tbuckley/cabot-search huggingface dataset:
AB0765 Development and assessment of a structured training program for patients with systemic sclerosis
Authors: H. Ahrens, E. Siegert, M. Kraft, K. Loewy, M. Worm
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Structured patient education programs are a key element of patient care in many chronic diseases. They are often based on the Stanford University chronic disease self-management program and aim to empower patients and to improve compliance and coping abilities. However, not in every condition self-management education programs yield the expected benefit.<sup>1</sup> <h3>Objectives</h3> To develop a structured patient education program for SSc patients and to prove training-specific effects on patients' quality of life and disability. <h3>Methods</h3> We developed a structured patient education program. The content of the program was created by a team of rheumatologists and dermatologists. The program consists of three modules focusing on general knowledge about the disease, gastrointestinal involvement, digital ulcers (DU), skin and wound care and a patient diary on disease symptoms. Patients were either included in the intervention or in the control group. Disease symptoms and severity as well as clinical parameters were assessed at baseline (intervention and control), at the follow-up visit at month 3 (intervention only) and at the final follow-up visit at month 6. In the intervention group satisfaction with the education program was analysed. Primary outcome measures were SHAQ, SF-12, BFI, SHAQ_DU. Secondary outcome measure was the satisfaction survey. For comparisons between different times analysis of variance for repeated measures was used. For description of cohorts Mann-Whitney Wilcoxon test was used. <h3>Results</h3> 58 SSc patients were included, 27 received the educational program (intervention group) and 31 patients served as a control group. Both groups were matched regarding demographics and disease subtype. Incidence of DUs was significantly higher in patients from intervention group resulting in a more frequent administration of vasoactive therapies. SHAQ, SF-12, BFI, SHAQ_DU were comparable between control and intervention group. However, patients in the intervention group rated the training program as helpful and reported an increase in knowledge about their disease afterwards. A positive impact of the training program on SHAQ, SF-12, BFI, SHAQ_DU was observed in individual patients. <h3>Conclusions</h3> Patients who participated in the training were overall satisfied with the program. However, no significant effects on quality of life after the intervention were observed. One reason for this finding might be the disease duration (mean 11.5 years). This needs to be further analysed in a consecutive study considering patients with shorter disease duration. <h3>Reference</h3> [1] Warsi, et al. "Self-management Education Programs in Chronic Disease: A Systematic Review and Methodological Critique of the Literature"Archives of Internal Medicine2004. <h3>Disclosure of Interest</h3> None declared
A live vaccine rapidly protects against cholera in an infant rabbit model
Authors: Troy P. Hubbard, Gabriel Billings, Tobias Dörr, Brandon Sit, Alyson R. Warr, Carole J. Kuehl, Minsik Kim, Fernanda Delgado, John J. Mekalanos, Joseph A. Lewnard, Matthew K. Waldor
Journal: Science Translational Medicine (2018)

An engineered cholera vaccine candidate mediates colonization resistance and disease protection within 1 day in an infant rabbit model.
CDK6 Antagonizes p53-Induced Responses during Tumorigenesis
Authors: Florian Bellutti, Anca-Sarmiza Tigan, Sofie Nebenfuehr, Marlies Dolezal, Markus Zojer, Reinhard Grausenburger, Svenja Hartenberger, Sebastian Kollmann, Eszter Doma, Michaela Prchal-Murphy, Iris Z Uras, Alexander Höllein, Donna S Neuberg, Benjamin L Ebert, Anna Ringler, Andre C Mueller, Joanna I Loizou, Philip W Hinds, Claus Vogl, Gerwin Heller, Stefan Kubicek, Johannes Zuber, Marcos Malumbres, Matthias Farlik, Andreas Villunger, Karoline Kollmann, Veronika Sexl
Journal: Cancer Discovery (2018)

Tumor formation is a multistep process during which cells acquire genetic and epigenetic changes until they reach a fully transformed state. We show that CDK6 contributes to tumor formation by regulating transcriptional responses in a stage-specific manner. In early stages, the CDK6 kinase induces a complex transcriptional program to block p53 in hematopoietic cells. Cells lacking CDK6 kinase function are required to mutate TP53 (encoding p53) to achieve a fully transformed immortalized state. CDK6 binds to the promoters of genes including the p53 antagonists Prmt5, Ppm1d, and Mdm4 The findings are relevant to human patients: Tumors with low levels of CDK6 have mutations in TP53 significantly more often than expected.Significance: CDK6 acts at the interface of p53 and RB by driving cell-cycle progression and antagonizing stress responses. While sensitizing cells to p53-induced cell death, specific inhibition of CDK6 kinase activity may provoke the outgrowth of p53-mutant clones from premalignant cells. Cancer Discov; 8(7); 884-97. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 781.
Neoplasms Reported With Liraglutide or Placebo in People With Type 2 Diabetes: Results From the LEADER Randomized Trial
Authors: Michael A. Nauck, Thomas Jon Jensen, Carina Rosenkilde, Salvatore Calanna, John B. Buse
Journal: Diabetes Care (2018)

OBJECTIVE This study explored neoplasm risk with liraglutide versus placebo in the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) cohort. RESEARCH DESIGN AND METHODS LEADER (NCT01179048) was an international, phase 3b, randomized, double-blind, controlled trial. Participants aged ≥50 years with type 2 diabetes and high cardiovascular risk were assigned 1:1 to receive liraglutide (≤1.8 mg daily; n = 4,668) or placebo (n = 4,672) in addition to standard care and monitored for 3.5–5 years (median follow-up 3.8 years). The occurrence of neoplasms was a prespecified, exploratory secondary end point. Post hoc analyses of the time to the first confirmed neoplasms were conducted using a Cox regression model. RESULTS Neoplasm was confirmed in 10.1% of patients with liraglutide versus 9.0% with placebo (hazard ratio [HR] 1.12 [95% CI 0.99; 1.28]). The HR (95% CI) for liraglutide versus placebo was 1.06 (0.90; 1.25) for malignant neoplasms and 1.16 (0.93; 1.44) for benign neoplasms. Sensitivity analyses excluding neoplasms occurring &amp;lt;1 year or &amp;lt;2 years after randomization and analyses by sex provided similar results. In our main analyses, the 95% CI for the HR included one for all malignant neoplasms evaluated (including pancreatic and thyroid neoplasms) except for prostate neoplasms, which occurred in fewer liraglutide-treated patients. CONCLUSIONS LEADER was not primarily designed to assess neoplasm risk. Firm conclusions cannot be made regarding numeric imbalances observed for individual neoplasm types (e.g., pancreatic cancer) that occurred infrequently. LEADER data do, however, exclude a major increase in the risk of total malignant neoplasms with liraglutide versus placebo. Additional studies are needed to assess longer-term exposure.
Primary Melanoma Histologic Subtype: Impact on Survival and Response to Therapy
Authors: Michael Lattanzi, Yesung Lee, Danny Simpson, Una Moran, Farbod Darvishian, Randie H Kim, Eva Hernando, David Polsky, Doug Hanniford, Richard Shapiro, Russell Berman, Anna C Pavlick, Melissa A Wilson, Tomas Kirchhoff, Jeffrey S Weber, Judy Zhong, Iman Osman
Journal: JNCI Journal of the National Cancer Institute (2018)

Abstract Background Two primary histologic subtypes, superficial spreading melanoma (SSM) and nodular melanoma (NM), comprise the majority of all cutaneous melanomas. NM is associated with worse outcomes, which have been attributed to increased thickness at presentation, and it is widely expected that NM and SSM would exhibit similar behavior once metastasized. Herein, we tested the hypothesis that primary histologic subtype is an independent predictor of survival and may impact response to treatment in the metastatic setting. Methods We examined the most recent Surveillance, Epidemiology, and End Results (SEER) cohort (n = 118 508) and the New York University (NYU) cohort (n = 1621) with available protocol-driven follow-up. Outcomes specified by primary histology were studied in both the primary and metastatic settings with respect to BRAF-targeted therapy and immunotherapy. We characterized known driver mutations and examined a 140-gene panel in a subset of NM and SSM cases using next-generation sequencing. All statistical tests were two-sided. Results NM was an independent risk factor for death in both the SEER (hazard ratio [HR] = 1.55, 95% confidence interval [CI] = 1.41 to 1.70, P &amp;lt; .001) and NYU (HR = 1.47, 95% CI = 1.05, 2.07, P = .03) cohorts, controlling for thickness, ulceration, stage, and other variables. In the metastatic setting, NM remained an independent risk factor for death upon treatment with BRAF-targeted therapy (HR = 3.33, 95% CI = 1.06 to 10.47, P = .04) but showed no statistically significant difference with immune checkpoint inhibition. NM was associated with a higher rate of NRAS mutation (P &amp;lt; .001), and high-throughput sequencing revealed NM-specific genomic alterations in NOTCH4, ANK3, and ZNF560, which were independently validated. Conclusions Our data reveal distinct clinical and biological differences between NM and SSM that support revisiting the prognostic and predictive impact of primary histology subtype in the management of cutaneous melanoma.
AB0725 Severe dysphagia “poor prognostic marker” in idiopathic inflammatory myopathies
Authors: A.C. Costi, L. Garcìa, C. Pena, A. Testi, P. Sansinanea, R. Aguila, M. Pera, S. Velloso, F. Savy, M. Garcìa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In Idiopathic Inflammatory Myopathies (MII), 18%–20% of patients have dysphagia. <h3>Objectives</h3> To evaluate the frequency of dysphagia in patients with MII, association with other manifestations of the disease, treatment and evolution. To evaluate clinical characteristics and evolution of severe dysphagia. To compare clinical characteristics and evolution of mild-moderate versus severe dysphagia. <h3>Methods</h3> Retrospective, observational study. Patients with a diagnosis of MII were included according to modified classification criteria of Bohan and Peter. Demographic, clinical and complementary studies were recorded. Serious dysphagia was considered: contraindication of oral feeding. Descriptive statistics were performed. Chi2 test, Student's test or Mann Whitney as appropriate. <h3>Results</h3> We included 91 of 106 patients evaluated from 1992 to 2017: 76% female, mean age at diagnosis 48±14 years. 53% presented dysphagia: mild/moderate 62.5% (30/48 pts), severe 37.5% (18/48). Idiopathic dermatomyositis was the most frequent MII in these patients (71%). In patients with dysphagia, proximal muscle weakness was 90%, weakness of neck muscles 45%, weakness of respiratory muscles 27%. A significant association was found between dysphagia and weakness of respiratory muscles, weak neck muscles, glucocorticoid pulses, gammaglobulin, grave infections and death. (Data not shown in the summary). In patients with <b>severe dysphagia</b>, we observed a significant association with the requirement for mechanical ventilation, hospitalisation in an intensive care unit, serious infections and death (table 1). When comparing mild-moderate dysphagia vs severe dysphagia, a statistically significant association was found with neck muscles weakness, respiratory muscle weakness, glucocorticoid pulses, gamma globulin use, requirement for mechanical ventilation, hospitalisation in an intensive care unit, severe infections and mortality (table 2). <h3>Conclusions</h3> Fifty-three percent of patients with MII had dysphagia at some point during their evolution. Severe dysphagia was associated with parameters of disease severity, poor prognosis and increased mortality. <h3>Disclosure of Interest</h3> None declared
TLR4-Binding DNA Aptamers Show a Protective Effect against Acute Stroke in Animal Models
Authors: Gerónimo Fernández, Ana Moraga, María I. Cuartero, Alicia García-Culebras, Carolina Peña-Martínez, Jesús M. Pradillo, Macarena Hernández-Jiménez, Silvia Sacristán, M. Irene Ayuso, Rafael Gonzalo-Gobernado, David Fernández-López, M. Elena Martín, María A. Moro, Victor M. González, Ignacio Lizasoain
Journal: Molecular Therapy (2018)

Since Toll-like receptor 4 (TLR4) mediates brain damage after stroke, development of TLR4 antagonists is a promising therapeutic strategy for this disease. Our aim was to generate TLR4-blocking DNA aptamers to be used for stroke treatment. From a random oligonucleotide pool, we identified two aptamers (ApTLR#1R, ApTLR#4F) with high affinity for human TLR4 by systematic evolution of ligands by exponential enrichment (SELEX). Optimized truncated forms (ApTLR#1RT, ApTLR#4FT) were obtained. Our data demonstrate specific binding of both aptamers to human TLR4 as well as a TLR4 antagonistic effect. ApTLR#4F and ApTLR#4FT showed a long-lasting protective effect against brain injury induced by middle cerebral artery occlusion (MCAO), an effect that was absent in TLR4-deficient mice. Similar effects were obtained in other MCAO models, including in rat. Additionally, efficacy of ApTLR#4FT in a model of brain ischemia-reperfusion in rat supports the use of this aptamer in patients undergoing artery recanalization induced by pharmacological or mechanical interventions. The absence of major toxicology aspects and the good safety profile of the aptamers further encourage their future clinical positioning for stroke therapy and possibly other diseases in which TLR4 plays a deleterious role.
FRI0226 Assessment of therapy adherence and treatment results in gout patients who attended schools for patients and in those who did not
Authors: M. Eliseev, O. Zhelyabina, M. Chikina, S. Vladimirov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Gout is a poorly controlled disease despite the availability of effective treatment methods. One of the main reasons for its poor controll is patients' low adherence to treatment, including due to insufficient knowledge of treatment principles. <h3>Objectives</h3> To assess adherence to therapy and results of treatment in gout patients who attended schools for patients and in those who did not. <h3>Methods</h3> All patients with crystal-verified gout were interviewed and invited to attend School for gout pts. Totally 301 pts with gout were observed, 36 (10%) females and 264 (90%) males, mean age 54.5±12,7 y., mean disease duration 9.02±1,12 y., with the gout diagnosis verified at average 48.71[<sup><sup>12;60</sup></sup> months after the onset, the target UA level &lt;360 µmol/l initially was in 72 pts (24%). All patients were divided into 3 groups: Group 1 included 111 (36%) patients who refused to attend the school, Group 2 included 90 (30%) patients who consented but failed to come, Group 3 consisted of 100 (34%) patients who attended the School (- 100 (34%)). The data from the questionnaires were used for baseline and on-treatment assessments of the following: patient's attitude to the disease, patient's compliance to treatment, satisfaction with quality of life, the fact of taking urate-lowering therapy, UA level control, achievement of the UA level of &lt;360 µmol/l. <h3>Results</h3> In all 3 groups, after the visit to the doctor, the number of the patients taking urate-lowering therapy who reached the target level of uric acid, significantly increased, the maximum values were noted in the group who attended the School for gout pts. The UA target level achievement results in Group 2, of those who agreed to attend the School but never did for various reasons, were better than in Group 1 and comparable to that in Group 3. Table 1 presents the results of questionnaire survey at baseline and after one year. Better adherence to treatment was noted in patients with poorer quality of life and a rational attitude toward their disease. The patients who report satisfaction with quality of life often decided to refuse to take their medications, visited the doctor less often and more seldom achieved the UA target level. <h3>Conclusions</h3> Patients' attendance of the School for gout pts increases their adherence to urate-lowering treatment and promote better quality of life. However, treatment adherence in gout patients largely depends on mental approach. Patients who are more actively involved in their health care achieve better results regardless of the source of information. <h3>Disclosure of Interest</h3> None declared
Volumetric laser endomicroscopy in the biliary and pancreatic ducts: a feasibility study with histological correlation
Authors: Juan E. Corral, Omar Y. Mousa, Murli Krishna, Iris J. M. Levink, Khela R. Pursell, Mohammad Afsh, Paul T. Kröner, Denise M. Harnois, Herbert C. Wolfsen, Michael B. Wallace, Frank J. Lukens
Journal: Endoscopy (2018)

Volumetric laser endomicroscopy (VLE) provides circumferential images 3 mm into the biliary and pancreatic ducts. We aimed to correlate VLE images with the normal and abnormal microstructure of these ducts.Samples from patients undergoing hepatic or pancreatic resection were evaluated. VLE images were collected using a low-profile VLE catheter inserted manually into the biliary and pancreatic ducts ex vivo. Histological correlation was assessed by two unblinded investigators.25 patients (20 liver and 5 pancreatic samples) and 111 images were analyzed. VLE revealed three histological layers: epithelium, connective tissue, and parenchyma. It identified distinctive patterns for primary sclerosing cholangitis (PSC), pancreatic cysts, neuroendocrine tumor, and adenocarcinoma adjacent to the pancreatic duct or ampulla. VLE failed to identify dysplasia in a dominant stricture and inflammatory infiltrates in PSC. Reflectivity measurements of the liver parenchyma diagnosed liver cirrhosis with high sensitivity.VLE can identify histological changes in the biliary and pancreatic ducts allowing real-time diagnosis. Further studies are needed to measure the accuracy of VLE in a larger sample and to validate our findings in vivo.
Diagnostic accuracy of a prototype rapid chlamydia and gonorrhoea recombinase polymerase amplification assay: a multicentre cross-sectional preclinical evaluation
Authors: E.M. Harding-Esch, S.S. Fuller, S.-L.C. Chow, A.V. Nori, M.A. Harrison, M. Parker, O. Piepenburg, M.S. Forrest, D.G. Brooks, R. Patel, P.E. Hay, N. Fearnley, M.J. Pond, J.K. Dunbar, P.D. Butcher, T. Planche, C.M. Lowndes, S.T. Sadiq
Journal: Clinical Microbiology and Infection (2018)

ObjectivesRapid and accurate sexually transmitted infection diagnosis can reduce onward transmission and improve treatment efficacy. We evaluated the accuracy of a 15-minute run-time recombinase polymerase amplification–based prototype point-of-care test (TwistDx) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG).MethodsProspective, multicentre study of symptomatic and asymptomatic patients attending three English sexual health clinics. Research samples provided were additional self-collected vulvovaginal swab (SCVS) (female participants) and first-catch urine (FCU) aliquot (female and male participants). Samples were processed blind to the comparator (routine clinic CT/NG nucleic acid amplification test (NAAT)) results. Discrepancies were resolved using Cepheid CT/NG GeneXpert.ResultsBoth recombinase polymerase amplification and routine clinic NAAT results were available for 392 male and 395 female participants. CT positivity was 8.9% (35/392) (male FCU), 7.3% (29/395) (female FCU) and 7.1% (28/395) (SCVS). Corresponding NG positivity was 3.1% (12/392), 0.8% (3/395) and 0.8% (3/395). Specificity and positive predictive values were 100% for all sample types and both organisms, except male CT FCU (99.7% specificity (95% confidence interval (CI) 98.4–100.0; 356/357), 97.1% positive predictive value (95% CI 84.7–99.9; 33/34)). For CT, sensitivity was ≥94.3% for FCU and SCVS. CT sensitivity for female FCU was higher (100%; 95% CI, 88.1–100; 29/29) than for SCVS (96.4%; 95% CI, 81.7–99.9; 27/28). NG sensitivity and negative predictive values were 100% in FCU (male and female).ConclusionsThis prototype test has excellent performance characteristics, comparable to currently used NAATs, and fulfils several World Health Organization ASSURED criteria. Its rapidity without loss of performance suggests that once further developed and commercialized, this test could positively affect clinical practice and public health.
AB1455-HPR The experience of living with fatigue among people with rheumatoid arthritis – a qualitative meta-synthesis
Authors: J Primdahl, A. Hegelund, A.G. Lorenzen, K.B. Loeppenthin, E. Dures, B.A. Esbensen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> People with Rheumatoid Arthritis (RA) experience fatigue as the most significant symptom of their illness. Despite a substantial body of knowledge about fatigue, there is a need for an overall comprehensive understanding of the experience of living with fatigue among people with RA <h3>Objectives</h3> To identify, appraise and synthesise qualitative studies on experiences of living with fatigue in people with RA <h3>Methods</h3> We conducted a qualitative meta-synthesis, inspired by Sandelowski and Barroso<sup>1</sup>. This included a systematic literature search conducted in February 2017, for studies published in the past 15 years, in the databases PubMed, Cinahl, Embase, SveMed, PsychInfo and Web of Science. To be included the studies had to include findings regarding the experience of adults with RA living with fatigue. The international Critical Appraisal Skills programme was used to assess the quality. The analysis and synthesis were inspired by Malterud's systematic text condensation<sup>2</sup> <h3>Results</h3> Eight qualitative articles were included. The synthesis resulted in an overall theme 'fatigue: the vicious cycle of an unpredictable symptom'. In addition, the analysis derived five subthemes, 'being alone with fatigue', 'necessary prioritising in everyday life', 'when time gets a different meaning', 'language as a tool for increased understanding' and 'strategies to manage fatigue'. Fatigue affects all areas of everyday life for people with RA. They strive to plan and prioritise, pace, relax and rest. In addition, they try to make use of a variety of words and language to help others understand that the RA-related fatigue they experience is not 'normal' fatigue. People with RA-related fatigue experience feeling alone with their symptom, but they develop their own strategies to manage fatigue in their everyday life <h3>Conclusions</h3> The unpredictability of RA-related fatigue is dominant, pervasive and is experienced as a vicious cycle, which can be described in relation to its physical, cognitive, emotional, social and behavioural impact. Acknowledgement and support from health professionals can make a difference to people with RA-related fatigue <h3>References</h3> [1] Sandelowski, M &amp; Barosso, J. 2007: Handbook for synthesizing qualitative research. New York, Springer. [2] Malterud, K. 2012: Systematic text condensation: a strategy for qualitative analysis. Scand J Public Health, 40, 795–805 <h3>Disclosure of Interest</h3> None declared
Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses
Authors: Giorgio Napolitani, Prathiba Kurupati, Karen Wei Weng Teng, Malick M. Gibani, Margarida Rei, Anna Aulicino, Lorena Preciado-Llanes, Michael Thomas Wong, Etienne Becht, Lauren Howson, Paola de Haas, Mariolina Salio, Christoph J. Blohmke, Lars Rønn Olsen, David Miguel Susano Pinto, Laura Scifo, Claire Jones, Hazel Dobinson, Danielle Campbell, Helene B. Juel, Helena Thomaides-Brears, Derek Pickard, Dirk Bumann, Stephen Baker, Gordon Dougan, Alison Simmons, Melita A. Gordon, Evan William Newell, Andrew J. Pollard, Vincenzo Cerundolo
Journal: Nature Immunology (2018)