tbuckley/cabot-search huggingface dataset:
AB0892 ACUTE POLYARTICULAR GOUT WITH SYSTEMIC INFLAMMATORY RESPONSE – A SINGLE TERTIARY CENTRE COHORT
Authors: Jan Toms, Tomas Soukup, Petr Bradna, Zbynek Hrncir
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Gout is a common, inflammatory, crystal-induced disease with increasing prevalence and incidence. Typical monoarticular involvement can be quite easily and effectively treated. In recent years, we have observed more frequently gout cases with severe polyarticular manifestation and with systemic inflammatory response syndrome (SIRS). In clinical practice such a complicated gout attack used to be identified with delay and therapy is not adequate. <h3>Objectives</h3> To assess clinical and laboratory parameters of systemic inflammatory polyarticular gout and to identify risk factors and convenient therapeutic strategy. <h3>Methods</h3> Retrospective analysis of 133 consecutive new patients (14 females) with gout (according to the classification criteria ACR/EULAR 2015) on the presence of acute polyarticular involvement (≥ 4 joints) and fullfilling criteria for SIRS. <h3>Results</h3> Seventeen (12.8%) of 133 gout patients had polyarticular manifestation and met SIRS criteria; 2 females and 15 males, average age 73.2±11.3 years, BMI 29.9±3.8. All these patients had to be admitted to inpatient department because of gout severity. Mean CRP was 204±113 mg/l, leucocytes 15.2±6.8 10<sup>9</sup>/l, serum uric acid 401±140 µmol/l. Procalcitonin was slightly positive in 2 patients (with concurrent respiratory infection). Mean 6 joints were affected, 13 (76,5%) patients had involvement of both upper and lower limbs, tophi were present in 7 of 17 patients. Synovial fluid analysis was performed with proving urate crystals and leukocyte count 24.4±17.3 10<sup>9</sup>/l. Typical gout features were found in 70.6% patients on joint X-ray and in 52.9% ones on musculoskeletal ultrasound. Risk factors for systemic inflammatory polyarticular manifestation were preceding renal function impairment, long-term diuretic therapy and alcohol above-average consumption. Monotherapy was not effective in any patients, combination of NSAID with colchicin or systemic glucocorticoids was used with success. <h3>Conclusion</h3> Acute polyarticular gout with systemic inflammatory response mimics septic status and mostly requires hospitalization. Complex management with combination therapy should be guided by an experienced rheumatologist. <h3>Reference</h3> [1] Schäfer VS, Krause A, Trauzeddel RF, Schmidt WA. Systemic Inflammatory Polyarticular Gout Syndrome – Description of a Previously Neglected Entity. JSM Arthritis 2017; 2: 1024. <h3>Disclosure of Interests</h3> None declared
PB2109 NICHEFORMING STRUCTURES OF BONE MARROW OF PATIENTS WITH MULTIPLE MYELOMA BEFORE AND AFTER AUTOHSCT
Authors: N. Semenova, V. Rugal, S. Bessmeltsev, I. Kostroma, N. Enukashvili, A. Chubar, D. Ivolgin, S. Gritsaev
Journal: HemaSphere (2019)

Background: Autologous transplantation of hematopoietic stem cells (AutoHSCT) is one of the most effective methods of treatment in patients with MM, which can significantly reduce the volume of cells of the pathological clone and improve the quality of the response. However, there remain groups of patients with ineffective AutoHSCT: patients with unsuccessful mobilization and with early relapse after AutoHSCT. AutoHSCT success depends on many factors, including the state of the niche of HSC, which has been subjected to toxic effects of aggressive treatment and damaged by the underlying disease. Aims: To investigate the morphological characteristics of the main stromal components of the niche HSC and cultural characteristics of MSC patients with multiple myeloma (MM) before and after treatment, including AutoHSCT. Methods 32 trepanobiopsy of bone marrow from patients diagnosed with MM the ages of 48 and 68 (median age 56) before and after AutoHSCT were used in the study. The study applied histological, immunohistochemical and cultural methods. 20 patients diagnosed with primary MM included in the study. 12 patients diagnosed with progressive MM: inefficient mobilization of HSC was noted for 5 patients and early relapse for seven. Results: Changes of stromal microenvironment of bone marrow (BM) showed of all patients with MM: increased microvascular density and the number of endosteal stromal cells, strengthening of reticulin fiber in subendosteal and perivascular spaces. Increased angiogenesis correlates with the number of plasma cells in the myelogram (r = 0.58; p < 0.05) and with the type of infiltration of BM (r = 0.85; P < 0,05), as well as with osteodestructive changes in the patient's history (r = 0.65; p < 0.05). Shown significant changes in cultures of mesenchymal stromal cells (MSC), both before and after therapy, including AutoHSCT. In cultural studies of MSC BM MM patients compared to healthy donors showed a decrease in the speed of proliferation (2.4 times on average), a decrease in the total time of passionation from 7 to 5 passages. A marked increase expression of markers associated with myofibroblastic phenotype and aging (smooth-muscle actin, β-galactosidase) - 45-80% of cells in the culture were positively stained with these markers. In MSC cultures of patients after AutoHSCT β-galactosidase were synthesized weaker than before treatment, but nevertheless higher than in the control group. MSCS of healthy donors BM of the enzyme is almost not synthesized. Fibrils smooth-muscle actin was detected in MSCS to AutoHSCT, after AutoHSCT was practically absent. Summary/Conclusion: Thus, the cultures of patients with MSC and BM nicheforming elements of patients with MM possess the features of tumor-associated microenvironment, despite the treatment of the underlying disease.
Abstract 16401: Characterization of the Cellular Inflammatory Response in Patients Undergoing Transfemoral Transcatheter Aortic Valve Implantation
Authors: Jedrzej Hoffmann, Silvia Mas, Felicitas Böckling, Tina Rasper, Stephan Fichtlscherer, Stefanie Dimmeler, Andreas M Zeiher, Mariuca Vasa-Nicotera
Journal: Circulation (2018)

Background: Systemic inflammatory response, preceded by a significant release of proinflammatory cytokines and elevation of leukocyte count, has been shown to be a strong predictor of mortality in ...
Validity of the Patient-Reported Outcome Measurement Information System (PROMIS) Sexual Interest and Satisfaction Measures in Men Following Radical Prostatectomy
Authors: Nnenaya Q. Agochukwu, Daniela Wittmann, Nicholas R. Boileau, Rodney L. Dunn, James E. Montie, Tae Kim, David C. Miller, James Peabody, Noelle E. Carlozzi
Journal: Journal of Clinical Oncology (2019)

Patient-reported outcomes after radical prostatectomy have focused on erectile function. To date, no studies have validated the Patient-Reported Outcome Measurement Information System (PROMIS) Sexual Interest and Satisfaction single item measures in patients with prostate cancer, nor have studies examined how these measures relate to erectile function. In addition, data are lacking with regard to the clinical responsiveness of these measures to treatment. We sought to validate and examine the clinical utility of these measures in men after radical prostatectomy.We identified men who underwent a robotic radical prostatectomy from May 2014 to January 2016 in the Michigan Urological Surgery Improvement Collaborative. A single item from the PROMIS Global Satisfaction With Sex Life subdomain and a single item from the PROMIS Interest in Sexual Activity subdomain were administered. Erectile function was also assessed. Differences between baseline and 24-month T-scores for both PROMIS interest and satisfaction were examined. Multilevel models were constructed to examine change over time.A total of 1,604 patients were included in the analysis. Convergent and discriminant validity of the PROMIS measures was supported. The mean PROMIS interest T-score decreased significantly from baseline to 3 months (P = .001) and significantly increased from 3 months to 24 months in this cohort, with 24-month scores exceeding baseline scores (P < .001). The mean PROMIS satisfaction T-score declined from baseline to 3 months and increased from 3 months to 24 months (P < .002).PROMIS Global Satisfaction With Sex Life and Interest in Sexual Activity single-item measures are fundamental measures in prostate cancer survivorship. Patients are interested in sex despite functional losses and can salvage satisfaction, thereby giving insight into attainable patient-centered survivorship goals for sexual recovery after radical prostatectomy.
Abstract 279: Mitochondrial Bioenergetic Signaling Drives Myofibroblast Transdifferentiation
Authors: Alyssa A Lombardi, Ehtesham Arif, Timothy S Luongo, John W Elrod
Journal: Circulation Research (2017)

When the heart is injured, quiescent fibroblasts differentiate into contractile, synthetic myofibroblasts. Initially fibrosis is reparative, but when chronic it becomes maladaptive and contributes to HF. Intracellular Ca 2+ ( i Ca 2+ ) signaling is reported to be necessary for myofibroblast transdifferentiation yet the role of mitochondrial Ca 2+ ( m Ca 2+ ) exchange has not been explored. The Mcu gene encodes the channel-forming subunit of the m Ca 2+ uniporter channel (MCUc) and is required for acute m Ca 2+ uptake. To examine the contribution of m Ca 2+ in cardiac fibrosis, we generated conditional, fibroblast-specific knockout mice by crossbreeding Mcu fl/fl mice with Col1a2-CreERT mice (Col1a2- Mcu -/- ), permitting tamoxifen-inducible gene deletion in adult mice. Col1a2- Mcu -/- mice and controls were subjected to ligation of the left coronary artery and cardiac function was examined by echocardiography. Loss of fibroblast Mcu worsened LV function and increased fibrosis, as evaluated by Mason’s trichrome staining and qPCR analysis of fibrotic gene expression. To examine the cellular mechanisms responsible for the increased fibrosis we isolated mouse embryonic fibroblasts (MEFs) from Mcu fl/fl mice and deleted Mcu with Cre-adenovirus. When challenged with pro-fibrotic ligands (TGF-β and AngII), Mcu -/- MEFs exhibited decreased m Ca 2+ uptake and enhanced i Ca 2+ transient amplitude. Loss of Mcu promoted myofibroblast transdifferentiation: increased α-SMA expression and contractile function (gel retraction) and decreased migration and proliferation. Mcu -/- MEFs were more glycolytic with increased phosphorylation (inactivation) of pyruvate dehydrogenase. Genetic activation of glycolysis with a Pfk2 mutant in WT MEFs promoted myofibroblast differentiation. Conversely, genetic inhibition of glycolytic flux ablated the increased transdifferentiation observed in Mcu -/- MEFs. Further, TGF-β and AngII altered the expression of regulatory MCUc components in WT MEFs. Our results suggest that alterations in m Ca 2+ uptake and bioenergetic pathways are necessary for myofibroblast transdifferentiation. Thus, energetic signaling represents a novel therapeutic target to impede HF progression and other progressive fibrotic diseases.
PF225 AZACITIDINE (AZA) ENHANCES ANTILEUKEMIC ACTIVITY OF THE MDM2 INHIBITOR MILADEMETAN IN TP53 WILD-TYPE ACUTE MYELOID LEUKEMIA (AML)
Authors: S. Noguchi, T. Seki, N. Adachi, H. Sumi, R. Nakano, K. Inaki, C. Wada, K. Wakita, K. Nakamaru, M. Murakami
Journal: HemaSphere (2019)

Background: Milademetan (DS-3032b) is a small-molecule MDM2 inhibitor that activates p53 and induces apoptosis by disrupting the MDM2-p53 interaction. Milademetan has demonstrated single-agent antileukemic activity in preclinical and clinical studies in AML. AZA, a hypomethylating agent, is used to treat AML and myelodysplastic syndromes by upregulating epigenetically silenced genes in AML cells. We conducted a preclinical study of milademetan in combination with AZA because both agents modulate gene expression related to cell growth or apoptosis. Aims: To investigate the efficacy of milademetan in combination with AZA in TP53 wild-type AML and to identify the underlying molecular mechanisms of action. Methods: The effects of milademetan and AZA as single agents and in combination were assessed in vitro and in vivo. The human TP53 wild-type AML cell lines MOLM-13, ML-2, and OCI-AML5 were investigated. Cell growth was evaluated in ATP assays, and apoptosis induction was assessed in annexin V assays. In vivo activity was evaluated in mice that were subcutaneously xenografted with MOLM-13 cells then treated with oral milademetan for 7 days and intravenous AZA for 5 days. Results: The growth inhibitory effects of milademetan and AZA in various treatment schedules as single agents and in combination were investigated in AML cell lines and in vivo using the MOLM-13 xenograft model. In the xenograft study, a sequential combination of AZA followed by milademetan caused greater tumor growth inhibition than single-agent and other combination schedules of milademetan and AZA. This sequential combination increased annexin V–positive cells and upregulated p53 and p21 protein expression in cell lines. Interestingly, AZA treatment induced a protein that may be a faster-migrating form of MDM2. Characterization of this protein and further analyses, including RNA sequencing and genome-wide DNA methylation profiling, to provide additional mechanistic insights are ongoing. Summary/Conclusion: Preclinical results demonstrated that a sequential combination treatment with AZA followed by milademetan enhanced antileukemic activity in cell lines and a mouse xenograft model. A phase 1 clinical trial of this combination has been initiated based on these results.
Abstract 14602: Risks and Outcomes for Patients That Undergo Thoracic versus Non Thoracic Magnetic Resonance Imaging Who Have a Magnetic Resonance Non Conditional Cardiac Implantable Electronic Device
Authors: Aakash Shah, Iwan Nyotowidjojo, Kristina Skinner, Jaskanwal Bisla, Satinder Singh, Rostam Khoubyari, Bobby Kalb, Peter Ott, Julia Indik
Journal: Circulation (2017)

Background: Observational studies have explored MR scanning of patients with cardiac implantable electronic devices (CIEDs) not FDA approved for MR scanning (“non-conditional”). However, concerns r...
The Healthy Pregnancy Research Program: transforming pregnancy research through a ResearchKit app
Authors: Jennifer M. Radin, Steven R. Steinhubl, Andrew I. Su, Hansa Bhargava, Benjamin Greenberg, Brian M. Bot, Megan Doerr, Eric J. Topol
Journal: npj Digital Medicine (2018)

Although maternal morbidity and mortality in the US is among the worst of developed countries, pregnant women have been under-represented in research studies, resulting in deficiencies in evidence-based guidance for treatment. There are over two billion smartphone users worldwide, enabling researchers to easily and cheaply conduct extremely large-scale research studies through smartphone apps, especially among pregnant women in whom app use is exceptionally high, predominantly as an information conduit. We developed the first pregnancy research app that is embedded within an existing, popular pregnancy app for self-management and education of expectant mothers. Through the large-scale and simplified collection of survey and sensor generated data via the app, we aim to improve our understanding of factors that promote a healthy pregnancy for both the mother and developing fetus. From the launch of this cohort study on 16 March 2017 through 17 December 2017, we have enrolled 2058 pregnant women from all 50 states. Our study population is diverse geographically and demographically, and fairly representative of US population averages. We have collected 14,045 individual surveys and 107,102 total daily measurements of sleep, activity, blood pressure, and heart rate during this time. On average, women stayed engaged in the study for 59 days and 45 percent who reached their due date filled out the final outcome survey. During the first 9 months, we demonstrated the potential for a smartphone-based research platform to capture an ever-expanding array of longitudinal, objective, and subjective participant-generated data from a continuously growing and diverse population of pregnant women.
On a Surgeon Poet
Authors: Eric James Forsbergh
Journal: JAMA (2019)

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Abstract 19220: Hepatic Steatosis is Independently Associated With an Increased Vascular Stiffness in Overweight Subjects
Authors: Inge v Munckhof, Tessa Brand, Marinette v Graaf, Leo Joosten, Mihai Netea, Jacqueline d Graaf, Joost Rutten
Journal: Circulation (2015)

Introduction: The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically during the past decades, affecting 50-75 % of the obese subjects. Subjects with NAFLD have an increased risk of cardiovascular diseases. We investigated whether an increase in hepatic steatosis is independently associated with an increase in vascular stiffness. Methods: We recruited a subcohort of the Nijmegen Biomedical Study, a large population based cohort, including 112 subjects, BMI &gt; 27 kg/m2, aged 55-81 years. The amount of liver fat was quantified by MR spectroscopy. Arterial stiffness was assessed by measurement of the carotid-femoral pulse wave velocity (PWV). The association between the hepatic steatosis and vascular stiffness was investigated by linear regression analysis with and without adjustment for the conventional cardiovascular risk factors. Results: In univariate analysis, hepatic steasosis was found to be correlated with PWV (r = 0.267; p = 0.005). After adjustment for age, sex, heart rate, alcohol use, and BMI still a significant positive association was present with a standardized beta of 0,298 (p=0.004). Even after adjustment for conventional cardiovascular risk factors including mean arterial pressure, blood pressure lowering and anti-diabetic drugs, hepatic steatosis remained independently associated with PWV ( standardized beta 0.269, p = 0.019). Conclusions: In a group of overweight subjects hepatic steatosis is associated with arterial stiffness. This association is independent of blood pressure, use of antihypertensives and the other traditional cardiovascular risk factors.
Re: The automation of systematic reviews
Authors: J.M. Thomas, A. O'Mara-Eves, John Mcnaught, S. Ananiadou
Journal: BMJ (2013)

We welcome the editorial by Tsafnat and colleagues, which is a timely statement of the potential for new information technologies to increase systematic review efficiency, and support the Rapid Responses by Barreto and Elliott et al. However, while the potential for automation is apparent, further methodological and evaluative work is needed to develop methods and an evidence base for their use; in particular, the amount of empirical data to support many of the purposes outlined in the editorial is very limited. Moreover, there are likely to be some situations in which such procedures operate better than others. For example, natural language processing may work well in highly technical literatures that contain considerable jargon and regularly employed acronyms, but operate less effectively in non-clinical literature, such as public health, where the same meaning can be expressed in multiple ways. With this in mind, developing fit for purpose tools can be best achieved through user engagement and cross-disciplinary collaboration between computer scientists, information specialists, and systematic reviewers.We currently hold an MRC grant that is aiming to develop methods for using text mining for use in systematic reviews ? and to evaluate the potential of such technologies to increase the efficiency of screening studies for eligibility. Part of the work involves simulations on existing review data, and part on using text mining in current reviews. We would like to encourage reviewers to contact us if they have data that we could use; might like to participate in a ?live? review; or would like to hear more about the study.
PB2053 STRONG EXPRESSION OF SLAMF7 IN NATURAL KILLER/T-CELL LYMPHOMA AND LARGE GRANULAR LYMPHOCYTE LEUKEMIA–A PROMINENT BIOMARKER AND POTENTIAL TARGET FOR ANTI-SLAMF7 ANTIBODY THERAPY
Authors: A. Elmaagacli, H. Salwender, C. Jehn, F. Dahmash, A. Singh, J. Shikova, M. Pannenbeckers, C. Niggemann, M. Vierbuchen
Journal: HemaSphere (2019)

Background: Signaling Lymphocyte Activation Marker Family member 7 (SLAMF7) is highly expressed on human plasma cells and malignant myeloma cells, which is a therapeutic target for the anti-SLAMF7 antibody elotuzumab. Lower expression of SLAMF7 is found in NK cells, NK-like T cells, CD8+ T cells, activated monocytes and dendritic cells. With the exception of plasmablastic lymphoma and multiple myeloma, SLAMF7 was never been reported to be expressed in other malignant hematological diseases. Aims: This prompted us to examine the expression of SLAMF7 also in T-cell lymphoma, NK/T-cell lymphoma, NK cell derived large granular lymphocyte (NK-LGL) and T-cell LGL. Methods We examined in biopsy tissue or blood samples of 11 patients with histologically proven NK/T-cell lymphomas, T-cell lymphoma, T-ALL, non-malignant Kikuchi necrotizing lymphadenitis, NK-LGL and T-LGL SLAMF7 expression by immunohistochemistry (IHC) or flow cytometry. We defined SLAMF7 as positive if we detected SLAMF7 expression in at least 20% of lymphoma cells by IHC or 10% by flow cytometer. As positive controls for SLAMF7 expression we used biopsy tissue from patients with multiple myeloma. Results: Here we found a strong expression of SLAMF7 by IHC in all 3 patients with NK/T-cell lymphoma, whereas no expression by IHC was found on T-cell lymphoma biopsy tissue of 3 patients with T-cell lymphoma and of 1 patient with T-ALL. Another patient who was suspected with T-cell lymphoma but later diagnosed as non-malignant Kikuchi necrotizing lymphadenitis, was tested weak positive for SLAMF7 expression by IHC as shown in table 1. Strong SLAMF7 expression was specific to lymphoma tissue in a patient with NK/T-cell lymphoma but not found in the surrounding healthy tissue of nasal epithelial cells as shown in figure 1, which identifies SLAMF7 as a suitable biomarker for NK/T-cell lymphoma. We detected SLAMF7 also in a patient with CD3-/CD56+/CD16+ NK-LGL cells and a further patient with CD3+/CD56+/CD8+ T-LGL by flow cytometer. Interestingly, 100% of NK-LGL cells (38,9% of all mononucleated cells in peripheral blood) and all T-LGL cells (17,2% of all mononucleated cells in peripheral blood) were SLAMF7 positive.Summary/Conclusion: Here we report for the first time expression of SLAMF7 in NK/T-cell lymphoma and NK-LGL and T-LGL, which has clinical relevance because it extends possible immunotherapy to SLAMF7 inhibitor elotuzumab. SLAMF7 might also be a suitable target for CAR-T cell therapies as already used successfully in multiple myeloma trials. Nevertheless, it might be useful as a biomarker for NK/T-cell lymphomas and LGL, too.