tbuckley/cabot-search huggingface dataset:
Ovarian Clear Cell Carcinoma in Cowden Syndrome
Authors: Kevin Yauy, Marion Imbert-Bouteille, Virginie Bubien, Clothilde Lindet-Bourgeois, Gauthier Rathat, Helene Perrochia, Gaëtan MacGrogan, Michel Longy, Didier Bessis, Julie Tinat, Stéphanie Baert-Desurmont, Maud Blanluet, Pierre Vande Perre, Karen Baudry, Pascal Pujol, Carole Corsini
Journal: Journal of the National Comprehensive Cancer Network (2019)

Cowden syndrome (CS) is an autosomal dominant mendelian disease related to germline pathogenic variants affecting the PTEN-gene. CS is characterized by macrocephaly, mucocutaneous lesions, and an increased risk of breast and thyroid cancers. Rare ovarian cancer cases (mostly embryonic tumors) associated with PTEN have been described in the literature, but no current CS guidelines are available for ovarian cancer risk management. We report on a woman diagnosed with ovarian clear cell carcinoma (OCCC) at 28 years of age. The patient displayed macrocephaly, trichilemmomas, oral papillomatosis, and acral keratosis. A family history of multiple cancer cases within the PTEN-related tumor spectrum was identified. In addition, PET scan and fine-needle biopsy results led to a diagnosis of thyroid follicular neoplasia. PTEN sequencing revealed that she carried a germline inherited pathogenic variant in exon 5 c.388C>T, p.(Arg130*) (NM_000314). Somatic mismatch repair immunohistochemistry analysis showed normal expression, and germline BRCA1/2 sequencing did not reveal pathogenic or likely pathogenic variants. An ovarian cell immunohistochemistry analysis reported total loss of PTEN expression, which strongly suggested the role of PTEN in the oncogenesis of this cancer. Hence, a total thyroid resection was performed instead of thyroid lobectomy and a risk-reducing bilateral mastectomy was discussed. Co-occurrence of this pathogenic germline mutation in PTEN in this patient, early development of OCCC at age 28 years, and total loss of PTEN expression in the tumor might support the involvement of PTEN in the carcinogenesis of her ovarian cancer. We describe a new ovarian cancer case with an atypical histologic type—clear cell carcinoma—in CS. This observation might be the first indication of the need to expand the PTEN-related tumor spectrum to incorporate OCCC. The CS diagnosis significantly changed the therapeutic outcome of this patient.
Abstract 21309: Transcatheter Aortic Valve Implantation Outcomes in Patients With History of Previous Cardiac Surgery: A National in Patient Sample Analysis
Authors: Nikhil Nalluri, Varun Kumar, Dixitha Anugula, Nileshkumar Patel, Sainath Gaddam, Deepak Asti, Samer Saouma, Roman Royzman, Gregory Maniatis, Ruben Kandov, Frank Tamburrino, James C Lafferty
Journal: Circulation (2017)

Introduction: The influence of previous cardiac surgery (CABG, Valve Replacement or both) on In-hospital clinical outcomes in patients(pts) undergoing Transcatheter Aortic Valve Implantation (TAVI) has not been well established. Methods: We analyzed the clinical characteristics and periprocedural in-hospital outcomes among pts undergoing TAVI using 2011-2014 HCUP-Nationwide Inpatient Sample database. ICD-9-CM codes were used to identify pts undergoing TAVI with and without history cardiac surgery. Propensity score matching has been attempted to minimize bias. SAS software was used for statistical analysis with p &lt; .05 used to indicate statistical significance. Results: Among a total of 8466 pts who underwent TAVI during the study period, 1982 had a history of previous cardiac surgery. It was noted that pts with prior cardiac surgery were dominantly male and had a higher prevalence of unfavorable clinical characteristics except pulmonary hypertension (Table). The propensity-matched analysis for 3834 patients showed that the incidence of periprocedural of stroke (2.61% vs1.62%,p=0.03) was lower in pts with previous cardiac surgery. Whereas the prevalence of In-hospital mortality(3.29% vs 2.35% p=0.07), vascular complications(9.96% vs 9.08%,p=0.34), transfusion(23% vs 20.45%,p=0.055), Acute Kidney Injury (AKI)(18.41% vs 16.95%, p=0.23), and pacemaker implantation(10.64 vs 9.29, p=0.16) were comparable for the two cohorts. Conclusions: In Pts with a history of previous cardiac surgery undergoing TAVI there is a lower incidence of periprocedural stroke compared to those without a history of cardiac surgery. The rates of in-hospital mortality, vascular complications, transfusion, Acute Kidney Injury (AKI), and pacemaker implantation were similar between both the groups.
Small-Molecule Targeting of Musashi RNA-Binding Activity in Acute Myeloid Leukemia
Authors: Gerard Minuesa Dinares, Steven K. Albanese, Arthur Chow, Alexandra Schurer, Sun Mi Park, Christina Z. Rotsides, James Taggart, Andrea Rizzi, Levi N. Naden, Timothy Chou, Saroj Gourkanti, Daniel Cappel, Maria C. Passarelli, Lauren Fairchild, Carolina Adura, Joseph Fraser Glickman, Jessica Schulman, Christopher Famulare, Minal Patel, Joseph K. Eibl, Gregory M. Ross, Derek Tan, Christina Leslie, Thijs Beuming, Yehuda Goldgur, John D. Chodera, Michael G. Kharas
Journal: Blood (2018)
Nivolumab Combined with Brentuximab Vedotin for Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma: Preliminary Results from the Phase 2 CheckMate 436 Trial
Authors: Alison J. Moskowitz, Armando Santoro, Giuseppe Gritti, Pauline Brice, David Cunningham, Paul Barr, Justin Kline, John Kuruvilla, Nathalie A Johnson, Neha Mehta-Shah, Thomas Manley, Manish Sharma, Stephen Francis, Joseph Cohen, Pier Luigi Zinzani
Journal: Blood (2018)
Empagliflozin reduces the risk of a broad spectrum of heart failure outcomes regardless of heart failure status at baseline
Authors: James Januzzi, João Pedro Ferreira, Michael Böhm, Sanjay Kaul, Christoph Wanner, Martina Brueckmann, Mark C. Petrie, Anne Pernille Ofstad, Cordula Zeller, Jyothis George, David Fitchett, Faiez Zannad
Journal: European Journal of Heart Failure (2019)
AB0960 Polymorbidity and cognition in ambulatory postmenopausal hip and knee osteoarthritis patients
Authors: A.A. Popov, N.V. Izmozherova, N.A. Getmanova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoarthritis (OA).has been reported to be a risk factor of morbidity, disability and premature cardiovascular mortality. <h3>Objectives</h3> to assess the impact of polymorbidity on cognitive function in postmenopausal women with primary OA. <h3>Methods</h3> cross-sectional study included ambulatory 682 postmenopausal women aged 48 to 62 (median 56; 25%–75%: 52.0 / 60.0). Inclusion criteria were: confirmed postmenopausal status and Kellgren stage 2 or 3 OA of the knee and/or hip joints fulfilling ARA criteria. Cognitive impairment (CI) was verified by MMSE scale (Mini Mental State Examination). For all patients expected individual risk of premature death and Charlson index were calculated. <h3>Results</h3> Median Charlson comorbidity index in women with OA was 4 (3 / 4). None of the patient had a comorbidity index of 0. The most frequent comorbidities were chronic heart failure (364 women (53.4%) and type 2 diabetes mellitus (180 women, 26,4%). Charlson index increase was associated with decline of cognitive function (see table 1) with incline of quantity and severity of CI cases. <h3>Conclusions</h3> Hip and knee joints OA in postmenopausal women is associated with polymorbidity. Polymorbidity in OA patients is associated with cognitive impairment. <h3>Disclosure of Interest</h3> None declared
THU0330 Obesity in psoriatic arthritis: comparative prevalence with skin psoriasis and associated factors
Authors: R. Queiro, A. Lorenzo, E. Pardo, A. Brandy, S. Alonso, M. Alperi, L. Arboleya, J. Ballina
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Obesity (BMI ≥30 kg/m<sup>2</sup>) is a common cardiovascular risk factor in psoriatic disease<sup>1</sup>. Although the prevalence of obesity is high, the factors associated with it in psoriatic arthritis (PsA) are poorly understood. <h3>Objectives</h3> We aimed to evaluate the prevalence and obesity-associated factors in patients with PsA. <h3>Methods</h3> Retrospective cross-sectional study that included 205 consecutive patients with PsA according to CASPAR criteria. The prevalence of obesity was compared with that of 310 patients with skin psoriasis of similar age (±3 years). The factors associated with obesity were first analysed by a conditional logistic regression. The significant factors in this first model were then introduced in a multivariate model using a backward step approach (p-values&lt;0.05 were considered significant). <h3>Results</h3> One-hundred twelve men and 94 women were included, with a mean age of 53±13 years. Obesity was more prevalent among psoriatics (36.5%) compared to PsA patients (24%), OR 1.6 (1.1–2.3), p&lt;0.05. The factors associated with obesity in the univariate analysis (p&lt;0.05) were: onset of psoriasis &gt;40 years (OR 2.4), onset of arthritis &gt;40 years (OR 2.1), PsA family history (OR 3.1), polyarticular presentation (OR 1.9), axial presentation (OR 2.5), polyarticular evolution (OR 2.4), axial evolution (OR 4.2), diabetes (OR 3.6), HBP (OR 3.9), and dyslipidemia (OR 3.5). After correcting for age, sex, disease duration and other confounders, independent associations with obesity found in the multivariate model (p&lt;0.05) were: PsA family history (OR 3.6, IC95%: 1.1–14.4), axial evolution (OR 4.4, IC95%: 1.0–22.4) and dyslipidemia (OR 3.5, IC95%: 1.5–8.6). <h3>Conclusions</h3> Obesity was more common among our patients with cutaneous psoriasis than in those with arthritis. The model that best explains obesity in this PsA series combines genetic factors (PsA family history), together with factors specific to the metabolic syndrome (dyslipidemia), with others owned to arthritis (axial evolution). <h3>Reference</h3> [1] Husni ME. Comorbidities in psoriatic arthritis. Rheum Dis Clin North Am2015;41:677–98. <h3>Disclosure of Interest</h3> None declared
AB1020 Pilot assessment of current chronic gout treatment in russia
Authors: A.A. Popov, O.V. Teplyakova, T.A. Popova, A.V. Sarapulova, P.A. Palabugina
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In 2016 EULAR evidence based clinical guidelines on Gout treatment have been updated.<sup>1</sup> <h3>Objectives</h3> to assess current daily practice physicians' approach to management of chronic gout patients <h3>Methods</h3> a cross-sectional anonymous survey had been offered to hospital and outpatient departments physicians dealing with gout patients resulting in 97 back-feed replies yielded. This publication deals with chronic gout treatment practice. <h3>Results</h3> all survey participants were divided into 3 groups. Group 1 consisted of 18 rheumatologists (professional experience median 19.6 years, range 1 to 43), group 2 included 60 general practitioners (GP, professional experience 27; 4–47), group 3 included other specialists (cardiologists, surgeons etc.) who reported frequent contacts with gout patients (professional experience 16.5; 1–44). Rheumatologists reported to contact median 15 (range 2–40) gouty subjects per month, while group 2 reported to see 3<sup>1 – 10</sup> and group 3 consults 4<sup>1 – 12</sup> patients per month. All rheumatologists and 45 GPs reported initiation of allopurinol or febuxostat after gouty arthritis resolution, while 11 general practitioners did not start antihyperuricemic drugs in subjects with kidney and/or cardiovascular comorbidities. In Group 3 only 6 responders had experience of antihyperuricemic drugs administration, but 3 of them reported allopurinol initiation during gout flare. Only 2 rheumatologists and 2 GPs were aware of gout flare low dose colchicin prophylaxis during allopurinol dose adjustment. Administration of maximal allopurinol daily maintenance doses over 300 mg was reported only by 7 rheumatologists and 7 GPs. Other specialists did not have any personal experience of allopurinol dose adjustment. By responders' assessment every 2–3 patient continues to experience gout flares in spite of prescribed treatmen <h3>Conclusions</h3> intensive educational intervention is urgently required to change current practice of chronic gout treatment in Russia. <h3>Reference</h3> [1] Richette P, et al. 2016updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis2017;76:29–42 <h3>Disclosure of Interest</h3> None declared
Post Transplant Prophylaxis with High Dose Valacyclovir through Day 100 Versus Day of Post Transplant Hospital Discharge Decreases Cytomegalovirus Reactivation in Adult Umbilical Cord Blood Transplant Recipients
Authors: Prashant Sharma, Jennifer MacDonald, Jeff Kaiser, Jennifer Tobin, Matthew Miller, Maheen Abidi, Esther Benamu, Enkhtsetseg Purev, Bradley M. Haverkos, Jonathan A Gutman
Journal: Blood (2018)
Whole genome sequencing suggests transmission of Corynebacterium diphtheriae-caused cutaneous diphtheria in two siblings, Germany, 2018
Authors: Anja Berger, Alexandra Dangel, Tilmann Schober, Birgit Schmidbauer, Regina Konrad, Durdica Marosevic, Sören Schubert, Stefan Hörmansdorfer, Nikolaus Ackermann, Johannes Hübner, Andreas Sing
Journal: Eurosurveillance (2019)

In September 2018, a child who had returned from Somalia to Germany presented with cutaneous diphtheria by toxigenic Corynebacterium diphtheriae biovar mitis. The child's sibling had superinfected insect bites harbouring also toxigenic C. diphtheriae. Next generation sequencing (NGS) revealed the same strain in both patients suggesting very recent human-to-human transmission. Epidemiological and NGS data suggest that the two cutaneous diphtheria cases constitute the first outbreak by toxigenic C. diphtheriae in Germany since the 1980s.
Development and Prospective Randomized Evaluation of a Decision Aid for Prostate-specific Antigen-based Early Detection of Prostate Cancer in Men Aged Between 55 and 69 Yr: The PSAInForm Trial
Authors: Axel Semjonow, Hans-Werner Hense, Kathrin Schlößler, Alexandra Simbrich, Matthias Borowski, Christiane Bothe, Klaus Kruse, Dorothee Tiedje, Kathrin Kuss, Charles Christian Adarkwah, Peter Maisel, Ralf Jendyk, Marc-André Kurosinski, Joachim Gerß, Oliver Heidinger, Christian Tschuschke, Ralf Becker, Monique J. Roobol, Chris Bangma, Norbert Donner-Banzhoff
Journal: European Urology (2019)
Nivolumab Versus Docetaxel in a Predominantly Chinese Patient Population With Previously Treated Advanced NSCLC: CheckMate 078 Randomized Phase III Clinical Trial
Authors: Yi-Long Wu, Shun Lu, Ying Cheng, Caicun Zhou, Jie Wang, Tony Mok, Li Zhang, Hai-Yan Tu, Lin Wu, Jifeng Feng, Yiping Zhang, Alexander Valerievich Luft, Jianying Zhou, Zhiyong Ma, You Lu, Chengping Hu, Yuankai Shi, Christine Baudelet, Junliang Cai, Jianhua Chang
Journal: Journal of Thoracic Oncology (2019)

IntroductionData on immuno-oncology agents in Chinese patients are limited despite a need for new therapies. We evaluated the efficacy and safety of nivolumab in a predominantly Chinese patient population with previously treated NSCLC.MethodsCheckMate 078 was a randomized, open-label, phase III clinical trial in patients from China, Russia, and Singapore with squamous or nonsquamous NSCLC that had progressed during/after platinum-based doublet chemotherapy (ClinicalTrials.gov: NCT02613507). Patients with EGFR/ALK alterations were excluded. Patients (N = 504) were randomized 2:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks), stratified by performance status, tumor histology, and tumor programmed death ligand 1 expression. The primary endpoint was overall survival (OS); secondary endpoints included objective response rate, progression-free survival, and safety.ResultsOS was significantly improved with nivolumab (n = 338) versus docetaxel (n = 166); median OS (95% confidence interval): 12.0 (10.4–14.0) versus 9.6 (7.6–11.2) months, respectively; hazard ratio (97.7% confidence interval): 0.68 (0.52–0.90); p = 0.0006. Objective response rate was 17% with nivolumab versus 4% with docetaxel; median duration of response was not reached versus 5.3 months. Minimum follow-up was 8.8 months. The frequency of grade 3 or greater treatment-related adverse events was 10% with nivolumab and 48% with docetaxel.ConclusionsThis is the first phase III study in a predominantly Chinese population reporting results with a programmed death 1 inhibitor. In this population with previously treated advanced NSCLC, nivolumab improved OS versus docetaxel. Results were consistent with global CheckMate 017 and 057 studies.
Characterization of Myeloid-Derived Suppressor Cells and Tumor Associated Macrophages Using MultiOmyxTM Hyperplexed Immunofluorescence Assay in Hodgkin Lymphoma
Authors: Qingyan Au, Jun Fang, Anna Juncker-Jensen, Judy Kuo, Eric Leones, Flora Sahafi, RaghavKrishna Padmanabhan, Nicholas Hoe, Josette William
Journal: Blood (2018)
Thymectomy abrogates resistance to ethylnitrosourea-induced carcinogenesis in the peripheral nervous system of BDIV rats
Authors: Judith A.-M. Marx, Ansgar J. Röhrborn, Andrea Kindler-Röhrborn
Journal: Cancer Research (2005)

3908  The knowledge about genes and effector mechanisms mediating susceptibility and resistance towards the development of malignant tumors is limited. The induction of malignant tumors of the peripheral nervous system (PNS; schwannomas) by the alkylating carcinogen N-ethyl-N-Nitrosourea (EtNU) in rats of the inbred BD strains is a suitable model to examine the mechanisms leading to differential tumor susceptibility. While > 85% of rats of the BDIX strain develop malignant schwannomas predominantly of the trigeminal nerves BDIV rats are almost completely resistant.A point mutation in the transmembrane region of the neu/erbB-2 gene is an early event in EtNU-incuced PNS carcinogenesis and has proved to be a marker of Schwann precursor cells at high risk of subsequent malignant transformation. Previous quantitative mutation analyses in trigeminal nerves of EtNU treated BDIV and BDIX rats revealed that tumor resistance mechanisms in the BDIV rat include recognition and elimination of neu-mutant premalignant cells.To uncover the underlying cellular and molecular processes, the involvement of a cellular immune response was investigated using immunohistochemistry on sections of trigeminal nerves from different time points after carcinogen exposure. A significant increase of CD8+ cytotoxic T cells, CD4+ T helper cells and ED1+ macrophages was detected in both rat strains after exposure to EtNU compared to the untreated controls. However there was no difference in cell numbers between resistant BDIV and sensitive BDIX rats making it uncertain whether T cells play a functional role in the elimination process. Therefore T cell maturation was prevented in BDIV rats by thymectomy after EtNU treatment on postnatal day one. In an ongoing study one group of rats was thymectomized for long time observation of tumor development (maximum 24 months). To monitor the efficiency of thymectomy peripheral blood T cells were quantified by FACS analysis at different time points. A second group of animals was operated for potential detection of residual T cells in trigeminal nerves by immunohistochemistry.So far a significant proportion (20%) of thymectomized BDIV rats developed malignant schwannomas, predominantly of the trigeminal nerves after a median latency time of 217 days with the great majority of thymectomized animals being still alive. These data demonstrate the important role of T cells in the prevention of EtNU-induced tumor development in the PNS of BDIV rats and suggest that the T cells in BDIX rats might display insufficient function regarding the elimination of premalignant Schwann cells, so that functional differences of the T cell response might translate into tumor susceptibility and resistance of BDIX and BDIV rats. Alternatively individual tumor risk in BD rats could be related to the different capability to escape or inhibit T cells by mechanisms yet unknown.
FRI0580 Quantitative mri of single vs. multiple joints in juvenile idiopathic arthritis as predictive measure of clinical outcomes
Authors: N. Tzaribachev, O. Kubassova, M. Hinton, M. Boesen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Clinical examination of juvenile idiopathic arthritis (JIA) patients does not always adequately reflect disease activity, whereas quantitative Dynamic Contrast Enhanced (DCE)-MRI based biomarkers extracted from images of multiple joints have been shown to reliably predict the course of the disease <sup>1</sup>. <h3>Objectives</h3> To investigate the association between DCE-MRI measures of inflammation in a single and in multiple joints and the treatment related clinical changes. <h3>Methods</h3> 18 patients (12 girls, med. age 12.6 years, med. disease 1.2 years) with polyarticular JIA with more than 3 affected joints or intolerance to more than 3 months of MTX were given Etanercept. Their most clinically affected hand was imaged with DCE-MRI (0.2T Esaote C-Scan) at baseline, 3 and 6 months following the treatment. DCE-MRI was analysed using dedicated software package (DYNAMIKA, IAG). Dynamic Enhanced MRI Quantification (DEMRIQ-V) was calculated as the volume of enhancing voxels within Region of Interest placed around a single or multiple MCPJs. DEMRIQ-V was also weighted by the mean of Maximum Enhancement (ME) and Initial Rate of Enhancement (IRE), the parameters corresponding to the height and slope of the signal intensity vs time curves extracted from the enhancing voxels.<sup>2</sup> Clinical scores included active joint (AJ) count. Involvement of less than 3 AJ was considered a clinical response. The differences in DEMRIQ-V between the visits were analysed using t-test, assuming p&lt;0.05* to be statistically significant and p&lt;0.25** to be clinically meaningful. <h3>Results</h3> In all patients, in clinically unaffected joints, MRI was able to detect subclinical disease, and in all but 3 patients, significant and/or clinically meaningful changes were documented for DEMRIQ-ME. In 4 patients, DEMRIQ-V scores showed corresponding clinical changes whereas all other patients these markers were non-concordant. DEMRIQ-V score was predictive of clinical outcome: - · in 5 patients, improvement of DEMRIQ-V at month 3 predicted response to treatment at month 6; - · in 4 patients, increase or persistence of a high DEMRIQ-V at month 3 predicted non-response to treatment at month 6; <h3>- ·</h3> DEMRIQ-V measured in a single most affected joint was as predictive as when it was measured in all MCPJs. <h3>Conclusions</h3> We conclude that DCE-MRI's ability to detect early disease can reliably support clinical examination. Use of DEMRIQ-V and DEMRIQ-ME scores, which either followed clinical response (DEMRIQ-ME) or predicted clinical outcomes at 6 months (DEMRIQ-V) in most patients can support early clinical and research decisions. <h3>References</h3> [1] Kubassova O, et al. Arthritis Rheumatol2017;69(suppl 10). [2] Kubassova O, et al. Eur J Radiol2010Jun;74(3):e67–72. <h3>Acknowledgements</h3> Support by Pfizer <h3>Disclosure of Interest</h3> None declared