tbuckley/cabot-search huggingface dataset:
SAT0403 Blood b cell subset profile disturbance in whipple’s disease
Authors: M. Le Goff, D. Cornec, D. Guellec, T. Marhadour, V. Devauchelle-Pensec, S. Jousse-Joulin, M. Herbette, J.M. Cauvin, C. Le Guillou, Y. Renaudineau, J.-O. Pers, A. Saraux
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Technological advances have improved phenotypical characterisation of blood cells, and flow cytometry is currently used in haematology, infectious disease, systemic auto-immune diseases. Abnormalities of blood B cell subset profile might provide a useful diagnostic tool in systemic auto-immune diseases, especially for primary Sjögren's Syndrome<sup>1</sup> in which the activated B cells to memory B cells ratio is increased. Nevertheless, we observed that some patients suffering from chronic infection had lymphocytes disturbances similar to those observed in primary Sjögren's Syndrome. <h3>Objectives</h3> Whipple'disease (WD) is a rare, systemic, disease caused by intracellular gram positive bacterium, <i>Tropheryma Whipplei</i> (TW). No previous study evaluated the role of B cells in WD. The aim of this study was to analyse whether the circulating blood B cell subset disturbances is characteristic of WD. <h3>Methods</h3> We collected characteristics of all patients coming for inflammatory rheumatism in our rheumatology department between April 2010 and December 2016. All of them had systematically routine examination, immunological tests, lymphocyte subsets in peripheral blood by flow cytometric analysis. We selected among this population those patients who also had PCR for <i>TW</i> for suspicion of WD, and compared the distribution of lymphocyte subsets of those with and without WD. Then, we evaluated their diagnostic value for WD using a ROC curve. <h3>Results</h3> Among 3494 patients with inflammatory rheumatism, 121 patients (212 visits) had a suspicion of WD and the diagnosis of WD was retained by an expert rheumatologist for 9 (7.4%) (22 visits). T cells and NK cells were not different whereas percentage of circulating memory B cells (IgD<sup>-</sup>CD38low) was lower (18.0%±9.7% vs 26.0±14.2%, p=0.041) and the ratio of activated B cells to memory B cells higher (4.4±2.0 vs 2.9±2.2, p=0.023), in patients compared with controls. More precisely, the analysis of the frequency of peripheral blood B cells showed that IgD +CD27 – naïve B cells were higher (66.2%±18.2% vs 54.6±18.4%, p=0.047) and IgD-CD27 +switched memory B cells lower (13.3%±5.7% vs 21.4±11.9%, p=0.023), in patients compared with the controls. The best diagnostic value was obtained for the IgD +CD27- naïve B cells (cut off 70.5, sensitivity 73%, specificity 80%). <h3>Conclusions</h3> Our study provides data on blood B cells disturbances and a first step towards understandings of immunological abnormalities in WD. These disturbances provide guidance for diagnosis and allow physiopathological hypothesis. <h3>Reference</h3> [1] Binard A, Le Pottier L, Devauchelle-Pensec V, Saraux A, Youinou P, Pers J-O. Is the blood B-cell subset profile diagnostic for Sjogren syndrome?Ann Rheum Dis2009;68(9):1447–52. <h3>Disclosure of Interest</h3> None declared
SP0109 Involvement of a patient organisation in health technology assessment
Authors: J. Clausen
Journal: Annals of the Rheumatic Diseases (2018)

The term "Health Technology Assessment" (HTA) designates the systematic evaluation of therapies (drugs and non-drug interventions) and technologies for cost effectiveness, clinical effectiveness and safety to form the basis for evidence-based priority setting and policy decisions (reimbursement and coverage decisions). Usually, therapeutic or diagnostic interventions are subject to the assessment, but also complex programs (e.g. prophylactic screening programs) may be investigated. The involvement of patient organisations in Health Technology Assessments improves outcomes and offers additional insights. It guarantees that the perspective of the most important group – the patients as consumers – is adequately addressed. A patient organisation may be involved in various ways in Health Technology Assessments: Patient organisations can identify gaps in healthcare coverage and initiate the generation of a respective Health Technology Assessment; they can provide additional registry data, complementing study data from randomised controlled trials for the Health Technology Assessment. The provision of information on patient-relevant outcomes and other patient-relevant aspects (e.g. mode of administration) is crucial to assess the benefit for patients of the therapy (or technology/program) under evaluation. Moreover, patient organisations may also be involved in the evaluation of the assessment report and in the execution of the results. Generation of an HTA can be a time-consuming process and a very demanding one for patient organisations and the involved volunteers. Staff members of the patient organisation can be involved directly in the various tasks, or indirectly, supporting voluntary patients. If voluntary patients attend panel groups, most of them will need intensive support by their respective patient organisation depending on the complexity of the respective topic. Finding qualified volunteers, willing to spend a substantial amount of their time and able to travel frequently, is another obstacle to overcome. This presentation provides some examples of the involvement in Health Technology Assessments of the German Rheumatism League, Germany's largest patient organisation with about 3 00 000 members, and the essential prerequisites for the participation of patient organisations in that process. <h3>Disclosure of Interest</h3> None declared
Immune Checkpoint Inhibitor-induced Reinvigoration of Tumor-infiltrating CD8+ T Cells is Determined by Their Differentiation Status in Glioblastoma
Authors: Junsik Park, Minsuk Kwon, Kyung Hwan Kim, Tae-Shin Kim, Seon-Hui Hong, Chang Gon Kim, Seok-Gu Kang, Ju Hyung Moon, Eui Hyun Kim, Su-Hyung Park, Jong Hee Chang, Eui-Cheol Shin
Journal: Clinical Cancer Research (2019)

Immune checkpoint inhibitors (ICI) are used for the treatment of various cancers, but clinical trials of anti-programmed cell death protein 1 (PD-1) with patients with recurrent glioblastoma (GBM) have failed to show clinical benefits. In this study, we examined the differentiation status of CD8+ tumor-infiltrating lymphocytes (TIL) from patients with primary GBM and their reinvigoration by ICIs to understand the nature of T-cell exhaustion in GBM.We isolated TILs from 98 patients with newly diagnosed GBM and examined the expression of immune checkpoint receptors and T-cell transcription factors using flow cytometry. TILs were ex vivo stimulated with anti-CD3 in the presence of anti-PD-1 and/or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) and their proliferation assessed.CD8+ TILs had significantly increased expression of immune checkpoint receptors, including PD-1 and CTLA-4, compared with peripheral blood CD8+ T cells. Among CD8+ TILs, PD-1+ cells exhibited more terminally differentiated phenotypes (i.e., EomeshiT-betlo) than PD-1- cells. These data were confirmed by analyzing NY-ESO-1157-specific CD8+ TILs. Evaluating the proliferation of CD8+ TILs after ex vivo stimulation with anti-CD3 and anti-PD-1, we found that proliferation inversely correlated with the percentage of EomeshiT-betlo cells among PD-1+CD8+ TILs. When anti-CTLA-4 was used in combination with anti-PD-1, an additional increase in CD8+ TIL proliferation was observed in patients with low percentages of EomeshiT-betlo CD8+ TILs, who responded well to anti-PD-1 in ex vivo assays, but not in patients with high percentages of EomeshiT-betlo CD8+ TILs, who did not respond to anti-PD-1.In primary GBM, the differentiation status of CD8+ TILs determines their reinvigoration ability upon ICI treatment.
THU0002 Novel pathogenic stop codon mutation in the nf-Κb p65 subunit (RELA) associated with both behÇet’s disease like syndrome and neuromyelitis optica in an irish family
Authors: F. Adeeb, E.R. Dorris, S. Tariq, W.L. Ng, A.G. Stack, A.G. Wilson, A.D. Fraser
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Behçet's disease (BD) has a complex multifactorial pathogenesis and presents with phenotypic heterogeneity predominantly mucocutaneous ulcerations, ocular lesions and skin manifestations. More recently, there have been reported cases of monogenic spectrum defects presented with BD-like similarities or phenotype. <h3>Objectives</h3> We investigated an Irish Caucasian family of eleven that included two half-sisters with early-onset BD, and another sister with neuromyelitis optica, all who were born to asymptomatic non-consanguines parents. More recently, one of the sisters' daughter developed recurrent oral aphthosis at the age of 10 years old. <h3>Methods</h3> Peripheral blood mononuclear cells were extracted from patients and non-affected donor blood using standard fractionation methods. Following quality assessment and quantification whole exome sequencing was performed on all participants. <h3>Results</h3> Whole exome sequencing data identified segregation of a novel pathogenic stop codon mutation in the nuclear factor NF-κB p65 subunit (RelA) resulting in a non-functional protein. The mutation involves cytosine deletion and results in a His487ThrfsTer7 frameshift (His487ThrfsTer7) <i>RelA</i> resulting in loss of transcription activation-1 (TA1) and a portion of TA2 from RelA. The mutation was seen within the three generations, including the three half-sisters, their father as well as one of the proband's daughter, potentially describing a new syndrome. <h3>Conclusions</h3> Our study suggests that loss-of-function mutations in the NF-κB pathway, a pivotal mediator of inflammation and apoptosis, are linked with the development of familial early-onset BD-like syndromes. Better insights and further understanding of this "orphan" immunogenetic syndrome carries high clinical impact to assist early disease recognition and potential discoveries of novel targeted therapies. <h3>Disclosure of Interest</h3> None declared
AB0605 Procalcitonin might be used for discriminating infections from increased disease activity in primary sjÖgren syndrome
Authors: B. Arican Tarim, M.E. Tezcan, A. Orcun, O. Keskin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Procalcitonin is a polypeptide which is secreted as a response to bacterial stimulus and accepted as an early and sensitive marker of infection. In healthy subjects procalcitonin should be &lt;0.1 ng/mL. In case of infection it may rises over 0.5 ng/mL[.<sup>1</sup>Its level in inflammatory diseases usually does not reach to such high levels as in infections. Differentiating infection and disease activation may be confusing in autoimmune diseases. For this purpose, there were several studies that evaluated the role of procalcitonin for excluding infection on suspicion of increased autoimmune disease activity.<sup>2</sup> <h3>Objectives</h3> As far as we know, there is no study in literature that evaluated procalcitonin levels in patients with primary Sjögren's syndrome (pSS). Our aim is to evaluate procalcitonin levels in pSS and determine whether we can use it as a marker to differentiate infection from disease activation. <h3>Methods</h3> The following two groups of patients were included in the study: Forty-eight patients with pSS, who met <sup>ACR 2012</sup> Classification Criteria for Sjögren's Syndrome; and fifty-three subjects as control group who have no chronic diseases. Patients with possible infection were excluded according to their clinical evaluation and laboratory data. Then, serum procalcitonin levels were compared between the groups. Finally, we evaluated the correlation between disease activity, measured by Sjögren's syndrome disease activity index (SSDAI) and procalcitonin levels. <h3>Results</h3> Procalcitonin levels in pSS group were found statistically higher than control group, whereas it was still in normal ranges (p&lt;0,01). Furthermore, no correlation was found between disease activation and the procalcitonin levels (p=0.63). <h3>Conclusions</h3> Procalcitonin levels were found higher in pSS patients. But, none of the patients had clinically significant increase in procalcitonin. We thought that with careful clinical evaluation, procalcitonin would be an indicator for differentiating infection from disease activation in pSS patients. <h3>References</h3> [1] Oczenski W, Fitzgerald RD, Schwarz S (1998) Procalcitonin: a new parameter for the diagnosis of bacterial infection in the peri-operative period. Eur J Anaesthesiol15: 202–9. [2] Korczowski B, Kowalczyk JR, Bijak M, Rusin J (2003) Concentration of procalcitonin and C-reactive protein in serum and erythrocyte sedimentation rate in active autoimmune diseases in children. Pol Merkur Lekarski. Aug;15(86):155–7. <h3>Disclosure of Interest</h3> None declared
AB1468-HPR Satisfaction with the bdmard etanercept biosimilar (SB4) pre-filled pen among rheumatoid arthritis and spondyloarthropathy patients; a german observational study
Authors: U Müller-Ladner, S. Zinke, P.M. Aries, C. Maucksch
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The TNFα inhibitor etanercept was the first targeted biological disease modifying anti-rheumatic drug (bDMARD) approved for treatment of RA; the first etanercept biosimilar (SB4) was authorised in the EU in January 2016. Various administration devices have been developed for convenient subcutaneous self-injection of bDMARDs including pre-filled pens. <h3>Objectives</h3> This study aims to document general patient satisfaction in day-to-day use of the SB4 pre-filled pen. Patients' experience regarding handling, convenience, other features and the associated training on self-injection is also evaluated. <h3>Methods</h3> This non-interventional, cross-sectional study is enrolling patients who are treated according to usual medical practice. Patients had experience with the SB4 pre-filled pen in accordance with the prescribing information for at least 3 months prior to completing the onetime standardised patient questionnaire. This study started in August 2017, is ongoing and plans to enrol 500 patients in total from 50 centres across Germany. Subgroup analyses by previous therapy, modality of administration and by indication group are pre-planned. <h3>Results</h3> By November 2017, completed surveys from 142 patients were available for interim analysis. Mean age was 55 years, 61% were female and the median duration of the disease was 6 years. The indications were rheumatoid arthritis in 63% (median disease activity score DAS28: 2.4), psoriatic arthritis in 19% (median DAS28: 2.5) and axial spondyloarthritis in 18% of patients (median BASDAI: 3.0). 68% of patients were new to bDMARD therapy. Previous therapies included conventional synthetic DMARDs (67% of patients), steroids (49%), non-steroidal anti-inflammatory drugs (43%) and bDMARDs (32%). Patient satisfaction response rates are shown in table 1. <h3>Conclusions</h3> High level of patient general satisfaction as well as satisfaction with the ease of use were reported with the etanercept biosimilar (SB4) pre-filled pen for patients who were new to bDMARDs or who had switched from other bDMARDs. <h3>Acknowledgements</h3> Biogen GmbH funded this study. Authors had full editorial control and provided final approval of all content. <h3>Disclosure of Interest</h3> U. Müller-Ladner Consultant for: Biogen, Speakers bureau: Biogen, S. Zinke Consultant for: Biogen, P. Aries Consultant for: Biogen, C. Maucksch Shareholder of: Biogen, Employee of: Biogen
Recent Progress on Liquid Biopsy Analysis using Surface-Enhanced Raman Spectroscopy
Authors: Yuying Zhang, Xue Mi, Xiaoyue Tan, Rong Xiang
Journal: Theranostics (2019)

Traditional tissue biopsy is limited in understanding heterogeneity and dynamic evolution of tumors. Instead, analyzing circulating cancer markers in various body fluids, commonly referred to as "liquid biopsy", has recently attracted remarkable interest for their great potential to be applied in non-invasive early cancer screening, tumor progression monitoring and therapy response assessment. Among the various approaches developed for liquid biopsy analysis, surface-enhanced Raman spectroscopy (SERS) has emerged as one of the most powerful techniques based on its high sensitivity, specificity, tremendous spectral multiplexing capacity for simultaneous target detection, as well as its unique capability for obtaining intrinsic fingerprint spectra of biomolecules. In this review, we will first briefly explain the mechanism of SERS, and then introduce recently reported SERS-based techniques for detection of circulating cancer markers including circulating tumor cells, exosomes, circulating tumor DNAs, microRNAs and cancer-related proteins. Cancer diagnosis based on SERS analysis of bulk body fluids will also be included. In the end, we will summarize the "state of the art" technologies of SERS-based platforms and discuss the challenges of translating them into clinical settings.
Abstract 19865: Remote Electrical Power Delivery to Run LVAD Across a Meter Distance: Innovation and Validation Using Free-Range Electrical Energy Delivery (FREE-D) System in vivo
Authors: Benjamin Waters, Joshua Smith, Pramod Bonde
Journal: Circulation (2017)

Introduction: Models of power delivery within an intact organism have been limited to ionizing radiation, sound & magnetic waves. We present experimental validation of remote electrical power delivery to an intact biological system using magnetic resonant coupling technology, allowing continuous operation of LVAD, without being dependent on implanted batteries alone at an unprecedented distance of one meter. Methods: Four Yorkshire pigs were implanted with HVAD device powered and controlled by a wireless power delivery. The implanted coil was separated from transmitting coil within a 3 dimensional space of one meter diameter. Results: All experiments were successfully concluded without any power drop or interruption. Electrical power was delivered to the implanted coil within a one meter diameter circle. Temperature rose to one degree celsius at the receiving coil. HVAD device could be run either in continuous or pulsed mode. The experiment used an implanted coil (5cm), a coil worn in a vest and a coil pl...
Suppression of astrocytic autophagy by αB-crystallin contributes to α-synuclein inclusion formation
Authors: Shen-zhao Lu, Yong-shun Guo, Pei-zhou Liang, Shu-zhen Zhang, Shu Yin, Yan-qing Yin, Xiao-min Wang, Fei Ding, Xiao-song Gu, Jia-wei Zhou
Journal: Translational Neurodegeneration (2019)

Parkinson's disease (PD) is characterized by a chronic loss of dopaminergic neurons and the presence of proteinaceous inclusions (Lewy bodies) within some remaining neurons in the substantia nigra. Recently, astroglial inclusion body has also been found in some neurodegenerative diseases including PD. However, the underlying molecular mechanisms of how astroglial protein aggregation forms remain largely unknown. Here, we investigated the contribution of αB-crystallin (CRYAB), a small heat shock protein, in α-synuclein inclusion formation in astrocytes. Small interfering RNA (siRNA)-mediated CRYAB (siCRYAB) knockdown or CRYAB overexpression was performed to investigate the impact of CRYAB on the autophagy in human glioblastoma cell line U251 cells. Co-immunoprecipitation (co-IP) and immunoblotting were used to dissect the interaction among multiple proteins. The clearance of α-synuclein in vitro was evaluated by immunocytochemistry. CRYAB transgenic mice and transgenic mice overexpressing A30P mutant form of human α-synuclein were used to examine the influence of CRYAB to α-synuclein accumulation in vivo. We found that knockdown of CRYAB in U251 cells or primary cultured astrocytes resulted in a marked augmentation of autophagy activity. In contrast, exogenous CRYAB disrupted the assembly of the BAG3-HSPB8-HSC70 complex via binding with BAG3, thereby suppressing the autophagy activity. Furthermore, CRYAB-regulated autophagy has relevance to PD pathogenesis. Knockdown of CRYAB remarkably promoted cytoplasmic clearance of α-synuclein preformed fibrils (PFFs). Conversely, selective overexpression of CRYAB in astrocytes markedly suppressed autophagy leading to the accumulation of α-synuclein aggregates in the brain of transgenic mice expressing human α-synuclein A30P mutant. This study reveals a novel function for CRYAB as a natural inhibitor of astrocytic autophagy and shows that knockdown of CYRAB may provide a therapeutic target against proteinopathies such as synucleinopathies.
A Novel Multimodal NIR-II Nanoprobe for the Detection of Metastatic Lymph Nodes and Targeting Chemo-Photothermal Therapy in Oral Squamous Cell Carcinoma
Authors: Yufeng Wang, Wansu Zhang, Pengfei Sun, Yu Cai, Wenguang Xu, Quli Fan, Qingang Hu, Wei Han
Journal: Theranostics (2019)

Current surgical treatment for oral squamous cell carcinoma (OSCC) must be as precise as possible to fully resect tumors and preserve functional tissues. Thus, it is urgent to develop efficient fluorescent probes to clearly identify tumor delineation, as well as metastatic lymph nodes. Chemo-photothermal therapy combination attracted a growing attention to increase anti-tumor effect in various types of cancer, including OSCC. In the present study, we designed a multimodal NIR-II probe that involves combining photothermal therapy with chemotherapy, imaging OSCC tumors and detecting metastatic lymph nodes. Methods: In this study, we synthesized a novel near infrared (NIR)-II probe named TQTPA [4,4'-((6,7-bis(4-(hexyloxy)phenyl)-[1,2,5]thiadiazolo [3,4-g]quinoxaline-4,9-diyl)bis(thiophene-5,2-diyl))bis(N,N-diphenylaniline)] via the Suzuki reaction and prepared multimodal nanoparticles (NPs) loading TQTPA and cis-dichlorodiammine platinum (CDDP) (HT@CDDP) by hyaluronic acid. The characteristics of the NPs, including their photothermal and imaging capabilities were investigated in vitro and in vivo. Their anti-tumor efficacy was evaluated using orthotopic, tongue tumor-bearing, nude mice. Results: The NPs possessed good stability and water solubility and were pH/hyaluronidase sensitive. The good tissue penetration quality and active targeting ability enabled the NPs to draw the outline of orthotopic tongue tumors and metastatic lymph nodes as small as 1 mm in nude mice by IR-808 under NIR exposure. In vitro and in vivo experiments validated the biocompatibility and low systematic toxicity of the NPs. At the same time, the NPs acted as multimodal therapy agents, combining photothermal therapy with chemotherapy. Conclusion: With a good imaging capability and anti-tumor efficacy, our NPs successfully outlined orthotopic tongue tumors and metastatic lymph nodes as well as enabled chemo-photothermal therapy combination. Our study established a solid foundation for the application of new clinical diagnosis and treatment patterns in the future.