tbuckley/cabot-search huggingface dataset:
PB2043 UPPER AND LOWER GASTROINTESTINAL ENDOSCOPY FINDINGS IN PATIENTS WITH ISOLATED FERRITIN DEFICIENCY
Authors: A. Bahadir, E. Sağ, M. Çakır
Journal: HemaSphere (2019)

Background: Iron deficiency without anemia is the most common nutritional disorder in children. Iron balancing is provided by intestinal absorption and iron transfer mechanisms. The most common causes of anemia are chronic blood loss from the gastrointestinal tract (peptic ulcer, hemorrhoids, parasites), inadequate dietary intake, gynecological problems (menorrhagia), decreased gastrointestinal mucosal absorption (celiac disease), Helicobacter pylori (Hp) infection and autoimmune gastritis. In the literature, there are not many studies about iron deficiency without decreasing hemoglobin (Hg) levels in the early period of iron deficiency. Aims: In our study, we aimed to evaluate the lower and upper endoscopic findings of patients with normal Hg levels and low ferritin levels. Methods: A total of 2391 patients aged between 0‐18 years and had normal Hg levels were included into the study performing upper and lower gastrointestinal system (GIS) endoscopy by the pediatric gastroenterology‐hepatology department between 2009 and 2018. The patients were divided into two groups as Hb level was normal, ferritin level below 15 mg / dl (group 1; n = 549) and Hb level was normal, ferritin level was above 15 mg / dl (group 2; n = 1143). In group 1, upper GIS endoscopy was performed to 520 patients, lower GIS endoscopy to 56 patients. In Group 2, upper GI endoscopy was performed to 1095 patients and lower GI endoscopy to 120 patients. All endoscopy results of the patients were evaluated and compared. Results: The most common complaint was abdominal pain in both groups (63%, 67.4%, respectively). And the most common endoscopic findings in both groups were reflux esophagitis in the esophagus (9.6%, 9.1%, respectively, p&gt;0.05), gastritis in the stomach (32.1%, 37.9%, respectively, p &gt; 0.05). Hp gastritis was the second most common endoscopic finding in group 1. When the both groups were compared, there was a significant difference between group for Hp gastritis (24%, 27.6%, respectively, p = 0.002). In duodenum findings, celiac disease was higher in group 1 and there was a significant statistically between group for celiac disease (6%, 2.1%, respectively, p = 0.000). In colonoscopic examination, lymphoid nodular hyperplasia and polyp were higher in group 1 and there were statistically significant between groups (14.3%, 5%, and 10.7%, 3.3% respectively, p = 0.03, 0.04). Summary/Conclusion: In the literature, generally the studies are about anemia and upper GIS findings. In our study, the patients with decreased ferritin and normal Hg levels and undergoing upper and lower GIS endoscopy were investigated. The risk of Hp gastritis and celiac disease was found to be increased in patients with ferritin deficiency without anemia (group 1). In addition, lymphoid noduler hyperplasia and polyps were also caused ferritin deficiency.
Activation of YAP attenuates hepatic damage and fibrosis in liver ischemia-reperfusion injury
Authors: Yuan Liu, Tianfei Lu, Cheng Zhang, Jin Xu, Zhengze Xue, Ronald W. Busuttil, Ning Xu, Qiang Xia, Jerzy W. Kupiec-Weglinski, Haofeng Ji
Journal: Journal of Hepatology (2019)
Abstract 160: Cardiomyocyte CaMKII Mediates Expression of Pro-inflammatory Chemokines and Cytokines, Macrophage Infiltration and Cardiac Remodeling in Response to Pressure Overload
Authors: Takeshi Suetomi, Andrew Willeford, Shigeki Miyamoto, Joan Heller Brown
Journal: Circulation Research (2017)

Background: There is evidence that inflammation is associated with pressure overload induced cardiac remodeling and heart failure, as well as evidence for a role of CaMKII in remodeling and heart failure development. Whether CaMKII mediates inflammatory responses that contribute to its role in adverse remodeling following TAC has not been established. Methods and Results: CaMKIIδ knockout (CKO) mice in which CaMKIIδ was selectively deleted from cardiomyocytes were subjected to pressure overload by transverse aortic constriction (TAC). By 3 days, the earliest time examined, there were marked increases in cardiac mRNA levels for pro-inflammatory chemokines CCL2 (MCP-1, ~15 fold), CCL3 (MIP1α, ~20 fold) and cytokines (IL-6, ~50 fold). These responses were markedly attenuated (by 56%, 43% and 42 % respectively) in the CKO mice. NFkB signaling was also increased in control heart at 3 days of TAC but not in CKO. Immunohistochemical analysis showed increases in CD68+ macrophage by 7 days TAC which further increased by 14days of TAC. Macrophages accumulation was also significantly attenuated in the CKO mice (50% decrease at 7day, 40% decrease at 14 days). Fibrosis was assessed by Masson trichrome staining and increases in collagen gene expression (col1a1 and col3a1 mRNA). Both were clearly elevated after 14 and 28 days TAC and significantly attenuated in the CKO mice. Conclusion: Our results indicate that activation of CaMKII localized in cardiomyocytes initiates an inflammatory transcriptional program within cardiomyocyte. We suggest that this drives immune cell recruitment and is in turn associated with development of fibrosis. Early inflammatory responses and their sequelae may thus be responsible for involvement of CaMKII in the progression from hypertrophy to heart failure.
AB0226 NEUTROPHIL EXTRACELLULAR TRAPS ACTIVATE LUNG FIBROBLAST TO INDUCE MYOSITIS-RELATED INTERSTITIAL LUNG DISEASES IN MICE
Authors: Sigong Zhang, Haili Shen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Excessive neutrophil extracellular traps (NETs) formation may contribute to myositis-associated interstitial lung diseases (ILD), but the underlying mechanism is not fully revealed. <h3>Objectives</h3> This research aimed to elucidate the mechanism by which NETs contribute to myositis-associated ILD. <h3>Methods</h3> Myositis mice model was established by injected with the rat skeletal muscle homogenate and pertussis toxin. Expressions of ACTA2, CCN2, ADAM12, miR-7 and Smad2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Smad2, α-SMA, CCN2 and TLR9 signaling-related proteins were measured by western blot. Soluble collagen I-IV were detected by Sircol collagen assay kit. The proliferation and apoptosis of lung fibroblasts (LFs) were detected by MTT assay or flow cytometry analysis. The interaction between miR-7 and the Smad2 was confirmed by dual-luciferase reporter gene assay. <h3>Results</h3> NET accelerated the progression of ILD and promoted pulmonary fibrosis <i>in vivo</i>. miR-7 expression was downregulated in lung tissue of myositis group than control group, and NETs further decreased miR-7 expression. TLR9 and Smad2 were upregulated in lung tissue of myositis group than control group, and NETs further increased TLR9 and Smad2 expressions. <i>In vitro</i> experiments showed that PMA-treated NETs accelerated the proliferation of LF and their differentiation into myofibroblast (MF), whereas DNAse I decreased the promotion effect of NETs. NETs components myeloperoxidase (MPO) and histone 3 also promoted the proliferation and differentiation of LF. In addition, we demonstrated that TLR9 involved in the regulation of NETs on LF proliferation and differentiation, and confirmed the interaction between miR-7 and Smad2 in LF. Finally, miR-7-Smad2 pathway was confirmed to be involved in the regulation of TLR9 on LF proliferation and differentiation. <h3>Conclusion</h3> NETs promote myositis-related ILD, and TLR9-miR-7-Smad2 signaling pathway is involved in the proliferation of LFs and their differentiation into MFs. <h3>References</h3> [1] A. Chrysanthopoulou, I. Mitroulis, E. Apostolidou, S. Arelaki, D. Mikroulis, T. Konstantinidis, E. Sivridis, M. Koffa, A. Giatromanolaki, D. Boumpas, K. Ritis, K. Kambas, Neutrophil extracellular traps promote differentiation and function of fibroblasts, J. Pathol. 233 (2014) 294-307. [2] D. Storisteanu, J. Pocock, A. Cowburn, J. Juss, A. Nadesalingam, V. Nizet, E. Chilvers, Evasion of Neutrophil Extracellular Traps by Respiratory Pathogens, Am. J. Respir. Cell Mol. Biol. 56 (2017) 423-431. <h3>Disclosure of Interests</h3> None declared
By the numbers: ratings and utilization of behavioral health mobile applications
Authors: Andrew D. Carlo, Reza Hosseini Ghomi, Brenna N. Renn, Patricia A. Areán
Journal: npj Digital Medicine (2019)

Although >10,000 behavioral health applications ("apps") are currently available on the Apple and Google Play marketplaces, they have been minimally evaluated or regulated and little is known about "real world" usage patterns. This investigation combined data from online behavioral health app rating frameworks and a mobile health market research firm to identify the most downloaded apps as well as determine rating and ranking concordance between frameworks. Findings demonstrated that the most commonly downloaded apps focus on relaxation, mindfulness, and meditation skills and that they often have notably discordant reviews across rating frameworks. Our results suggest that there is a growing need for: (1) standardized behavioral health app quality and effectiveness measures, (2) up-to-date behavioral health app guidance for clinicians and consumers, and (3) evidence-based apps that incorporate revealed consumer preferences.
PB2050 USING A FUNCTIONAL SCREEN TO IDENTIFY NOVEL ANTI‐PROLIFERATIVE MIRNAS IN DIFFUSE LARGE B‐CELL LYMPHOMA (DLBCL)
Authors: C. Sole, I. Goicoechea, C.H. Lawrie
Journal: HemaSphere (2019)

Background: Diffuse large B‐cell lymphoma (DLBCL) is the most common B‐cell lymphoma, accounting for around 40% of all newly diagnosed non‐Hodgkin lymphoma (NHL) malignancies worldwide. Thanks to R‐CHOP therapy, the majority of DLBCL patients survive their disease. However, around 15% of patients treated have refractory disease, and of the patients that do respond to therapy, an additional 20‐25% will relapse. Proliferation is an important hallmark of cancer and in DLBCL has been associated with poor prognostic outcome. Consequently, several studies have focused on targeting molecules responsible for DLBCL proliferation as a novel therapeutic approach. MicroRNAs (miRNAs) are small non‐coding RNA molecules that act as key regulators of many biological and pathological processes including lymphomagenesis. miRNAs have been shown to be involved in many aspects of DLBLCL pathogenesis including initialization and progression of the disease, as well as having prognostic value. Aims: Identify miRNAs responsible the sustainment of proliferative signaling in DLBCL with the goal to develop novel anti‐lymphoma therapies. Methods: DLBCL cell lines (RIVA, SU‐DHL‐10, SU‐DHL‐4 and Oci‐ly‐10) were infected with a lentiviral library encoding for 698 miRNAs. We used a pooled‐approach using a MOI of 50. An empty vector was used as the control. Stable cell lines were produced by puromycin selection and cells maintained in culture for 4 months in triplicate. Both DNA and RNA were extracted at time 0, 2 months and 4 months post‐infection and the resultant DNA sequenced by NGS (Ion Torrent PGM). Differentially expressed miRNAs were detected by differential expression analysis (P &lt; 0.05). For validation, selected miRNAs were infected individually in cell lines and proliferation rate (CFSE assay) and apoptosis (AnnexinV/TO‐PRO‐3) were determined by flow cytometry. Results: More than eighty miRNAs were identified as being differentially expressed between time 0 and time 4 months in each cell and five of these were differentially expressed in all cell lines. We validated five miRNAs by infecting cell lines with individual lentiviral vectors. Summary/Conclusion: We have demonstrated that the use of functional miRNA screens is a reliable tool for elucidating the phenotype‐genotype interface of cancers such as DLBCL. From our experiments, we propose that miRNA over‐expression could be used to decrease cell proliferation in DLBCL.
AB1317 WHAT IS A TOTAL KNEE OR TOTAL HIP ARTHROPLASTY FAILURE? A PATIENT PERSPECTIVE USING NOMINAL GROUPS
Authors: Jasvinder Singh, Bella Mehta, Serene Mirza, Mark Figgie, Peter Sculco, Michael Parks, Susan Goodman
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Total joint replacements (TJR) are commonly performed elective surgeries for people with end-stage arthritis. However, there is relative lack of qualitative research to define the patient perspective of what constitutes a failure of TJR <h3>Objectives</h3> To discover when a TJR is considered a failure from the patients' perspective using nominal group technique (NGT). <h3>Methods</h3> Patients who had undergone elective total hip (THR) and/or knee replacements (TKR) met in nominal groups to answer the question "When would you consider a knee or hip replacement to be a failure?". Patients competed questionnaires including demographics, pain, function, and satisfaction, independently listed their ideas and then ranked them with the group after clarification. <h3>Results</h3> Six groups with 35 patients were held, all of whom had undergone THR and/or TKR between 2016 and 2018. Of these, 42% were male, 17% black <b>(Table 1).</b> Overall pain and function scores were high; Hip Disability and Osteoarthritis Outcome Score (HOOS) JR 95.3 (SD+/-11) and Knee Injury and Osteoarthritis Outcome Score (KOOS) JR 83.7 (SD+/-12.8) (range 0-100, higher score=less pain/functional limitation), and 86.1% were very/somewhat satisfied with their quality of life. The concerns ranked highest by the patients equating a TJR failure were A) refractory index joint pain (67 votes); B) unable to resume normal activities or go back to work (38 votes); C) minimal or no improvement in quality of life (24 votes); D) post-operative adverse events (40 votes); E) early revision surgery (32 votes); F) death (7 votes); G) expectation-outcome mismatch (1 vote); continuing secondary depression (1 vote) <b>(Table 2).</b> <h3>Conclusion</h3> Poor results for pain, function, quality of life, or adverse events are the outcomes ranked highest by patients, defining TJR failure from the patients' perspective. <h3>Disclosure of Interests</h3> jasvinder singh Shareholder of: Amarin pharmaceuticals and Viking therapeutics, Consultant for: Crealta/Horizon, Fidia, UBM LLC, Medscape, WebMD, the National Institutes of Health and the American College of Rheumatology, Bella Mehta: None declared, Serene Mirza: None declared, Mark Figgie: None declared, Peter Sculco: None declared, Michael Parks Grant/research support from: Zimmer Biomet, Employee of: Zimmer Biomet, Susan Goodman Grant/research support from: Novartis: research support, Consultant for: Novartis, UCB, Pfizer: consulting
Advanced endometrial cancer: Is there a benefit to neoadjuvant therapy?
Authors: Sarah Czok, Jenna R. Zechmeister, Andrea Jewell, Leslie R. Boyd
Journal: Journal of Clinical Oncology (2012)

e15548 Background: The majority of endometrial cancers present as early stage tumors, yet those that are advanced at diagnosis are associated with poor outcomes. The role of radical debulking surgery for endometrial cancer is not clear. However, the use of neoadjuvant chemotherapy is also unproven. We sought to evaluate if utilizing neoadjuvant chemotherapy for advanced endometrial cancer affected outcomes. Methods: A retrospective review from two hospitals served by one academic center from 2002 to 2011 was performed. All patients with stage 3 or 4 disease were identified. Patients with non-epithelial cell types, including carcinosarcoma, were excluded. Patients who received neoadjuvant treatment prior to surgery were identified. A case-control design was utilized matching patients 1:3 or 1:4 stratified by age, stage, grade, histology and performance status. Descriptive statistics and nonparametric analyses were utilized. Results: A total of 115 patients with advanced endometrial cancer were identified. 19 were excluded due to wrong cell type and 1 due to stage 3 disease based on positive cytology. 6 patients had a neoadjuvant treatment approach (NAs). 20 patients were identified as matched controls (CTRLs). The average age was 61 for the NAs, and 63 for the CTRLs. The average BMI was 26.9 for the NAs, and 27.4 for the CTRLs. NAs were more likely to have stage 4 disease—5/6 NAs versus 5/20 CTRLs. Both groups had a high proportion of grade 3 tumors—4/6 NAs versus 15/20 CTRLs. The performance status was similar in both groups. The median number of chemotherapy cycles was 11 in the NAs, and 4 in the CTRLs. 18/20 CTRLs received adjuvant treatment, and 17 included systemic chemotherapy. In the NAs, with a median follow-up of 17 months, 4 were alive with disease (AWD) and 2 were dead of disease (DOD). In the CTRLs, with a median follow-up of 14 months, 7 patients were NED, 8 were AWD, and 5 were DOD. Conclusions: Despite a small sample size, our results indicate that primary surgery remains the preferred strategy for patients with advanced endometrial cancer. However, prospective data is needed to determine to what extent neoadjuvant chemotherapy affects outcomes.
AB1091 THE RELATIONSHIP BETWEEN NAILFOLD CAPILLAROSCOPY FINDINGS IN BEHÇET’S PATIENTS AND COURSE OF THE DISEASE
Authors: Recep Yılmaz, MüÇteba Enes Yayla, Murat Torgutalp, Gülay Kınıklı
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> BehÇet's disease is a chronic, recurrent and systemic vasculitis that may affect veins and arteries at all diameters. Small vessel involvement is responsible for most of its pathological signs. <h3>Objectives</h3> We aimed to compare the nailfold capillaroscopy findings of patients with BehÇet's disease to a healthy control group and examine the relationships, as well as revealing the relationships with the sub-type, activity and other characteristics of BehÇet's disease. <h3>Methods</h3> We conducted a cross-sectional analysis of 153 patients with BehÇet's disease and 165 healthy volunteers in a single center. The capillaroscopic findings of the 2nd-5th fingers of both hands of the participants in the BehÇet's patients and control groups were included in the analysis. Capillaroscopic findings were evaluated by two different experts who were experienced in this field by using the scoring at Atlas of Capillaroscopy in Rheumatic diseases by Maurizio Cutolo (1). <h3>Results</h3> There was no statistically significant difference between the two groups in terms of age or sex (respectively p=0.189 and p=0.585). There was no difference between the BehÇet's patients and healthy volunteers in the qualitative analysis on capillary density, capillary visibility, aneurism, capillary tortuosity, capillary enlargement and presence of avascular areas (p values respectively: 0.610, 0.147, 0.481, 0.057, 0.514 and 0.110). In the BehÇet's patients, bushy capillaries (24.2%, 37/153), capillary dilatation (32%, 49/153) and microhemorrhage (39.2%, (60/153) rates were significantly higher than those in the healthy control group (p&lt;0.001). In the quantitative analysis, total capillaroscopy score was significantly higher in the BehÇet's patients than those in the healthy control group (p&lt;0.001) (Table 1). No statistically significant relationship was found between the presence of clinical signs and capillaroscopy scores, except for erythema nodosum. Conclusion: the BehÇet's patients had significantly higher total capillaroscopy scores in comparison to those in the healthy control group. Based on these data, we believe that the capillaroscopic changes found in BehÇet's patients, though unspecific, may support clinical diagnosis in uncertain cases where BehÇet's disease is considered as a probability. There is a need for well-planned prospective studies to support this our thought. <h3>References</h3> [1] Cutolo M. Atlas of Capillaroscopy in Rheumatic Diseases. Elsevier, Milan 2010, 77-86 <h3>Keywords</h3> BehÇet's disease, nailfold, vasculitis, videocapillaroscopy N, number of patients, *Data were given as median (minimum - maximum) <h3>Disclosure of Interests</h3> None declared
Abstract 420: MMI-0100 Inhibits Cardiac Fibrosis in a Model of Cardiac Myosin Binding Protein C Hypertrophic Cardiomyopathy
Authors: Qinghang Meng, Bidur Bhandary, Na Xu, Hanna Osinska, Kritton Shay-Winkler, Monte Willis, Jeffrey Robbins
Journal: Circulation Research (2017)

Background: Hypertrophic cardiomyopathy is considered one of the most common genetic heart disorders, occurring with a frequency of about 1 in 200, with approximately 30% of those affected showing mutations within the cardiac myosin-binding protein C (cMyBP-C) gene ( MYBPC3 ). Cardiac stress, as well as cMyBP-C mutations, can trigger production of a 40kDa truncated fragment derived from the amino terminus of cMyBP-C. Genetic expression of this 40kDa fragment in mouse cardiomyocytes (MyBP-C 40k ) leads to hypertrophic cardiomyopathy), fibrosis and heart failure. Fibrosis can occur in many cardiovascular diseases and the p38-MK2 signaling pathway has been implicated in a variety of fibrotic processes. Recent studies demonstrated that MK2 inhibition using the cell-permeant peptide inhibitor MMI-0100 is protective in the setting of acute myocardial infarction. We hypothesized that MMI-0100 might also be protective in a chronic model of fibrosis, produced as a result of cMyBP-C 40k cardiomyocyte expression. Methods and Results: Non-transgenic and MyBP-C 40k transgenic (Dtg) mice were given MMI-0100 or PBS daily for 30 weeks. In control groups, long term MMI-0100 was benign, with no measurable effects on cardiac anatomy, function, cell viability, hypertrophy or probability of survival. In the Dtg group, MMI-0100 treatment reduced cardiac fibrosis, decreased cardiac hypertrophy and prolonged survival. Conclusions: Pharmaceutical inhibition of p38-MK2 signaling via MMI-0100 treatment is beneficial in the context of fibrotic MyBPC 40k disease.