tbuckley/cabot-search huggingface dataset:
AB0659 CARDIOPULMONARY EXERCISE TEST (CPET) IS A POTENTIAL NON-INVASIVE METHOD TO PREDICT DISEASE PROGRESSION IN SYSTEMIC SCLEROSIS
Authors: Rita Hemelein, Attila Somfay, László Kovács, Imre Lajkó, Gergely Ágoston
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> CPET is a widely used examination to predict the prognosis of chronic obstructive pulmonary disease or post-transplant lung function, and it has also been examined in the context of respiratory tract involvement and pulmonary hypertension in systemic slerosis (SSc). <h3>Objectives:</h3> As CPET provides a general overview of the aerobic metabolism, influenced by pulmonary, cardiac and vascular function, the purpose of this investigation was to assess if development of poor overall disease outcome could be predicted by CPET. <h3>Methods:</h3> Twenty-nine SSc patients (M/F=5/24 DcSSc/LcSSc=16/13) were investigated repeatedly with CPET and followed for a mean of 3.7 (range 1-7) years. The clinical features of the patients were the following: alveolitis (n=15), pulmonary fibrosis (n=16), digital ulcers (n=13), 5 of them required bosentan therapy, macroangiopathy (n=8), GERD (n=26), Barrett metaplasia (n=19), gastrintestinal angiopathy (n=5), motility disorder (n=10), pulmonary artery hypertension (pPulm &gt;40 mmHg) (n=4). The average disease duration was 8.9 years. A composite end point was set up: death or digital ulceration necessitating bosentan therapy or pulmonary hypertension (Ppulm&gt;40mmHg) or the decrease of carbon-monoxide diffusion capacity (δDLCO) &gt; 2%/year, or increase in pulmonary artery pressure (δPpulm) &gt;3mmHg/year). Paralell with the CPET, conventional disease activity check-ups have been performed too (echocardiography, chest CT, resting lung function tests, clinical examinations). The correlations between the CPET mesurements and conventional findings and the predictive value of CPET parameters at the first visit to the future development of the composite end-point have been examined. <h3>Results:</h3> Various CPET results (anaerobic threshold (AT), work rate (WR), desaturation) have significantly correlated with worsening DLCO (p&lt;0,05; Pearson's correlation). The change of aT per year (δAT/yr) and the degree of desaturation during exercise predicted the development of poor prognostic end-point (p&lt;0.05 with logistic regression), and the detection of desaturation at the first CPET test was associated with a higher risk of poor prognosis (OR: 5,265 [95% CI 1,077-29,38] p=0.057). In contrast, none of the standard pulmonary or cardiac parameters have proved to be predictive to the end-point in this cohort. <h3>Conclusion:</h3> CPET parameters correlate well with the standard assessment tools, indicating that this test is feasible in SSc patients too. The changes of aT during follow-up and desaturation are predictive to the appearence of the end point designed to comprise multiple features of the disease. This makes CPET a promising non-invasive examination method to estimate the progression of disease in patients suffering from systemic sclerosis. <h3>Disclosure of interests:</h3> None declared
Brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine for nonbulky limited-stage classical Hodgkin lymphoma
Authors: Jeremy S. Abramson, Jon E. Arnason, Ann S. LaCasce, Robert Redd, Jeffrey A. Barnes, Lubomir Sokol, Robin Joyce, David Avigan, Donna Neuberg, Ronald W. Takvorian, Ephraim P. Hochberg, Celeste M. Bello
Journal: Blood (2019)
Genomic prediction of celiac disease targeting HLA-positive individuals
Authors: Gad Abraham, Alexia Rohmer, Jason A. Tye-Din, Michael Inouye
Journal: Genome Medicine (2015)

Genomic prediction aims to leverage genome-wide genetic data towards better disease diagnostics and risk scores. We have previously published a genomic risk score (GRS) for celiac disease (CD), a common and highly heritable autoimmune disease, which differentiates between CD cases and population-based controls at a clinically-relevant predictive level, improving upon other gene-based approaches. HLA risk haplotypes, particularly HLA-DQ2.5, are necessary but not sufficient for CD, with at least one HLA risk haplotype present in up to half of most Caucasian populations. Here, we assess a genomic prediction strategy that specifically targets this common genetic susceptibility subtype, utilizing a supervised learning procedure for CD that leverages known HLA-DQ2.5 risk.Using L1/L2-regularized support-vector machines trained on large European case-control datasets, we constructed novel CD GRSs specific to individuals with HLA-DQ2.5 risk haplotypes (GRS-DQ2.5) and compared them with the predictive power of the existing CD GRS (GRS14) as well as two haplotype-based approaches, externally validating the results in a North American case-control study.Consistent with previous observations, both the existing GRS14 and the GRS-DQ2.5 had better predictive performance than the HLA haplotype approaches. GRS-DQ2.5 models, based on directly genotyped or imputed markers, achieved similar levels of predictive performance (AUC = 0.718-0.73), which were substantially higher than those obtained from the DQ2.5 zygosity alone (AUC = 0.558), the HLA risk haplotype method (AUC = 0.634), or the generic GRS14 (AUC = 0.679). In a screening model of at-risk individuals, the GRS-DQ2.5 lowered the number of unnecessary follow-up tests for CD across most sensitivity levels. Relative to a baseline implicating all DQ2.5-positive individuals for follow-up, the GRS-DQ2.5 resulted in a net saving of 2.2 unnecessary follow-up tests for each justified test while still capturing 90 % of DQ2.5-positive CD cases.Genomic risk scores for CD that target genetically at-risk sub-groups improve predictive performance beyond traditional approaches and may represent a useful strategy for prioritizing individuals at increased risk of disease, thus potentially reducing unnecessary follow-up diagnostic tests.
Lateral Gene Transfer Shapes the Distribution of RuBisCO among Candidate Phyla Radiation Bacteria and DPANN Archaea
Authors: Alexander L Jaffe, Cindy J Castelle, Christopher L Dupont, Jillian F Banfield
Journal: Molecular Biology and Evolution (2018)

Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is considered to be the most abundant enzyme on Earth. Despite this, its full diversity and distribution across the domains of life remain to be determined. Here, we leverage a large set of bacterial, archaeal, and viral genomes recovered from the environment to expand our understanding of existing RuBisCO diversity and the evolutionary processes responsible for its distribution. Specifically, we report a new type of RuBisCO present in Candidate Phyla Radiation (CPR) bacteria that is related to the archaeal Form III enzyme and contains the amino acid residues necessary for carboxylase activity. Genome-level metabolic analyses supported the inference that these RuBisCO function in a CO2-incorporating pathway that consumes nucleotides. Importantly, some Gottesmanbacteria (CPR) also encode a phosphoribulokinase that may augment carbon metabolism through a partial Calvin-Benson-Bassham cycle. Based on the scattered distribution of RuBisCO and its discordant evolutionary history, we conclude that this enzyme has been extensively laterally transferred across the CPR bacteria and DPANN archaea. We also report RuBisCO-like proteins in phage genomes from diverse environments. These sequences cluster with proteins in the Beckwithbacteria (CPR), implicating phage as a possible mechanism of RuBisCO transfer. Finally, we synthesize our metabolic and evolutionary analyses to suggest that lateral gene transfer of RuBisCO may have facilitated major shifts in carbon metabolism in several important bacterial and archaeal lineages.
The Case | Acute kidney injury in an African woman with microangiopathic hemolytic anemia and HIV
Authors: Hatem Elabd, Tarek Rashid, Mennallah Elkholi, M. Barry Stokes
Journal: Kidney International (2019)

A 59-year-old African woman was admitted with generalized weakness. The history consisted of hypertension, which was treated with lisinopril and nifedipine for many years. She denied any use of nonsteroidal anti-inflammatory drugs, herbal medications, or illicit drugs. Physical examination revealed normal vital signs, dry mucous membranes, and no evidence of lymphadenopathy, salivary gland enlargement, or rash. Laboratory evaluation revealed a serum creatinine level of 12.9 mg/dl and a blood urea nitrogen level of 149 mg/dl (baseline, 1.1 and 23 mg/dl, respectively, 3 months ago), a hemoglobin level of 8.2 g/dl, a platelet count of 67 cells/mm3, ≥2 schistocytes in the peripheral smear, and a lactate dehydrogenase level of 365 U/l. Urine microscopy showed innumerable white blood cells per high power field, but no red blood cells or casts. The spot urine protein-to-creatinine ratio was 1.7 g/g.
When Cancer Vaccines Go Viral
Authors: David Repáraz, Diana Llopiz, Pablo Sarobe
Journal: Clinical Cancer Research (2019)

Induction of antitumor responses by vaccines requires strong immunogens. Heterologous viral prime/boost immunization with the BN-CV301 vaccine promotes activation of immune responses that provide a clinical benefit to patients with cancer. This viral platform may be used to harbor different antigens and prime tumor immunity potentially useful for combinatorial strategies.See related article by Gatti-Mays et al., p. 4933.
AB0381 CERTOLIZUMAB PEGOL IN AUTOIMMUNE DISEASES. REAL LIFE EXPERIENCE IN PREGNANCY
Authors: Renato Guzman Moreno, Karina Guzman Roa, Gladys Roa Montes
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Certolizumab pegol (CZP) is a Pegylated, Fc free monoclonal antibody that is useful in different autoimmune conditions. It does not bind FcRn and is not expected to undergo transfer across the placenta and probably there is a minimal placenta transfer of CZP in humans. On the other hand, most chronic inflammatory diseases are prevalent in women and 50% of these diseases need active treatment. We describe our experience for more than 7 years in patients with inflammatory arthritis and pregnancy that received CZP. <h3>Objectives</h3> We describe our experience in patients with inflammatory artropathy that received CZP during their pregnancy. <h3>Methods</h3> We review our cohort of patients with Rheumatoid Arthritis, Spondyloarthritis and psoriatic arthritis from 2011 to 2017 that received CZP and analyzed those cases of pregnancy and described the clinical characteristic, the medication concomitant and the course of the pregnancy. <h3>Results</h3> We review more than 750 patients with inflammatory arthritis that received CZP and found 15 cases that was in pregnancy. See table 1. <h3>Conclusion</h3> CZP is a useful alternative of treatment for pregnant patients and with inflammatory arthropaties that required therapeutic agent. This topic has been recently review and show that this agent is safe for pregnant women and for those breastfeeding and support continuation of CZP during pregnancy, when considered necessary. There has been clear evidence during the last few years that this is the treatment of choice for women in fertile age with autoimmune diseases which requires immunomodulation. <h3>References</h3> [1] Mariette X., et al. Ann Rheum Dis2017.doi.10.1136/2017-212196. [2] Clowse MEB., et al. Arthritis Rheumatol 2017.69.suppl 100. Abstract 1309. <h3>Disclosure of Interests</h3> None declared
Is implantation of autologous chondrocytes superior to microfracture for articular-cartilage defects of the knee? A systematic review of 5-year follow-up data
Authors: Yuyan Na, Yuting Shi, Wanlin Liu, Yanbo Jia, Lingyue Kong, Ting Zhang, Changxu Han, Yizhong Ren
Journal: International Journal of Surgery (2019)

Autologous chondrocyte implantation (ACI) and microfracture are two of the main surgical treatment options for articular cartilage lesions of the knee. Consensus regarding the best clinical options to repair knee cartilage lesions is lacking. We undertook a systematic review to clarify the clinical efficacy of ACI and microfracture at minimum mean 5-year follow-up.A literature search was conducted using the MEDLINE, Embase and Cochrane Library databases up to August 2018. Only comparative clinical studies of ACI and microfracture for the treatment of articular cartilage lesions of the knee with level I/Ⅱ evidence were included. Clinical outcomes and the prevalence of treatment failure from each study were extracted and compared. The methodological quality of the included studies was analyzed by means of the PEDro scale.Five comparative studies (three randomized controlled trials and two prospective cohort studies) met our eligibility criteria. ACI and microfracture elicited significant improvement in clinical outcomes after 5 years. However, better clinical results with significant differences were found with modified versions of ACI (ACI with a modified collagen membrane [ACI-C] or matrix-applied chondrocyte implantation [MACI]) than with microfracture as determined by the Knee Injury and Osteoarthritis Outcome Score, activities of daily living assessment, Tegner Activity Scale score, and the International Knee Documentation Committee objective and subjective scores. No significant difference was observed in the treatment failure rate between these two methods within a particular study.Currently, the best-available evidence suggests that some clinical outcomes of articular cartilage lesions of the knee treated with modified versions of ACI (ACI-C or MACI) can significantly improve patient outcomes at the mid-term follow-up of 5 years compared with those obtained using microfracture.
Oral presentations
Authors: B Kasztelewicz, I Jankowska, J Pawlowska, K Dzierzanowska, A Gautheret-Dejean, B Géraudie, M Charrier, D Heurté, M Desmonet, M-A Bartoletti, P Bonnafous, C Penasse, H Agut, B Buchan, N Anderson, P Jannetto, N Ledeboer, S Ko, H Oh, C Park, J Lee
Journal: Clinical Microbiology and Infection (2011)
AB0789 AN EHEALTH TOOL TO PREPARE A FIRST ORTHOPAEDIC CONSULTATIONS: A USE AND USABILITY STUDY
Authors: Aniek Claassen, Thea Vliet Vlieland, Vincent Jjf Busch, Henk J. Schers, Frank van den Hoogen, Cornelia van den Ende
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The use of eHealth technology to prepare first orthopaedic consultations for patients with hip or knee osteoarthritis seems promising. Exploration of data on use and usability of an educational eHealth tool can reveal potential modifications that may increase engagement and effectiveness. <h3>Objectives</h3> 1) to identify use and usability of a standalone educational eHealth tool for patients with suspected hip or knee osteoarthritis (OA), 2) to explore if recorded questions in the eHealth tool were in line with an existing widely used question prompt list, and 3) to investigate if user characteristics are related to use and usability. <h3>Methods</h3> We used data of 144 patients who used the educational eHealth tool to prepare an upcoming first orthopaedic consultation. We defined 'users' and 'non-users' based on opening the tool at least once or not. 'Users' were specified as 'active' and 'passive'. Recorded questions in preparation for the upcoming consultation were categorized into 3 themes: 'What are my options?', 'What are the possible benefits and harms of those options?' and 'How likely are each of the benefits and harms to happen to me?', or in a 'remaining' category. Usability was measured using the System Usability Scale (SUS, 0-100). We collected data on demographic and clinical characteristics, knowledge on OA and internet and smartphone usage in daily life. Characteristics associated with 'users' and 'non-users' were analysed using multivariable logistic regression analysis. <h3>Results</h3> A total of 116 (81%) participants used the educational eHealth tool, of whom 87 (75%) were 'active users'. Out of 3 components ('Information', 'My consultation' and 'Medication), 'Medication' was least used (34%). Based on the recorded questions of users a fourth predefined question could be proposed, i.e. "What is my situation at this moment?". Mean (SD) SUS score was 64.8 (16.0). No difference was found in SUS scores between superficial and active users (mean difference (95% CI): 0.04 (-7.69, 7.77)). Participants with higher baseline knowledge on OA (OR (95% CI): 1.2 (1.0, 1.4)), who used the internet less frequent in daily life (OR (95% CI): 0.6 (0.5, 0.9)) were more likely to use the educational eHealth tool. We found no differences in demographic and clinical characteristics between superficial and active users. <h3>Conclusion</h3> Based on the results of this study it can be concluded that the use of an educational eHealth tool to prepare a first orthopaedic consultation in patients with hip and knee OA is feasible. Results provide points for improvements to the content of the tool to improve usability. No clear practical implications were found in this study to support implementation of the educational eHealth tool in specific subgroups. <h3>Disclosure of interests</h3> None declared
PB2274 PROPHYLAXIS ADHERENCE RELATIVE TO QUALITY OF LIFE AND ANXIETY LEVEL IN TURKISH PATIENTS WITH SEVERE HEMOPHILIA A
Authors: Z. Kaya, N. İsmayılova, C. Muluk, M. Albayrak, E. Güney, S. Aytaç, N. Özbek, T. Gürsel
Journal: HemaSphere (2019)

Background: For patients with severe hemophilia A, bleeding increases anxiety and reduces quality of life (QoL). Prophylaxis is a therapeutic approach that enhances QoL for these individuals, but compliance is a major issue. Aims: This study investigated adherence to prophylaxis relative to QoL and anxiety level among patients with this condition. Methods: Forty-three patients with severe hemophilia A were stratified by age: 12 children in Group 1 (2-13 years), 17 adolescents in Group 2 (14-21 years), and 14 young adults in Group 3 (>21 years). Regular prophylaxis (RP) 25-40 IU/kg was prescribed three times weekly for 30 patients, and pharmacokinetic (PK) prophylaxis was prescribed for the remaining 13. Quality of life and anxiety level were assessed in parents of Group 1 patients and Group 2/3 patients using the 36-Item Short Form Health Survey (SF36) and the State-Trait Anxiety Inventory (STAI), respectively. The present study was approved by Gazi University ethical committee.Results were analysed using SPSS-15.0 program. Results: All 12 Group 1 patients (100%; nine RP, three PK) and 10 Group 2 patients (59%; all PK) adhered completely to prophylaxis. Seven Group 2 patients (41%) and four Group 3 patients (29%) received irregular prophylaxis. The remaining 10 Group 3 patients (71%) received on-demand treatment. Group 1 patients experienced vascular access problems due to young age. Seven (58%) of them were receiving home treatment. Nine Group 3 patients (64%) were reluctant to receive prophylaxis because they lived a sedentary life and were not participating in sports activities. Median QoL score was lower in Group 3 than in Group 1 parents and Group 2 patients (p<0.05 for both). Median anxiety level was higher in Group 1 parents and Group 3 patients than in Group 2 patients (p<0.05 for both). Summary/Conclusion: The results suggest that PK prophylaxis would improve QoL and reduce anxiety for young adults with severe hemophilia A. The findings also indicate that improved family education about vascular access for home treatment would improve QoL and reduce anxiety for children with this condition.
Role of Chemotherapy, VEGFR Inhibitors, and mTOR Inhibitors in Advanced Perivascular Epithelioid Cell Tumors (PEComas)
Authors: Roberta Sanfilippo, Robin L. Jones, Jean-Yves Blay, Axel Le Cesne, Salvatore Provenzano, Georgios Antoniou, Olivier Mir, Giovanni Fucà, Elena Fumagalli, Rossella Bertulli, Silvia Stacchiotti, Mehdi Brahmi, Federica Grosso, Armelle Dufresne, Nadia Hindi, Marta Sbaraglia, Alessandro Gronchi, Paola Collini, Angelo P. Dei Tos, Paolo G. Casali
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Perivascular epitheliod cell tumors (PEComas) are rare mesenchymal neoplasms for which the role of systemic treatments is not established as there are no published prospective clinical trials or sufficiently large retrospective case series. The aim of this study is to clarify the activity of conventional chemotherapy and biological agents in advanced/metastatic PEComas. Experimental Design: This was an observational, retrospective, international study that included patients with advanced/metastatic PEComa treated with systemic therapy at 5 European sarcoma reference centers and within the Italian Rare Cancer Network. Survival analyses were performed using the Kaplan–Meier method and the Cox hazards regression models. Results: A total of 53 patients were included. Cytotoxic chemotherapy regimens were active only in a small proportion of PEComas. Gemcitabine-based regimens [objective response rate (ORR): 20%, median progression-free survival (PFS): 3.4 months] seemed to have the same activity of anthracycline-based regimens (ORR: 13%, median PFS: 3.2 months). Antiangiogenic agents resulted in disease stabilization in some patients, with a number having density changes/tissue response on imaging, with an ORR of 8.3% and a median PFS of 5.4 months. mTOR inhibitors were the most active agents, with an ORR of 41% and a median PFS of 9 months. Conclusions: Our study provides data for the selection of systemic therapy in patients with advanced/metastatic PEComa: mTOR inhibitors are the most active agents. Antiangiogenics and chemotherapy with gemcitabine-based regimens or anthracycline-based regimens are options in further line, but with a lower response rate and PFS.