
Citation Inaccuracies in Influential Surgical Journals
Authors: Jeff Choi, Anshal Gupta, Aydin Kaghazchi, Thinzar S. Htwe, Michael Baiocchi, David A. Spain
Journal: JAMA Surgery (2021)

This study investigates the prevalence and potential etiologies of citation inaccuracies in surgical literature by systematically characterizing influential surgical articles and references they cited.
AB0442 CLINICAL FEATURES OF POLYMYOSITIS AND DERMATOMYOSITIS PATIENTS WITH SEVERE DYSPHAGIA
Authors: Y. Hayashi, K. Izumi, S. Hama, M. Higashida-Konishi, M. Ushikubo, H. Oshima, Y. Okano
Journal: Annals of the Rheumatic Diseases (2021)

Background: Polymyositis (PM) and dermatomyositis (DM) are autoimmune inflammatory diseases characterized by proximal myositis. Dysphagia has been reported to develop in 35 to 62% of PM/DM patients and known as poor prognosis factor. Objectives: The purpose of this study is to determine the clinical characteristics of PM/DM patients who present with deglutition disorder. Methods: Consecutive patients with PM/DM who visited National Hospital Organization Tokyo Medical Center between April 2010 and January 2021 are included in this study. We compared clinical features between the patients with and without dysphagia. The diagnosis of dysphagia was based on videofluorography swallow study, and dysphagia requiring gastrostomy was defined as severe dysphagia. The clinical characteristics compared in this study were following: age of onset, levels of serum creatine kinase (CK) and lactate dehydrogenase(LDH), sense of dysphagia, manual muscle test (MMT) score, and complication of malignancy or interstitial pneumonia. Results: A total of 73 patients with PM/DM were identified. Among them, 12 patients were diagnosed with dysphagia, and 5 patients developed severe dysphagia. Patients with dysphagia had the following characteristics compared to patients without dysphagia: higher levels of serum LDH (833.7 ± 500.1 U/L vs 471.9 ± 321.0 U/L, p = 0.0088), higher levels of serum CK at initial examination (6070.3 ± 7184.8 IU/L vs 1534.7 ± 2978.8 IU/L, p = 0.0086) and more frequent sense of dysphagia (90.9% vs 10.6%, p&lt; 0.0001), lower MMT score(3.18 ± 1.07 vs 4.31 ± 0.75, p = 0.0017). In addition to those, patients with severe dysphagia presented older age of onset (mean age 69.4 ± 12.0 vs 51.7 ± 14.8, p = 0.014), more frequent complication of malignancy (80.0% vs 14.8%, p= 0.0048) and less frequent complication of interstitial pneumonia (0.0% vs 55.5%, p= 0.023). Conclusion: These results indicate that dysphagia develops frequently in PM/DM patients with higher levels of serum LDH or CK, sense of dysphagia and low MMT score. Among them, patients with elderly onset or malignancy are at risk for sever dysphagia, and should be treated carefully. Disclosure of Interests: None declared.
CRISPR-targeted<i>MAGT1</i>insertion restores XMEN patient hematopoietic stem cells and lymphocytes
Authors: Julie Brault, Taylor Liu, Ezekiel Bello, Siyuan Liu, Colin L. Sweeney, Ronald J. Meis, Sherry Koontz, Cristina Corsino, Uimook Choi, Guillaume Vayssiere, Marita Bosticardo, Kennichi Dowdell, Cicera R. Lazzarotto, Aaron B. Clark, Luigi D. Notarangelo, Juan C. Ravell, Michael J. Lenardo, Benjamin P. Kleinstiver, Shengdar Q. Tsai, Xiaolin Wu, Gary A. Dahl, Harry L. Malech, Suk See De Ravin
Journal: Blood (2021)
The Strong Link between Pancreas and Heart in Thalassemia Major
Authors: Antonella Meloni, Laura Pistoia, Giulia Guerrini, Alessia Sallì, Carlo Cosmi, Roberto Sarli, Maria Paola Smacchia, Annamaria Carrà, Aurelio Maggio, Vincenzo Positano, Massimiliano Missere, Alessia Pepe
Journal: Blood (2017)