tbuckley/cabot-search huggingface dataset:
Radiation-Induced Amplification of TGFB1-Induced Mesenchymal Stem Cell–Mediated Sodium Iodide Symporter (<i>NIS</i>) Gene 131I Therapy
Authors: Christina Schug, Carolin Kitzberger, Wolfgang Sievert, Rebekka Spellerberg, Mariella Tutter, Kathrin A. Schmohl, Bernadette Eberlein, Tilo Biedermann, Katja Steiger, Christian Zach, Markus Schwaiger, Gabriele Multhoff, Ernst Wagner, Peter J. Nelson, Christine Spitzweg
Journal: Clinical Cancer Research (2019)

The innate tumor homing potential of mesenchymal stem cells (MSCs) has been used for a targeted delivery of the theranostic sodium iodide symporter (NIS) transgene into solid tumors. We have previously shown that external beam radiotherapy (EBRT) results in the enhanced recruitment of NIS-expressing MSCs into human hepatocellular carcinoma (HuH7). In parallel, the tumor-associated cytokine TGFB1 becomes strongly upregulated in HuH7 tumors in response to EBRT.We therefore evaluated the effects of combining focused EBRT (5 Gy) with MSC-mediated systemic delivery of the theranostic NIS transgene under control of a synthetic TGFB1-inducible SMAD-responsive promoter (SMAD-NIS-MSCs) using 123I-scintigraphy followed by 131I therapy in CD1 nu/nu mice harboring subcutaneous human hepatocellular carcinoma (HuH7).Following tumor irradiation and SMAD-NIS-MSC application, tumoral iodide uptake monitored in vivo by 123I-scintigraphy was enhanced as compared with nonirradiated tumors. Combination of EBRT and SMAD-NIS-MSC-mediated 131I therapy resulted in a significantly improved delay in tumor growth and prolonged survival in therapy mice as compared with the combined therapy using CMV-NIS-MSCs or to control groups receiving EBRT or saline only, or EBRT together with SMAD-NIS-MSCs and saline applications.MSC-based NIS-mediated 131I therapy after EBRT treatment dramatically enhanced therapeutic efficacy when a TGFB1-inducible SMAD-responsive promoter was used to drive NIS expression in adoptively applied MSCs. The remarkable therapeutic effect seen is thought to be linked in large part to the enhanced TGFB1 produced in this context, which leads to a highly selective and focused amplification of MSC-based NIS expression within the tumor milieu.
AB0320 FATIGUE PATTERNS IN RHEUMATOID ARTHRITIS PATIENTSWHO RECEIVE BIOLOGICAL AND TARGETED SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS
Authors: Dalifer Freites Nuñez, Marta Redondo, Judit Font, Alfredo Madrid García, Cristina Vadillo, Lydia Abasolo, Leticia León
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Fatigue is one of the most frequent symptoms in patients with rheumatoid arthritis (RA), affecting more than 80% of them. The experience of fatigue is multidimensional. <h3>Objectives</h3> To identify the factors associated with fatigue on its different subscales (Physical, Living, Cognitive and Emotional). <h3>Methods</h3> Cross-sectional study. 60 patients were included, they were being followed up in the rheumatology outpatient clinic of Hospital Clínico San Carlos, Madrid, Spain. Data were collected between July 2018 and January 2019. All patients met the ACR/EULAR 2010 criteria and they were in treatment with Biological or Targeted Synthetic DMARD. <b>Main variable:</b> Fatigue was assessed by the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ). <b>Covariables:</b> Demographic, clinical and treatment. <b>Statistical analysis.</b> A descriptive analysis was carried out for the different variables. To identify factors independently associated to BRAF-MDQ and its subscales, multivariable linear regression was applied. Results were expressed as coef with their corresponding 95% CI. A value of p &lt; 0.05 was accepted as statistically significant. <h3>Results</h3> A total of 60 patients, comprising of 53 females (88%) and 7 males (12%) with a mean age of 56.4±11.8 years and mean disease duration of 14.1±7.7 years were evaluated. RF was positive in 60% of patients. 65% were in active on work and 23% retired. Regarding comorbidities, 43% had dyslipidemia, 42% hypertension, 17% hypothyroidism and 15% depression. The DAS28-ESR and SDAI scores of the patients were 2.6±0.8, 8.5±5.9 respectively. The HAQ was 0,86 ± 7.7. The rest of the clinical, treatment characteristics, and the scores of the fatigue instruments are shown in <b>Table 1.</b> The factors affecting the BRAF-MDQ and its subscales was evaluated in multivariate analyze<b>Table 2.</b> Our results shows a correlation between disability and the different dimensions (p &lt;0.001). Patients who reported good sleep quality had less physical fatigue, while those under Non Anti-TNF treatment perceived more physical and living fatigue. In addition, an association was observed between depression and cognitive fatigue, disease activity (DAS28-ESR) and living fatigue and between VAS-pain score and emotional fatigue. A positive RF was associated with less physical and living. <h3>Conclusion</h3> It is important to evaluate fatigue in a multidimensional perspective, each of the different subscales could be modulated by different factors. The results of our study indicated that disability predicts in all subscales of fatigue, however, other factors can configure different patterns of fatigue in RA patients, and identify them is key to the approach of this complex symptom. <h3>Disclosure of Interests</h3> None declared
Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types
Authors: Hilary K. Finucane, Yakir A. Reshef, Verneri Anttila, Kamil Slowikowski, Alexander Gusev, Andrea Byrnes, Steven Gazal, Po-Ru Loh, Caleb Lareau, Noam Shoresh, Giulio Genovese, Arpiar Saunders, Evan Macosko, Samuela Pollack, John R. B. Perry, Jason D. Buenrostro, Bradley E. Bernstein, Soumya Raychaudhuri, Steven McCarroll, Benjamin M. Neale, Alkes L. Price
Journal: Nature Genetics (2018)
JAK selectivity for inflammatory bowel disease treatment: does it clinically matter?
Authors: Silvio Danese, Marjorie Argollo, Catherine Le Berre, Laurent Peyrin-Biroulet
Journal: Gut (2019)

The two major forms of inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated conditions characterised by an increased production of pro-inflammatory cytokines that act as critical drivers of intestinal inflammation. Anti-cytokine therapy has been shown to improve clinical outcomes in IBD. Janus kinases (JAKs) are tyrosine kinases that bind different intracellular cytokine receptors, leading to phosphorylation of signal transducer and activation of transcription molecules implicated on targeted gene transcription. Four isoforms of JAKs have been described: JAK1, JAK2, JAK3 and TYK2. Oral JAK inhibitors (JAKi) have been developed as synergic anti-cytokine therapy in IBD, showing different selectivity towards JAK isoforms. Tofacitinib, a pan-JAK inhibitor, has been recently approved for the treatment of moderate-to-severe UC. With the aim of improving the benefit: risk ratio of this drug class, several second-generation subtype-selective JAKi are under development. However, whether selective inhibition of JAK isoforms is associated with an increased clinical efficacy and/or a better safety profile remains debatable. The aim of this review is to critically review the preclinical and clinical data for the differential selectivity of JAK inhibitors and to summarise the potential clinical implications of the selective JAK inhibitors under development for UC and CD.
PB2172 THE EFFECTS OF CURCUMIN ADDITION ON REMISSION STATUS OF MULTIPLE MYELOMA PATIENTS
Authors: D. Santosa, C. Suharti, I. Riwanto, E. Dharmana, E. Adi Pangarsa, B. Setiawan, S. Suyono, M. Lumban Tobing
Journal: HemaSphere (2019)

Background: The standard treatment for multiple myeloma (MM) which ineligible transplant is melphalan prednisone (MP). Curcumin has anti‐inflamatory, anti angiogenesis, decrease proliferation and delay progression of monoclonal gammopathy undetermined significant or smoldering myeloma. There is no study of curcumin in MM patients Aims: To evaluate the effect of curcumin addition to remission status at MM patient with regiment MP Methods This experimental study was involved 35 patients which randomly into treatment (n = 17) and control (n = 16). The treatment group was given melphalan 4 mg/m2, prednisone 40 mg/m2 (MP) for 7 days and curcumin 8 gram daily for 28 days. The control group was given MP and placebo. Remision status was evaluated after 4 cycles treatment. The difference between two groups was analysed by Mann‐Whitney U‐Test. Trend analysis was evealuated by Friedman. Remission status was evaluated by Chi‐square. Multivariate analysis was evaluated by multiple logistic regression. Results: There was a significant decrease of NF‐KB, VEGF, TNF‐α, LDH levels in the treatment group compared with control. There was a decreasing trend of IL‐6 levels in the treatment group significantly. There was significant difference of remission status beetween the treatment and control group [(75 vs 33.3), X 2 = 6.89,df = 1, p = 0.009]. There was significant correlation between TNF‐α levles and remission status [OR = 1.35; (95% CI = 1.03‐1.7.6), p = 0.03]. Summary/Conclusion: The curcumin addition on MM patient with MP regiment improved the remision status through decreased of TNF‐α levels.
AB0318 BAROPODOMETRIC COMPARISON OF PLANTAR PRESSURE IN KNEE OSTEOARTHRITIS PATIENTS AND RHUMATOID ARTHRITIS PATIENTS
Authors: Safaa Fellous, Jihad Moulay Berkchi, Hanan Rkain, Tahiri Latifa, Régis Guieu, Yves Jammes, Fadoua Allali
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Objectives</h3> To compare the plantar pressure between patients with Knee Osteoarthritis and patients with rhumatoid arthritis <h3>Methods</h3> This is a cross-sectional study, included 41 patients with rheumatoid arthritis (87.8% female, mean age 49 ± 11.9 [27-83] years, median duration of evolution was 9 (4.20)) months, and 40 knee osteoarthrosis patients (100% female, mean age 57.6 ± 5.2 [50-67] years, median evolution time was 36 (24, 69) months). The two groups were matched by BMI (27.5 vs. 29.6, p&gt; 0.05). In the rheumatoid arthritis group: The mean DAS28 was 3.9 ± 1.3 [2-6] and the knee joint was affected in 22% of cases. In the knee osteoarthritis group: The knee osteoarthrosis was bilateral in 80% of the cases and the radiological severity (Stages 3 or 4 of Kellgren and Lawrence classification) was found in 27.5%. The baropodometric study was performed using a PRESSCAM® platform (SIDAS®, 38,000 VOIRON, MEDICAPTEURS®). The static analysis was done in free position, for 30 seconds at 50 Hz with measure of plantar pressure parameters. <h3>Results</h3> <h3>Conclusion</h3> This comparative static baropodometric study of patients with RA and patients with knee osteoarthritis shows significant differences in bearing surface, which appears to be lower in the RA group, especially in the forefoot. The thrust on the forefoot is also less important in the RA group. these results could be explain by the rheumatoid forefoot, which decreased support and pressure on the forefoot. <h3>Disclosure of Interests</h3> None declared
Engaging NHS staff in research
Authors: Jill Maben, Angela King
Journal: BMJ (2019)

Calls by the Royal College of Physicians (RCP) for more research in NHS trusts and the Care Quality Commission’s (CQC) decision to award extra points to trusts doing research, seem to signal a new era for research in the NHS.  The RCP statement Delivering Research for All says every NHS clinician should be supported to take part in research. Highlighting evidence that research active trusts have better patient outcomes, the college calls for protected time for doctors, nurses, and other clinicians to undertake research. In collaboration with the National Institute for Health Research, the CQC will add questions to the leadership inspection framework for providers (the well led framework) that recognise the role of research in high quality patient care and strengthen the assessment of research activity.  An increase in research capacity is welcome, but there are serious challenges to implementation. Substantial change, some might say a revolution, will be required in the way research is conducted in the NHS.
Effects of Exercise in Addition to a Family-Based Lifestyle Intervention Program on Hepatic Fat in Children With Overweight
Authors: Idoia Labayen, María Medrano, Lide Arenaza, Edurne Maíz, Maddi Osés, Vicente Martínez-Vizcaíno, Jonatan R. Ruiz, Francisco B. Ortega
Journal: Diabetes Care (2019)

OBJECTIVE Pediatric hepatic steatosis is highly prevalent and closely related to type 2 diabetes. This study aimed to determine whether the addition of supervised exercise to a family-based lifestyle and psycho-educational intervention results in greater reduction of percentage of hepatic fat (HF), adiposity, and cardiometabolic risk factors in children with overweight/obesity. RESEARCH DESIGN AND METHODS The study subjects of this nonrandomized, two-arm, parallel design clinical trial were 116 overweight/obese children (10.6 ± 1.1 years of age, 53.4% girls) living in Vitoria-Gasteiz (Spain). For 22 weeks, they followed either a lifestyle and psycho-education program (control intervention [CInt], N = 57), consisting of two family-based education sessions/month, or the same plus supervised exercise (intensive intervention [II], N = 59) focused mainly on high-intensity aerobic workouts (3 sessions/week, 90 min/session). The primary outcome was the change in percentage of HF (as measured by MRI) between baseline and the end of the intervention period. Secondary outcomes included changes in BMI, fat mass index (FMI), abdominal fat (measured by DEXA), blood pressure, triglycerides, HDL, LDL, γ-glutamyl transferase, glucose, and insulin concentrations. RESULTS A total of 102 children completed the trial (N = 53 and N = 49 in the CInt and II groups, respectively). Percentage of HF decreased only in the II group (−1.20 ± 0.31% vs. 0.04 ± 0.30%, II and CInt groups, respectively), regardless of baseline value and any change in adiposity (P &amp;lt; 0.01). BMI, FMI, abdominal fat (P ≤ 0.001), and insulin (P &amp;lt; 0.05) were reduced in both groups. CONCLUSIONS Multicomponent intervention programs that include exercise training may help to reduce adiposity, insulin resistance, and hepatic steatosis in overweight/obese children.
SAT0498 THE IMPACT OF OVERWEIGHT ON THE OUTCOME OF JUVENILE IDIOPATHIC ARTHRITIS
Authors: Juliane Riess, Ivan Foeldvari
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Overweight and obesity are considered to have a negative impact on Rheumatoid Arthritis in adults and there is less information regarding the correlation in juvenile idiopathic arthritis(JIA). <h3>Objectives</h3> To assess the effect of overweight on the activity of JIA as well as the stability and ability to achieve a remission using the cJADAS-10 score. <h3>Methods</h3> This is a longitudinal retrospective study design. We collected data of 164 patients suffering from JIA from three consecutive visits. Treatment was conducted between 2012 and 2015 at our centre in accordance to current guidelines. Remission was defined by cJADAS10 score ≤0,5 in Oligoarthritis and ≤0,7 in Polyarthritis. Patients were categorized by weight-for-age percentiles as heavily underweight (less than 3<sup>rd</sup> percentile) underweight (4<sup>th</sup> up to 10<sup>th</sup> percentile) healthy (11<sup>th</sup> up to 90<sup>th</sup> percentile) overweight (91<sup>th</sup> up to 96<sup>th</sup> percentile) and obese (97<sup>th</sup> up to 100<sup>th</sup> percentile). We compared the cJADAS10 of normal-weighted children with the cJADAS10 of the overweight and the obese patients, respectively. <h3>Results</h3> Of all patients, 13 were "underweight" (7,9%), 109 were defined as "normal weight" (66,5%) and 42 patients were categorized as "overweight" (25,6%) of which 16 children (9,8%) were "obese". 95 (57.9%) reached a remission during follow-up visits. Overweight was associated with higher disease activity compared to healthy weight children at the first visit (mean 9,5 vs. 8,5) and a wider range of the cJADAS10 score (0-22 vs.0-20,5). Results from the 3-months-follow-up revealed an overall good response to the prescribed medication. At 6-months-follow-up, overweight children couldn't stabilize the improvement since cJADAS10 range rises while it stays stable in healthy weight children. At the same time, while interpreting the disease activity of "overweight" and "obese" children separately, obese children show significantly less disease activity than overweight children, especially at the 3- and 6-months-follow-ups. <h3>Conclusion</h3> Overweight seems to have a negative influence on the disease activity and remission of JIA patients but it is most likely not the only influencing factor since obese patients show a better result regarding the cJADAS10 score than overweight patients. In the future, factors like socioeconomic status, BMI of the parents or physical activity level of the patient should be included in the evaluation. Also, the 7 subtypes of JIA should be analyzed individually since they show heterogeneous etiology, phenotype and prognosis. <h3>Disclosure of Interests</h3> Juliane Riess: None declared, Ivan Foeldvari Consultant for: Chugai
When Does Meta-analysis of a Network Not Work?
Authors: Murray B. Stein, Sonya B. Norman
Journal: JAMA Psychiatry (2019)

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Changes in early- and late-stage colorectal cancer incidence during the era of screening: 1976-2009.
Authors: Daniel X Yang, Cary Philip Gross, James B. Yu
Journal: Journal of Clinical Oncology (2013)

1522 Background: Ideally, screening detects cancer at a more curable stage, and as a result decreases the incidence of subsequent diagnosis at a late stage. Whereas breast cancer screening is suggested to have led to a substantial increase in the number of early-stage cancers diagnosed in the United States with only marginal reductions in the number of late stage cancers, the impact of colorectal cancer screening on cancer incidence is unknown. Methods: Colorectal cancer incidence data spanning over three decades, 1976—2009, were collected from the Surveillance, Epidemiology, and End Result (SEER) database. Screening utilization data spanning 1986—2010 were collected from the National Health Survey (NHS) progress reports. We examined trends in the incidence of early-stage (in situ, local) and late-stage (regional, distant) colorectal cancer among adults 50 years or older. Results: Over the past three decades, the incidence of late-stage colorectal cancer decreased significantly, from 118 to 74 cases per 100,000 people—a 37% decrease. The incidence of early-stage colorectal cancer also decreased, from 77 to 67 cases per 100,000 people. There was also an associated increase in the utilization rates of screening colonoscopy. From 1987 to 2010—the years for which NHS data were available—the percentage of adults 50 and older who received screening colonoscopy rose from 27% to 63%. After adjusting for trends in cancer incidence in non-screened populations, we estimated that colorectal screening was associated with a reduction of approximately 550,000 cases of colorectal cancer over the past three decades in the United States. Using the most conservative assumption of constant cancer incidence during the past three decades, 235,000 cases of colorectal cancer were prevented. Conclusions: There has been a significant decline in both early and late stage colorectal cancer diagnoses, during a time of increasing rates of increased screening.
AB1275 COMPARATIVE ANALYSIS OF LOCAL COMPLICATIONS OF HIP AND KNEE ARTHROPLASTY IN PATIENTS WITH RHEUMATOID ARTHRITISAND OSTEOARTHRITIS
Authors: Alexander Khramov, Maxim Makarov, Sergey Makarov, Alexey Rybnikov, Sergey Maglevaniy, Vera Amirdzhanova, Gayane Vardikova
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Surgical treatment of patients with rheumatoid arthritis (RA) is associated with an increased risk of complications. It can be caused by: an inflammatory process, the osteoporosis, the reduced physical activity, the severity of functional impairment, long-term glucocorticoid therapy, biologic and disease-modifying antirheumatic drugs. All of the above reasons provide elongated wound healing period, the development of infectious complications, increased risk of periprosthetic fractures. Objectives: to provide a comparative analysis of local complications of hip and knee arthroplasty in RA and osteoarthritis (OA) patients. <h3>Methods:</h3> We analyzed 2142 operations: hip (n = 1177) and knee (n = 965) replacement, which were performed to patients with RA and OA between 1998 and 2018. <h3>Results:</h3> There were 2142 hip and knee arthroplasty performed, including 1118 operations on patients with RA and 1024 operations on patients with OA. The number of local complications after total hip replacement was 155 (7.24%): 96 (8.59%) of them were patients with RA and 59 (5.76%) patients with OA. There were 1177 hip arthroplasty performed, including 467 operations on patients with RA and 710 operations on patients with OA. The number of local complications after total hip replacement was 85 (7.22%): 48 (10.28%) of them were patients with RA and 37 (5.21%) patients with OA. There were 965 knee arthroplasty performed, including 651 operations with RA patients and 314 operations in patients with OA were performed. The number of local complications after total knee replacement was 70 (7,25%): 48 (7.37%) of them were patients with RA and 22 (7.00%) patients with OA. We revealed a significantly greater number of complications in patients with RA (p&lt;0.005). <h3>Conclusion:</h3> Local complications after hip and knee arthroplasty with RA patients (8.59%) more than in OA patients (5.76%) in 1.5 times. It shows us that the operative treatment of patients with RA requires a special approach and more gentle management of patients with RA in co-operation with rheumatologist and careful treatment of the bone with surrounding tissues during the surgery. <h3>Disclosure of Interests:</h3> None declared