tbuckley/cabot-search huggingface dataset:
AB0485 INTRAVENOUS HIGH DOSE GLUCOCORTICOIDS CAUSE PROLONGATION OF QT INTERVAL IN CONNECTIVE TISSUE DISEASE PATIENTS EXCEPT ANTI-RO POSITIVE SUBGROUP
Authors: Tomáš Soukup, Jan Toms, Radek Pudil, Jakub Simka, Lenka Pollak, Nikola Jurikova, Martin Dosedel, Jiri Vlcek
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Recent literature indicates that anti-Ro antibodies may be associated with prolongation of corrected QT (QTc) interval in the adult patients with connective tissue diseases. Moreover, glucocorticoids (frequently used in the therapy) are known to probably induce electrocardiographic changes including prolongation of QT interval. Prolongation of QTc interval is a risk factor for malignant ventricular arrhythmias. We hypothetised that patients with anti-Ro positivity have a higher risk of QT prolongation especially in the case of high dose intravenous glucocorticoids (IVGC) treatment. <h3>Objectives:</h3> The aim of the study was to analyse risk of QTc interval prolongation in anti-Ro and anti-La positive patients before and after high dose IVGC treatment in patients with connective tissue diseases. <h3>Methods:</h3> We performed a retrospective study of 115 patients (21 males), mean age of 48±14.7 years, range 19-78 years with connective tissue disease. Anti-Ro antibodies were examined in all patients before IVGC treatment. The patients were given 5x1000 mg methyprednisolon i.v. during five consecutive days. ECG recording was performed at baseline and after IVGC. The QT intervals were measured in each of 12-lead standard ECGs from two consecutive cycles. The QT intervals were measured from the onset of QRS complex to the end of the T wave by the means of a tangential method. Fridericia formula was used to obtain heart rate-corrected values for QT intervals. <h3>Results:</h3> Comparing patients with anti-Ro positivity (n=39; 33.9%) and anti Ro-negativity (n=76, 66.1%), we found insignificant difference in QTc interval; QTcRo+ =417.2±28.4ms and QTcRo- =420,8±26.4ms (P=0.51), respectively. Admission of IVGC showed significant prolongation of QTc in all patients, mean QTc1 before treatment was 399.4±26.2ms, and QTc2 after therapy 412.7±27.2ms, P=0.00021. On the other hand, anti-Ro and anti-La positivity showed shorter QTc interval 391±18.7ms, to compare patients without these antibodies QTc=414.8±25.7ms, P=0.019 after treatment. <h3>Conclusion:</h3> IVGC treatment significantly prolongs QT interval. Prolongation of QT over 445 ms was found in nine patients, but ventricular arrythmias were not observed. The presence of anti-Ro and anti-La antibodies did not show QT prolongation. Therefore, shortening of QT/QTc iterval needs further confirmation. Motivated by this experience, we consider ECG monitoring and careful observation of patients during IVGC treatment. <h3>Acknowledgement:</h3> Charles University research projects [PROGRES Q40-15, PROGRES Q47] <h3>Disclosure of Interests:</h3> None declared
Isolation and characterization of oral cancer stem cells in oral squamous cell carcinoma
Authors: Cheng-Chia Yu, Shih-Hwa Chiou, Jeng-Fan Lo
Journal: Cancer Research (2007)

1315  Discovery of cancer stem cells (CSCs) from solid tumors intrigues a new target for therapeutic treatment of cancer. To isolate the oral CSCs we performed the enrichment of oral CSCs from oral cancer cell lines of oral squamous cell carcinomas (OSCCs) with different malignancy through serum free medium selection. After five weeks of selection we successfully isolated cancer cell spheres from OSCCs which resembled the characteristics of CSCs. Expression of stemness genes of isolated CSCs including Nanog and Oct4 were significantly up-regulated through immunofluorescence stain, microarray, real-time PCR and western blot analysis. CSCs isolated from OSCC cancer cell lines grew intensively in serum free medium when compared to the parental cells. Elevation of in vitro invasion ability and anchorage-independent growth in soft agar of enriched CSCs was consistent to the characteristics of CSCs from other solid tumors. In agreement to the enhancement of invasion ability the S100A4 protein, a metastasis factor, was significantly up-regulated in oral CSCs. Along with the up-regulation of S100A4, elevation of vimentin and down-regulation of P53 protein were also shown in isolated CSCs. Currently, in vivo tumorigenicity of enriched CSCs is evaluated through xenograft growth in SCID mice. This is the first research to isolate the oral CSCs from OSCCs. With the isolated oral CSCs we want to develop a new therapeutic treatment for oral cancer.
The global prevalence of latent tuberculosis: a systematic review and meta-analysis
Authors: Adam Cohen, Victor Dahl Mathiasen, Thomas Schön, Christian Wejse
Journal: European Respiratory Journal (2019)

In 1999, the World Health Organization (WHO) estimated that one-third of the world's population had latent tuberculosis infection (LTBI), which was recently updated to one-fourth. However, this is still based on controversial assumptions in combination with tuberculin skin test (TST) surveys. Interferon-γ release assays (IGRAs) with a higher specificity than TST have since been widely implemented, but never used to estimate the global LTBI prevalence. We conducted a systematic review and meta-analysis of LTBI estimates based on both IGRA and TST results published between 2005 and 2018. Regional and global estimates of LTBI prevalence were calculated. Stratification was performed for low, intermediate and high TB incidence countries and a pooled estimate for each area was calculated using a random effects model. Among 3280 studies screened, we included 88 studies from 36 countries with 41 IGRA (n=67 167) and 67 TST estimates (n=284 644). The global prevalence of LTBI was 24.8% (95% CI 19.7–30.0%) and 21.2% (95% CI 17.9–24.4%), based on IGRA and a 10-mm TST cut-off, respectively. The prevalence estimates correlated well to WHO incidence rates (Rs=0.70, p&lt;0.001). In the first study of the global prevalence of LTBI derived from both IGRA and TST surveys, we found that one-fourth of the world's population is infected. This is of relevance, as both tests, although imperfect, are used to identify individuals eligible for preventive therapy. Enhanced efforts are needed targeting the large pool of latently infected individuals, as this constitutes an enormous source of potential active tuberculosis.
PB1782 TWO‐YEAR SURVIVAL WITH AXICABTAGENE CILOLEUCEL IN RELAPSED OR REFRACTORY LARGE B‐CELL LYMPHOMA: AN UPDATED ANALYSIS
Authors: I. Diakite, V.W. Lin, S. Klijn, L. Navale, A.G. Purdum, E. Fenwick, M. Botteman, B. van Hout
Journal: HemaSphere (2019)

Background: Relapsed/refractory large B cell lymphoma is historically associated with a poor prognosis, with a median overall survival (OS) of 6.3 months. In the 2‐year update of the ZUMA‐1 trial of axicabtagene ciloleucel (axi‐cel), median OS was not reached after a median follow‐up of 27.1 months. Prior analysis at 1‐year suggests that traditional parametric survival models cannot accurately estimate long‐term OS with axi‐cel when a large proportion of patients achieve durable remissions, thereby supporting the use of a mixture cure model (MCM) for survival extrapolations (Bansal, et al. Biol Blood Marrow Transplant. 2018). Aims: We analyzed the updated 2‐year ZUMA‐1 data to further explore the robustness of MCM. Methods: The ZUMA‐1 data were analyzed using a traditional parametric model, MCM, a general mixture model (GMM), and an integrated Markov cure model (IMCM). The MCM assumed patients with long‐term OS would have similar mortality as the age‐adjusted general population. The GMM relaxed this assumption by separately fitting and then combining parametric survival functions for poor‐ and good‐prognosis patients in a single survival function. The IMCM simultaneously accounted for OS and disease progression in a single framework. All parameters were estimated via maximum likelihood estimations, and model fit was assessed via Akaike information criterion (AIC). Results: The best‐fitting traditional model estimated a mean OS of 10.6 years (AIC = 444.3). The best‐fitting MCM estimated a mean OS of 13.5 years, with a 51.0% long‐term OS fraction (AIC = 439.3). The best‐fitting GMM produced a mean OS of 13.5 years, with a 52.7% long‐term OS fraction (AIC = 442.1). The best‐fitting IMCM estimated a mean OS of 13.4 years, with a 50.5% long‐term OS fraction (AIC = 916.6). The higher AIC for GMM and IMCM is partly because of specifying more parameters than MCM. Summary/Conclusion: Analyzing the updated ZUMA‐1 2‐year data, both the GMM and IMCM showed good model fit and results consistent with those of the MCM. These results support the long‐term survival associated with axi‐cel in relapsed/refractory large B cell lymphoma driven by the ≥ 50% long‐term OS rates.
PB1850 DENTAL MANAGEMENT OF PATIENTS TAKING NOVEL ORAL ANTICOAGULANTS (NOAS): DABIGATRAN.
Authors: A. Kapsali, G. Papakitsos
Journal: HemaSphere (2019)

Background: A new group of oral anticoagulants with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. Aims: Patients being treated with oral anticoagulants are at higher risk for bleeding when undergoing dental treatments. Methods: A literature search was conducted through April 2015 for publications in the ISI Web of Knowledge, PubMed and Cochrane Library using the keywords “dabigatran”, “new oral anticoagulants”, “bleeding” and “dental treatment”. Results: There is no need for regular coagulation monitoring of patients on dabigatran therapy. Whether or not to temporarily discontinue dabigatran must be assessed according to the bleeding risk involved in the dental procedure to be performed. Summary/Conclusion: The number of patients under treatment with new oral anticoagulants will increase in the coming years. It is essential to know about the pharmacokinetics and pharmacodynamics of new oral anticoagulants and about their interactions with other drugs. It is necessary to develop clinical guidelines for the perioperative and postoperative management of these new oral anticoagulants in oral surgical procedures and to carefully evaluate the bleeding risk of dental treatment, as well as the thrombotic risk of suppressing the new oral anticoagulant.
1 The integrity of the scapholunate ligament in competitive divers
Authors: AJ Beck
Journal: British Journal of Sports Medicine (2019)

Aim Wrist pain and injury is common condition in competitive, elite divers. Literature has shown that divers sustain high impacts of force through the wrists on water entry. It is likely this and the repetitive nature of the sport that results in wrist injuries. 1 2 No studies have yet looked at the structures injured when divers have wrist pain. This study was conducted to ascertain the demographics of the diving population within the United Kingdom at competitive level and how many of them experienced wrist pain. It was also used to investigate if one of the crucial stabilising ligaments in the wrist was disrupted, the scapholunate ligament (SLL). Methods Data was collected at the British Diving Championships, 2018. 51 divers were eligible for inclusion and 43 divers took part. Two divers were excluded due to previous wrist surgery. Participants completed a questionnaire on diving career to date and wrist injuries. They then underwent wrist examination using Watson’s test and ultrasound imaging of both SLL. Results This study found that 78% of divers had disruption of one or both SLL. Of these, 65.9% had disruption of the ligament in the supporting hand rather than the entry hand. No significant difference was found between springboard and platform divers. Those divers who taped were found to reduce ligament disruption by 28 times over those who did not (OR 27.9, 95% CI 3.31 to 234, P=0.002). It was demonstrated that Watson’s test has poor sensitivity and specificity, with reasonable positive predicted value. Conclusion Springboard and Platform divers at a competitive level are at high risk of SLL disruption. The supporting hand is more at risk than the entry hand. Taping confers a significant reduction in risk of disruption and should be used to prevent injury. Watson’s test is a poor clinical test in diagnosis of SLL disruption. References Harrison S, Cohen R, Cleary P, et al. A coupled biomechanical-smoothed particle hydrodynamics model for predicting the loading on the body during elite platform diving. Appl Math Model 2015;40:3812–31. Prien A, Mountjoy M, Miller J, et al. Injury and illness in aquatic sport: how high is the risk? A comparison of results from three FINA world championships. Br J Sports Med 2016;51:277–82.
PF571 IDENTIFICATION OF HLA‐E AS A KEY GENE IN MULTIPLE MYELOMA BASED ON BIOINFORMATIC ANALYSIS AND DESIGN HIGH‐AFFINITY PEPTIDES TARGETING HLA‐E BASED ON COMPUTATIONAL TECHNIQUES
Authors: Y. Yang, M. sun, Z. yu, Z. Liu, M. Wei
Journal: HemaSphere (2019)

Background: Multiple myeloma (MM) is a common plasma cell malignancy that is currently incurable. Finding potential drug targets and new drugs are crucial for the treatment of thisdisease. Microarray technology is widely used to investigate differential mRNA expression and identify biomarkers in disease, which provides important clues to identifying new treatment targets and then new drugs could be designed. Aims: To find new treatment target for MM and design targeting affinity peptide. Methods: Two datasets (GSE6691 and GSE39754) were obtained from the Gene Expression Omnibus (GEO) database, and a protein‐protein interaction (PPI) network of differentially expressed genes (DEGs) was constructed to identify hub genes.Key clusters in the PPI network were analyzed by Molecular Complex Detection (MCODE). The gene both in hub genes and key clusters could be considered as potential treatment target and will be verified in clinical patients’ bone marrow samples. As the treatment target identified, crystal structure is obtained from Protein Data Bank and affinity peptide drug designed by Molecular Operating Environment (MOE) software. Results: HLA‐E was identified as hub gene and also located in one of the key clusters which could be a potential therapeutic target for MM.The high expression of HLA‐E in myeloma cells was confirmed by measuring HLA‐E mRNA expression in bone marrow samples from MM patients and healthy volunteers from Shengjing Hospital.The crystal structure of HLA‐E from the Protein Data Bank(PDB ID: 3CDG) was used to find the key active area of HLA‐E. MOE softwarewas used to design high‐affinity targeting peptides using key interaction amino acids as model peptides. A peptide library was constructed and screened to identify peptides with the highest stability and affinity for HLA‐E. Three high‐affinity peptides were selected and verified by peptide‐protein docking. Thus, these peptides could serve as targeting heads to find myeloma cells that express high levels of HLA‐E. Summary/Conclusion: HLA‐E could be recognized as a new treatment target for MM. At the meanwhile, affinity peptide(NALDEYCEDKNR) could be considered as a new targeting drug. image
Effect of Including Important Clinical Variables on Accuracy of the Lung Allocation Score for Cystic Fibrosis and Chronic Obstructive Pulmonary Disease
Authors: Carli J. Lehr, Melissa Skeans, Elliott Dasenbrook, Aliza Fink, Gabriela Fernandez, Albert Faro, Maryam Valapour
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Clinical variables associated with shortened survival in patients with advanced-stage cystic fibrosis (CF) are not included in the lung allocation score (LAS).Objectives: To identify variables associated with wait-list and post-transplant mortality for CF lung transplant candidates using a novel database and to analyze the impact of including new CF-specific variables in the LAS system.Methods: A deterministic matching algorithm identified patients from the Scientific Registry of Transplant Recipients and the Cystic Fibrosis Foundation Patient Registry. LAS wait-list and post-transplant survival models were recalculated using CF-specific variables. This multicenter, retrospective, population-based study of all lung transplant wait-list candidates aged 12 years or older from January 1, 2011, to December 31, 2014, included 9,043 patients on the lung transplant waiting list and 6,110 lung transplant recipients between 2011 and 2014, comprising 1,020 and 677 with CF, respectively.Measurements and Main Results: Measured outcomes were changes in LAS and lung allocation rank. For CF candidates, any Burkholderia sp. (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.2-6.6), 29-42 days hospitalized (HR 2.8; CI 1.3-5.9), massive hemoptysis (HR 2.1; CI 1.1-3.9), and relative drop in FEV1 ≥30% over 12 months (HR 1.7; CI 1.0-2.8) increased wait-list mortality risk; pulmonary exacerbation time 15-28 days (1.8; 1.1-2.9) increased post-transplant mortality risk. A relative drop in FEV1 ≥10% in chronic obstructive pulmonary disease (COPD) candidates was associated with increased wait-list mortality risk (HR 2.6; CI 1.2-5.4). Variability in LAS score and rank increased in patients with CF. Priority for transplant increased for COPD candidates. Access did not change for other diagnosis groups.Conclusions: Adding CF-specific variables improved discrimination among wait-listed CF candidates and benefited COPD candidates.
Tumor purity as a prognostic factor in colon cancer.
Authors: Jianmin Xu, Yihao Mao, Qingyang Feng, Peng Zheng, Liangliang Yang, Dexiang Zhu, Wenju Chang, Meiling Ji, Li Ren, Ye Wei, Guodong He
Journal: Journal of Clinical Oncology (2018)

e15646 Background: Tumor purity is the proportion of cancer cells in the tumor tissue. The impact of tumor purity on colon cancer (CC) prognosis, genetic profile and microenvironment has not been thoroughly accessed. Methods: Clinical and transcriptomic data from three public datasets, GSE17536/17537, GSE39582, and TCGA were retrospectively collected (n = 1248). Tumor purity of each sample was inferred by a computational method based on transcriptomic data. Results: Stage III and MMR-deficient (dMMR) CC patients showed a significantly lower tumor purity (both P < 0.05). Low purity CC conferred worse survival and tumor purity was identified as an independent prognostic factor in multivariate Cox regression analysis (P = 0.015, HR = 0.369, 95% CI = 0.165 - 0.823). Moreover, high tumor purity CC patients benefited more from adjuvant chemotherapy (P = 0.010, HR = 0.148, 95% CI = 0.035 - 0.635). Subsequent genomic analysis found that the mutation burden was negatively associated with tumor purity (R = -0.206, P < 0.001) with only APC and KRAS significantly more mutated in high purity CC (both P < 0.05). However, no somatic copy number alteration event was correlated with tumor purity. Furthermore, immune-related pathways and immunotherapy-associated markers (PD-1, PD-L1, CTLA-4, LAG-3, and TIM-3) were highly enriched in low purity samples. Notably, the relative proportion of M2 macrophages and neutrophils, which indicated worse survival in CC (both P < 0.05), was negatively associated with tumor purity. Conclusions: Tumor purity exhibited potential value for CC prognostic stratification as well as adjuvant chemotherapy benefit prediction. The relative worse survival in low purity CC may attribute to higher mutation frequency in key pathways and purity-related microenvironmental changing.
AB1104 GENETIC ASPECTS OF SARCOIDOSIS IN A TUNISIAN POPULATION
Authors: sameh sayhi, Rim Dhahri, Najah Boussetta, Souha Hannachi, Feida Laajili, Bassem Louzir, Hajer Derbali, Linda Mrisa, Ridha Mrisa
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> <h3>Objectives</h3> To determine the frequencies of the HLA alleles and genotypes of the ACE gene. <h3>Methods</h3> This is a cross sectional study of 65 patients with sarcoidosis, followed in the departments of internal medicine and neurology at the Military Hospital of Tunis.The genetic study involved only 50 patients. DNA extraction was performed to determine the frequencies of the HLA alleles and genotypes of the ACE gene. <h3>Results</h3> 1. HLA typing The analysis of HLA typing allowed us to estimate the different frequencies of alleles in patients. The calculation of the allelic frequency found that the most frequent alleles are HLA-DRB1 * 1501 alleles with a frequency of 38% and HLA-DRB1 * 0301 of 28%. Other alleles are at lower frequencies (Table1). 2. Genotyping of the ECA gene Genotyping of the polymorphism of the angiotensin converting enzyme (ACE) involved 50 patients. Genotypic frequencies (II, ID and DD) and allele frequencies (I and D) were estimated in order to evaluate the frequencies of each genotype and the 2 alleles for this pathology. The genotypic and allelic frequency results were summarized in Table 2. <h3>Conclusion</h3> The most frequent alleles in Tunisian patients with sarcoidosis are HLA-DRB1 * 1501 alleles with a frequency of 38% and HLA-DRB1 * 0301 of 28%. The genotypic and allelic results showed that genotype ID was the most frequent with 48% with a predominance of the D allele in 54%. <h3>References</h3> <h3>Disclosure of Interests</h3> None declared
Incidence, Severity and Impact of Influenza: a joint meeting organised by the ISIRV Epidemiology Group and ECDC, Stockholm, 2019
Authors: Barbara Rath, Pasi Penttinen
Journal: Eurosurveillance (2019)

Preview this article: Incidence, Severity and Impact of Influenza: a joint meeting organised by the ISIRV Epidemiology Group and ECDC, Stockholm, 2019, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/24/23/eurosurv-24-23-3-1.gif
SP0055 CLINICAL MULTI-OMICS
Authors: Timothy R. Radstake
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> It is becoming clear that the field of medicine needs to change to stay affordable. One way of doing that is by optimizing the patients journey with true personalized medicine approaches. In other words, how to give every patient the right drug, at the right moment for the optimal duration. Recent advances in molecular techniques have truly revolutionized research into molecular fingerprinting – classification of clinical phenomena on the basis of a molecular basis rather than a diagnosis based on organ, symptoms or clinical criteria. This makes personalized medicine reachable within the coming years. In my presentation I will dive in to the various molecular technologies (multi-omics) to achieve molecular fingerprinting of patients. Next, I will explain the computational techniques necessary to process the big data originating from the molecular processes enabling researchers to visualize big data from clinicians and patients. Finally, I will provide several examples of how these exercises might improve care for patients covering the space of rheumatic and musculoskeletal diseases (RMDs). At the end of my presentation I will show how big data can be used for drug discovery, immune monitoring in clinical trials and/or daily clinical practice as well as drug repurposing. Together, I will provide a glimpse of the future on personalized healthcare within the field of RMDs. <h3>Disclosure of Interests:</h3> None declared
Abstract 17149: The Ratio of Pulmonary Artery to Aorta Diameter Can Predict the Clinical Adverse Events in Acute Decompensated Heart Failure
Authors: Hirotaka Ieki, Yuji Nagatomo, Mayuko Yagawa, Keitaro Mahara, Mitsuaki Isobe, Shun Kohsaka, Tsutomu Yoshikawa
Journal: Circulation (2017)

Introduction: We previously reported that the ratio of pulmonary artery (PA) to ascending aorta (Ao) diameter measured by CT (PA/Ao) was well correlated with directly measured pulmonary artery pres...