tbuckley/cabot-search huggingface dataset:
Validation of a questionnaire algorithm based on repeated open application testing with the constituents of fragrance mix I
Authors: M. Bruze, M. Engfeldt, R. Ofenloch, P. Elsner, M. Goncalo, M. Isaksson, L. Naldi, M.‐L. Schuttelaar, Å. Svensson, T. Diepgen
Journal: British Journal of Dermatology (2019)

In a European study on contact allergy in the general population, it was hypothesized that the combination of contact allergy to a fragrance together with a history indicating dermatitis at exposure, and thereafter subsequent avoidance of scented products, implied a diagnosis of allergic contact dermatitis. The primary aim of this study was to validate this hypothesis and algorithm. The secondary aim was to investigate whether there was any association between the outcome of the repeated open application test (ROAT) and the patch test reactivity. In total, 109 patients with and without contact allergy to fragrance mix (FM) I were recruited. Volunteers from six European dermatology clinics participated in the study including a patch test and a ROAT. Positive ROAT reactions were noted in 26 of the 44 volunteers with contact allergy to FM I. None of the volunteers reacted to the vehicle (P < 0·001). More individuals with a positive algorithm had positive ROATs than those with a negative algorithm. However, the difference was not statistically significant. The lower the patch test concentration eliciting a positive test reaction, the more likely a positive ROAT and the more likely that the positive ROAT appeared early during the investigative period. The algorithm used in this study was not substantiated in this ROAT set‐up. The stronger the patch test reactivity the more likely was a positive ROAT and the more likely it was that the positive ROAT appeared early during the application period. What's already known about this topic? To the best of our knowledge, a scientifically designed and conducted repeated open application test (ROAT) has never been performed before to validate a diagnosis of allergic contact dermatitis partly based on a questionnaire. What does this study add? This is the largest controlled, randomized and blinded ROAT performed to date. Higher patch test reactivity to fragrance mix I indicated a greater likelihood of a positive ROAT. What are the clinical implications of this work? Further refinement of the questions is required in order to diagnose allergic contact dermatitis from fragrances based on a questionnaire.
THU0542 THE PSYCHIATRIC DISORDERS IN CHILDHOOD, ADOLESCENCE AND YOUNG ADULTS WITH JUVENILE IDIOPATHIC ARTHRITIS PATIENTS IN FINLAND
Authors: Minna Kyllönen, Hannu Kautiainen, Kari Puolakka, Paula Vähäsalo
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Reported psychiatric morbidity among juvenile idiopathic arthritis (JIA) patients has varied between 9.3-51% (1-3). The variation between studies can be explained by differences in the study populations (age, disease duration and disease state) and differences in the study methods (1-3). Depression and anxiety are the most common disorders, but most studies were based on questionnaires to investigate incidence of only these two diseases (1,3). <h3>Objectives</h3> To explore mental and behavioral disorders in JIA patients compared to the control population. <h3>Methods</h3> All incidents patients with JIA during 2000-2014 were collected from the nationwide register, maintained by the Social Insurance Institution of Finland (4). The National Population Registry identified three controls (similar regarding age, sex and residence) for each case. They were followed up together until 31<sup>st</sup>Dec 2015. ICD-10 codes of psychiatric diagnosis (F10-F99) were picked up from the Care Register for Health Care of the National Institute for Health and Welfare. <h3>Results</h3> During 28,941 follow-up years, 974 (23%) JIA patients were diagnosed with mental or behavioral disorders, whereas the number in the control group was 1,807 (15%), (p&lt;0.001). Neurotic, stress-related and somatoform disorders (F40-48) and mood (affective) disorders (F30-39) were the most common psychiatric diagnoses in the JIA (10.41% and 8.18%) and in the control group (5.44% and 5.13%). The odds ratio for neurotic disorders (F40-48) was 2.02 (95% Cl 1.78-2.29) and for mood disorders (F30-39) 1.65 (95% Cl 1.44-1.89). Additionally, JIA was statistically significantly associated with behavioral and emotional disorders and disorders of psychological development (Table). Female patients with JIA had higher odds ratios than males for all mental and behavioral disorders except behavioral syndromes (F50-59), for which males with JIA had higher odds ratio. <h3>Conclusion</h3> The risk of psychiatric disorders in JIA patients is increased. <h3>References</h3> [1] Raab A, Sengler C, Niewerth M, Klotsche J, Horneff G, Zink A, et al. Comorbidity profiles among adult patients with juvenile idiopathic arthritis: results of a biologic register. Clin Exp Rheumatol 2013;31(5): 796-802. [2] Vandvik I. Mental Health and psychosocial functioning in children with recent onset of rheumatic disease. J. Child Psychol. Psychiat. 1990; 3:961-971. [3] Packham JC, Hall MA &amp; Pimm TJ. Long-term follow-up of 246 adults with juvenile idiopathic arthritis: predictive factors for mood and pain. Rheumatology (Oxford) 2002;41(12): 1444-1449. [4] Kyllönen MS, Kautiainen H, Puolakka K, Vähäsalo P. The mortality rate and causes of death among juvenile idiopathic arthritis patients in Finland. Clin exp Rheumatol. 2019; in press. <h3>Disclosure of Interests</h3> None declared
PB1833 PRIMARY CARDIAC LYMPHOMA
Authors: J.M. Freue, R. Marin Castellanos, D. Silveyra, N. Lalor, J.L. Scapellato, R. Campestri
Journal: HemaSphere (2019)

Background: Primary cardiac lymphomas (PCL) are rare, with a fatal course unless diagnosed and treated in time. Non‐neoplastic causes such as infections and thrombi account for most cardiac masses. The most common cardiac tumors are benign, such as myxomas, being sarcomas the most frequent malignancy. Symptoms are inespecific, PCL can present as heart failure, arrythmias, vena cava thrombosis, thromboembolic disease. Patients must examined thoroughly, including echocardiography, CT or MRI and bone marrow biopsy. Final diagnosis will require a biopsy of the cardiac mass. Treatment is with chemotherapies according to lymphoma subtype, usually anthracycline based regimens. If ventricular outflow tract is compromised surgery may be needed due to hemodynamic instability which is associated with a very bad prognosis Aims: To describe a case of a patient with PCL Methods: A case report Results: Case: a 59 years old woman consulted for bilateral lower extremities edema and abdominal distension. She had a previous history of HIV infection diagnosed 10 years ago treated with nevirapine, lamivudine and zidovudine. Last CD4 count was 283/mm3 and viral load undetectable. Laboratory: Hg 13,5 g/dl, WBC 9400/mm3 (Neutrophil 80%, no atypical cells or blast in blood smear), platelet 344000/mm3, coagulation test, protein electrophoresis, hepatic and renal function were normal, D‐dimer 6 mg/l (normal&lt; 0,5), Hepatitis C and B test were negative, LDH 1200U/l(100‐210) Abdominal ultrasound showed ascites, liver and spleen were normal. Serum‐Ascites albumin gradient was &gt; 1,1 g/dl (suggestive of transudate). AngioCT: ascites, thrombosis of iliac, right renal and inferior cava vein (IVC) thrombosis, cardiac mass in both auricles and right ventricle extending to IVC, signs of segmentary pulmonary embolism (PE). Echocardiogram: atrial mass invading interauricular septum and occupying almost 50% of atrial surface. Anticoagulation with enoxaparin 1 mg/kg BID was initiated and an angiography guided biopsy was done. Preliminary results were compatible with lymphoma so we added metilprednisolone 500 mg/day for 3 days with no clinical improvement. Chemotherapy was initiated with CHOP + methotrexate. Bone marrow biopsy showed no lymphoma infiltration and pathology results of the cardiac mass were compatible with pax5, CD10 and TDT positive b cell lymphoblastic lymphoma. On day 9, despite clinical improvement, she presented cardiac arrest and died. An echocardiogram done than day showed a 50% reduction in the mass size and fragmentation of it. An angio CT was done to rule out PE but was negative. Summary/Conclusion: PCL diagnoses is challenging and may have a dismal clinical course. A prompt diagnostic is necessary as soon as possible. We present this case due to the rarity of a solitary cardiac mass as the presentation of lymphoblastic lymphomas. image
Type I interferon suppresses tumor growth through activating the STAT3-granzyme B pathway in tumor-infiltrating cytotoxic T lymphocytes
Authors: Chunwan Lu, John D. Klement, Mohammed L. Ibrahim, Wei Xiao, Priscilla S. Redd, Asha Nayak-Kapoor, Gang Zhou, Kebin Liu
Journal: Journal for ImmunoTherapy of Cancer (2019)

Type I interferons (IFN-I) have recently emerged as key regulators of tumor response to chemotherapy and immunotherapy. However, IFN-I function in cytotoxic T lymphocytes (CTLs) in the tumor microenvironment is largely unknown.
Chromosome evolution at the origin of the ancestral vertebrate genome
Authors: Christine Sacerdot, Alexandra Louis, Céline Bon, Camille Berthelot, Hugues Roest Crollius
Journal: Genome biology (2018)

It has been proposed that more than 450 million years ago, two successive whole genome duplications took place in a marine chordate lineage before leading to the common ancestor of vertebrates. A precise reconstruction of these founding events would provide a framework to better understand the impact of these early whole genome duplications on extant vertebrates.We reconstruct the evolution of chromosomes at the beginning of vertebrate evolution. We first compare 61 extant animal genomes to reconstruct the highly contiguous order of genes in a 326-million-year-old ancestral Amniota genome. In this genome, we establish a well-supported list of duplicated genes originating from the two whole genome duplications to identify tetrads of duplicated chromosomes. From this, we reconstruct a chronology in which a pre-vertebrate genome composed of 17 chromosomes duplicated to 34 chromosomes and was subject to seven chromosome fusions before duplicating again into 54 chromosomes. After the separation of the lineage of Gnathostomata (jawed vertebrates) from Cyclostomata (extant jawless fish), four more fusions took place to form the ancestral Euteleostomi (bony vertebrates) genome of 50 chromosomes.These results firmly establish the occurrence of two whole genome duplications in the lineage that precedes the ancestor of vertebrates, resolving in particular the ambiguity raised by the analysis of the lamprey genome. This work provides a foundation for studying the evolution of vertebrate chromosomes from the standpoint of a common ancestor and particularly the pattern of duplicate gene retention and loss that resulted in the gene composition of extant vertebrate genomes.
Interlesional Heterogeneity of Metastatic Neuroendocrine Tumors Based on 18F-DOPA PET/CT
Authors: Lotte D. de Hosson, Aline M. van der Loo–van der Schaaf, Ronald Boellaard, Johannes H. van Snick, Elisabeth G. E. de Vries, Adrienne H. Brouwers, Annemiek M. E. Walenkamp
Journal: Clinical Nuclear Medicine (2019)

Neuroendocrine tumors (NETs) can produce neuroendocrine amines resulting in symptoms. Selecting the most active amine-producing tumor lesions for local treatment might be beneficial for patients with metastatic small intestinal NET. Tumor burden correlates with catecholamine pathway activity. We analyzed interlesional heterogeneity with F-DOPA PET scans in patients with small intestinal NET and investigated if lesions with substantially higher F-DOPA uptake could be identified.In this retrospective, observational study, the F-DOPA uptake was calculated by dividing SUVpeak of the lesion by the SUVmean of the background organ. The magnitude of heterogeneity between lesions within a patient was calculated by dividing the lesion with the highest by the one with the lowest F-DOPA uptake. Lesions with a higher F-DOPA uptake than the upper inner or outer fence (>1.5 or 3 times the interquartile range above the third quartile) were defined as lesions with mild or extreme high F-DOPA uptake, respectively, and presence of these was determined in patients with 10 lesions or more.F-DOPA was detected over 680 lesions in 38 patients, of which 35 were serotonin producing. F-DOPA uptake varied with a median of 8-fold up to 44-fold between lesions within a patient. In 12 of 20 evaluable patients, lesions with mild high F-DOPA uptake were found, and in 5, lesions with extreme high F-DOPA uptake.F-DOPA-PET showed considerable heterogeneity in F-DOPA uptake between tumor lesions and identified lesions within patients with mild or extreme high F-DOPA uptake.
AB0205 TREATMENT OF INFLAMMATORY MYOSITIS IN CLINICAL PRACTICE: ANALYSIS OF THE REGISTRY OF INFLAMMATORY MYOSITIS FROM THE MADRID COMMUNITY (REMICAM)
Authors: Beatriz Joven-Ibáñez, Laura Nuño, Francisco J. López-Longo, Julia Martinez-Barrio, Carmen Larena, Valentina Maldonado, Carmen Barbadillo, Paloma García de la Peña, Irene Llorente, Eva Tomero Muriel, Ana Pérez Gómez, Henry Moruno, Tatiana Cobo-Ibáñez, Raquel Almodovar, Leticia Lojo, María Jesús García de Yébenes, Patricia Carreira
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Although glucocorticoids (GC) remain the cornerstone in the treatment of inflammatory myositis (IM), the management of these processes is not yet standardized. Experts recommend early use of immunosuppressants (IS), in order to prevent GC side effects. It is not known what is the actual management in clinical practice. <h3>Objectives</h3> To describe the management of IM in REMICAM registry, and to identify differences according to disease subtype (polymyositis (PM), or dermatomyositis (DM)), and to the year of diagnosis (before or after 2000). <h3>Methods</h3> All patients from REMICAM were included (1). A descriptive analysis of the different therapies (GC, IS, biologics, IV immunoglobulins (IVIG), and hydroxychloroquine HCL) was performed, attending to possible differences between IM subtype and the year of diagnosis. T student and Chi square tests were used for quantitative and qualitative variables, respectively. <h3>Results</h3> From 479 patients (74% females, 52% PM, 44±22 y at diagnosis, 10±8 y follow up), 473 (99%) received oral GC, 50/344 (15%) pulses GC, 78 (16%) HCL, 355 (74%) IS (methotrexate MTX 228, leflunomide 10, azathioprine AZA190, cyclophosphamide 44, mycophenolate MP 38, cyclosporine 32), 55 (12%) biologics (rituximab 45, abatacept 2, aTNF 16) and 79 (17%) IVIG. Differences according to IM subtype (1), and to the year of diagnosis (2), are shown in Tables. <h3>Conclusion</h3> The therapeutic management of IM has changed over the last few years, with a clear increase and earlier use of IS in patients diagnosed after 2000. In spite of a more aggressive approach in recent years, severe infections are less frequent, perhaps as a consequence of lower GC doses. The management of PM and DM is similar. <h3>Reference</h3> [1] Nuño L, Rheumatol Clin2017; 13:331-337 <h3>Disclosure of Interests</h3> Beatriz Joven-Ibáñez Speakers bureau: Celgene, Novartis, MSD, Pfizer, AbbVie, and Janssen, Laura Nuño: None declared, Francisco J López-Longo: None declared, Julia Martinez-Barrio: None declared, Carmen Larena: None declared, Valentina Maldonado : None declared, Carmen Barbadillo: None declared, Paloma García de la Peña: None declared, Irene Llorente : None declared, Eva Tomero Muriel: None declared, Ana Pérez Gómez: None declared, Henry Moruno : None declared, Tatiana Cobo-Ibáñez: None declared, RAQUEL ALMODOVAR: None declared, LETICIA LOJO : None declared, María Jesús García de Yébenes: None declared, Patricia Carreira: None declared
Left Atrial Appendage Morphology Is Associated With Cryptogenic Stroke
Authors: Agne Adukauskaite, Fabian Barbieri, Thomas Senoner, Fabian Plank, Christoph Beyer, Michael Knoflach, Christian Boehme, Florian Hintringer, Silvana Mueller, Fabiola Cartes-Zumelzu, Wolfgang Dichtl, Gudrun Feuchtner
Journal: JACC. Cardiovascular imaging (2019)
PB2404 ARE DAA SAFE AND EFFECTIVE IN TREATMENT OF THALASSEMIA PATIENTS WITH CHRONIC HCV?
Authors: S. El Ashwah, N. Eisa, E. A. Ghoneem, S. El‐Etreby
Journal: HemaSphere (2019)

Background: Hepatitis C virus (HCV) infection is a major cause of liver‐related morbidity and mortality among thalassemic patients. Direct‐acting antivirals agents (DAAs) are highly effective and well‐tolerated by chronic HCV patients. Aims: This study was conducted to evaluate the safety and efficacy of DAAs in treatment of thalassemic patients with chronic HCV. Methods: This prospective study enrolled 22 thalassemic patients with chronic HCV infection proved by positive RT PCR HCV RNA from a total 40 patients who were positive for HCV ELISA test. Severity of liver disease was assessed in all patients. They received treatment of HCV according to guidelines of the National Committee for Control of Viral Hepatitis (NCCVH) in Egypt. About, 16 (72.72%) patients were treated with a sofosbuvir plus daclatasvir, and the other 6 (27.27 %) patients received sofosbuvir plus ledipasvir for 3 months. Primary end point was assessed by achievement of sustained virological response (SVR) at 12 weeks. Secondary end point was assessed by recording any side effects, transfusion requirements if need or stoppage of treatment. Results: The mean age of our patients was 29 years and 50% of them were male. Only 2 (9.09%) of them had compensated cirrhosis. SVR 12 was achieved in all patients (100%). Only one case required treatment discontinuation for one week due to acute kidney injury after prolonged use of NSAIDs then resumed DAAs after decline of creatinine to normal value. The most common side effects were fatigue (18%), progressive anemia (13.63%), requiring blood transfusion that occurred in three of the patients who received sofosbuvir plus daclatasvir, and lastly, headache (4.5%). There was no statistically significant difference in the level of hemoglobin before and after DAAs (8.5 ± 1.34 gm/dl vs 8.6 ± 1.38 gm/dl with p value = 0.484). There was significant improvement of mean ALT values after treatment compared to baseline one (42.45 ± 18.56 vs 57.29 ± 35.07 with p value &lt; 0.0005). Summary/Conclusion: Direct acting antiviral drugs namely sofosbuvir plus daclatasvir or sofosbuvir plus ledipasvir are safe, effective, and well tolerated regimens in thalassemic patients with chronic HCV.
Randomized phase II study of carboplatin and paclitaxel with either linifanib or placebo for advanced nonsquamous NSCLC.
Authors: Suresh S. Ramalingam, Mikhail Shtivelband, Ross A. Soo, Carlos H. Barrios, Anatoly Makhson, J.G.M. Segalla, Kenneth B. Pittman, Petr Kolman, Jose Rodrigues Pereira, Gordan Srkalovic, Chandra Prakash Belani, Rita Axelrod, Taofeek Kunle Owonikoko, Jiang Qian, Mark D. McKee, Justin L. Ricker, Dawn M. Carlson, Vera A. Gorbunova
Journal: Journal of Clinical Oncology (2012)

7512 Background: Linifanib is a potent and selective inhibitor of VEGF and PDGF receptors with modest single-agent activity in NSCLC. We evaluated the combination of linifanib with carboplatin (C) and paclitaxel (P) for first-line therapy of advanced non-squamous NSCLC. Methods: Patients (pts) with stage IIIB/IV, non-squamous NSCLC, stratified by ECOG PS and gender, were randomized to receive up to six 3-wk cycles of C (AUC 6 mg/ml/min) and P (200 mg/m 2 ) with daily placebo (Arm A), linifanib 7.5 mg (Arm B), or linifanib 12.5 mg (Arm C). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), 12 m survival rate, and objective response rate (ORR). Safety was assessed by NCI-CTCAE v3.0. Results: 138 pts were randomized at 37 sites in 6 countries. Baseline characteristics were: median age, 61 y; men, 57%; smoker, 84%. Efficacy results are shown in the table. Thrombocytopenia was the only Grade 3/4 AE significantly higher on linifanib (Arm B: 16.7%; Arm C: 29.8%) vs. placebo (2.1%). Other adverse events (AEs) related to the dose of linifanib were diarrhea, thrombocytopenia, hypertension, weight loss, palmar-plantar erythrodysaesthesia syndrome, and hypothyroidism. Analysis of samples for predictive biomarkers including serum VEGF and placental growth factor are underway. Conclusions: The addition of linifanib to chemotherapy was tolerable at the doses tested and resulted in a significant improvement in PFS, with a modest survival improvement for Arm C in first-line therapy of advanced non-squamous NSCLC. [Table: see text]
Vitamin C kills thyroid cancer cells through ROS-dependent inhibition of MAPK/ERK and PI3K/AKT pathways via distinct mechanisms
Authors: Xi Su, Zhen Shen, Qi Yang, Fang Sui, Jun Pu, Jingjing Ma, Sharui Ma, Demao Yao, Meiju Ji, Peng Hou
Journal: Theranostics (2019)

Background:Vitamin C has been demonstrated to kill BRAF mutant colorectal cancer cells selectively.BRAF mutation is the most common genetic alteration in thyroid tumor development and progression; however, the antitumor efficacy of vitamin C in thyroid cancer remains to be explored. Methods:The effect of vitamin C on thyroid cancer cell proliferation and apoptosis was assessed by the MTT assay and flow cytometry.Xenograft and transgenic mouse models were used to determine its in vivo antitumor activity of vitamin C. Molecular and biochemical methods were used to elucidate the underlying mechanisms of anticancer activity of vitamin C in thyroid cancer.Results: Pharmaceutical concentration of vitamin C significantly inhibited thyroid cancer cell proliferation and induced cell apoptosis regardless of BRAF mutation status.We demonstrated that the elevated level of Vitamin C in the plasma following a high dose of intraperitoneal injection dramatically inhibited the growth of xenograft tumors.Similar results were obtained in the transgenic mouse model.Mechanistically, vitamin C eradicated BRAF wild-type thyroid cancer cells through ROS-mediated decrease in the activity of EGF/EGFR-MAPK/ERK signaling and an increase in AKT ubiquitination and degradation.On the other hand, vitamin C exerted its antitumor activity in BRAF mutant thyroid cancer cells by inhibiting the activity of ATP-dependent MAPK/ERK signaling and inducing proteasome degradation of AKT via the ROS-dependent pathway.Conclusions: Our data demonstrate that vitamin C kills thyroid cancer cells by inhibiting MAPK/ERK and PI3K/AKT pathways via a ROS-dependent mechanism and suggest that pharmaceutical concentration of vitamin C has potential clinical use in thyroid cancer therapy.