tbuckley/cabot-search huggingface dataset:
AB0927 Reliability and validity of turkish version of fibromyalgia participation questionnaire
Authors: L Altan, R Çeliker, I Ercan, M Birtane, K Akgün, C Zateri, N Taştekin, A Rezvani, I Aktaş, S Özdolap, E Dursun, N Dursun, S Sarıkaya
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Fibromyalgia (FMS) is a chronic health problem characterized by a wide range of physical and psychological symptoms. There are few high-quality instruments to evaluate the participation and social functioning of fibromyalgia patients. Farin et al. designed the Fibromyalgia Participation Questionnaire (FPQ) as an instrument for measuring the participation and social functioning of FMS patients. The original version of FPQ has been demonstrated to have acceptable internal consistency, reliability and criterion validity. <h3>Objectives</h3> To test reliability and validity of Turkish version of Fibromyalgia Participation Questionnaire (FPQ-T) <h3>Methods</h3> One hundred and eighty-four female fibromyalgia syndrome patients were included in the study. All patients filled FPQ-Turkish (FPQ-T) questionnaire which was obtained by translation from German according to the guideline for the cross-cultural adaptation process. The patients filled the revised Fibromyalgia Impact Questionnaire (FIQ) and reevaluated FPQ-T two hours later. Internal consistency reliability of FPQ-T was assessed by calculating "if item deleted" using Cronbach alpha and "item-total correction" coefficient for each item of the questionnaire. Consistency of sub-scales and correlation of test-retest values were assessed. Test-retest values were compared using Wilcoxon test. Criterion validity was measured using FIQ scales by Spearman9s rho correlation coefficient. <h3>Results</h3> For internal reliability, Cronbach alpha coefficient was calculated as 0.957 for non-working and 0.958 for working patients. Cronbach alpha values of 0.939, 0.871, and 0.914 were obtained for daily, social, and work life, respectively. Correlation coefficients were 0.888 for daily life, 0.859 for social life, and overall 0.901 in non-working group versus 0.896 in working group. Comparison of scores obtained from test-retest measurements showed no significant difference except for Item-3. Correlation of symptom severity score (SSS) and FPQ-T were r=0.385 (p&lt;0.001) and r=0.390 (p&lt;0.001) for the non-working and working sub-groups, respectively. Construct validity evaluation showed significant correlation between SSS and FPQ-T. <h3>Conclusions</h3> The results of our study showed that FPQ-T is reliable and valid for assessing participation and social functioning in fibromyalgia patients in our society. <h3>References</h3> Williams DA, Clauw DJ (2009) Understanding fibromyalgia: Lessons from the broader pain research community. J Pain 10:777–791. Farin E, Ullrich A, Hauer J (2013) Participation and social functioning in patients with fibromyalgia: development and testing of a new questionnaire. Health Qual Life Outcomes 11:135. <h3>Disclosure of Interest</h3> None declared
Expression of PD-L1 in colorectal cancer that lack mutations in RAS or TP53 genes.
Authors: Maher Albitar, Sucha Sudarsanam, Wanlong Ma, Shiping Jiang, Wayne Chen, Vincent Anthony Funari, Sally Agersborg
Journal: Journal of Clinical Oncology (2017)

e14500 Background: PD-L1 expression as detected by immunohistochemistry (IHC) is significantly lower in colorectal cancers (CRC) when compared with lung cancer or other types of cancer. We explored if mutations in the RAS/RAF gene family, TP53 or PIK3CA can define a subgroup of CRC that express PD-L1. Methods: Tissue samples collected from 107 patients with CRC were studied for the expression of PD-L1 using clone SP142. The same samples were also tested for mutations in NRAS, KRAS, HRAS, BRAF, TP53, and PIK3CA using Next Generation Sequencing (NGS). Results: Of the 107 CRC samples only 15 (14%) showed PD-L1 positive tumor cells (≥1%) and 8 of the 15 (7.5% of total) had PD-L1 in ≤5% of tumor cells. Detected mutations in these samples were as follows: TP53 65%, KRAS 49.5%, PI3KCA 22.5%, NRAS 5%, HRAS 1%, and BRAF 17%. There was no correlation between PD-L1 expression and mutation status in any of the RAS/RAF genes. There was also no correlation between TP53 mutation and PD-L1 expression. This was true irrespective if PD-L1 expression is considered as a continuous variable or when cut-off points of 5%, 20%, or 50% were used. However, patients without any mutation in RAS or TP53 had significantly (P = 0.005) more expression of PD-L1 when cut-off point of 5% is used. This remained true if PD-L1 expression is considered as a continuous variable (P = 0.04). There was no correlation between PIK3CA and PD-L1 expression. Conclusions: PD-L1 expression is significantly more common in CRC that lack mutations in RAS or TP53. PD-L1 expression is detected in 31% of patients with wild-type RAS/TP53 as compared with 12% in patients with RAS/TP53 mutations (P = 0.04). If a cut-off point of 5% is used, 31% of RAS/TP53-wild-type CRC were positive for PD-L1, while only 6% of RAS/TP53- mutant CRC were positive for PD-L1 (P = 0.005). This suggests that in CRC without RAS/TP53 mutation, the PD-L1 may play a more important role in oncogenesis. Exploring immunotherapy in this group of CRC patients might be justified.
Crohn Disease
Authors: Yan Epelboym, Paul B. Shyn, Jeffrey Forris Beecham Chick, Matthew J. Hamilton, Stacy D. O'Connor, Stuart G. Silverman, Chun K. Kim
Journal: Clinical Nuclear Medicine (2017)

Purpose Clinical assessments of Crohn disease activity are limited in their capacity to assess treatment response to biologic therapy. The purpose of this study was to determine if changes in FDG activity between baseline PET and repeat PET performed prior to the second dose of induction anti–tumor necrosis factor (TNF) therapy correlate with clinical response. Methods In this prospective, institutional review board–approved, Health Insurance Portability and Accountability Act–compliant pilot study of 8 adult patients with active Crohn disease, FDG activity before and 2 weeks after initiation of anti-TNF therapy was assessed using low-dose PET/CT. FDG activity was measured in the most inflamed bowel loop using an SUVratio (SUVmax/liver SUVmean). Changes in SUVratio were compared with a blinded gastroenterologist assessment of clinical response and steroid-free remission, as well as C-reactive protein (CRP), during a 12-month follow-up period. Results Of 8 patients, 7 showed FDG activity decline at 2 weeks, 5 of whom achieved a clinical response and steroid-free remission at 8, 26, and 52 weeks. The remaining 2 patients with FDG activity decline did not achieve a clinical response or steroid-free remission at these time points, but there were reductions in CRP. The 1 patient without FDG activity decline was a clinical nonresponder, had no reduction in CRP, and did not achieve steroid-free remission. Conclusions A change in FDG activity at FDG PET/CT performed prior to the second induction dose of anti-TNF therapy has the potential to predict clinical response and steroid-free remission in patients with Crohn disease.
Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen–specific CTLs
Authors: Michael C. Brown, Eda K. Holl, David Boczkowski, Elena Dobrikova, Mubeen Mosaheb, Vidya Chandramohan, Darell D. Bigner, Matthias Gromeier, Smita K. Nair
Journal: Science Translational Medicine (2017)

PVSRIPO infection of tumors elicits antitumor immunity by damaging neoplastic cells and activating type I IFN responses in antigen-presenting cells.
FRI0704 Analysis of risk factor for pregnancy outcomes in 142 pregnancies complicated with connective tissue disease
Authors: H Shimada, K Kanenishi, T Kameda, M Izumikawa, S Nakashima, H Ozaki, R Wakiya, A Kondo, N Kadowaki, H Dobashi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Recently, many connective tissue disease (CTD) patients wish to become a mother because immunosuppressants and biologics enable to improve the outcome of underlying CTD and quality of life respectively. However, Pregnancies in CTD patients often have problems including underlying disease exacerbation, some complications during pregnancy especially in preterm birth, light for date (LFD) and premature rapture of membrane (PROM). Previous study identified that high clinical activities with hypocomplementemia and positive anti-dsDNA antibody were at highest risk for pregnancy loss and preterm delivery in SLE<sup>1)</sup>. It is unclear whether these problems are associated with the activity of underlying CTD or immunosuppressant treatment. <h3>Objectives</h3> We examine the issue of pregnancy and delivery complicated with CTD by the analysis of the cases in our institution. <h3>Methods</h3> We investigated the risk factors of preterm birth, LFD (light for dates) and perinatal complication from exacerbation of underlying disease, anti SS-A antibody, antiphospholipid antibody, doses of corticosteroid, immunosuppressants or biologics before pregnancy in 142 cases which were delivered in our institution. <h3>Results</h3> In 23 among all cases underlying diseases were exacerbated, and these occurred more often in PM/DM (60%), MCTD (33.3%), RA (15.3%) and SLE (13.3%). In SLE, SS, MCTD and PM/DM, preterm births and LFD were closely related to disease exacerbation and dose of corticosteroid, pulse therapy, and these were extracted as risk factors for these perinatal complications. Preterm birth was also associated with low complement (CH50) and high titer of anti-dsDNA antibody, and LFD was associated with high titer of anti-dsDNA antibody before pregnancy. However, there was no significant association with these factors in threatened premature delivery and PROM. In RA, perinatal complications were not influenced by methotrexate and biologics before pregnancy. However, only LFD was related with doses of corticosteroid during pregnancy. <h3>Conclusions</h3> We extracted disease exacerbation and dose of corticosteroid, pulse therapy during pregnancy and also low complement, high titer of anti-double stranded DNA antibody before pregnancy as risk factors of pregnancy outcomes. In pregnancy complicated with CTD, we need to control the disease activity strictly, however, we should consider the increase or pulse therapy of corticosteroid carefully. <h3>References</h3> Clowse ME, Maqder LS, et al. The clinical utility of measuring complement and anti-dsDNA antibodies during pregnancy in patients with systemic lupus erythematosus. J Rheumatol. 2011 Jun; 38(6):1012–6. <h3>Disclosure of Interest</h3> None declared
AB0237 Prevalence and clinical characteristics of malignancy in seropositive rheumatoid arthritis patients
Authors: J Park, C Lee
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) are at an increased risk of malignancies compared with the general population. <h3>Objectives</h3> The aim of this study was to evaluate the prevalence and risk factors of malignancy in National Health Insurance Service Ilsan hospital patients with seropositive RA. <h3>Methods</h3> We found patients with seropositive RA who fulfilled the American College of Rheumatology criteria and American College of Rheumatology criteria/European League Against Rheumatism criteria, from May 2008 to September 2015. Occurrence of malignancy was originally collected by electronic medical record reports and diagnostic code. We consecutively enrolled patients with newly diagnosed malignancy. Control group was selected as five times the number of patients randomized. <h3>Results</h3> Total 12 malignancies in 647 patients were newly identified during the retrospective observation period of 2051 person-years. Malignancy types were 3 lung cancers, 2 colon cancers, gastric cancer, breast cancer, thyroid cancer, cervix cancer, cholangiocarcinoma, lymphoma and parotid gland cancer. In multivariate logistic regression, the variables with independent predictive value were older age (age: odds ratio =1.11, 95% CI =1.01–1.22, p-value =0.02), rheumatoid factor (RF) negativity (RF positivity: odds ratio =0.06. 95% CI =0.01–1.27, p-value 0.07) In cox regression, the variables with independent predictive value were older age (age: hazard ratio =1.12, 95% CI =1.01–1.24, p-value =0.02), negative RF (RF positivity: hazard ratio =0.12. 95% CI =0.02–0.78, p-value 0.02), lower anti-cyclic citrullinated peptide (CCP) antibody titer (anti-CCP antibody titer: hazard ratio =0.98. 95% CI =0.96–0.99, p-value 0.03) and positive antinuclear-antibody (ANA) (ANA positivity: hazard ratio =14.97, 95% CI =0.87–255.05, p-value 0.06). <h3>Conclusions</h3> Age, RF positivity, anti-CCP antibody titer, ANA positivity may be associated with malignancy risk in seropositive rheumatoid arthritis. So, continued vigilance and regular cancer screening are recommended for case of older age, RF negativity, lower anti-CCP antibody titer and ANA positivity. <h3>Disclosure of Interest</h3> None declared
Painful red eyes in a contact lens wearer
Authors: Katherine McVeigh, Kaveh Vadhani, Shokufeh Tavassoli, Derek Tole
Journal: BMJ (2017)

A 21 year old woman from Singapore presented to the eye hospital with a two week history of painful red eyes, where the severity of the pain was continuing to worsen. She was short-sighted and wore rigid gas permeable contact lenses on most days and admitted to sometimes sleeping with them in situ. She had last worn contact lenses a week before presentation. She reported that she had been cleaning the lenses with tap water over the past two months, including during a holiday in Thailand. She had not been unwell recently, in close proximity to anyone with conjunctivitis, or been subject to trauma. No previous ophthalmic or medical history was noted.

On examination, the best corrected visual acuity was 6/36 right eye and 6/9 left eye, tested with glasses. The conjunctival vessels were diffusely injected. The corneas stained bilaterally in a punctate fashion with fluorescein over a patchy area of whitish haze within the centre and mid peripheries (fig 1⇓).



Fig 1  Colour photograph of the right and left eye on the day of presentation captured using a slit lamp. Whitish hazy patches of infection and injected conjunctival blood vessels are noted bilaterally





### 1. What differential diagnoses need to be considered?

#### Short answer

The most likely diagnosis is a contact lens related microbial keratitis, which is usually caused by bacteria. However, with no improvement on antibiotics, acanthamoeba should be …
AB0613 Pulmonary artery diameter and pulmonary hypertension in systemic sclerosis
Authors: BE Schreiber, CP Denton, G Robinson, AU Wells, G Keir, N Sverzelatti, J Suntharalingam, G Coghlan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic sclerosis may be complicated by pulmonary hypertension. CT-determined pulmonary artery diameter has been shown to correlate with presence of pulmonary hypertension in idiopathic patients and in interstitial lung disease but not in scleroderma. <h3>Objectives</h3> To determine the utility of CT-determined main pulmonary artery diameter (MPAD) for predicting pulmonary hypertension (PH) in 97 patients with systemic sclerosis who had CT chest within six months of right heart catheterisation. <h3>Methods</h3> Retrospective review of right heart catheter and CT data done within six months in 97 patients. The CT scans were blindly scored by two radiologists. <h3>Results</h3> 97 patients (75 female, 22 male) with systemic sclerosis who underwent CT scan and right heart catheterization were analysed. About 2/3 had the limited subtype (64 limited, 24 diffuse, 6 undefined). Pulmonary hypertension was present in 55 patients (57%) and interstitial lung disease affecting 20% of the lung or more was present in 42 patients (43%). Survival was worse in those with pulmonary hypertension. Median survival was 9.3 years in those without pulmonary hypertension (8.1–10.5) and 4.4 years in those with pulmonary hypertension (2.6–6.2). Presence of interstitial lung disease and pulmonary hypertension were independent predictors of survival. An ROC curve shows area under the curve of 0.864. MPAD threshold of 25 mm or greater has a sensitivity of 98% and a specificity of 33% for the presence of pulmonary hypertension; 30 mm has a sensitivity of 73% and a specificity of 81% for the presence of pulmonary hypertension; 32 mm has a sensitivity of 56% and a specificity of 88% for the presence of pulmonary hypertension and 34 mm has a sensitivity of 35% and a specificity of 98% for the presence of pulmonary hypertension. Survival was worse in those with a MPAD of 30mm or greater, with median survival of 5.5 years (3.8–7.2) compared to survival of 9.3 years (7.9–10.7) in those with MPAD smaller than 30mm. It was not a significant predictor of survival after adjustment for presence of pulmonary hypertension and interstitial lung disease. <h3>Conclusions</h3> The CT determined MPAD correlates strongly with the presence of pulmonary hypertension in patients with systemic sclerosis. <h3>Disclosure of Interest</h3> None declared
Phase three studies of biologics for severe asthma: could do better?
Authors: Douglas S. Robinson, Harsha H. Kariyawasam, Liam G. Heaney
Journal: European Respiratory Journal (2017)

It is an exciting time for those of us treating patients with severe asthma. We now have more effective ways of assessing patients, monitoring adherence, and defining airway inflammation [1–5]. Current trials should inform on the role of biomarkers in determining treatment response [6], as we move away from a one-size-fits-all approach with oral prednisolone as the best alternative available. We can now select patients for intervention with biologics. We need to reconsider how we assess biologics for severe asthma <http://ow.ly/j7Mw30efCHb>
Emerging Advances in Nanotheranostics with Intelligent Bioresponsive Systems
Authors: Junqing Wang, Wei Tao, Xiaoyuan Chen, Omid C. Farokhzad, Gang Liu
Journal: Theranostics (2017)

The confluence of therapeutics and diagnostics based on the advantages of nanotechnology offers significant opportunities for personalized and precision medicine.Intelligent nanotheranostics based on bioresponsive systems have recently emerged and offer the promise of high specificity and efficiency via "on-demand" activation of both therapeutic and diagnostic capabilities.
Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma
Authors: Daniel S W Tan, Fui Teen Chong, Hui Sun Leong, Shen Yon Toh, Dawn P Lau, Xue Lin Kwang, Xiaoqian Zhang, Gopinath M Sundaram, Gek San Tan, Mei Mei Chang, Boon Tin Chua, Wan Teck Lim, Eng Huat Tan, Mei Kim Ang, Tony K H Lim, Prabha Sampath, Balram Chowbay, Anders J Skanderup, Ramanuj DasGupta, N Gopalakrishna Iyer
Journal: Nature Medicine (2017)
Endothelial Epas1 Deficiency Is Sufficient To Promote Parietal Epithelial Cell Activation and FSGS in Experimental Hypertension
Authors: Yosu Luque, Olivia Lenoir, Philippe Bonnin, Lise Hardy, Anna Chipont, Sandrine Placier, Sophie Vandermeersch, Yi-Chun Xu-Dubois, Blaise Robin, Hélène Lazareth, Michèle Souyri, Léa Guyonnet, Véronique Baudrie, Eric Camerer, Eric Rondeau, Laurent Mesnard, Pierre-Louis Tharaux
Journal: Journal of the American Society of Nephrology (2017)

FSGS, the most common primary glomerular disorder causing ESRD, is a complex disease that is only partially understood. Progressive sclerosis is a hallmark of FSGS, and genetic tracing studies have shown that parietal epithelial cells participate in the formation of sclerotic lesions. The loss of podocytes triggers a focal activation of parietal epithelial cells, which subsequently form cellular adhesions with the capillary tuft. However, in the absence of intrinsic podocyte alterations, the origin of the pathogenic signal that triggers parietal epithelial cell recruitment remains elusive. In this study, investigation of the role of the endothelial PAS domain-containing protein 1 (EPAS1), a regulatory α subunit of the hypoxia-inducible factor complex, during angiotensin II-induced hypertensive nephropathy provided novel insights into FSGS pathogenesis in the absence of a primary podocyte abnormality. We infused angiotensin II into endothelial-selective Epas1 knockout mice and their littermate controls. Although the groups presented with identical high BP, endothelial-specific Epas1 gene deletion accentuated albuminuria with severe podocyte lesions and recruitment of pathogenic parietal glomerular epithelial cells. These lesions and dysfunction of the glomerular filtration barrier were associated with FSGS in endothelial Epas1-deficient mice only. These results indicate that endothelial EPAS1 has a global protective role during glomerular hypertensive injuries without influencing the hypertensive effect of angiotensin II. Furthermore, these findings provide proof of principle that endothelial-derived signaling can trigger FSGS and illustrate the potential importance of the EPAS1 endothelial transcription factor in secondary FSGS.
“CHARTA”: FOLFOX/Bevacizumab vs. FOLFOXIRI/Bevacizumab in advanced colorectal cancer—Final results, prognostic and potentially predictive factors from the randomized Phase II trial of the AIO.
Authors: Hans-Joachim Schmoll, Fabian Maximilian Meinert, Franziska Cygon, Benjamin Garlipp, Christian Junghanss, Malte Leithäuser, Arndt Vogel, Michael Schaefers, Ulrich Kaiser, Heinz-Gert Hoeffkes, Axel Florschütz, Jörn Rüssel, Stephan Kanzler, Thomas Edelmann, Helmut Forstbauer, Thomas Goehler, Carla Hannig, Bert Hildebrandt, Jörg Steighardt, Alexander Stein
Journal: Journal of Clinical Oncology (2017)

3533 Background: FOLFOXIRI/Bevacizumab (Bev) is superior to FOLFIRI/Bev in the TRIBE trial (F Loupakis, NEJM 2014). The CHARTA trial was developed parallel to TRIBE with the same 4-drug-protocol but vs. FOLFOX/B ev as control arm. Methods: From 7/11 to 12/14 250 patients were randomized, including ECOG 0-2, ≥ 1 measurable lesion &gt; 1cm, stratified by ESMO-Group 1,2,3 (HJ Schmoll, Ann Oncol 2012). Induction: 6 months, maintenance Capecitabine+Bev until progression or max.12 months, at P reinduction by investigators decision. 25% dose reduction was allowed in cycle 1 + 2 on the investigator’s discretion. Primary EP: significant improvement of PFS-rate @ 9 months (p&lt;0.1, 2-sided Fisher’s-exact test); secondary EP: RR, PFS, OS, toxicity. Results: 241 pts. (1 not elig., 8 prot. violation) are evaluable after a follow up of 31.4 (0.1-51) months. m/f: 65%/35%, age 61y (21-82), ECOG 0-1/2: 96%/4%. The Primary Endpoint was met: PFS @ 9 months 56% vs. 68%, p= 0.086. PFS was improved: 9.8 vs. 12.0 months, HR 0.7 (ns.), identical to TRIBE with 9.7 vs. 12.1 months. Response rate (A/B): CR: 5%/5%, CR/PR 60%/70%, SD 25%/21%, PD 14%/9%. Final OS will be available at the meeting. Toxicity was low to moderate without major differences except ° ¾ diarrhea (12%/16%) and neutrophils (14%/20%). Clinical/molecular prognostic or predictive factors are equally distributed (stratification by ESMO groups) (see table). There are major, but mostly not significant differences in RR/ PFS in most subgroups, however, not strong enough to safely identify patients with high potential to benefit from the 4-drug combination. Therefore, a multivariate analysis to model a common prognostic and predictive risk score is ongoing and will be presented at the meeting. Conclusion: “CHARTA” supports the superiority of FOLFOXIRI/Bev. A combined prognostic and predictive classification is required to better select those patients with most potential benefit from the 4-drug combination. Clinical trial information: NCT01321957. [Table: see text]