tbuckley/cabot-search huggingface dataset:
Tumor-targeted IL-12 combined with tumor resection yields a survival-favorable immune profile
Authors: Qingnan Zhao, Jiemiao Hu, Abhisek Mitra, Jeffry Cutrera, Wendong Zhang, Zhongting Zhang, Jun Yan, Xueqing Xia, Kris Michael Mahadeo, John Andrew Livingston, Richard Gorlick, Shulin Li
Journal: Journal for ImmunoTherapy of Cancer (2019)

Although accumulated evidence provides a strong scientific premise for using immune profiles to predict survival in patients with cancer, a universal immune profile across tumor types is still lacking, and how to achieve a survival-associated immune profile remains to be evaluated.We analyzed datasets from The Cancer Genome Atlas to identify an immune profile associated with prolonged overall survival in multiple tumor types and tested the efficacy of tumor cell-surface vimentin-targeted interleukin 12 (ttIL-12) in inducing that immune profile and prolonging survival in both mouse and patient-derived xenograft tumor models.We identified an immune profile (IFNγHiCD8HiFOXP3LowCD33Low) associated with prolonged overall survival across several human tumor types. ttIL-12 in combination with surgical resection of the primary tumor transformed tumors to this immune profile. Intriguingly, this immune profile transformation led to inhibition of metastasis and to prolonged survival in both mouse and patient-derived xenograft malignant models. Wild-type IL-12 combined with surgery was significantly less effective. In the IL-12-sensitive C3H mouse strain, in fact, wild-type IL-12 and surgery resulted in shorter overall survival than in mice treated with control pDNA; this surprising result is believed to be attributable to IL-12 toxicity, which was absent in the mice treated with ttIL-12. The ttIL-12-induced immune profile associated with longer overall survival was also associated with a greater accumulation of CD8+ T cells and reduced infiltration of regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. The underlying mechanism for this transformation by ttIL-12 treatment was induction of expression of CXCL9 and reduction of expression of CXCL2 and CCL22 in tumors.ttIL-12 when combined with surgery led to conversion to the IFNγHiCD8HiFOXP3LowCD33Low immune profile, eliminated relapse and metastasis, and prolonged overall survival.
Machine learning detection of obstructive hypertrophic cardiomyopathy using a wearable biosensor
Authors: Eric M. Green, Reinier van Mourik, Charles Wolfus, Stephen B. Heitner, Onur Dur, Marc J. Semigran
Journal: npj Digital Medicine (2019)

Hypertrophic cardiomyopathy (HCM) is a heritable disease of heart muscle that increases the risk for heart failure, stroke, and sudden death, even in asymptomatic patients. With only 10-20% of affected people currently diagnosed, there is an unmet need for an effective screening tool outside of the clinical setting. Photoplethysmography uses a noninvasive optical sensor incorporated in commercial smart watches to detect blood volume changes at the skin surface. In this study, we obtained photoplethysmography recordings and echocardiograms from 19 HCM patients with left ventricular outflow tract obstruction (oHCM) and a control cohort of 64 healthy volunteers. Automated analysis showed a significant difference in oHCM patients for 38/42 morphometric pulse wave features, including measures of systolic ejection time, rate of rise during systole, and respiratory variation. We developed a machine learning classifier that achieved a C-statistic for oHCM detection of 0.99 (95% CI: 0.99-1.0). With further development, this approach could provide a noninvasive and widely available screening tool for obstructive HCM.
Semiconducting polymer nanotheranostics for NIR-II/Photoacoustic imaging-guided photothermal initiated nitric oxide/photothermal therapy
Authors: Jie Li, Rongcui Jiang, Qi Wang, Xiang Li, Xiaoming Hu, Yan Yuan, Xiaomei Lu, Wenjun Wang, Wei Huang, Quli Fan
Journal: Biomaterials (2019)
THU0582 THE TNF RECEPTOR-ASSOCIATED PERIODIC SYNDROME (TRAPS): CLINICAL AND GENETIC CHARACTERIZATION OF A COHORT OF ADULTS DIAGNOSED OF TRAPS SYNDROME
Authors: Alberto Ruiz Román, Salvador García Morillo, Marco Montes Cano, Clara Aguilera Cros, Manuel Leon Luque, Maria Jose Valenzuela Porcel, Maria Arcila Duran, Lara Mendez, Isabel Madroñal García
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a disease that is included within of hereditary syndromes of periodic fever. It presents an autosomal dominant pattern of inheritance. It's due to mutations of TNFRSF1A gene. It is usually present in childhood although it can also appear in adulthood and it tends to cause high levels of acute phase reactants, fever, musculoskeletal symptoms (myalgias, arthralgias, arthritis), rash, abdominal pain, etc <h3>Objectives:</h3> To describe the clinical characteristics and genetic variants of patients diagnosed with TRAPS syndrome in a cohort of patients with autoinflammatory syndromes with follow-up in a tertiary hospital from 2013 to the present <h3>Methods:</h3> Retrospective descriptive study of adult patients diagnosed with autoinflammatory syndrome since 2013 (year of introduction of genetic tests in the hospital laboratory) until now. The data was obtained from the review of medical records. All patients with mutations in TNRFSF1A gene and clinically compatible with this diagnosis were reviewed <h3>Results:</h3> Of a total of 44 adult patients diagnosed with hereditary syndromes of periodic fever (FMF, TRAPS, cryopyrinopathies, HIDS) and compatible genetic mutations (excluding polymorphisms), 13 (29.5%) presented mutations in the TNFRSF1A gene. Of those 13 patients, 9 (69.2%) were women. The most frequent mutations were the mutation in heterozygosis in exon 4 (p.R92Q) with 12 cases (92.3%) and one case (7.6%) with mutation in heterozygosis in exon 3 (p.P46L). The mean age at diagnosis was 27.92 years (IR 12-55 years). 5 patients showed simultaneous genetic variants in other genes related to autoinflammatory syndromes. Signs and/or symptoms were myalgia and elevation of acute-phase reactants with 12 patients (86%) followed by fever and joint symptoms (arthralgias and/or arthritis) with 11 patients (79%) were the most frequent. 2 patients (14%) had conjunctivitis. 9 patients (64%) presented cutaneous involvement. 2 cases (14%) presented lymphadenopathy. Regarding treatment, 5 patients (36%) had received treatment with biological therapy (anti-IL-1 or anti-TNF) and another 5 patients (36%) had used colchicine. The corticoids were used in 6 patients (43%) <h3>Conclusion:</h3> The TRAPS syndrome is a clinical entity to consider when making a differential diagnosis in patients with suspected autoinflammatory syndrome, that present fever, acute phase reactants elevation, arthromyalgia and its confirmation diagnosis is with genetic test <h3>Disclosure of Interests:</h3> None declared
AB0112 EVALUATION OF A NEW MULTIPLEX TECHNOLOGY ASSAY FOR ANTI-CITRULLINATED PEPTIDE ANTIBODIES DETERMINATION
Authors: Mounira Benidir, Samir Salah, Dalila Fodil, Hachemi Djoudi, Malik Djennane, Habiba Amroun, Nabila Attal
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Anti-citrullinated peptides antibodies (ACPA) are highly specific RA markers. In 2010, experts included them in the ACR/EULAR criteria for disease diagnosis, usually, measured by ELISA. However, a new assay has been developed, recently: Multiplex technology, which allows searching IgG ACPA directed against four citrullinated peptides: Human (HCP1 and 2) and Viral (VCP1 and 2). <h3>Objectives:</h3> First, assess ACPA diagnostic performances using Multiplex technology and then compare them to those obtained with the reference technique (ELISA). <h3>Methods:</h3> We studied sera of 273 RA patients versus 165 controls (64 healthy controls and 101 patients with other pathologies). We realized ACPA dosage by Multiplex technology and compared them with ELISA assay results. In the end, we looked for a correlation between ACPA production and shared epitope expression in RA patients. <h3>Results:</h3> The overall agreement calculated between the two methods was about 91.3%. As to the comparison of diagnostic values of Multiplex technology vs. ELISA, it revealed a sensitivity of 80.2% vs. 82.4% and a specificity of 95.8% vs. 95.5%. Then, for a better evaluation, we plotted ROC curves for ACPA detected by Multiplex technology and ELISA ones. Therefore, we obtained the following areas under the curve (AUC) (p value &lt;0.0001): Anti-: HCP1 (0.775), HCP2 (0.798), VCP1 (0.715) and VCP2 (0.837) and ACPA ELISA (0.867). Finally, our results reveal higher serum levels of ACPA detected by Multiplex technology, in case of SE expression [SE (+) vs. SE (-)] (p value &lt;0.0001). <h3>Conclusion:</h3> Diagnostic performance of ACPA detection methods is comparable with relatively good agreement. Our study demonstrated an association between elevated serum levels of anti-HCP and anti-VCP and SE expression, in RA patients. <h3>References</h3> [1] Toussirot E, Roudier J. Joint Bone Spine. 2007Oct;74(5):418-26. [2] Pratesi F, Dioni I, Tommasi C, Alcaro MC, Paolini I, Barbetti F, Boscaro F, Panza F, Puxeddu I, Rovero P, Migliorini P. Ann Rheum Dis. 2014Jul;73(7):1414-22. [3] Johansson L, Pratesi F, Brink M, ärlestig L, D'Amato C, Bartaloni D, Migliorini P and Rantapää-Dahlqvist S. Arthritis Res Ther. 2016Jun3;18(1):127. <h3>Disclosure of Interests:</h3> None declared
SAT0294 ANALYSIS OF POLIAUTOIMMUNITY IN THE DIFFERENT SUBSETS OF SCLERODERMA
Authors: Daniel Sánchez-Cano, Norberto Ortego, Jose Luis Callejas-Rubio, Carles Tolosa, Alfredo Guillén del Castillo, Dolores Colunga Argüelles, Luis Sáez-Comet, Manuel Rubio-Rivas, Ana Argibay, Vicent Fonollosa-Pla, Carmen Pilar Simeón-Aznar
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Coexistence of different connective tissue diseases based on their common autoimmune base is a feasible circumstance, which is known as poliautoimmunity (PAI). <h3>Objectives:</h3> Evaluation of the occurrence of PAI in systemic sclerosis (SSc) according to subtypes in the patients included in the Spanish SSc Registry (RESCLE). Causes of death were also analyzed. <h3>Methods:</h3> A nationwide, cross-sectional study was carried out. All participating centers had obtained local ethics committee approval. <h3>Results:</h3> PAI was present in 46% out of 1911 patients, of whom, 33% had more than one association. Most of these patients were women (93%, p&lt;0.001), with no significant differences regarding first manifestation: Raynaud’s phenomenon, puffy hands, arthralgia or skin sclerosis. Isolated SSc was more frequent in all subsets (table 1). Sjogren’s syndrome was by far the most frequent associated disorder, with a RR of 1376 (table 2). Causes of death (SSc-related or not) did not significantly differ whether PAI was present or not. <h3>Conclusion:</h3> A rather higher prevalence than reported was observed, although distribution of the associated disorders was similar. No remarkable differences were found regarding SSc subsets, either PAI prevalence, initial manifestations or causes of death. <h3>Disclosure of Interests:</h3> None declared
PB2037 CHANGES IN ERYTHROPOIESIS IN MALARIA‐INDUCED ANEMIA
Authors: A.C. Pêgo, I. Lima, G. Martins, I. Sá Pereira, A.C. Martins, A. Kapitão, A. Nai, C. Camaschella, L. Silvestri, R. Gozzelino
Journal: HemaSphere (2019)

Background: Severe malarial anemia (SMA) is a complication developed in the course of Plasmodium infection, which is often associated with increased rates of malaria‐related morbidity and mortality. Possibly linked to a dysregulated immune response and unbalanced production of inflammatory mediators, one of the main features of SMA involves an impaired and/or ineffective erythropoiesis, which seems to critically contribute to the high number of deaths due to malaria infection. Erythropoiesis is regulated by the hormone erythropoietin, which upon binding to its receptor, activates a signaling cascade that leads to an increased consumption of iron used for the production of red blood cells. Aims: To gain new insights into the pathogenesis of malaria infection, our study aims to assess how erythropoiesis changes in mice exposed to different strains of Plasmodium parasites, known to cause severe forms of malaria, and/or in response to multiple re‐infections. Methods: Flow cytometry analyses were used to show the complementarity between the bone marrow and spleen in regulating the erythropoietic response in infected‐mice and its correlation with parasite load. Results: The interplay between this phenomenon and the expression of genes regulating iron metabolism was also analyzed, showing a strict association with the severity the disease. The extent of immune response activation upon exposure to Plasmodium infection was also evaluated and linked to the degree of induced SMA. Summary/Conclusion: The results obtained demonstrated that malaria infection significantly alters the erythropoietic process. In particular, we observed an early response of the spleen, as to compensate the loss of an appropriate bone marrow erythropoiesis during the infection.
A Sequential Cohort Study Comparing Kappamab Alone to Kappamab, Lenalidomide and Low Dose Dexamethasone in Kappa-Restricted Relapsed Refractory Multiple Myeloma (AMaRC 01-16)
Authors: Anna Kalff, Jake Shortt, Flora Yuen, John Reynolds, Hang Quach, Craig Thomas Wallington-Beddoe, Patricia Walker, Simon Harrison, Rosanne Dunn, Andrew Spencer
Journal: Blood (2019)
PS1056 ACUTE MYELOID LEUKEMIA OR MYELODYSPLASTIC SYNDROME WITH CHROMOSOME 17 ABNORMALITIES AND LONG‐TERM OUTCOMES WITH OR WITHOUT HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: G.R. Mohyuddin, A. Britt, B. Skikne, A. Singh, T. Lin, J. McGuirk, B. McClune, S. Ganguly, S. Abhyankar, L. Shune, N. Dunavin, A. Dias
Journal: HemaSphere (2019)

Background: Chromosome 17 (ch17) abnormalities, especially loss of the 17p region and P53 gene mutations (p53mut) result in very low rates of cure for patients with acute myeloid leukemia (AML) treated with conventional chemotherapy or allogenic stem cell transplant (ASCT). Aims: We assessed whether such poor outcomes extend to patients with all types of ch17 abnormalities and whether p53mut has further prognostic value. Methods: We retrospectively analyzed 98 patients at our institution with AML/myelodysplastic syndrome (MDS) who had ch17 abnormalities noted on cytogenetics. p53mut was analyzed by next generation sequencing (NGS). Results: 61 patients with AML and 37 patients with MDS were included. Patient characteristics are in Table 1. 95 out of the 98 patients had 17p abnormalities as part of a complex karyotype, whereas 67 out of the 98 patients had a monosomal karyotype. Complete remission (CR) with first line treatment was similar between induction chemotherapy or hypomethylating agents, 22.9% vs 21.6 % (p = 0.33). Median overall survival (OS) for all patients was 10 months. Ch17 abnormalities were classified into those resulting in deletion of the p53 loci such as 17p deletion and monosomy 17 (17pdel/mono17) and all other ch17 abnormalities (ch17oth). Amongst patients with 17pdel/mono17with NGS available, 19 of 26 had p53mut, while for ch17oth, 13 of 17 had p53mut (p = 0.72).Patients having both p53mut and abnormal ch17 exhibited poorer OS compared to patients with no p53mut (10 vs 23 months, p = 0.02). 30 patients (19 AML, 11 MDS) underwent ASCT, with a median post‐transplant OS of 11 months. For AML ASCT patients, 18 were in CR (13 with cytogenetic remission) and 1 had refractory disease at transplant, whereas for MDS patients, 3 were in CR (2 with cytogenetic remission) and 8 had stable disease. The post‐ASCT survival between AML/MDS cohorts did not differ (p = 0.6), although cytogenetic CR at time of ASCT trended towards improved OS (17 vs 8 months; p = 0.6). At last follow‐up, only 5 of 30 patients were alive, 4 in CR. Summary/Conclusion: AML/MDS patients with all types of ch17 abnormalities have a poor prognosis with or without ASCT, representing a distinct subset of patients amongst that that have complex cytogenetics. TP53 abnormalities detected by NGS are not limited to patients with 17pdel/mono17 and can be seen with other ch17 abnormalities. Drugs targeting the TP53 pathway and improving depth of response prior to ASCT are needed for improved outcomes in these patients. image
Can we be certain that storage duration of transfused red blood cells does not affect patient outcomes?
Authors: Marialena Trivella, Simon J Stanworth, Susan Brunskill, Peter Dutton, Douglas G Altman
Journal: BMJ (2019)

Large pragmatic randomised trials have found no evidence that the age of red blood cells affects patient survival, but <b>Trivella and colleagues</b> say that problems with their design and analysis leave unanswered questions about safety
The fibrogenic process and the unleashing of acute-on-chronic liver failure
Authors: Guillermo Nahúm López-Sánchez, Mayra Dóminguez-Pérez, Misael Uribe, Natalia Nuño-Lámbarri
Journal: Clinical and Molecular Hepatology (2019)

Acute-on-chronic liver failure (ACLF) is a life-threatening condition characterized by a rapid deterioration of previously well-compensated chronic liver diseases. One of the main obstacles in ACLF is the lack of knowledge of the pathogenesis and specific broad-spectrum treatments. An excessive systemic inflammatory response has been proposed to explain the pathogenesis of ACLF; this hypothesis involves stellate cells, which are implicated in many liver homeostatic functions that include vitamin A storage, regulation of sinusoidal blood flow, local inflammation, maintenance of the hepatocyte phenotype and extracellular matrix remodeling. However, when there is damage to the liver, these cells are the main target of the inflammatory stimulus, as a result, the secretion of the extracellular matrix is altered. Activated hepatic stellate cells raise the survival of neutrophils by the stimulation of granulocytes colonies and macrophages, which exacerbates liver inflammation and promotes damage to hepatocytes. Elevation of pathogen-associated molecular patterns is related to liver damage by different pathophysiological mechanisms of decompensation, showing ballooning degeneration and cell death with a predominance of cholestatic infection. Moreover, patients with ACLF present a marked elevation of C-reactive protein together with an elevation of the leukocyte count. Chronic liver disease is a complex pathological state with a heterogeneous pathophysiology in which genetic factors of the host and external triggers interact and culminate in hepatic insufficiency. The better understanding of such interactions should lead to a better comprehension of the disease and to the discovery of new treatment targets that will make acute decompensations preventable and even decrease mortality.
THU0204 ASSOCIATION OF LILRA3 GENE WITH LYMPHOMAGENESIS RISK IN YOUNG SS PATIENTS
Authors: Evangelia Argyriou, Petros Roussos, Adrianos Nezos, Aliki Venetsanopoulou, Kyriaki A. Boki, Athanasios Tzioufas, Haralampos M. Moutsopoulos, Clio Mavragani
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Primary Sjögren's Syndrome (SS) is a systemic autoimmune disease, characterized by increased risk of non-Hodgkin's lymphoma development. A functional polymorphism of the immunoreceptor LILRA3 (Leukocyte immunoglobulin-like receptor A3) has been recently identified as a potential etiopathogenic factor for both pSS susceptibility and lymphomagenesis in the general population. <h3>Objectives:</h3> The aim of the current study was to explore the potential contribution of the LILRA3 functional polymorphism in primary SS susceptibility and SS related lymphomagenesis. <h3>Methods:</h3> In this study, 346 primary SS patients (ACR/EULAR classification criteria, 2016) and 350 healthy controls were included. The presence of LILRA3 functional polymorphism was detected by polymerase chain reaction (PCR), whereas serum levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA), respectively. Statistical analysis was performed by Graph Pad Prism. <h3>Results:</h3> LILRA3 wild type gene variant was detected in 84% of healthy controls, 86.3% of pSS non-Lymphoma patients and 89.7% of patients complicated with lymphoma. Of interest, in pSS patients ≤40 years complicated by lymphoma, LILRA3 wild type variant was detected in 100% in contrast to pSS - non lymphoma patients (81.8%) and healthy controls (HC) (83.2%) [p=0.03]. In line with these results, LILRA3 protein serum levels were increased in pSS-lymphoma patients with pSS onset ≤40 years compared to healthy controls (p=0.009). <h3>Conclusion:</h3> Increased LILRA3 protein levels, as a result of predominance of the LILRA3 wild type gene variant in the young pSS onset patients complicated by lymphoma, imply a potential role of the LILRA3 gene in pSS related lymphomagenesis. <h3>Disclosure of Interests:</h3> Evangelia Argyriou: None declared, Petros Roussos: None declared, Adrianos Nezos: None declared, Aliki Venetsanopoulou: None declared, Kyriaki A. Boki: None declared, Athanasios Tzioufas Grant/research support from: ABBVIE, PFIZER, AMGEN, NOVARTIS, GSK, Haralampos M. Moutsopoulos: None declared, Clio Mavragani: None declared
Abstract 20616: Treatment of Primary Cardiomyocytes With Serum From Dilated Cardiomyopathy Patients Induces Gene Expression and Functional Changes Observed in the Pediatric Heart
Authors: Kathleen C Woulfe, Xuan Jiang, Elisabeth K Phillips, Danielle A Jeffrey, Genevieve C Sparagna, Kathryn C Chatfield, Shelley D Miyamoto, Brian L Stauffer, Carmen C Sucharov
Journal: Circulation (2017)

Introduction: Current treatment for pediatric dilated cardiomyopathy (DCM) patients is extrapolated from evidence-based practices in adults with heart failure (HF); however, these therapies fail to...
Abstract 14459: Genome-Wide Association Analysis Identifies 3 Common Variants Predisposing to Brugada Syndrome, a Rare Disease With High Risk of Sudden Cardiac Death
Authors: Julien Barc, Connie Bezzina, Yuka Mizusawa, Carol Remme, Jean-Baptiste Gourraud, Arie Verkerk, Peter Schwartz, Pascale Guicheney, Charles Antzelevitch, Eric Schulze-Bahr, Elijah Behr, Jacob Tfelt-Hanson, Stefan Kaab, Hiroshi Watanabe, Minoru Horie, Naomasa Makita, Wataru Shimizu, Philippe Froguel, Dan Roden, Vincent Christoffels, Manfred Gessler, Arthur Wilde, Vincent Probst, Jean-Jacques Schott, Christian Dina, Richard Redon
Journal: Circulation (2013)

Introduction: Brugada Syndrome (BrS) is considered as a rare Mendelian disorder with autosomal dominant transmission and is associated with ST-segment elevation in the right precordial leads and an...