tbuckley/cabot-search huggingface dataset:
The exposome in atopic dermatitis
Authors: Nicholas Stefanovic, Carsten Flohr, Alan D. Irvine
Journal: Allergy (2019)

Abstract Atopic dermatitis (AD) is a complex inflammatory disorder with multiple interactions between genetic, immune and external factors. The sum of external factors that an individual is exposed to throughout their lifetime is termed the exposome. The exposome spans multiple domains from population to molecular levels and, in combination with genetic factors, holds the key to understanding the phenotypic diversity seen in AD patients. Exposomal domains are categorized into nonspecific (human and natural factors affecting populations), specific (eg humidity, ultraviolet radiation, diet, pollution, allergens, water hardness) and internal (cutaneous and gut microbiota and host cell interaction) exposures. The skin, as the organ that most directly interacts with and adapts to the external environment, is a prime target for exploration of exposomal influences on disease. Given the well‐recognized physical environmental influences on AD, this condition could be much better understood through insightful exposomal research. In this narrative review, we examine each domain in turn, highlighting current understanding of the mechanisms by which exposomal influences modulate AD pathogenesis at distinct points in time. We highlight current approaches to exposome modification in AD and other allergic disease and propose future directions for exposome characterization and modification using novel research techniques.
Medical associates: junior doctors should pick their battles
Authors: Norman Briffa
Journal: BMJ (2019)

The BMA junior doctors’ vote against professional equivalency for medical associate professionals is counterintuitive and shortsighted.1 What is professional equivalency? Doctors are doctors, with their own terms and conditions, pay, regulator, and undergraduate and postgraduate courses and exams, and physician associates and surgical care practitioners are what they are.

In cardiothoracic surgery, surgical care practitioners have performed surgical tasks such as conduit harvest since the early 1990s. Senior house officers …
THU0451 CHONDROITIN SULFATE USE AND INCIDENCE OF CANCER: A LONGITUDINAL ANALYSIS OF THE OSTEOARTHRITIS INITIATIVE DATA
Authors: Ivan Shirinsky, Valery Shirinsky
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Chondroitin sulfate (CS) is widely used nutritional supplement for the treatment of osteoarthritis. There is growing <i>in vitro</i> evidence that CS may play a role in oncogenesis and metastasis of several solid tumors including melanoma [1] and breast cancer [2]. The data evaluating pro-oncogenic effects of CS in humans are lacking. <h3>Objectives</h3> To assess influence of CS use on incidence of cancer. <h3>Methods</h3> For the current study we used 6-year longitudinal data obtained from the Osteoarthritis Initiative (OAI) progression (n= 1390) and incidence (n = 3284) subcohorts, which are publically available at https://oai.nih.gov. To reduce the risk of bias, only participants who did not take CS at baseline were included in the analysis (a "new-user" design). Incident cancer was defined as an occurrence of self-reported cancer, other than skin cancer, leukemia or lymphoma. The information on self-reported cancer was collected from the Charlson Comorbidity Index. CS users with cancer were defined using the following criteria (1) a person who used CS for at least 6 months (2) chondroitin use was at least 1 year before the incident self-reported cancer. For CS users without a cancer, the duration of CS use had to be at least 6 months. All other participants were classified as non-users. To examine the cancer risk for CS users compared with non-users, we calculated the incidence rate ratios (IRRs), adjusting for age (2-year age groups), using the Mantel-Haenszel test. <h3>Results</h3> A total of 3167 participants neither having cancer nor taking CS at baseline were included in the analysis. There were 570 (21.95%) new users of CS. We identified 160 (6.2%) and 37 (6.5%) cases of incident self-reported cancer in the non-users and users groups, respectively. The adjusted IRR for the association between CS use and cancer was 0.22 (95% CI 0.77-1.62) which was not statistically significant (p = 0.64). <h3>Conclusion</h3> CS use was not associated with excess overall incidence of self-reported cancers. Nonetheless, given the strong <i>in vitro</i> evidence of CS pro-oncogenic effects on several types of tumors there is a need for further epidemiological data evaluating CS effects on specific kinds of cancer. <h3>References</h3> [1] Lin R, Xia S, Shan C, Chen D, Liu Y, Gao X, Wang M, Kang HB, Pan Y, Liu S, et al: The Dietary Supplement Chondroitin-4-Sulfate Exhibits Oncogene-Specific Pro-tumor Effects on BRAF V600E Melanoma Cells. Mol Cell 2018, 69(6):923-937 e928. [2] Cooney CA, Jousheghany F, Yao-Borengasser A, Phanavanh B, Gomes T, Kieber-Emmons AM, Siegel ER, Suva LJ, Ferrone S, Kieber-Emmons T, et al: Chondroitin sulfates play a major role in breast cancer metastasis: a role for CSPG4 and CHST11 gene expression in forming surface P-selectin ligands in aggressive breast cancer cells. Breast Cancer Res 2011, 13(3):R58. <h3>Disclosure of Interests</h3> None declared
Letter to the editor: Chikungunya infection in travellers to Thailand: additional United Kingdom cases identified by specialist laboratory
Authors: Kirsten MacGregor, Gemma Buckland-Merrett, Daniel Bailey, Emma Aarons
Journal: Eurosurveillance (2019)

Preview this article: Letter to the editor: Chikungunya infection in travellers to Thailand: additional United Kingdom cases identified by specialist laboratory, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/24/24/eurosurv-24-24-5-1.gif
Drug-coated balloon for treatment of de-novo coronary artery lesions in patients with high bleeding risk (DEBUT): a single-blind, randomised, non-inferiority trial
Authors: Tuomas T Rissanen, Sanna Uskela, Jaakko Eränen, Pirjo Mäntylä, Annika Olli, Hannu Romppanen, Antti Siljander, Mikko Pietilä, Mikko J Minkkinen, Jerry Tervo, Jussi M Kärkkäinen, Aija Vatanen, Anssi Perälä, Miriam Müller, Pekka Porela, Eeva Palojoki
Journal: The Lancet (2019)
PB1855 UPFRONT HAPLOIDENTICAL TRANSPLANT IN YOUNG SEVERE APLASTIC ANEMIA PATIENTS ‐ RESULTS OF A PILOT STUDY FROM SOUTH INDIA
Authors: K. Kumar, C. Subash
Journal: HemaSphere (2019)

Background: Haploidentical bone marrow transplant is one of the second line treatment option in severe aplastic anemia patients failing immunosuppressive therapy. In younger patients, allogeneic bone marrow transplant from a matched sibling donor gives more than 80% long‐term remission rates. But unfortunately, only 30% patients will have a matched sibling donor. In a middle‐income country like India, the availability and affordability of patients to an unrelated donor is limited. Most of our patients have got a single chance for treatment and many relapsed patients go into palliative care. Aims: Aim of the present study is to evaluate the efficacy and safety of upfront Haploidentical bone marrow transplant in less than 40 years old severe aplastic anemia patients not having a 10/10 matched donor. Methods: This is a prospective non‐randomized single center study conducted during the period from January 2017 to June 2018. Eleven patients less than 40 years old underwent upfront Haploidentical bone marrow transplantation for severe aplastic anemia during the above period. Peripheral blood stem cell was used in all patients.FLU‐ATG‐PTcy was the conditioning regimen used in all patients with Cyclosporine + MMF based GVHD prophylaxis. This study got clearance from institutional review board and the transplant was sponsored by government. Results: In six patient's donors were parents (Mother in four and father in two) and rest of the donors were siblings. Two were Fanconi positive and none had a PNH clone. Seven were 5/10 matched, three were 6/10 and one was 7/10 matched. All patients had engraftment at a median of 11 days (range 8 to 13 days). One patient had fatal grade IV acute GVHD and succumbed to GVHD on day +36. Seven patients (64%) had grade I/II GVHD and three patients (27%) had grade III GVHD. 64% patients had grade I/II chronic GVHD at date cut off of January 2019. 10 patients (89%) attained complete remission and were alive till January 2019.The overall survival rate at one year post transplant was around 89% which is better than immuno‐supressive therapy in this age group. No differnces were observed in engraftment dates or survival outcomes based on type of donor and degree of mismatch. The study patients are very small to get statistically significant rates. Summary/Conclusion: With nearly 90% overall remission and survival rate at one year, upfront haploidentical transplant seems to be a safe and effective option in young patients with severe aplastic anemia. This will help to reduce the cost of Matched unrelated donor stem cells significantly in resource poor countries and increase the number of patients opting for a curative treatment.
Oxidative stress in vagal neurons promotes parkinsonian pathology and intercellular α-synuclein transfer
Authors: Ruth E. Musgrove, Michael Helwig, Eun-Jin Bae, Helia Aboutalebi, Seung-Jae Lee, Ayse Ulusoy, Donato A. Di Monte
Journal: Journal of Clinical Investigation (2019)

Specific neuronal populations display high vulnerability to pathological processes in Parkinson's disease (PD). The dorsal motor nucleus of the vagus nerve (DMnX) is a primary site of pathological α-synuclein deposition and may play a key role in the spreading of α-synuclein lesions within and outside the CNS. Using in vivo models, we show that cholinergic neurons forming this nucleus are particularly susceptible to oxidative challenges and accumulation of reactive oxidative species (ROS). Targeted α-synuclein overexpression within these neurons triggered an oxidative stress that became significantly more pronounced after exposure to the ROS-generating agent paraquat. A more severe oxidative stress resulted in enhanced production of oxidatively modified forms of α-synuclein, increased α-synuclein aggregation into oligomeric species and marked degeneration of DMnX neurons. Enhanced oxidative stress also affected neuron-to-neuron protein transfer, causing an increased spreading of α-synuclein from the DMnX toward more rostral brain regions. In vitro experiments confirmed a greater propensity of α-synuclein to pass from cell to cell under pro-oxidant conditions, and identified nitrated α-synuclein forms as highly transferable protein species. These findings substantiate the relevance of oxidative injury in PD pathogenetic processes, establish a relationship between oxidative stress and vulnerability to α-synuclein pathology and define a new mechanism, enhanced cell-to-cell α-synuclein transmission, by which oxidative stress could promote PD development and progression.
Abstract 13420: Risk Factors Associated with Development of Paroxysmal versus Persistent Atrial Fibrillation
Authors: Roopinder K Sandhu, David Conen, Usha B Tedrow, Kate Fitzgerald, Robert Glynn, Christine M Albert
Journal: Circulation (2012)

Introduction: Several lifestyle and cardiovascular risk factors are associated with incident atrial fibrillation (AF). However, few studies have examined whether these risk factors differ with rega...
THU0091 DEPRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS: UNDER RECOGNIZED, UNDERTREATED AND ASSOCIATED WITH POORER CLINICAL STATUS AND LOWER RATES OF REMISSION IN ROUTINE CARE
Authors: Rosa Morla, Mariam Riad, Theodore Pincus, Isabel Castrejon
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Depression in patients with rheumatoid arthritis (RA) may be pre-existent, amplified, or newly-developed after onset of RA. Together with other comorbidities, socioeconomic, or affective factors can influence perception of pain, functional disability, and health status. The prevalence of depression in RA patients is 19% and affect remission rates according to a classical composite index.<sup>1</sup> <h3>Objectives</h3> We compared patient self-reported scores included on the Multidimensional Health-Assessment Questionnaire (MDHAQ) and levels of remission according to RAPID3 in patients who self-reported depression versus no depression. <h3>Methods</h3> All patients complete a MDHAQ at each visit, which includes physical function (FN), three 0-10 visual analogue scales (VAS) for pain (PN), patient global estimate (PATGL), fatigue (FT), RADAI self-report joint count, a review of 60 symptoms (ROS) on a checklist, three evaluations for depression, anxiety and sleep quality (0-3.3), and demographics. RAPID3 (0-30) is the sum of FN, PN, and PATGL; being remission RAPID3 &lt;3. Patients with RA (ICD10) were classified according to self-reported depression on the ROS. Agreement between MDHAQ-depression and by the Patient Health Questionnaire (PHQ-9) was evaluated in 57 patients. Demographic and clinical characteristics were compared by self-reported depression status using Student t-test and chi-square test. <h3>Results</h3> 464 RA patients were studied: 118 (25%) self-reported depression. In 57 patients, who also completed the PDQ-9, agreement with MDHAQ depression was 93% (kappa=0.80 95% IC 0.61-0.99). Only 37 (31%) of all patients reporting depression had evidence in the medical record of treatment and/or specialist evaluation for depression. No differences between depression groups were seen for mean age or sex. Patients reporting depression had lower education level (12.5 vs 14.3, p&lt;0.001) and poorer scores for physical function, pain, and patient global leading to higher RAPID3 and lower percentage of patient in remission (12.4 vs 4%, p&lt;0.001) (Table). Depressed patients also reported higher scores for fatigue, number of painful joints, number or symptoms, and more difficulty with sleep, and anxiety. <h3>Table</h3> MDHAQ patient self-report scores in patients with RA according to depression status. Data are presented as mean (SD) and percentages. *p&lt;0.001 <h3>Conclusion</h3> The prevalence of self-reported depression in our RA patients was 25%, with only 31% treated for this condition. RA patients with self-reported depression exhibit higher scores for all MDHAQ scores, and a lower rate of RAPID3 remission. MDHAQ may be useful to identify patients with depression in busy clinical settings. <h3>Reference</h3> [1] Leblanc-Trudeau, C, et al. Rheumatology 2015;54:2205-14. <h3>Disclosure of Interests</h3> None declared
PB1796 VALIDATION OF THE NEW PROGNOSTIC MODEL FOR PERIPHERAL T CELL LYMPHOMA OTHERWISE SPECIFIED DEVELOPED (PTCL-NOS) BY THREE INSTITUTIONS
Authors: B. Sanchez-Gonzalez, S. Novelli, S.A. Jimenez, F. Garcia-Pallarols, G. Aspas, I.G. Parraga, L. Bento, M. Corrochano, E. Gimeno, A. Gutierrez, J. Briones, A. Salar
Journal: HemaSphere (2019)

Background: Recently, a new prognostic model (T cell score) has been developed by the International T cell Project Network that identifies a group of peripheral T cell lymphoma otherwise specified (PTCL-NOS) with very unfavorable outcomes. However, validation in independent cohorts remains as an essential step for models to gain widespread use. Aims: To validate T cell score, based on series of three hospitals from Spain. Furthermore, we explore the usefulness of T score in other subtypes of peripheral T cell lymphomas (PTCLs). Methods: T cell score is based on four covariates: serum albumin, ECOG-performance status, stage and absolute neutrophil count (ANC). The T cell score is categorized in three risk groups as describe in the original paper. T cell score was applied retrospectively to series of all PTCLs in three Institutions. Validation was performed following the guidelines by Royston et al. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier estimators, comparison between categories performed by log-rank test and Cox PH regression, and the effect of covariates reported with 95% confidence interval (95 CI). Results: Between 1993 and 2018, 129 cases of PTCLs were identified for developing the prognostic model. The median age was 56 years (range 15-91), 62 % of patients (pts) were male, and advanced stage disease was found in 77%. PTCLs subtypes: PTCL-NOS 52 pts (40%), AITL 24 pts (26%), ALCL (ALK+)10 pts (8%), ALCL (ALK-)17 pts (13%) and others 16 pts (12%). 77% of PTCL had advanced disease and 35% had ECOG ≥ 2. 71% of PTLC had albumin <35 g/l, 68% >6.5x109 cells/l. 84% of PTCLs were treated with anthracyclines. At a median follow-up of 102 months, the median OS and PFS was 30 and 9.5 months, respectively. Three groups of PTCL-NOS were separated for OS at low risk (LR, 6 patients, 11.5%, score 0), intermediate risk (IR, 29 patients, 55.8%, score 1–2), and high risk (HiR, 17 patients, 32.7%, score 3–4) (figure 1). The three risk groups had a 5-year OS of 100%, 42 % [95 CI 24–61], and 6% [95 CI 0–17], respectively for patients at LR, IR and HiR respectively (p < 0.001) (Fig 1). The model also proved to be a potential tool for PFS; the 3-year PFS was 33% [95 CI 0-70], 38 % [95 CI 19-56] and 0, respectively for patients at LR, IR and HiR respectively (p < 0.001; data not shown).Summary/Conclusion: Validation of the T cell score was performed in our series of PTCL-NOS from three hospitals. T cell score clearly identified three risk groups for OS. Further validation of the T cell score in other independent series and analyze its potential application in other subtypes of PTCL, need to be performed.
PB1864 MORE THAN 2 YEARS DELAY IN DIAGNOSIS OF PNH DUE TO GASTROINTESTINAL MASK OF BONE MARROW INSUFFICIENCY
Authors: M. Karwacki, A. Adamowicz-Salach, M. Matysiak
Journal: HemaSphere (2019)

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is an ultrarare bone marrow insufficiency of childhood consisted of the triad of diagnostic symptoms: hemolytic anemia, thrombosis, and peripheral blood cytopenias. Acute abdominal pain is one of the most important prodrome of PNH mostly due to venous thrombosis of intra-abdominal veins, including hepatic, portal, mesenteric, and splenic blood vessels. Aims: To show how a complicated course of diseases due to “abdominal mask” resulted in more than 2 years delay in diagnosis might be fatal to a PNH patients. Methods: We report a boy of 15th, suffered from PNH, who presented long before the diagnosis with seasonal (spring and autumn only) paroxysmal acute and severe (8-9 VAS score) abdominal pain with cramps and tenderness and no other hematological presentation of disease. There were a couple attacks observed during the season with complete resolution of abdominal symptoms in between. He had been diagnosed as acute appendicitis, peptic ulcer disease, pancreatitis or cholecystitis especially when hyperbilirubinemia emerge, Crohn and atypical celiac disease for more than 2 years. Since a peripheral pancytopenia followed by severe anemia required erythrocyte transfusions during the last 2 attacks occurred, hematologist had been asked for consultation. Due to severe anemia with reticulocytosis, hyperbilirubinemia, highly elevated LDH, meaningful splenomegaly and almost nondetectable concentration of serum haptoglobin and a dark urine with confirmed hemoglobinuria, with a weak bone marrow aplasia, the diagnosis of PNH was feasible. The cytometric results, which revealed no expression of GPI proteins in 93.8% of type III PMNs, confirmed the diagnosis (percentage of RBC lacking GPI was not persuasive, as he has been previously transfused). Up to this point of his disease, except of transient, he had no fixed postembolic lessons in liver and kidney, and a negligible bowel signs revealed for the several time in CT/MR-angiography. He had no other embolic events in other organs as well. Results: As the results of HSCT are questionable in PNH, especially in children, we decided to start eculizumab. The complete clinical remission assessed as complete symptoms resolution had been achieved with the 2nd dose, and complete biochemical remission, based on LDH normalization, was confirmed with the 3rd dose of a MoAb therapy. The presence and percentage of PNH clones tested twice since diagnosis in both PNMs and RBCs did not change till now. We have not observed any complications during a year and half of treatment up to date of publication. Summary/Conclusion: The insidious and hidden course of thrombosis of intra-abdominal veins even accompanied by hemolysis may mask the real reason and significantly prolong the diagnosis of ultrarare disease such as a PNH, especially in children. Eculizumab is a treatment of choice of childhood PNH.
AB0777 PSA PATIENTS REACHING MINIMAL DISEASE ACTIVITY5/7 IMPROVE IN ALL FIELDS OF PSAID
Authors: Jose Pinto-Tasende, Clara Ventin, María Caeiro, Alvaro Seijas, Rodrigo Aguirre, Maria Teresa Silva, Francisco Blanco
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Patients with psoriatic arthritis (PsA) show impact on physical and psychological aspect of the disease and it can be measured with the PsA Impact of Disease (PsAID) questionnaire. Impact of disease should improve if patient reach a minimal disease activity (MDA). <h3>Objectives:</h3> To assess the association between MDA and PsAID questionnaire in patients with PsA from daily clinical practice. <h3>Methods:</h3> A cross-sectional study was carried out in consecutive patients who fulfilled CASPAR criteria and who were treated according to routine clinical practice (EULAR/GRAPPA recommendations). Patients were considered in MDA if they met at least 5/7 of the MDA criteria. PsAID was also recorded. Continuous variables were reported as median (Q1-Q3). Categorical variables were reported as percentages and frequencies. All analyses were performed using SPSS software. Differences were considered statistically significant if p&lt;0.05 (two tailed). <h3>Results:</h3> Seventy-two patients were included, 40 males (55.6%), median of age 53.5 years old (47.0-62.7) and disease duration 5 years (3-10). Obesity was 29.6% and C-RP level was 0.31mgr/dl (0.10-0.97). Patient treatments were: NSAID 22.2%, corticosteroids 31.9%, csDMARD 55.6% and biological therapy 20.8%. DAPSA was 9.0 (2.2-19.4) being in VLDA (0-4) 37.5%, LDA (5-14) 22.2%, MDA (15-28) 30.6% and HAD (&gt;28) 9.7%. Patients in MDA 5/7 state were 36 (50%) and median of total score of PsAID was 4.70 (0.85-9.40). All fields of PsAID improved if they reached MDA 5/7 (p &lt;0.01). MDA 5/7 was also related to age, duration of the disease, CRP and DAPSA (see table). <h3>Conclusion:</h3> Fifty percent of PsA patients achieve MDA in daily clinical practice. MDA patients had a significantly lower impact of the disease according to PsAID. <h3>References</h3> [1] Queiro R, et al. Arthritis Res ther. 2017Mar29;19(1):72. <h3>Acknowledgement:</h3> Sociedade Galega de Reumatoloxía <h3>Disclosure of interests:</h3> Jose Pinto-Tasende Speakers bureau: Janssen, Novartis, Celgene, BMS, abbvie, Pfizer, Clara Ventin: None declared, María Caeiro: None declared, alvaro Seijas: None declared, Rodrigo aguirre: None declared, Maria Teresa Silva: None declared, Francisco Blanco Speakers bureau: Celgene, Pfizer, abbvie
In vivo irreversible albumin-binding near-infrared dye conjugate as a naked-eye and fluorescence dual-mode imaging agent for lymph node tumor metastasis diagnosis
Authors: Wenjuan Zhang, Sichen Song, Hanxun Wang, Qiu Wang, Dan Li, Shunzhe Zheng, Zhuangyan Xu, Haotian Zhang, Jian Wang, Jin Sun
Journal: Biomaterials (2019)
Re: Paul C.M.S. Verhagen, Egbert R. Boevé. The European Association of Urology Guideline on Renal Cell Carcinoma (RCC) is Not Concise in its Recommendation to Perform Partial Nephrectomy in T1b RCC. Eur Urol 2019:76:136–7
Authors: Lorenzo Marconi, Karim Bensalah, Axel Bex
Journal: European Urology (2019)