tbuckley/cabot-search huggingface dataset:
AB0005 HLA CLASS II CONFERS RESISTANCE OR SUSCEPTIBILITY TO HIDRADENITIS SUPPURATIVA IN A CAUCASIAN SPANISH POPULATION (NORTHERN SPAIN)
Authors: M. Calderón-Goercke, J. G. Ocejo-Vinyals, M. A. González-Gay, M. A. Fernández-Viña, J. Cantos-Mansilla, I. Vilanova, R. Blanco, M. González-López
Journal: Annals of the Rheumatic Diseases (2020)

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease affecting terminal hair follicles in apocrine glands bearing skin. The pathogenesis of HS remains unknown, although increasing evidence suggests that the immune system plays an important role. To date, two previous studies, did not find any association between HLA and HS. Objectives: Our aim was to analyze the association of HLA class II with HS in a Caucasian population from Cantabria (northern Spain). Methods: In this study we analyzed the HLA-A, -B, -C, DRB1, -DQA1 and –DQB1 allele distribution in 106 HS patients and 262 age- and sex-matched controls from a Caucasian population of Cantabria (northern Spain). Results: HLA-A *29 and B *50 were significantly more frequent in HS patients and A *30 and B *37 in controls, but these associations disappeared after correction. On the other hand, DRB1 *07, DQA1 *02 and DQB1 *02 were significantly more frequent in controls ( p 0.026, p 0.0012 and p 0.0005 respectively), and the HLA allele DQB1 *03:01 was significantly more frequent in HS patients ( p 0.00007) all of them after Bonferroni correction. Furthermore, the DRB1 *07; DQA1 *02; DQB1 *02 haplotype was significantly more frequent in controls ( p 0.0005). Conclusion: This is the first study showing an association of HLA-class II with HS. Our results suggest that HLA-II alleles ( DRB1 *07, DQA1 *02, DQB1 *02 and DQB1 *03:01) and the DRB1 *07~ DQA1 *02~ DQB1 *02 haplotype could influence on resistance or susceptibility to HS. References: [1]González-López MA. J Am Acad Dermatol. 2016; Aug;75(2):329-35. [2]González-López MA. PLoS One. 2018 Jan 4;13(1). [3]Vilanova I. J Eur Acad Dermatol Venereol. 2018 May;32(5):820-824. [4]Durán-Vian C, et al. J Eur Acad Dermatol Venereol. 2019 Nov;33(11):2131-2136. Disclosure of Interests: Monica Calderón-Goercke: None declared, J. Gonzalo Ocejo-Vinyals: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Marcelo A. Fernández-Viña: None declared, Juan Cantos-Mansilla: None declared, Iosune Vilanova: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD, Marcos González-López: None declared
Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study
Authors: Luca Carsana, Aurelio Sonzogni, Ahmed Nasr, Roberta Simona Rossi, Alessandro Pellegrinelli, Pietro Zerbi, Roberto Rech, Riccardo Colombo, Spinello Antinori, Mario Corbellino, Massimo Galli, Emanuele Catena, Antonella Tosoni, Andrea Gianatti, Manuela Nebuloni
Journal: The Lancet Infectious Diseases (2020)

COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital. Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes.We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020. The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h. Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation.All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases). The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases). Electron microscopy revealed that viral particles were predominantly located in the pneumocytes.The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent. Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.None.
Abstract B13: A novel mouse model for small-cell carcinoma of bladder
Authors: Dongbo Xu, Qiang Cao, Li Wang, Yanqing Wang, Xiaojing Zhang, Yue Wu, Gary Smith, Bo Xu, David Goodrich, Qiang Li
Journal: Cancer Research (2020)

Abstract Background: Molecular characterization studies suggest the neuronal subtype muscle invasive bladder cancer (MIBC) is associated with a high response rate to immune checkpoint inhibitor. We sought to establish a mouse model for small-cell carcinoma of bladder. Materials and Methods: Three canonical signaling pathways (TP53, RB1, and RTK/PI3K/AKT) are commonly altered in small-cell bladder cancer. Keratin 5 promoter-driven adenovirus Cre (Ad-K5-Cre, University of Iowa) was instilled into the bladder of female triple floxed (Trp53f/f:Pten f/f:Rb1 f/f) mice for 30 min. The mice were monitored for hematuria and bladder mass using ultrasound. Results: One Ad-K5-Cre:Trp53-/-: Pten-/-: Rb1-/- mouse died from urinary obstruction at 22 weeks. An obstructive tumor was noted in bladder trigone. Immunohistochemistry analysis of bladder tumor demonstrated negative cytokeratin 7 (CK7) expression and strong synaptophysin expression. Disseminated metastatic foci in lung were noted with positive synaptophysin expression as of primary tumor in the bladder. PCR demonstrated Cre mediated recombined alleles of the Trp53, Pten, and Rb1 in the tumor DNA but not in the tail DNA. The bladder tumor was dissociated to generate an organoid line. The organoid after 5 passages was tested for drug response of standard chemotherapy regimens. IC50 of cisplatin, etoposide, and gemcitabine were 3.1 μM, 0.8 μM, and 92.3 nM, respectively. Further characterization of more mice will address the limitation of small sample size. Conclusion: Inactivation of Trp53, Pten, and Rb1 is sufficient to induce metastatic small-cell carcinoma of bladder. This mouse model provides a powerful tool to study molecular mechanism of neuroendocrine differentiation and screen novel therapeutic drugs for small-cell carcinoma of bladder. Citation Format: Dongbo Xu, Qiang Cao, Li Wang, Yanqing Wang, Xiaojing Zhang, Yue Wu, Gary Smith, Bo Xu, David Goodrich, Qiang Li. A novel mouse model for small-cell carcinoma of bladder [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B13.
Diagnosing and Treating Systemic Racism
Authors: Michele K. Evans, Lisa Rosenbaum, Debra Malina, Stephen Morrissey, Eric J. Rubin
Journal: New England Journal of Medicine (2020)

Diagnosing and Treating Systemic Racism Our country’s long and troubled history of racism has permeated the physician–patient relationship with mistrust. Now, amid an acute public health crisis tha...
AB0693 TIM-3-EXPRESSING NEUTROPHILS AS A NOVEL INDICATOR TO ASSESS DISEASE ACTIVITY AND SEVERITY IN ANKYLOSING SPONDYLITIS
Authors: X. Huang, T. Li, J. Chen, Y. Wang, S. Chen, W. Deng, Q. Huang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Ankylosing spondylitis (AS) is a type of chronic inflammatory disease that compromises the axial skeleton and sacroiliac joints. Many studies have shown that neutrophils play an important roles in the inflammatory process of AS. However, the immunomodulatory roles and mechanisms of neutrophils in AS are poorly understood. T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) has been reported as an important regulatory molecule, expressed and regulated on different innate immune cells, plays a pivotal role in several autoimmunity diseases. Recent study indicates that Tim3 is also expressed on neutrophils. However, the frequency and roles of Tim3-expressing neutrophils in AS was not clear. Objectives: In this study, we investigated the expression of Tim3 on neutrophils in AS patients and analyzed the correlation between the level of Tim3-expressing neutrophils and the disease activity of AS. Methods: AS Patients were recruited from Guangdong Second Provincial General Hospital (n=49). Age/sex-matched volunteers as Healthy controls (HC) (n=39). The medical history, clinical manifestations, physical examination, laboratory measurements were recorded. The expression of costimulatory molecules including programmed death 1 (PD-1), Tim-3 on neutrophils were determined by flow cytometry. The frequencies of Tim3-expressing neutrophils in AS patients were further analyzed for their correlation with markers of inflammation ESR and CRP, disease activity and severity of AS. Results: The expression of Tim3 on neutrophils in patients with AS was increased compared to the HC (Figure 1A). The frequency of Tim3-expressing neutrophils in patients with AS showed an positive correlation with ESR, CRP and ASAS-endorsed disease activity score (ASDAS) (Figure 1B). Moreover, the frequency of Tim3-expressing neutrophils in active patients(ASDAS≥1.3) was increased as compare with the inactive patients (ASDAS&lt;1.3) (Figure 1C). Conclusion: Increased Tim-3 expression on neutrophils may be a novel indicator to assess disease activity and severity in AS, which may serves as a negative feedback mechanism preventing potential tissue damage caused by excessive inflammatory responses in AS patients. References: [1]Han, G., Chen, G., Shen, B. &amp; Li, Y., Tim-3: an activation marker and activation limiter of innate immune cells. FRONT IMMUNOL 4 449 (2013). [2]Vega-Carrascal, I. et al. , Galectin-9 signaling through TIM-3 is involved in neutrophil-mediated Gram-negative bacterial killing: an effect abrogated within the cystic fibrosis lung. J IMMUNOL 192 2418 (2014). Figure 1. (A )The expression of Tim3 on neutrophils in AS and HC. (B )The correction between Tim3-expressing neutrophils and ESR,CRP,ASDAS. (C ) The expression of Tim3 on neutrophils in active and inactive patients. Disclosure of Interests: None declared
Mucoactive agents for acute respiratory failure in the critically ill: a systematic review and meta-analysis
Authors: Rohan Anand, Daniel F McAuley, Bronagh Blackwood, Chee Yap, Brenda ONeill, Bronwen Connolly, Mark Borthwick, Murali Shyamsundar, John Warburton, David van Meenen, Frederique Paulus, Marcus J Schultz, Paul Dark, Judy M Bradley
Journal: Thorax (2020)

Acute respiratory failure (ARF) is a common cause of admission to intensive care units (ICUs). Mucoactive agents are medications that promote mucus clearance and are frequently administered in patients with ARF, despite a lack of evidence to underpin clinical decision making. The aim of this systematic review was to determine if the use of mucoactive agents in patients with ARF improves clinical outcomes.We searched electronic and grey literature (January 2020). Two reviewers independently screened, selected, extracted data and quality assessed studies. We included trials of adults receiving ventilatory support for ARF and involving at least one mucoactive agent compared with placebo or standard care. Outcomes included duration of mechanical ventilation. Meta-analysis was undertaken using random-effects modelling and certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation.Thirteen randomised controlled trials were included (1712 patients), investigating four different mucoactive agents. Mucoactive agents showed no effect on duration of mechanical ventilation (seven trials, mean difference (MD) -1.34, 95% CI -2.97 to 0.29, I2=82%, very low certainty) or mortality, hospital stay and ventilator-free days. There was an effect on reducing ICU length of stay in the mucoactive agent groups (10 trials, MD -3.22, 95% CI -5.49 to -0.96, I2=89%, very low certainty).Our findings do not support the use of mucoactive agents in critically ill patients with ARF. The existing evidence is of low quality. High-quality randomised controlled trials are needed to determine the role of specific mucoactive agents in critically ill patients with ARF.CRD42018095408.
Prevalence and prognostic impact of the coexistence of multiple frailty domains in elderly patients with heart failure: the <scp>FRAGILE‐HF</scp> cohort study
Authors: Yuya Matsue, Kentaro Kamiya, Hiroshi Saito, Kazuya Saito, Yuki Ogasahara, Emi Maekawa, Masaaki Konishi, Takeshi Kitai, Kentaro Iwata, Kentaro Jujo, Hiroshi Wada, Takatoshi Kasai, Hirofumi Nagamatsu, Tetsuya Ozawa, Katsuya Izawa, Shuhei Yamamoto, Naoki Aizawa, Ryusuke Yonezawa, Kazuhiro Oka, Shin‐ichi Momomura, Nobuyuki Kagiyama
Journal: European Journal of Heart Failure (2020)
THU0103 COMPARISON OF BONE SCINTIGRAPHY AND FDG- PET/CT IN THE EVALUATION OF DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS: VALIDATION OF BONE SCINTIGRAPHY
Authors: S. J. Lee, C. M. Hong, E. J. Nam, Y. M. Kang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Clinical joint count assessment is important for detecting synovitis but its reliability is controversial Objectives: This study assessed the correlation between bone scintigraphy and positron emission tomography (PET)-derived parameters in 28 joints with disease activity and compared the reliability of joint counts between bone scintigraphy and clinical assessment in rheumatoid arthritis (RA). Methods: We enrolled 86 patients with active RA who underwent bone scintigraphy, fluorine-18-fluorodeoxyglucose (FDG) PET/CT and disease activity evaluation at the same time. This two-step study involved a development (n=67) and validation (n=19) group. Bone scintigraphy-derived joint assessment were compared with PET/CT derived and clinical joint assessment. Subsequently, we developed a disease activity score (DAS) using bone scintigraphy-positive joints and validated it in an independent group. Results: The number of bone scintigraphy-positive joints in 28 joints was significantly correlated with the swollen (SJC)/ tender (TJC) joint counts and PET/CT derived joint counts. Intra- and inter-observer reliabilities of bone scintigraphy for the affected joint counts were excellent. Inter-observer reliability between nuclear medicine physicians and rheumatologists was good for SJC/TJC and PET/CT derived joint counts in 28 joints except shoulders. After multivariate analyses including erythrocyte sediment rate (ESR) and patients global assessment (PGA) in addition to bone scintigraphy-derived parameters, bone scintigraphy/DAS was derived as 0.056 × number of bone scintigraphy-positive joints in 28 joints + 0.012 × ESR + 0.030 × PGA. A significant correlation between bone scintigraphy/DAS and DAS28-ESR was confirmed in the validation group (p&lt;0.001). Conclusion: Bone scintigraphy-derived joint assessment significantly correlated with PET/CT derived joint counts. Bone scintigraphy could serve as a sensitive and reliable method for evaluating disease activity in RA patients. References: Lee SJ, Jeong JH, Lee CH et al. Development and Validation of an 18 F-Fluorodeoxyglucose-Positron Emission Tomography With Computed Tomography-Based Tool for the Evaluation of Joint Counts and Disease Activity in Patients With Rheumatoid Arthritis. Arthritis Rheumatol. 2019 Aug;71(8):1232-1240. doi: 10.1002/art.40860. Epub 2019 Jun 17. Disclosure of Interests: None declared
AB1076 COLOR DOPPLER HIGH- FREQUENCY ULTRASOUND OF DIGITAL ARTERIES IN PATIENTS WITH SYSTEMIC SCLEROSIS
Authors: O. Alekseeva, N. Yudkina, A. Demina, A. Volkov, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic sclerosis (SSc) can lead to vascular complications such as digital ulcers or pitting scars (DU/PS). These changes develop in most patients with SSc and exacerbate their condition. However, there are no methods for dynamic assessment of the vascular involvement. The dynamics of capillaroscopic changes is very slow. Objectives: The aim of the study was to compare blood flow parameters of digital arteries in SSc patients and healthy individuals and to compare with nailfold capillaroscopy and clinical signs of ischemia (DU/PS). Methods: 32 SSc patients, mean age 49,5 [42,0; 59,0] yrs and 26 ‘healthy’, mean age 43,5 [33,0; 57,0], were included. Groups of patients differed by gender and age. The exclusion criterion was the presence of obliterating vascular disease of the upper extremities. An Esaote MyLab Twice US system with 22 MHz linear probe was used. A total of SSc patients and controls underwent Color Doppler ultrasonography (CDUS) of 376 (256 + 208) digital arteries to compare blood flow velocity, resistive indices (RIs) and presence of occlusion. Nailfold capillaroscopy, clinical and laboratory data were also evaluated. Results: In digital arteries, pulsatility index (PI), peak systolic velocity (PSV) and end-diastolic velocity (EDV) were significantly lower and RI higher in SSc patients compared with controls (PSV: 13,28 [9,88; 16,7] vs17,45 [12,65; 22,5] cm/s, p=0,008; EDV: 2,68 [1,78, 4,05] vs 6,37 [4,75; 8,5] cm/s, p=0,000; RI: 0,78 [0,69; 0,81] vs 0,68 [0,59; 0,74], p=0,005; PI: 1,73 [1,32; 2,19] vs 1,22 [0,99; 1,55], p=0,002). We did not find any correlation between two methods. Also, we did not reveal any correlation between DU/PS, clinical, laboratory data and CDUS, but we found relationship between DU/PS and avascular areas or capillaroscopic findings (r= 0,37, p=0,045 and r= 0,40, p=0,03 correspondingly). Conclusion: Blood flow is significantly decreased in digital arteries in SSc, but clinical features of vasculopathy depend on microcirculatory disorders. It is important to continue research to find methods for dynamic evaluation of microcirculatory changes. References: no Disclosure of Interests: None declared
New Medications Are Needed for Children With Juvenile Idiopathic Arthritis
Authors: Hermine I. Brunner, Laura E. Schanberg, Yukiko Kimura, Anne Dennos, Dominic O. Co, Robert A. Colbert, Robert C. Fuhlbrigge, Ellen Goldmuntz, Daniel J. Kingsbury, Cathy Patty‐Resk, Sandra Mintz, Karen Onel, Lisa G. Rider, Rayfel Schneider, Allen Watts, Emily von Scheven, Daniel J. Lovell, Timothy Beukelman
Journal: Arthritis & Rheumatology (2020)

To document the need for additional Food and Drug Administration (FDA)-approved medications for the treatment of juvenile idiopathic arthritis (JIA).The electronic medical records of JIA patients treated at Cincinnati Children's Hospital Medical Center (CCHMC) and data from JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry were included in this study. Unmet medication need was defined in 2 ways: (a) the presence of chronically uncontrolled JIA, defined as a physician global assessment of JIA activity ≥3 (on a 0-10 scale, where 0 = inactive) OR ≥3 joints with active arthritis OR a patient global assessment of well-being ≥3 (on a 0-10 scale, where 0 = very well), despite sequential use of ≥2 biologic disease-modifying antirheumatic drugs (bDMARDs); and (b) the use of ≥1 bDMARD not approved for any JIA category.At CCHMC, 829 of 1,599 JIA patients (52%) were treated with ≥1 bDMARD, and 304 (19%) had been exposed to ≥1 unapproved bDMARD. In the CARRA Registry, 4,766 of 7,379 children (65%) had received ≥1 bDMARD, and 1,122 (15%) had been prescribed ≥1 unapproved bDMARD. Of those children treated with ≥2 bDMARDs for whom complete data were available, 52% (255 of 487) at CCHMC and 45% (527 of 1,159) in the CARRA Registry had chronically uncontrolled JIA despite the use of ≥2 bDMARDs.Despite the availability of bDMARDs currently approved for JIA, there is persistent need for additional therapies to control JIA signs and symptoms. Since FDA approval is critical to ensure access to bDMARDs, the study and licensing of new medications is critical to address the unmet medication need and to further improve JIA outcomes.
Abstract IA05: Signaling networks in small-cell lung cancer
Authors: Julien Sage
Journal: Cancer Research (2020)

Abstract SCLC is a lethal neuroendocrine (NE) cancer that accounts for ~15% of all lung cancers and causes ~250,000 deaths worldwide each year. SCLC is linked to heavy cigarette smoking and exposure to carcinogens. Unfortunately, the number of SCLC-related deaths continues to rise. A major clinical challenge is that ~70% of SCLC patients have disseminated disease at the time of diagnosis; these patients have a 5-year survival of &amp;lt;1%. Even patients with localized disease at diagnosis have dismal survival rates. A second major challenge is that treatments for SCLC are inefficient and have remained mostly unchanged for the past 30 years, with no new approved treatments since 1996 and no approved targeted therapies. SCLC is managed with first-line chemoradiation. Patients usually respond well initially, but almost all relapse within months. There is a need to better understand the mechanisms underlying the aggressive growth and spread of SCLC and its rapid chemoresistance. At a gross level, SCLC tumors are quite “homogeneous” histologically (with fields of similar-looking small, blue, round cancer cells) and genetically (with near-ubiquitous loss of the Rb and p53 tumor suppressors). However, accumulating evidence has recently highlighted several levels of heterogeneity, and it has become clear that a better characterization and understanding of both genetic and epigenetic heterogeneity during SCLC progression will be critical to identify new therapeutic options. We have used mouse genetics combined with genomic and proteomic approaches to identify key signaling pathways that are implicated in the expansion of SCLC cell populations. In particular, we have recently identified kinases and phosphatases that control the expansion of long-term propagating cells (aka cancer stem cells) in SCLC. Citation Format: Julien Sage. Signaling networks in small-cell lung cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA05.
Outbreak of tularemia among commercially distributed prairie dogs, 2002.
Authors: C. Lindley, S. Avashia, K. Hendricks, J. Rawlings, J. Buck, J. Kool, K. Gage, M. Schriefer, D. Dennis, M. Chu, J. Peterson, J. Montenieri, D. Kim, T. Demarcus, M. Cetron
Journal: MMWR Morbidity and Mortality Weekly Report (2002)