tbuckley/cabot-search huggingface dataset:
Mycosis fungoides‐derived exosomes promote cell motility and are enriched with microRNA‐155 and microRNA‐1246, and their plasma‐cell‐free expression may serve as a potential biomarker for disease burden
Authors: L. Moyal, C. Arkin, B. Gorovitz‐Haris, C. Querfeld, S. Rosen, J. Knaneh, I. Amitay‐Laish, H. Prag‐Naveh, J. Jacob‐Hirsch, E. Hodak
Journal: British Journal of Dermatology (2021)

Literature regarding exosomes as mediators in intercellular communication to promote progression in mycosis fungoides (MF) is lacking.To characterize MF-derived exosomes and their involvement in the disease.Exosomes were isolated by ultracentrifugation from cutaneous T-cell lymphoma (CTCL) cell lines, and from plasma of patients with MF and controls (healthy individuals). Exosomes were confirmed by electron microscopy, NanoSight and CD81 staining. Cell-line exosomes were profiled for microRNA array. Exosomal microRNA (exomiRNA) expression and uptake, and plasma-cell-free microRNA (cfmiRNA) were analysed by reverse-transcriptase quantitative polymerase chain reaction. Exosome uptake was monitored by fluorescent labelling and CD81 immunostaining. Migration was analysed by transwell migration assay.MyLa- and MJ-derived exosomes had a distinctive microRNA signature with abundant microRNA (miR)-155 and miR-1246. Both microRNAs were delivered into target cells, but only exomiR-155 was tested, demonstrating a migratory effect on target cells. Plasma levels of cfmiR-1246 were significantly highest in combined plaque/tumour MF, followed by patch MF, and were lowest in controls (plaque/tumour > patch > healthy), while cfmiR-155 was upregulated only in plaque/tumour MF vs. controls. Specifically, exomiR-1246 (and not exomiR-155) was higher in plasma of plaque/tumour MF than in healthy controls. Plasma exosomes from MF but not from controls increased cell migration.Our findings show that MF-derived exosomes promote cell motility and are enriched with miR-155, a well-known microRNA in MF, and miR-1246, not previously reported in MF. Based on their plasma expression we suggest that they may serve as potential biomarkers for tumour burden.
Association of Body Mass Index, Central Obesity, and Body Composition With Mortality Among Black Breast Cancer Survivors
Authors: Elisa V. Bandera, Bo Qin, Yong Lin, Nur Zeinomar, Baichen Xu, Dhanya Chanumolu, Adana A. M. Llanos, Coral O. Omene, Karen S. Pawlish, Christine B. Ambrosone, Kitaw Demissie, Chi-Chen Hong
Journal: JAMA Oncology (2021)

Obesity disproportionately affects Black women, who also have a higher risk of death after a breast cancer diagnosis compared with women of other racial/ethnic groups. However, few studies have evaluated the association of measures of adiposity with mortality among Black breast cancer survivors.
Anticentromere Antibody Levels and Isotypes and the Development of Systemic Sclerosis
Authors: Nina M. van Leeuwen, Maaike Boonstra, Jaap A. Bakker, Annette Grummels, Suzana Jordan, Sophie Liem, Oliver Distler, Anna‐Maria Hoffmann‐Vold, Karin Melsens, Vanessa Smith, Marie‐Elise Truchetet, Hans U. Scherer, René Toes, Tom W. J. Huizinga, Jeska K. de Vries‐Bouwstra
Journal: Arthritis & Rheumatology (2021)

Little is known on the disease course of very early systemic sclerosis (SSc). Among the information yet to be elucidated is whether anticentromere antibody (ACA) isotype levels can serve as biomarkers for future SSc development and for organ involvement. This study was undertaken to evaluate whether IgG, IgM, and IgA ACA levels in IgG ACA-positive patients are associated with disease severity and/or progression from very early SSc to definite SSc.IgG ACA-positive patients from 5 different cohorts who had very early SSc or SSc fulfilling the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 criteria were included. A diagnosis of very early SSc was based on the presence of IgG ACAs and Raynaud's phenomenon, and/or puffy fingers and/or abnormal nailfold capillaroscopy, but not fulfilling the ACR/EULAR 2013 criteria for SSc. Multivariable regression analyses were performed to determine the association between baseline ACA isotype levels and progression to definite SSc with organ involvement.Six hundred twenty-five IgG ACA-positive patients were included, of whom 138 (22%) fulfilled the criteria for very early SSc and 487 (78%) had definite SSc. Levels of IgG ACAs (odds ratio 2.5 [95% confidence interval 1.8-3.7]) and IgM ACAs (odds ratio 1.8 [95% confidence interval 1.3-2.3]) were significantly higher in patients with definite SSc. Of 115 patients with very early SSc with follow-up, progression to definite SSc occurred within 5 years in 48 (42%). Progression to definite SSc was associated with higher IgG ACA levels at baseline (odds ratio 4.3 [95% confidence interval 1.7-10.7]).ACA isotype levels may serve as biomarkers to identify patients with very early SSc who are at risk for disease progression to definite SSc.
Clinical Profile of Posterior Reversible Encephalopathy Syndrome(PRES)-Related Epilepsy in Patients Following Haploidentical Hematopoietic Stem Cell Transplantation:a 10-Year Study
Authors: Xin Zhao, Ying-Jun Chang, Huan Chen, Wei Han, Yao Chen, Yu Wang, Yuan-Yuan Zhang, Jing-Zhi Wang, Yu-Hong Chen, Feng-Rong Wang, Hai-Xia Fu, Xiao-Dong Mo, Ting-Ting Han, Fei-Fei Tang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Xiaohui Zhang
Journal: Blood (2017)
Comparison of Adverse Events Among Home- vs Facility-Administered Biologic Infusions, 2007-2017
Authors: Matthew C. Baker, Yingjie Weng, Robert Fairchild, Neera Ahuja, Nidhi Rohatgi
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Infusion reactions occur in 7% to 20% of patients receiving biologics. Home infusions are convenient and incur lower costs but may be associated with more adverse events; the safety of receiving biologic infusions for immune-mediated diseases at home remains unclear. <h3>Objective</h3> To assess whether patients receiving home biologic infusions have increased adverse events requiring emergency department (ED) or hospital admission compared with patients receiving facility infusions. <h3>Design, Setting, and Participants</h3> This retrospective cohort study used administrative claims data from a large national insurer for adult patients who received biologic infusions for immune-mediated disease between January 2007 and December 2017. Patients with hematologic malignant neoplasms or bone marrow transplantation were excluded. Data were analyzed from August 2019 to October 2020. <h3>Main Outcomes and Measures</h3> ED or hospital admission on the same or next day after administration of a biologic infusion at home vs at a facility; secondary outcomes included discontinuation of the biologic after an ED or hospital admission and postinfusion mortality. <h3>Results</h3> Of a total of 57 220 patients (mean [SD] age, 50.1 [14.8] years; 512 314 [68.1%] women) who received 752 150 biologic infusions (34 078 home infusions [4.5%] to 3954 patients and 718 072 facility infusions [95.5%] to 54 770 patients), patients who received home infusions were younger (mean [SD] age, 43.2 [13.2] vs 51.3 [14.8] years), more likely to be men (14 031 [41.2%] vs 225 668 [31.4%]), and had a lower Charlson comorbidity score compared with patients who received facility infusions (mean [SD] score, 0.5 [1.0] vs 1.1 [1.3]). Home infusions were associated with 25% increased odds of ED or hospital admission on the same or next day after the infusion (odds ratio [OR], 1.25; 95% CI, 1.09-1.44;<i>P</i> = .002) and 28% increased odds of discontinuation of the biologic after the ED or hospital admission (OR, 1.28; 95% CI, 1.08-1.51;<i>P</i> = .005). There was no difference in postinfusion mortality between home or facility infusions. The rates of adverse events were highest with home infusions of tocilizumab (48 of 481 infusions [10.0%]), vedolizumab (150 of 2681 infusions [5.6%]), and infliximab (1085 of 20 653 infusions [5.3%]), although the number of tocilizumab and vedolizumab infusions was low. <h3>Conclusions and Relevance</h3> In this study, biologic infusions administered at home, compared with those administered at a facility, were associated with increased adverse events requiring escalation of care. Because the number of home infusions has increased and is expected to continue to rise, the safety implications of administering biologic infusions at home needs to be further assessed.
Correction to: COVID-19 in critical care: epidemiology of the first epidemic wave across England, Wales and Northern Ireland
Authors: Alvin Richards-Belle, Izabella Orzechowska, Doug W. Gould, Karen Thomas, James C. Doidge, Paul R. Mouncey, Michael D. Christian, Manu Shankar-Hari, David A. Harrison, Kathryn M. Rowan, Yemi Banjo, Kasia Borowczak, Tom Cousins, Peter Cummins, Keji Dalemo, Robert Darnell, Hanna Demissie, Laura Drikite, Andrew Fleming, Ditte Frederiksen, Sarah Furnell, Abdo Hussein, Abby Koelewyn, Tim Matthews, Sam Peters, Tyrone Samuels, Michelle Saull
Journal: Intensive Care Medicine (2021)

A correction to this paper has been published: https://doi.org/10.1007/s00134-021-06413-2
CD19 target evasion as a mechanism of relapse in large B-cell lymphoma treated with axicabtagene ciloleucel
Authors: Vicki Plaks, John M. Rossi, Justin Chou, Linghua Wang, Soumya Poddar, Guangchun Han, Zixing Wang, Shao-Qing Kuang, Fuliang Chu, Richard E. Davis, Francisco Vega, Zahid Bashir, Caron A. Jacobson, Frederick L. Locke, Patrick M. Reagan, Scott J. Rodig, Lazaros J. Lekakis, Ian W. Flinn, David B. Miklos, Adrian Bot, Sattva S. Neelapu
Journal: Blood (2021)
AB0811 DIRECT COST OF BIOLOGICS IN RHEUMATOID ARTHRITIS PATIENTS IN A DEVELOPING COUNTRY: RESULTS FOR THE MOROCCAN RBSMR REGISTRY
Authors: S. Farih, H. Rkain, S. Fellous, S. Ahid, R. Abouqal, T. Latifa, I. Hmamouchi, L. Achemlal, I. El Bouchti, A. EL Maghraoui, I. Ghozlani, H. Hassikou, T. Harzy, I. Linda, O. Mkinsi, R. Niamane, R. Bahiri, F. Allali
Journal: Annals of the Rheumatic Diseases (2021)

Objectives: The aim of this study was to calculate direct costs amount in rheumatoid arthritis (R.A) patients in the Moroccan register of biologicals RBSMR registry. Methods: Patients in the Moroccan register of biologicals RBSMR registry with available 1-year data were included. Variables related to socio-economic status, disease and biological therapy were collected. Direct costs included prices of biologics, costs of infusions, and subcutaneous injections. Biologic use and costs were compared. Results: 197 patients data (female sex (86,8%), mean age (52,3± 11 years), illiteraty (45,7%)) were analyzed. The median annual direct costs per patient were €1,665 [€1,472 - €9,879]. For all patients, the mean annual direct costs per treated patient for each biological agent is presented in Figure 1. The total annual direct costs of biological agents in the RBSMR registry were 978 494 €. Rituximab was given to 67% of patients and constituted 25.7% of the total annual budget. TNF-blockers and Tocilizumab were prescribed in 14.2% and 18.8% of cases and represented respectively 27.3% and 47% of this overall budget. Conclusion: This study presents a global overview of the direct costs of biological therapy associated with RA patients, taking as a source the Moroccan registry of biological therapies in rheumatic diseases. Those results show that overall cost of biological agents according to the Moroccan register is very high. There is a real need for development of strategies for better governance of those costs. Disclosure of Interests: None declared
The antigen‐binding moiety in the driver's seat of CARs
Authors: Heleen Hanssens, Fien Meeus, Kim De Veirman, Karine Breckpot, Nick Devoogdt
Journal: Medicinal Research Reviews (2021)

Abstract Immuno‐oncology has been at the forefront of cancer treatment in recent decades. In particular immune checkpoint and chimeric antigen receptor (CAR)‐T cell therapy have achieved spectacular results. Over the years, CAR‐T cell development has followed a steady evolutionary path, focusing on increasing T cell potency and sustainability, which has given rise to different CAR generations. However, there was less focus on the mode of interaction between the CAR‐T cell and the cancer cell; more specifically on the targeting moiety used in the CAR and its specific properties. Recently, the importance of optimizing this domain has been recognized and the possibilities have been exploited. Over the last 10 years—in addition to the classical scFv‐based CARs—single domain CARs, natural receptor‐ligand CARs, universal CARs and CARs targeting more than one antigen have emerged. In addition, the specific parameters of the targeting domain and their influence on T cell activation are being examined. In this review, we concisely present the history of CAR‐T cell therapy, and then expand on various developments in the CAR ectodomain. We discuss different formats, each with their own advantages and disadvantages, as well as the developments in affinity tuning, avidity effects, epitope location, and influence of the extracellular spacer.
Abstract 15999: An Innovative Application of Artificial Intelligence Techniques and Machine Learning in Diagnostic Evaluation of Pulmonary Hypertension
Authors: Demi A Adedinsewo, Elizabeth Lesser, Mohamad H Yamani, Rickey Carter
Journal: Circulation (2019)

Introduction: Current non-invasive diagnostic modalities (including echocardiography, computed tomography and magnetic resonance imaging) have limited capacity to differentiate the two major hemody...
AB0517 THE HIDDEN FACE OF SMOKING IN AXIAL SPONDYLOARTHRITIS
Authors: S. Bouden, L. Kharrat, A. Ben Tekaya, O. Saidane, R. Tekaya, I. Mahmoud, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2021)

Background: The deleterious effect of smoking on spondyloarthritis has been studied for several decades. Indeed, smoking increases inflammation and disease activity, hence, promotes bone damage. Objectives: The aim of our study was to evaluate the clinical, biological and radiological impact of smoking on axial spondyloarthritis (axSpA). Methods: We conducted a retrospective study including patients meeting the Assessment of SpondyloArthritis international Society (ASAS) criteria between 2000 and 2020. The following parameters were collected: age, smoking, ASDAS, BASDAI, and BASFI. We also measured inflammatory biomarkers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)). Results: We included 138 patients. Sixty-eight per cent of them were males. The mean age was 45.73 ± 12.66 years. The mean age at the disease onset was 28.89 ± 12.54 years. The mean CRP was 33.38 ± 39.65 mg/dL. The mean BASDAI and ASDAS-CRP were 4.21 ±2.23 and 3.06 ± 1.26, respectively. The mean BASFI was 4.77 ± 2.58. Fifty-one of our patients were smokers (37%). They were 48 men and 3 women. The mean pack-year was 45 ± 17.15. Smokers had a significantly younger age of the disease onset (25.21 ± 11.37 versus 31.96 ± 12.67, p=0.009). Moreover, patients who smoke Tabaco had developed significantly more ankylosis compared to patients who don’t (p=0.026). Osteoporosis was also more frequent in smoking patients (p=0.032). However, no association was found between smoking and ESR, CRP, ASDAS-CRP, BASDAI and BASFI. Conclusion: Our results reveal that smoking can be responsible of a younger axSpA onset, and can lead to more severe structural damages regardless the disease activity. This highlights the importance of smoking cessation in preventing early bone damage in axSpA. Disclosure of Interests: None declared.
Integration of Systemic and Liver-Directed Therapies for Locally Advanced Hepatocellular Cancer: Harnessing Potential Synergy for New Therapeutic Horizons
Authors: Eric H. Bent, Eric Wehrenberg-Klee, Eugene J. Koay, Lipika Goyal, Jennifer Y. Wo
Journal: Journal of the National Comprehensive Cancer Network (2021)

Treatment options in locally advanced hepatocellular carcinoma (HCC) have evolved considerably over the past few years with the recent approval of multiple systemic therapies and significant advances in locoregional therapy. Given the poor prognosis for patients with unresectable HCC, there is significant interest in rationally designed combination therapies. This article reviews the treatment options available to patients with locally advanced HCC and discusses the rationale, ongoing trials, and future prospects for combining locoregional and systemic therapy in both the definitive and neoadjuvant settings.
Association between industry payments and prescriptions of long-acting insulin: An observational study with propensity score matching
Authors: Kosuke Inoue, Yusuke Tsugawa, Carol M. Mangione, O. Kenrik Duru
Journal: PLoS Medicine (2021)

Background The rapidly increased spending on insulin is a major public health issue in the United States. Industry marketing might be one of the upstream determinants of physicians’ prescription of long-acting insulin—the most commonly used and costly type of insulin, but the evidence is lacking. We therefore aimed to investigate the association between industry payments to physicians and subsequent prescriptions of long-acting insulin. Methods and findings Using the databases of Open Payments and Medicare Part D, we examined the association between the receipt of industry payments for long-acting insulin in 2016 and (1) the number of claims; (2) the costs paid for all claims; and (3) the costs per claim of long-acting insulin in 2017. We also examined the association between the receipt of payments and the change in these outcomes from 2016 to 2017. We employed propensity score matching to adjust for the physician-level characteristics (sex, years in practice, specialty, and medical school attended). Among 145,587 eligible physicians treating Medicare beneficiaries, 51,851 physicians received industry payments for long-acting insulin worth $22.3 million. In the propensity score–matched analysis including 102,590 physicians, we found that physicians who received the payments prescribed a higher number of claims (adjusted difference, 57.8; 95% CI, 55.8 to 59.7), higher costs for total claims (adjusted difference, +$22,111; 95% CI, $21,387 to $22,836), and higher costs per claim (adjusted difference, +$71.1; 95% CI, $69.0 to $73.2) of long-acting insulin, compared with physicians who did not receive the payments. The association was also found for changes in these outcomes from 2016 to 2017. Limitations to our study include limited generalizability, confounding, and possible reverse causation. Conclusions Industry marketing payments to physicians for long-acting insulin were associated with the physicians’ prescriptions and costs of long-acting insulin in the subsequent year. Future research is needed to assess whether policy interventions on physician–industry financial relationships will help to ensure appropriate prescriptions and limit overall costs of this essential drug for diabetes care.
Platinum-crosslinking polymeric nanoparticle for synergetic chemoradiotherapy of nasopharyngeal carcinoma
Authors: Yuxun Ding, Xiaohui Xiao, Lingli Zeng, Qiuping Shang, Wei Jiang, Sha Xiong, Xiaohui Duan, Jun Shen, Ruibing Wang, Jinshan Guo, Yue Pan
Journal: Bioactive Materials (2021)

Despite extensive use of radiotherapy in nasopharyngeal carcinoma (NPC) treatment because of its high radiosensitivity, there have been huge challenges in further improving therapeutic effect, meanwhile obviously reducing radiation damage. To this end, synergistic chemoradiotherapy has emerged as a potential strategy for highly effective NPC therapy. Here, we developed RGD-targeted platinum-based nanoparticles (RGD-PtNPs, denoted as RPNs) to achieve targeted chemoradiotherapy for NPC. Such nanoparticles consist of an RGD-conjugated shell and a cis-platinum (CDDP) crosslinking core. Taking advantage of RGD, the RPNs may effectively accumulate in tumor, penetrate into tumor tissues and be taken by cancer cells, giving rise to a high delivery efficiency of CDDP. When they are fully enriched in tumor sites, the CDDP loaded RPNs can act as radiotherapy sensitizer and chemotherapy agents. By means of X-ray-promoted tumor cell uptake of nanoparticle and CDDP-induced cell cycle arrest in radiation-sensitive G2/M phases, RPNs may offer remarkable therapeutic outcome in the synergistic chemoradiotherapy for NPC.
AB0165 CENTRAL SENSITIZATION IN RHEUMATOID ARTHRITIS
Authors: E. Filatova, E. Pogozheva, V. Amirdzhanova, A. Karateev, A. Lila
Journal: Annals of the Rheumatic Diseases (2021)

Background: Central Sensitization (CS) is a proposed physiological phenomenon in which dysregulation in the central nervous system causes neuronal dysregulation and hyperexcitability, resulting in hypersensitivity to both noxious and non-noxious stimuli. The term Central Sensitivity Syndrome (CSS) describes a group of medically indistinct (or nonspecific) disorders, such as fibromyalgia (FM) (1, 2). The prevalence of FM has been estimated at 2-7% in general population, but 10-30% patients with several rheumatic diseases fulfill the FM criteria, which suggests that they have not only nociceptive pain, but signs of CS or nocyplastic pain. (3) Objectives: to identify the signs of central sensitization (CS) in patients with rheumatoid arthritis (RA) with the central sensitization inventory (CSI). Methods: We examined 43 RA patients (mean age 45.5 [29.0; 53.0] years) with chronic pain. The patients underwent rheumatological examinations; CS was diagnosed using the CSI(4).; inflammation severity (DAS28 index), pain intensity (VAS), affective disorders (HADS), and quality of life (EQ-5D) were assessed. Results: We recruited 36 women and 7 men, mostly with moderate and high disease activity according to the DAS28 index. Using the CSI subclinical CS was found in 9 patients (20.9%), mild in 7 (16.3%), moderate in 8 (18.6%), severe in 16 (37.2%), and extremely severe sensitization in 3 (6.7%). Thus, 62.5% of patients with RA had had clinically significant CS (CS&gt;40 points according to the CSI questionnaire). Patients with the presence of CS were characterized by more severe anxiety (10.0 [7.0; 11.0] vs 5.0 [3.0; 6.0], p=0.001) and lower quality of life (0.52 [-0.02; 0.52] vs 0.52 [0.52; 0.69], p= 0.02). The CSI tests not only pain but also other diseases associated with CS. Comorbid disorders associated with CS were found in patients with RA: 34.9% had cognitive impairment, 39.5% had signs of depression. Conclusion: Central sensitization was detected in 62.5% of patients with RA using the CSI questionnaire. CS is associated with anxiety and depression and negatively affects the patients’ quality of life. Chronic pain in RA can be of a mixed nature: nociceptive and neoplastic, which must be taken into account in the selection of personalized therapy. References: [1]Wolfe F. Fibromyalgianess. Arthritis Rheum. 2009; 61: 715-6. [2]Martins Rocha T, Pimenta S, Bernardo A, et al. Determinants of non-nociceptive pain in Rheumatoid Arthritis. Acta Reumatol Port. 2018 Oct-Dec;43(4):291-303. [3]Halioglu S, Carlioglu A., Akdeniz D., Karaaslan Y., Kosar A. Fibromyalgia in patients user rheumatic patients with several rheumatic diseases: prevalence and relationship with disease activity. Reumatol. Int. 2014 Sep; 34(90:1275-80 doi:10.1007/s00296-014-2972. Disclosure of Interests: None declared