tbuckley/cabot-search huggingface dataset:
FRI0588 Ultrasound could have prevented dmard escalation in rheumatoid arthritis with fibromyalgia
Authors: R. Chakr, J.C.O. Santos, L.D.S. Alves, N. P. B.D. Andrade, A. Ranzolin, C.V. Brenol
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Despite the growing body of evidence, the proper use of ultrasound (US) in monitoring disease activity still needs better understanding.<sup>1,2</sup> As an objective measure, US could prevent overtreatment in situations of overestimation of clinical disease activity, such as fibromyalgia, present in up to 20% of patients with rheumatoid arthritis (RA).<sup>3–5</sup> <h3>Objectives</h3> To verify how ultrasound (US) could impact rheumatoid arthritis (RA) treatment decision in real life when fibromyalgia (FM) was also present. <h3>Methods</h3> A retrospective cohort study was performed from 2011 through 2016, including RA patients with FM. Patients were grouped according to US examination (Group DAS28: never performed US examination; Group US: at least one US exam). RA was considered active if DAS28 ≥3.2 in Group DAS28 or PD ≥2 in any single joint in Group US. <h3>Results</h3> Out of 230 RA patients, 22 women with concomitant FM (Group DAS28=10 and Group US=12) were seen in 280 visits from 2011 through 2016. DAS28 was 4.4 (2.5–6.3) vs. 4.0 (2.0–5.0) (p=0,592) in Groups DAS28 and US, respectively. DMARD treatment was escalated in 12.9% of visits in Group DAS28 versus 8.2% in Group US (p=0.791) (table 2). The relative risk (RR) for DMARD escalation in Group US compared to Group DAS28 was 1.08 (95%CI 0.60–1.95). However, in 74% of visits in Group US, DMARD was escalated despite a negative US result. In a theoretical scenario where US result oriented treatment decision, DMARD was escalated in 3.6% of visits in Groups DAS28 and US, respectively (table 1). Also, in this US-based scenario, the RR for DMARD escalation in Group US compared to Group DAS28 was 0.39 (0.19–0.83). The proportion of visits with US evaluation increased over time, nonetheless the level of agreement between US synovitis (PD ≥2) and DMARD escalation decreased (figure 1). Despite indicating US examination more frequently, rheumatologists did not base their DMARD escalation decision on PD synovitis. <h3>Conclusions</h3> In this real-life study of RA patients with FM, the growing use of US for evaluating RA activity over time was associated with an increasing discordance between US result and clinical judgement. When clinical judgement and US findings were discordant, RA treatment decision was mostly based on clinical judgement. If US result oriented treatment decision, DMARD escalation risk would be 61% smaller. <h3>References</h3> [1] Dale J, et al. Ann Rheum Dis. 2016;75(6):1043–50. [2] Haavardsholm EA, et al. BMJ2016;354:i4205. [3] Ranzolin A, et al. Arthritis Rheum. 2009;61(6):794–800. [4] Chakr RM, et al. Rev Bras Reumatol2016. doi:10.1016/j.rbr.2016.11.004 [5] Lage-Hansen PR, et al. Scand J Rheumatol2015. doi:10.3109/03009742.2015.1046484:1-4 <h3>Acknowledgements</h3> This study was funded by Hospital de Clínicas de Porto Alegre. <h3>Disclosure of Interest</h3> None declared
Estimating retention in HIV care accounting for patient transfers: A national laboratory cohort study in South Africa
Authors: Matthew P. Fox, Jacob Bor, Alana T. Brennan, William B. MacLeod, Mhairi Maskew, Wendy S. Stevens, Sergio Carmona
Journal: PLoS Medicine (2018)

Systematic reviews have described high rates of attrition in patients with HIV receiving antiretroviral therapy (ART). However, migration and clinical transfer may lead to an overestimation of attrition (death and loss to follow-up). Using a newly linked national laboratory database in South Africa, we assessed national retention in South Africa's national HIV program.Patients receiving care in South Africa's national HIV program are monitored through regular CD4 count and viral load testing. South Africa's National Health Laboratory Service has maintained a database of all public-sector CD4 count and viral load results since 2004. We linked individual laboratory results to patients using probabilistic matching techniques, creating a national HIV cohort. Validation of our approach in comparison to a manually matched dataset showed 9.0% undermatching and 9.5% overmatching. We analyzed data on patients initiating ART in the public sector from April 1, 2004, to December 31, 2006, when ART initiation could be determined based on first viral load among those whose treatment followed guidelines. Attrition occurred on the date of a patient's last observed laboratory measure, allowing patients to exit and reenter care prior to that date. All patients had 6 potential years of follow-up, with an additional 2 years to have a final laboratory measurement to be retained at 6 years. Data were censored at December 31, 2012. We assessed (a) national retention including all laboratory tests regardless of testing facility and (b) initiating facility retention, where laboratory tests at other facilities were ignored. We followed 55,836 patients initiating ART between 2004 and 2006. At ART initiation, median age was 36 years (IQR: 30-43), median CD4 count was 150 cells/mm3 (IQR: 81-230), and 66.7% were female. Six-year initiating clinic retention was 29.1% (95% CI: 28.7%-29.5%). After allowing for transfers, national 6-year retention was 63.3% (95% CI: 62.9%-63.7%). Results differed little when tightening or relaxing matching procedures. We found strong differences in retention by province, ranging from 74.2% (95% CI: 73.2%-75.2%) in Western Cape to 52.2% (95% CI: 50.6%-53.7%) in Mpumalanga at 6 years. National attrition was higher among patients initiating at lower CD4 counts and higher viral loads, and among patients initiating ART at larger facilities. The study's main limitation is lack of perfect cohort matching, which may lead to over- or underestimation of retention. We also did not have data from KwaZulu-Natal province prior to 2010.In this study, HIV care retention was substantially higher when viewed from a national perspective than from a facility perspective. Our results suggest that traditional clinical cohorts underestimate retention.
<i>Tbx20</i> Is Required in Mid-Gestation Cardiomyocytes and Plays a Central Role in Atrial Development
Authors: Cornelis J. Boogerd, Xiaoming Zhu, Ivy Aneas, Noboru Sakabe, Lunfeng Zhang, Debora R. Sobreira, Lindsey Montefiori, Julius Bogomolovas, Amelia C. Joslin, Bin Zhou, Ju Chen, Marcelo A. Nobrega, Sylvia M. Evans
Journal: Circulation Research (2018)

Rationale: Mutations in the transcription factor TBX20 (T-box 20) are associated with congenital heart disease. Germline ablation of Tbx20 results in abnormal heart development and embryonic lethality by embryonic day 9.5. Because Tbx20 is expressed in multiple cell lineages required for myocardial development, including pharyngeal endoderm, cardiogenic mesoderm, endocardium, and myocardium, the cell type–specific requirement for TBX20 in early myocardial development remains to be explored. Objective: Here, we investigated roles of TBX20 in midgestation cardiomyocytes for heart development. Methods and Results: Ablation of Tbx20 from developing cardiomyocytes using a doxycycline inducible cTnTCre transgene led to embryonic lethality. The circumference of developing ventricular and atrial chambers, and in particular that of prospective left atrium, was significantly reduced in Tbx20 conditional knockout mutants. Cell cycle analysis demonstrated reduced proliferation of Tbx20 mutant cardiomyocytes and their arrest at the G1-S phase transition. Genome-wide transcriptome analysis of mutant cardiomyocytes revealed differential expression of multiple genes critical for cell cycle regulation. Moreover, atrial and ventricular gene programs seemed to be aberrantly regulated. Putative direct TBX20 targets were identified using TBX20 ChIP-Seq (chromatin immunoprecipitation with high throughput sequencing) from embryonic heart and included key cell cycle genes and atrial and ventricular specific genes. Notably, TBX20 bound a conserved enhancer for a gene key to atrial development and identity, COUP-TFII/Nr2f2 (chicken ovalbumin upstream promoter transcription factor 2/nuclear receptor subfamily 2, group F, member 2). This enhancer interacted with the NR2F2 promoter in human cardiomyocytes and conferred atrial specific gene expression in a transgenic mouse in a TBX20-dependent manner. Conclusions: Myocardial TBX20 directly regulates a subset of genes required for fetal cardiomyocyte proliferation, including those required for the G1-S transition. TBX20 also directly downregulates progenitor-specific genes and, in addition to regulating genes that specify chamber versus nonchamber myocardium, directly activates genes required for establishment or maintenance of atrial and ventricular identity. TBX20 plays a previously unappreciated key role in atrial development through direct regulation of an evolutionarily conserved COUPT-FII enhancer.
New Subsolid Pulmonary Nodules in Lung Cancer Screening: The NELSON Trial
Authors: Joan E. Walter, Marjolein A. Heuvelmans, Uraujh Yousaf-Khan, Monique D. Dorrius, Erik Thunnissen, Anna Schermann, Harry J.M. Groen, Carlijn M. van der Aalst, Kristiaan Nackaerts, Rozemarijn Vliegenthart, Harry J. de Koning, Matthijs Oudkerk
Journal: Journal of Thoracic Oncology (2018)
AB0253 Rapid remission during the first year in early active rheumatoid arthritis is associated with better 5 years structural damage outcomes
Authors: J. Legrand, T. Kirchgesner, T. Sokolova, B. Vande Berg, P. Durez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Remission is arguably the best and ultimate therapeutic goal in early rheumatoid arthritis (ERA). ERA patients who reach rapid and sustained remission are likely to retain good radiographic outcomes. <h3>Objectives</h3> The aim of this study was to evaluate the radiographic progression and the newly pathological joints in a Belgian ERA cohort during a 5 to 15 years follow-up and to correlate the Sharp score index with different indices of clinical remission observed during the first year. <h3>Methods</h3> This was a retrospective analysis of mean (95% CI) change from baseline (BL) to 5 years Sharp/Van der Heijde (SVdH) scoring according to DAS28, SDAI, CDAI and ACR/EULAR Boolean remission scores for patients at Month 3, 6 and 12. Newly pathological joint defined by a SVdH score of 0 at baseline and a score greater than or equal to 1 at follow up were analysed as a secondary objective. 133 ERA patients naïve to DMARDs therapies were analysed (100 women and 33 men) with a mean age ±SD (49.9±13.3), mean DAS 28-CRP (4.89±1.3), mean HAQ (1.25±0.67), mean SDAI (28.4±15.5), mean CDAI (25.8±14.8) and mean SVdH (6±14). Differences were statistically tested using t tests. <h3>Results</h3> ERA patients were divided in 2 groups: "Xrays Stable" if the delta of SVdH score was &lt;10 (n=90) or "Xrays Progressive" if the delta of SVdH score was &gt;10 (n=43). As expected, presence of ACPA and baseline erosion were significantly higher in the Xrays progressive group. No significant baseline characteristics differences were observed for DAS28-CRP, CDAI, SDAI, HAQ. smoking status, swollen joint count or CRP.% of patients reaching DAS 28CRP, SDAI, CDAI and Boolean remission rates observed at 6 months were statistically significant different between groups (fig). There was no significant difference in clinical responses between subgroups of patients who developed new pathological joints and those who did not. <h3>Conclusions</h3> These results demonstrate that remission is an important therapeutic goal to protect joint damage in ERA. All remission criteria were able to predict the radiological prevention. The identification of a new pathologic joint is not associated with lack of response. <h3>Disclosure of Interest</h3> None declared
FRI0281 Transcriptomic profiling of pdcs from patients with pss identifies consistently altered gene networks that indicate an activated phenotype and enhanced anti-viral state
Authors: M.R. Hillen, A. Pandit, S.L.M. Blokland, S.A.Y. Hartgring, K.M.G. Van der Wurff-Jacobs, A.A. Kruize, M. Rossato, J.A.G. van Roon, T. R. D.J. Radstake
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Primary Sjögren's syndrome is an autoimmune disease characterised by lymphocytic infiltration of the exocrine glands and dryness of mouth and eyes. Type-I interferons (IFN) are thought to play an important role in pSS pathogenesis and plasmacytoid dendritic cells (pDCs) are capable of producing high levels of IFN. These cells infiltrate the salivary glands of pSS patients and their numbers correlate with local IFN-production. <h3>Objectives</h3> To understand the molecular mechanisms behind systemic dysregulation of pDCs, we performed RNA sequencing on pDCs isolated from peripheral blood of patients with pSS, non-Sjögren's sicca (nSS) and healthy controls. <h3>Methods</h3> We established two independent cohorts (each n=31), of patients and controls. pSS patients (n=25) were classified according to the 2002 AECG criteria. nSS patients (n=20) presented with dryness complaints without a known cause, did not have any generalised autoimmune disease, and did not fulfil the classification criteria for pSS. Healthy donors (n=17) were included as control group. Peripheral blood pDCs were isolated using MACS and RNA sequencing was performed for both cohorts.±20 million paired-end sequencing reads per sample were obtained using using Illumina HiSeq 2500 platform. <h3>Results</h3> 8556 genes were differentially expressed (p-value&lt;0.05) between all three groups in the discovery cohort. Of these, 3144 genes were also differential in the replication cohort. We generated gene modules from both cohorts and found 5 gene clusters comprising 1259 genes that were consistently dysregulated in both analyses. Pathway analysis showed that the 5 modules contain genes associated with cellular activation, including a group of genes involved in IFN-signalling and viral sensing, as well as regulation of intracellular transport. Generally, pDCs from patients with nSS displayed an intermediate phenotype. <h3>Conclusions</h3> We mapped transcriptomic differences in circulating pDCs from patients with nSS and pSS and identified gene clusters that are robustly replicated in two independent cohorts. We found 5 gene clusters that are dysregulated in patients with pSS and indicate enhanced cellular activation, including IFN-signalling and viral sensing which are key pathways in pSS pathogenesis. nSS patients showed similar transcriptomic dysregulation at an intermediate level. These data can help us better understand the role of pDCs in pSS. <h3>Disclosure of Interest</h3> None declared
SP0085 The evidence for physical activity in inflammatory arthritis and osteoarthritis
Authors: A.-K. Rausch
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objective</h3> To evaluate the effectiveness of physical activity in people with rheumatoid arthritis, spondyloarthritis and osteoarthritis. <h3>Methods</h3> A Systematic review and meta-analysis were performed searching he databases Pubmed/Medline, CENTRAL, Embase, Web of Science, Emcare, PsycInfo up to April 2017. We included randomised controlled trials (RCT)s in adults (≥18 years) with rheumatoid arthritis (RA), spondyloarthritis (SpA) and osteoarthritis (OA) investigating the effect of exercise or physical activity (PA) promotion on cardiovascular fitness, muscle strength, flexibility, neuromotor performance, and daily PA. Additionally we applied public health recommendations for PA based on the American College of Sports Medicine (ACSM) principles for effective interventions. Outcomes included assessments done directly after the intervention; If suitable, pooled in a meta-analysis using a random-effect model presented as standardised mean difference (SMD). Study registration in PROSPERO (CRD42017082131). <h3>Results</h3> The systematic review included 63 RCTs, of which 44 (3469 people with RA, SpA, OA) were included in the meta-analysis. Moderate effects were found of aerobic exercises and resistance training on cardiovascular fitness (SMD 0.6 (95% CI 0.38 to 0.81)) and muscle strength (SMD 0.54 (95% CI 0.35 to 0.72)) respectively, but no effect of combined exercises on flexibility (SMD 0.12 (95% CI −0.16 to 0.41)). PA promotion interventions produced a small increase in PA behaviour (SMD 0.21 (95% CI 0.03 to 0.38)). <h3>Conclusion</h3> Exercising and PA promotion according to public recommendations for PA were effective on cardiovascular fitness and muscle strength, with moderate, and thus clinically relevant effect sizes in people with SpA, RA and OA. <h3>Disclosure of Interest</h3> None declared
Relevance of placental type I interferon beta regulation for pregnancy success
Authors: Ja-Young Kwon, Paulomi Aldo, Yuan You, Jiahui Ding, Karen Racicot, Xiaoyan Dong, John Murphy, Guy Glukshtad, Michelle Silasi, Jian Peng, Li Wen, Vikki M. Abrahams, Roberto Romero, Gil Mor
Journal: Cellular and Molecular Immunology (2018)
End of life care in gynaecological cancer patients: A population-based study of cancer deaths from the Swedish Register of Palliative Care.
Authors: Kristina Lindemann, Lisa Martinsson, David Lindquist
Journal: Journal of Clinical Oncology (2018)

10028 Background: The quality of end of life care for gynecological cancer patients in Europe is unknown. Patient age may affect of end of life care. Methods: Patients who died expectably from gynaecological cancer between 2013 and 2015 were identified in the population-based Swedish Register of Palliative Care (N = 2,970). We investigated if age-dependent differences were present with respect to twelve indicators of palliative care quality. Patients were categorized in five pre-defined age groups. Odds ratios (OR) with 95% confidence intervals (CIs), adjusted for type of end-of-life care unit where appropriate, were calculated using logistic regression, with the oldest group (≥85 years) as reference. Results: Age-dependent differences in implementation rate were present for three out of 12 end-of-life care quality indicators, some of which were progressively less well met with each increment in age group. Compared to elderly cancer patients, younger patients (40-59 years) were more often informed about imminent death, (OR, 2.29; 95% CI, 1.41-3.71; p = 0.001). They were also more likely to be cared for by a specialised palliative care service (OR, 5.02; 95% CI, 3.78-6.65;p < 0.001). There was no difference between age groups in the assessed for the presence and severity of pain, injections prescribed as needed against pain, nausea, anxiety or death rattle. However, younger patients were more likely to receive fluids via enteral tube or intravenously during last 24 hours of life (OR, 4.86; 95% CI, 3.174-7.445; p = 0.001). Conclusions: Elderly gynaecological cancer patients are at high risk to die without the care of specialized palliative care services. Still, also institutions outside specialized care seem to increasingly adhere to palliative care quality guidelines.
Early BCR-ABL1 decline in imatinib-treated patients with chronic myeloid leukemia: results from a multicenter study of the Chinese CML alliance
Authors: Jingru Zhang, Yingqiao Wang, Jianxiang Wang, Jianda Hu, Suning Chen, Jie Jin, Ting Liu, Jianfeng Zhou, Yu Hu, Daoxin Ma, Xiaojun Huang, Chunyan Ji, Ming Hou
Journal: Blood Cancer Journal (2018)

Abstract An early molecular response is spectacularly predictive of outcome in chronic myeloid leukemia (CML) and early response landmarks may identify the high-risk patients likely to be benefit from an early therapy switch. In this study, we evaluated the most relevant cutoffs for early molecular response markers (BCR-ABL1 values at 3 months, log reduction and halving time between diagnosis and 3 months) in 476 first-line imatinib-treated Chinese patients with chronic phase CML. All outcomes were significantly superior for the 324 patients with 3-month BCR-ABL1 ≤10%, so did for the 270 patients with BCR-ABL1 &gt;0.61 log reduction. BCR-ABL1 halving time ≤22 days was identified for patients with the most favorable outcome. Moreover, the prognosis was significantly poorest for patients with both halving time &gt;44 days and BCR-ABL1 &gt;10%. Importantly, multivariate regression analysis demonstrated that a BCR-ABL1 log reduction calculated at 3 months of 0.61 was the only variable that significantly predicted for OS. Our results highlight the importance of rapid initial decline of BCR-ABL1 in predicting satisfactory outcome. Our data support the evidence that monitoring BCR-ABL1 values at an early time point could contribute to accurately assess response and ultimately guide clinical decisions regarding the timing of therapeutic intervention.
Are we entering a golden age for changing lives in sports and exercise medicine?
Authors: Steve Aspinall
Journal: British Journal of Sports Medicine (2018)

It is an exciting time to be working in healthcare and medicine! Despite the myriad of challenges, the opportunities we have to genuinely and lastingly change people’s lives for the better are legion. How many professions have the opportunity to change a person’s current health, future health, sports and work performance alongside having a positive impact on social and family life? To enable us to do this we need not only the right knowledge and skill set, but we also need to be able to apply it to our patients in the real world, without becoming bogged down in seeing patients only as a specific pathology or an injury to treat. They are so much more than that and so are we. This issue of the British Journal of Sports Medicine ( BJSM ) offers real world application of knowledge that can change many areas of our practice with lots of clear take home messages. If you are new to this, check out the BJSM social media including Facebook, Twitter, podcasts, blog and …
AB0006 Mir-26a polymorphism is associated with susceptibility of rheumatoid and psoriatic arthritis
Authors: J. Swierkot, R. Sokolik, M. Kozlowski, L. Korman, P. Wiland, K. Bogunia-Kubik
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Serum levels of miR-26a has been reported to act as potential biomarker of rheumatic diseases. <h3>Objectives</h3> The aim of the study was to analyse the genetic variation and expression of miR-26a as potential diagnostic and/or prognostic markers of rheumatoid diseases. <h3>Methods</h3> The miR-26a polymorphism was examined in 111 patients with rheumatoid arthritis (RA), 86 patients with psoriatic arthritis (PsA) and 162 healthy blood donors that served as a control group. Genotyping for miR-26a rs7372209 was performed using a LightSNiP assay. For analysis of the miR-26a expression, RNA was isolated from sera of 15 RA patients (before and 3 months after anti-TNF treatment) and 10 controls (NucleospinmiRNA Plasma; MACHEREY-NAGEL GmbH and Co. KG) followed by cDNA synthesis (TaqMan MicroRNA Reverse Transcription Kit; Applied BiosystemsTM by Life Technologies) and Real-time PCR amplifications with hsa-miR-26a TaqMan specific and U6 snRNA control primers for each probe. The results were analysed using the (ΔΔCt) calculations. <h3>Results</h3> It was found that the presence of miR-26a TT genotype (rs7372209) more than 5 times increases the risk of RA (OR=5.28, p=0.003) while the presence of CC homozygotes is associated with the risk of PsA (OR=1.77, p=0.037). There was no significant difference in the miR-26a serum levels between patients and controls. Also miR-26a serum levels did not significantly differed between RA patients before, 3 and 6 months after the implementation of biological therapy with TNF-alpha inhibitors. <h3>Conclusions</h3> These results imply that miR-26a rs7372209 allelic variants differentially affect the risk of rheumatoid and psoriatic arthritis while anti-TNF biological treatment seems not to affect the miR-26a expression in RA patients. <h3>Disclosure of Interest</h3> None declared