tbuckley/cabot-search huggingface dataset:
AB0565 HOSPITALIZATION IN A COHORT OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY: WHAT IS HAPPENING IN ARGENTINA?
Authors: F. Arizpe, M. Cosentino, A. C. Costi, V. Martire, A. Testi, M. García
Journal: Annals of the Rheumatic Diseases (2020)

Background: Inflammatory myopathies are rare diseases that affect multiple organs and systems, with poor prognosis and high in-hospital mortality. (1,2) In Argentina there are few reported data regarding hospitalization and its outcomes in these patients. Objectives: To analyze the characteristics of hospitalizations and the factors associated with poor outcome in adult patients with Idiopathic Inflammatory Myopathy (IIM). Methods: Retrospective, analytical study. We included patients ≥ 18 years with IIM, according to Bohan and Peter and/or ACR / EULAR 2017 criteria, who were admitted in our hospital between 2003 and 2019 at least once. Sociodemographic and clinical data were recorded. We defined “unfavorable outcome” as the presence of one of the following events: death, mechanical respiratory assistance and/or critical care unit requirement. Continuous variables were compared by Student’s or Mann Whitney’s T test, and categorical variables by Chi 2 test or Fisher’s exact test. Binary logistic regression was performed to identify independent factors associated with an unfavorable outcome. Results: 61 hospitalizations of 40 patients with IIM were evaluated; 67.5% of the patients were female (27/40), with a mean age of 52.5 years (SD± 13). The most frequent reason of admission was for diagnosis (44.3%) followed by disease activity (31.1%). In 78.7% of hospitalizations (48/61) the diagnosis was dermatomyositis. The median of hospitalization days was 14 (IQR 8-30). In 21 out of 61 hospitalizations (34.4%), an unfavorable outcome was observed, of which 17 (80.9%) ended in death. Respiratory muscle involvement (p = 0.01), thrombocytopenia (p &lt; 0.001), treatment with intravenous methylprednisolone pulses (p = 0.032), Intravenous Immunoglobulin (p = 0.001), longer hospitalization (p = 0.001) and severe infections (p = 0.001) were associated with adverse outcomes. In the multivariate analysis, serious infections (OR: 21.7; IC95 1.77 - 266; p = 0.016) and the requirement of Intravenous Immunoglobulin (IVIg) (OR: 54.5; IC95 1.4 - 214; p = 0.033) were found to be independently associated with an unfavorable outcome. Conclusion: IIMs are diseases with high morbidity and mortality rate. In this cohort of hospitalized patients, we found a high percentage of unfavorable outcomes. Seriously ill patients received IVIg more frequently, and severe infections were associated with worse prognosis. References: [1]Selva-O’Callaghan, A., Pinal-Fernandez, I., Trallero-Araguás, E., Milisenda, J. C., Grau-Junyent, J. M., &amp; Mammen, A. L. (2018). Classification and management of adult inflammatory myopathies. The Lancet Neurology, 17(9), 816–828. [2]Wu C, Wang Q, He L, Yang E, Zeng X (2018) Hospitalization mortality and associated risk factors in patients with polymyositis and dermatomyositis: A retrospective case-control study. PLoS ONE 13(2): e0192491. Disclosure of Interests: None declared
CD103+ tumor-resident CD8+ T cell numbers underlie improved patient survival in oropharyngeal squamous cell carcinoma
Authors: Rehana Hewavisenti, Angela Ferguson, Kevin Wang, Deanna Jones, Thomas Gebhardt, Jarem Edwards, Mei Zhang, Warwick Britton, Jean Yang, Angela Hong, Umaimainthan Palendira
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Human Papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is one of the fastest growing cancers in the Western world. When compared to OPSCCs induced by smoking or alcohol, patients with HPV+ OPSCC, have better survival and the mechanisms remain unclear. Methods The Cancer Genome Atlas (TCGA) database was examined for genes associated with tissue-resident CD8+ T cells. Multiplex immunohistochemistry (IHC) staining was performed on tumor specimen taken from 35 HPV+ and 27 HPV- OPSCC patients. Results TCGA database revealed that the expression of genes encoding CD103 and CD69 were significantly higher in HPV+ head and neck SCCs (HNSCC) than in HPV- HNSCC. Higher expression levels of these two genes were also associated with better overall survival. IHC staining showed that the proportion of CD103+ tumor-resident CD8+ T cells were significantly higher in HPV+ OPSCCs when compared to HPV- OPSCC. This higher level was also associated with both lower risk of loco-regional failure, and better overall survival. Importantly, patients with HPV- OPSCC who had comparable levels of CD103+ tumor-resident CD8+ T cells to those with HPV+ OPSCC demonstrated similar survival as those with HPV+OPSCC. Conclusion Our results show that CD103+ tumor-resident CD8+ T cells are critical for protective immunity in both types of OPSCCs. Our data further suggest that the enhanced local protective immunity provided by tumor-resident T cell responses is the underlying factor driving favorable clinical outcomes in HPV+ OPSCCs over HPV- OPSCCs.
Comparative efficacy and safety of intralesional bleomycin relative to topical bleomycin with microneedling in the treatment of warts: A systematic review
Authors: Subuhi Kaul, Elena Gonzalez Caldito, Deepak Jakhar, Ishmeet Kaur, Shawn G. Kwatra, Shilpa Mehta
Journal: Journal of the American Academy of Dermatology (2020)
AB0865 EPIDURITIS IN INFECTIOUS SPONDYLODISCITIS
Authors: J. Mahbouba, O. Jomaa, S. Zrour, I. Bejia, M. Touzi, N. Bergaoui
Journal: Annals of the Rheumatic Diseases (2020)

Background: The main problem with infectious spondylodiscitis (ISD) is the diagnosis difficulty. Tuberculosis, with deceptive clinical semiology, remains to date the most common cause in underdeveloped and developing countries. Objectives: To report the frequency and characteristics of epiduritis in ISD and to specify its short and medium-term impact through a series of 70 cases. Methods: A descriptive retrospective study was conducted including patients with ISD, hospitalized in the rheumatology department at Fattouma bourguiba Hospital,Monastir TUNISIA between January 2009 and August 2019. Socio-demographic, clinico_biological and radiological data were collected. Results: 34 male and 36 female were included. The average age was 53.91 ±15.3 years. The mean time to visit was 80.3±89 days [4,520]. Co-morbidity was noted in 66.7% of patients: diabetes (22), hypertension (18), hemodialysis (8), heart disease (4), and long term corticosteroid therapy (4). Tuberculosis contagion was present in 7.2% of patients. The most frequent reason for consultation was low back pain (63.8%) with a root syndrome in most patients (&gt;50%). Neurological abnormalities were noted in 8.7% of patients. Skin swelling was noted in 4.3% of patients. Biological inflammatory syndrome and hyperleukocytosis were the moost biological abnormalities reported respectively in 81.2% and 30.4% of patients,. Among 70 ISD: 29 were with common germ, 18 with tuberculosis, 8 with brucellosis, and 14 with an undetermined germ. 91.3% of patients underwent a spinal magnetic resonance imaging (MRI): epiduritis was documented in 72% of cases, frequently anterior (53%). The epidural abscesses association was noted in 33 patients. It was pronounced mostly at the lumbar (19) and dorsal (14) levels. Epiduritis was frequently associated with para-vertebral soft tissues infiltration: pre-vertebral thickening (32), pre-vertebral collection (17), psoas muscle abscesses, (13). Spinal cord compression was noted in 2 patients. On 3-month visit, the ISD associated with epiduritis evolution was characterized by persistence of pain, hence radiological control was justified in 6 patients. A persistent biological inflammatory syndrome was noted in 27% of cases. Furthermore, 2 deaths were observed in this group of patients. Conclusion: Epiduritis rate in ISD requires a well-codified diagnostic and therapeutic strategy that will consider carfelly the neurological prognosis involved. References: doi: 10.1155/2019/7413089. doi: 10.1515/folmed-2016-0035. Acknowledgments: Rheumatology Department Disclosure of Interests: None declared
THU0137 ASSESSING THE MULTIMORBID PROFILE (CIRS) IN RHEUMATOID ARTHRITIS. FIRST RESULTS.
Authors: A. Gordeev, E. Galushko, N. Savushkina, A. Misiyuk
Journal: Annals of the Rheumatic Diseases (2020)

Background: Objectives: To assess the presence and nature of multimorbidity in patients with rheumatoid arthritis (RA) and the impact of multimorbidity on disease activity. Methods: The investigation enrolled 117 patients (mean age, 54.8±14.8 years) with RA according to the 2010 ACR/EULAR criteria, who had been examined and treated at the V.A. Nasonova Research Institute of Rheumatology in 2018–2019. The median disease duration was 5.0 [1.5; 9.5] years; the mean DAS28 score was 5.0±1.3. Documentation and anamnesis data were analyzed with emphasis on associated diseases. The Cumulative Illness Rating Scale (CIRS) was used to assess the profile of multimorbidity. Results: The patients with RA had a high index of the spectrum of multimorbidity; concomitant diseases were detected in 96 (82%) cases. The median number of diseases in one patient was 2 [1; 4], the mean total CIRS score was 6.7±3.3; the median value was 2.5 [1; 6]. The number of concomitant diseases diagnosed before using the CIRS was significantly lower (by 48%; p&lt;0.01) than was found in the investigation conducted. Chronic kidney disease that occurred in almost half (42.5%) of cases was most commonly undiagnosed in the cohort under study; on average, every three patients were not found to have signs of metabolic syndrome (hyperglycemia in 29%, hypercholesterolemia in 20%, obesity in 13.5%), chronic hypoxia (new-onset anemia verified in 24% of cases). In 12% of cases lung damages were not found before using the CIRS. There was a correlation of the quantitative equivalent of multimorbidity with the clinical and laboratory measures of RA activity, including the number of painful joints (r = 0.39; p&lt;0.001), overall patient assessment (r=0.37; p=0.03), physician’s global assessment of disease activity (r = 0.37; p &lt; 0.01), DAS28 (r = 0.42; p&lt;0.001), CDAI (r=0.37; p&lt;0.001), SDAI (r=0.34; p&lt; 0.001), HAQ (r=0.34; p&lt;0.001). The total CIRS score did not differ in patients with early- and advanced- or end-stage RA: 6.6±3.5 and 6.7±3.3, respectively (p=0.9). Conclusion: A systematic screening of multimorbidity should be carried out in all patients with RA. It is advisable to use the CIRS to estimate the prevalence of multimorbidity, its consequences and the risk factors for the development of multimorbidity in the long term. Disclosure of Interests: None declared
Histone Deacetylase 9 Activates IKK to Regulate Atherosclerotic Plaque Vulnerability
Authors: Yaw Asare, Thomas A. Campbell-James, Yury Bokov, Lydia Luya Yu, Matthias Prestel, Omar El Bounkari, Stefan Roth, Remco T.A. Megens, Tobias Straub, Kyra Thomas, Guangyao Yan, Melanie Schneider, Natalie Ziesch, Steffen Tiedt, Carlos Silvestre-Roig, Quinte Braster, Yishu Huang, Manuela Schneider, Rainer Malik, Christof Haffner, Arthur Liesz, Oliver Soehnlein, Jürgen Bernhagen, Martin Dichgans
Journal: Circulation Research (2020)

Arterial inflammation manifested as atherosclerosis is the leading cause of mortality worldwide. Genome-wide association studies have identified a prominent role of HDAC (histone deacetylase)-9 in atherosclerosis and its clinical complications including stroke and myocardial infarction. To determine the mechanisms linking HDAC9 to these vascular pathologies and explore its therapeutic potential for atheroprotection. We studied the effects of Hdac9 on features of plaque vulnerability using bone marrow reconstitution experiments and pharmacological targeting with a small molecule inhibitor in hyperlipidemic mice. We further used 2-photon and intravital microscopy to study endothelial activation and leukocyte-endothelial interactions. We show that hematopoietic Hdac9 deficiency reduces lesional macrophage content while increasing fibrous cap thickness thus conferring plaque stability. We demonstrate that HDAC9 binds to IKK (inhibitory kappa B kinase)-α and β, resulting in their deacetylation and subsequent activation, which drives inflammatory responses in both macrophages and endothelial cells. Pharmacological inhibition of HDAC9 with the class IIa HDAC inhibitor TMP195 attenuates lesion formation by reducing endothelial activation and leukocyte recruitment along with limiting proinflammatory responses in macrophages. Transcriptional profiling using RNA sequencing revealed that TMP195 downregulates key inflammatory pathways consistent with inhibitory effects on IKKβ. TMP195 mitigates the progression of established lesions and inhibits the infiltration of inflammatory cells. Moreover, TMP195 diminishes features of plaque vulnerability and thereby enhances plaque stability in advanced lesions. Ex vivo treatment of monocytes from patients with established atherosclerosis reduced the production of inflammatory cytokines including IL (interleukin)-1β and IL-6. Our findings identify HDAC9 as a regulator of atherosclerotic plaque stability and IKK activation thus providing a mechanistic explanation for the prominence of HDAC9 as a vascular risk locus in genome-wide association studies. Its therapeutic inhibition may provide a potent lever to alleviate vascular inflammation. Graphical Abstract: A graphical abstract is available for this article.
Abstract 387: Weighted Gene Co-Expression Network Analysis Identification and Experimental Validation of Genetic Determinants of Right Ventricular Function
Authors: Christoph Rau, Katie Lee, Jeffrey Chukwuneke, Yanan Liu, Qing Li, Yibin Wang, Emily J Tsai
Journal: Circulation Research (2017)

Right ventricular dysfunction (RVD) portends worse outcomes in chronic heart failure (HF), irrespective of left ventricular function. Despite the significance and prevalence of RVD, its molecular pathobiology is poorly understood. Gene networks can identify and explore complex relationships between genes, gene pathways, and phenotypes. We used weighted gene co-expression network analysis (WGNA) of human heart samples to identify genetic determinants of RV function and validated candidate genes in animal models of RV versus LV dysfunction. We isolated and sequenced total RNA from explanted left and right ventricles of ischemic cardiomyopathy (ICM) patients (n=10) who underwent cardiac transplantation. Non-failing donor hearts that were declined for transplant were used as controls (n=5). Half the ICM patients had severe RV failure (RVF) based upon hemodynamic indices (mean±SEM) with mean RA 25.8±1.7 mmHg, RA:PCWP ratio 1.05±0.11, and PA pulsatility index 1.6±0.2. Using direct gene membership comparison and z-score analysis, we found that more than half the modules in RV-specific networks are shared by combined RV-LV gene networks. We used principle component analysis to examine modules that correlated with RVF-related phenotypes. Two modules unique to the RV network identified selenium-binding protein gene Selenbp1 as a potential driver of RVF. We also identified a strong association between anti-apoptotic gene Mif and vesicle fusion gene Snap47 with RA:PCWP and PA pulsatility indices, suggesting potential important roles of these genes in RVF. Finally, peroxiredoxin 5 PRDX5 and E3 ubiquitin-protein ligase SHPRH were associated with protection against RVF. We sought to validate these candidate gene drivers of RV function in mouse models of RV versus LV-specific dysfunction induced by pulmonary artery banding (PAB) and transverse aortic constriction (TAC), respectively. PRDX5 expression was markedly reduced in RV of PAB versus Sham but unchanged in LV of TAC versus Sham. Selenbp1 was diminished in both RV of PAB and LV of TAC mice, relative to Sham. Expression of other candidate genes did not vary significantly with PAB or TAC. Our preliminary findings suggest that cardiac PRDX5 may play an important role in regulating RV function.
Response to: ‘Telerheumatology in COVID-19 era: a study from a psoriatic arthritis cohort’ by Costa <i>et al</i>
Authors: Latika Gupta, Durga Prasanna Misra, Vishwesh Agarwal, Suma Balan, Vikas Agarwal
Journal: Annals of the Rheumatic Diseases (2020)

Costa has raised a relevant question of switching to online platforms for maintaining continuity of medical care in patients with chronic rheumatic diseases (RDs).1 A near-total focus of healthcare systems on COVID-19, non-availability of medical consultations and medicines at some places, and delayed infusions have seriously undermined the care of chronic RDs. The unprecedented situation has heralded a felt need for a shift to virtual consulting, ranging from telephonic to instant messaging, email-based and video consultations.

In our survey, 114 of 221 (51.6%) rheumatologists in India had adopted virtual consultations in March 2020, with half of them (57) delivering patient care over WhatsApp, and 22.8% (26) and 27.1% (31) resorting to emails and video consultations.2 Merely 10% of physicians were continuing their clinics at the time of the survey. The choice of the platform might differ, with WhatsApp being more prevalent in certain countries like India and WeChat in China.3 The delivery of …
Abstract 16: Landscape and outcome of TRK fusion-positive Cancers
Authors: Ezra Y. Rosen, Debra A. Goldman, Jaclyn F. Hechtman, Ryma Benayed, Alison M. Schram, Emiliano Cocco, Sophie Shifman, Yixiao Gong, Ritika Kundra, James P. Solomon, Alberto Bardelli, Maurizio Scaltriti, Alexander Drilon, Alexia Iasonos, Barry S. Taylor, David M. Hyman
Journal: Clinical Cancer Research (2020)

Abstract TRK inhibitors achieve marked tumor-agnostic efficacy in TRK fusion-positive cancers and consequently are now an established standard of care. Little is known, however, about the demographics, clinical outcomes, response to alternative standard therapies, or genomic characteristics of TRK fusion-positive cancers. Utilizing a center-wide screening program involving more than 26,000 prospectively sequenced patients, genomic and clinical data from all cases with identified TRK fusions were extracted. An integrated analysis was performed of genomic, therapeutic, and phenomic outcomes. In total, we identified 76 cases with confirmed TRK fusions (0.27% overall prevalence) involving 48 unique rearrangements and 17 distinct cancer types. The presence of a TRK fusion was associated with depletion of concurrent oncogenic drivers (p=4.4E-7) and lower tumor mutation burden (p=4.2E-9), with the exception of colorectal cancer where TRK fusions co-occur with microsatellite instability (MSI-H). Longitudinal profiling in a subset of patients indicated that TRK fusions were present in all sampled timepoints in 82% (14/17) of cases. Progression-free survival on first-line therapy, excluding TRK inhibitors, administered for advanced disease was 9.6 months (95% CI: 4.8-13.2). The best ORR achieved with chemotherapy containing-regimens across all lines of therapy was 63% (95% CI: 41-81). Among 12 patients treated with checkpoint inhibitors, the only response observed was in an MSI-H colorectal patient. TRK fusion-positive cancers can respond to alternative standards of care, although efficacy of immunotherapy in the absence of other predictive biomarkers (MSI-H) appears limited. TRK fusions are present in tumors with simple genomes lacking in concurrent drivers that may partially explain the tumor-agnostic efficacy of TRK inhibitors. Citation Format: Ezra Y. Rosen, Debra A. Goldman, Jaclyn F. Hechtman, Ryma Benayed, Alison M. Schram, Emiliano Cocco, Sophie Shifman, Yixiao Gong, Ritika Kundra, James P. Solomon, Alberto Bardelli, Maurizio Scaltriti, Alexander Drilon, Alexia Iasonos, Barry S. Taylor, David M. Hyman. Landscape and outcome of TRK fusion-positive Cancers [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 16.
mTOR/p70S6K signaling pathway constitutively activated in esophageal squamous cell carcinona cell lines and inhibition of the pathway by rapamycin and siRNA against mTOR
Authors: Guiqin Hou, Peirong Xu, Yanli Xue, Lexun Xue
Journal: Cancer Research (2007)

5351  The mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (p70S6K) signaling pathway is considered a central regulator of protein synthesis, and of cell proliferation, differentiation and survival. Some inhibitors of mTOR as anticancer reagents have been evaluated in various malignant tumors. However, the role of the mTOR/p70S6K signaling pathway in esophageal squamous cell carcinoma (ESCC), which is a common cause of mortality in China, and the sensitivity of ESCC to rapamycin, a mTOR inhibitor, remain unknown. In the present study, mTOR/p70S6K signaling pathway, and mRNA and protein expressions of mTOR/p70S6K signaling pathway in the ESCC cells treated with rapamycin and siRNA against mTOR were respectively investigated using immunocytochemistry, Western blots and reverse transcription polymerase chain reaction (RT-PCR). The result showed that mTOR /p70S6K signaling pathway was activated in the two ESCC cell lines, EC9706 and Eca109, and mRNA and protein levels of mTOR in EC9706 was higher than in Eca109 cells(P
Bioenergetic Crosstalk between Mesenchymal Stem Cells and various Ocular Cells through the intercellular trafficking of Mitochondria
Authors: Dan Jiang, Fang-Xuan Chen, Heng Zhou, Yang-Yan Lu, Hua Tan, Si-Jian Yu, Jing Yuan, Hui Liu, Wenxiang Meng, Zi-Bing Jin
Journal: Theranostics (2020)

Rationale: Mitochondrial disorders preferentially affect tissues with high energy requirements, such as the retina and corneal endothelium, in human eyes. Mesenchymal stem cell (MSC)-based treatment has been demonstrated to be beneficial for ocular degeneration. However, aside from neuroprotective paracrine actions, the mechanisms underlying the beneficial effect of MSCs on retinal and corneal tissues are largely unknown. In this study, we investigated the fate and associated characteristics of mitochondria subjected to intercellular transfer from MSCs to ocular cells. Methods: MSCs were cocultured with corneal endothelial cells (CECs), 661W cells (a photoreceptor cell line) and ARPE-19 cells (a retinal pigment epithelium cell line). Immunofluorescence, fluorescence activated cell sorting and confocal microscopy imaging were employed to investigate the traits of intercellular mitochondrial transfer and the fate of transferred mitochondria. The oxygen consumption rate of recipient cells was measured to investigate the effect of intercellular mitochondrial transfer. Transcriptome analysis was performed to investigate the expression of metabolic genes in recipient cells with donated mitochondria. Results: Mitochondrial transport is a ubiquitous intercellular mechanism between MSCs and various ocular cells, including the corneal endothelium, retinal pigmented epithelium, and photoreceptors. Additionally, our results indicate that the donation process depends on F-actin-based tunneling nanotubes. Rotenone-pretreated cells that received mitochondria from MSCs displayed increased aerobic capacity and upregulation of mitochondrial genes. Furthermore, living imaging determined the ultimate fate of transferred mitochondria through either degradation by lysosomes or exocytosis as extracellular vesicles. Conclusions: For the first time, we determined the characteristics and fate of mitochondria undergoing intercellular transfer from MSCs to various ocular cells through F-actin-based tunneling nanotubes, helping to characterize MSC-based treatment for ocular tissue regeneration.