tbuckley/cabot-search huggingface dataset:
LUBAC determines chemotherapy resistance in squamous cell lung cancer
Authors: E. Josue Ruiz, Markus E. Diefenbacher, Jessica K. Nelson, Rocio Sancho, Fabio Pucci, Atanu Chakraborty, Paula Moreno, Alessandro Annibaldi, Gianmaria Liccardi, Vesela Encheva, Richard Mitter, Mathias Rosenfeldt, Ambrosius P. Snijders, Pascal Meier, Marco A. Calzado, Axel Behrens
Journal: The Journal of Experimental Medicine (2019)

Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10+, but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-κB signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-κB activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.
Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007–2016
Authors: Michael Chen‐Xu, Chio Yokose, Sharan K. Rai, Michael H. Pillinger, Hyon K. Choi
Journal: Arthritis & Rheumatology (2019)

Objective To estimate the current prevalence rates and decadal trends of gout and hyperuricemia in the US, as well as the prevalence of urate‐lowering therapy (ULT) among gout patients, using 2007–2016 data from a nationally representative survey of American men and women (the National Health and Nutrition Examination Survey [NHANES]). Methods Using data from 5,467 participants in the NHANES 2015–2016, we estimated the most recent prevalence rates of gout and hyperuricemia. When the NHANES was conducted, all participants were asked about their history of gout (as diagnosed by a health professional) and medication use. Hyperuricemia was defined as having a serum urate level of &gt;7.0 mg/dl in men and &gt;5.7 mg/dl in women. We examined decadal trends in these estimates using data from the NHANES 2007 – 2016 and investigated ULT usage trends using the NHANES 2007–14 (the most recent data available to date). Results In 2015–2016, the prevalence of gout was 3.9% among adults in the US (9.2 million people), with 5.2% [5.9 million] in men and 2.7% [3.3 million] in women. Mean serum urate levels were 6.0 mg/dl in men and 4.8 mg/dl in women, and hyperuricemia prevalence rates were 20.2% and 20.0%, respectively. The prevalence rates of gout and hyperuricemia remained stable between 2007 and 2016 ( P for trend &gt; 0.05). The prevalence of ULT use among patients with gout was 33% in 2007 – 2014 and remained stable over time ( P for trend &gt; 0.05). Conclusion In this nationally representative survey sample of adults in the US, the prevalence rates of gout and hyperuricemia remained substantial, albeit unchanged, between 2007 and 2016. Despite these rates, only one‐third of gout patients were receiving ULT.
FRI0589 A joint procedural recommendation on fdg-pet/ct(A) imaging in large vessel vasculitis and polymyalgia rheumatica from the cardiovascular and inflammation & infection committees of the eanm, the cardiovascular council of the snmmi, the pet interest group (PIG), and endorsed by the asnc
Authors: R. Slart
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> [18F]-fluorodeoxyglucose positron emission tomography combined with anatomical computed tomography angiography, (FDG-PET/CTA) is increasingly used in Large Vessel Vasculitis (LVV, consisting of Giant Cell Arteritis (GCA) and Takayasu Arteritis (TA)) and Polymyalgia Rheumatica (PMR), and may be of value for optimal diagnosis, disease activity monitoring, and evaluation of damage development. There are currently no general accepted procedural guidelines regarding PET imaging acquisition for LVV and PMR. <h3>Objectives</h3> The aim of our study is to provide recommendations and statements, based on the available evidence in the literature combined with consensus of experts in the field, for patient preparation, FDG-PET/CT(A) acquisition and interpretation. <h3>Methods</h3> A systematic literature review was conducted to retrieve data on FDG-PET/CT(A) imaging in LVV and PMR. Expert consensus was used to propose recommendations in the absence of sufficiently robust data. Levels of evidence and grades of recommendations were attributed to the statements of different indications according to published criteria. <h3>Results</h3> Based on the literature review combined with expert consensus recommendations and statements that could be formulated: <i>see</i>table 1. <h3>Conclusions</h3> This joint recommendation highlights that standardisation and general consensus regarding the optimal procedural performance of FDG-PET/CT(A) imaging in LVV and PMR are highly needed. Some recommendations and statements could be formulated however, there are also a lot of open issues which need to be studied for optimal performance of FDG-PET/CT(A) in the diagnosis, (treatment)monitoring and future theranostics in LVV/PMR to increase the levels of evidence and improve the grades of the recommendations. <h3>Disclosure of Interest</h3> None declared
AB1441-HPR Does the incidence of infections increase in patients with chronic arthritis and osteoporosis treated with denosumab and biological therapy?
Authors: A Lopez Esteban, F. Garcia, I. Janta, J.G. Ovalles, B. Serrano, J.C. Sanchez, C. Garaballu, C. Gonzalez, T. Del Rio, J. Lopez Longo, C. Gonzalez, I. Monteagudo, J.C. Nieto
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Biological therapies (BT) have changed the prognosis of chronic arthritis (CA); however, they have associated the increased risk of infections. Denosumab (DNS) is the first biologic approved for the treatment of osteoporosis (OP) and is also associated with an increased risk of infections. <h3>Objectives</h3> To evaluate the incidence of infections in patients with CA and OP treated with DNS alone or associated to another biological treatment. <h3>Methods</h3> A prospective observational study was designed in which all patients with OP who received treatment with DNS between January 2013 and December 2017 were included. The group of patients with CA (RA, EA, PsA) were treated, in addition to DNS as treatment for their OP, with BT. Follow-up was carried out in the rheumatology nursing examination room every 6 months. Demographic data, disease charaacteristics, infections and associated comorbidities were collected. Serious infections were defined as those that required admission, suspension of therapy or death. <h3>Results</h3> 220 patients were included (81.1% women). The main diagnoses were OP 112 (51%) and AC 76 (34.5%) [RA 58 patients (26.3%), SpA 8 (3.6%), Psa 10 (4.5%)] and other rheumatologic diagnoses 32 (14.5%). Demographic data are shown in Table 1. Both groups were similar except for the higher GC consumption and the higher lumbar bone mass of the CA group. Of the patients with CA, 41 patients received a synthetic DMARD (MTXmainly, 90%), and 40 patients (53.9%) received GC. The average dose of DNS injections was 4.5 (1–10), with average treatment duration (range and DS) of 23.03 months (6–66, 13.3).The incidence of infections was 74 (39.3%), 31 patients had repeated infections. The most frequent were urinary tract infections (UTI), respiratory, mouth and other infections. There were 4 serious infections, 2 UTI and 2 pneumonias (both concluded in death, in patients with RA). The incidence of infections among patients with OP and with CA was similar in both groups (40 (35.7%) vs. 34 (44.7%), p&lt;0.209). Multiple regression including age, synthetic DMARD, GC and duration of treatment with DNS showed that the duration of treatment with DNS [Exp (B=1.058, p&lt;0.001] and GC [Exp (B)=2.484, p=0.010] were the only predictors of increased risk of infections. <h3>Conclusions</h3> Patients with CA and OP who receive DNS and TB have a similar incidence of infections. However, the risk of infection is higher in CA patients related with the use of GC. The most frequent infection was UTI followed by respiratory infections, but they did not suppose the suspension of the treatment in the majority of the cases. <h3>Disclosure of Interest</h3> None declared
LOH and mutation analyses of candidate Wilms’ tumor suppressor genes from 7p15-21
Authors: Karen L. Head, Xiurong Li, Norma J. Nowak, John K. Cowell, Khalid Sossey-Alaoui
Journal: Cancer Research (2004)

2716  Wilms tumor is a pediatric lesion of the kidney and is one of the most common solid malignancies of childhood. Disease can occur in one or both kidneys, approximately 8% of cases being bilateral. The suggestion of a genetic component in the etiology of the tumor has come from several observations. Firstly, bilateral disease is associated with an early age of onset. Secondly, there is a high incidence of bilateral tumors in cases with a family history of Wilms tumor and in patients with associated congenital anomalies. Histological features indicate that the tumor occurs as a result of aberrant embryological development of the kidney. The kidney is therefore a model for studying the association between processes involved in tissue development and predisposition to malignancy. Although a gene for Wilms tumor (WT1) has been cloned, less than 10% of cases could be explained by mutations and/or alterations of this gene. Several other loci have been implicated in the etiology of Wilms tumors, including the 7p15-21 locus which was shown to be involved in 15-25% of Wilms tumors cases, strongly suggesting that a tumor suppressor gene for this disease must lie within this region. Since homozygous deletions are hallmarks of tumor suppressor genes, we have characterized a homozygous deletion in a Wilms tumor within the 7p15-21 locus and we have now defined the extent of this deletion, using BAC array CGH and PCR-based assays as a first step towards the identification of the Wilms tumor suppressor gene. We have also identified several candidate genes which we screened for point mutations in a large cohort of Wilms tumors, including those tumors that we have identified to show loss of heterozygosity at the 7p15-21 locus using WAVE DHPLC. We have also analyzed the methylation status of the promoter-associated CpG islands which we identified associated with candidate genes from the Wilms tumor critical region. Here, we present a summary of the LOH analysis, the mutation screening, and the methylation analysis of candidate genes for the Wimls tumor suppressor gene from 7p15-21.
Blood Pressure Assessment in Adults in Clinical Practice and Clinic-Based Research
Authors: Paul Muntner, Paula T. Einhorn, William C. Cushman, Paul K. Whelton, Natalie A. Bello, Paul E. Drawz, Beverly B. Green, Daniel W. Jones, Stephen P. Juraschek, Karen L. Margolis, Edgar R. Miller, Ann Marie Navar, Yechiam Ostchega, Michael K. Rakotz, Bernard Rosner, Joseph E. Schwartz, Daichi Shimbo, George S. Stergiou, Raymond R. Townsend, Jeff D. Williamson, Jackson T. Wright, Lawrence J. Appel
Journal: Journal of the American College of Cardiology (2019)
A New Prognostic Score for Advanced Systemic Mastocytosis Based on Clinical and Genetic Characteristics of 210 Consecutive Patients
Authors: Mohamad Jawhar, Juliana Schwaab, Nicole Naumann, Georgia Metzgeroth, Hans-Peter Horny, Karl Sotlar, Manja Meggendorfer, Torsten Haferlach, Nicholas C.P. Cross, Alice Fabarius, Wolf-Karsten Hofmann, Peter Valent, Andreas Reiter
Journal: Blood (2018)
Introducing Network Intervention Analysis to Investigate Sequential, Symptom-Specific Treatment Effects: A Demonstration in Co-Occurring Insomnia and Depression
Authors: Tessa F. Blanken, Tanja Van Der Zweerde, Annemieke Van Straten, Eus J.W. Van Someren, Denny Borsboom, Jaap Lancee
Journal: Psychotherapy and Psychosomatics (2019)

Gemcitabine-based salvage therapy is considered an effective treatment for relapsed and refractory Non-Hodgkin's lymphoma (NHL). We analyzed the outcome of 41 consecutive NHL patients treated with gemcitabine-based regimens between January 2007 and October 2015. Twenty-eight males and 13 females (median age 66.4 years) were included. The median follow-up from gemcitabine initiation was 7.3 months. Thirty patients (73%) had B-cell, and eleven (27%) had T-cell, lymphoma. All patients received a median of 2 prior regimens, of which at least 1 was anthracycline based. Twenty-eight patients (78%) received full-dose while 9 (22%) received reduced-dose regimens. The overall response rate was 37%, with 24% (n = 10) complete response, 12% (n = 5) partial response, and 63% (n = 22) progressive disease or stable disease. The median progression-free survival (PFS) was 47 days (range 12-1,318), the median overall survival (OS) was 1.9 years. Twenty patients (49%) died during follow-up. Grade 3-4 hematological toxicity was reported in 21 patients (51%). Relapsed vs. refractory disease, as well as a response to gemcitabine, predicted better PFS and OS. Use of a full-dose regimen predicted a better OS. Compared to previously published data, we observed less favorable outcomes. The administration of gemcitabine-based therapy as a salvage regimen for patients with relapsed or refractory NHL had limited success. Innovative therapies for these patients are an unmet need.
FRI0325 Rituximab in primary sjÖgren’s syndrome: a systematic review on its efficacy
Authors: M. Greco, J. Del Pino Montes, P. Díaz del Campo, M. Fernández Castro, F. Francisco, J.L. Andreu
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Primary Sjögren's syndrome (pSS) is a systemyc autoimmune disease that produces a limpho-plasmocitary infiltrate of the exocrine glands. Considering the primary role attributed to B-lymphocytes in pSS pathophysiology, it has been suggested that Rituximab (RTX) may have certain role in controlling the disease. <h3>Objectives</h3> To evaluate RTX efficacy in the treatment of xerostomia, xerophthalmia and systemic manifestations (including fatigue) in patients with pSS. <h3>Methods</h3> In the framework of the preparation of a recommendations document of the Spanish Society of Rheumatology on the use of biologics in pSS, a systematic search of the literature was carried out (until May 2017). Were included adults older than 18 years who met the 2002 American European Consensus Criteria, treated with RTX, with desired comparison to groups treated with other drugs or with placebo and a follow-up time of 6 months. The quality of the studies was assessed through the levels of evidence (LOE) of SIGN scale. <h3>Results</h3> The search resulted in a total of 749 articles and only 9 of them were selected <b>(figure 1)</b>. The best available evidence for each variable studied is summarised in <b>chart 1</b> ("+" significant improvement; "-" no significant improvement). The most relevant results obtained in the studies with <b>LOE 1+</b>, showed significant differences comparing RTX with lacebo (p&lt;0.05) in: 1) Souza 2016: Salivary flow rate at 24 w (weeks) (0.09; 95% CI 0.02 to 0.16). 2) Meijer 2010: Ocular dryness VAS score at 24 (-27.00, 95% CI −46.28 to −7.72), 36 and 48 w. Lissamine green test at 24 w (−2.00, 95% CI −3.52 to −0.48). Absolute number of B cells from 5 to 48 w (−0.23; IC 95%–0.31 to −0.15). Rheumatoid Factor at 12, 24 and 36 w. Tendomyalgia at 12 and 36 w. Vasculitis at 24 w. 3) Devauchelle-Pensec 2014: <sup>I</sup>mmunoglobulin's G (1.2 g/L; 95% CI 0.4 to 2 g/L), A, M and beta2-microglobulin (1.6 g/L; 95% CI 0.5 to 2 g/L) at 24 w. The studies with <b>LOE 3</b> also report improvement in a percentage of patients in other systemic manifestations, but without demonstrating statistical significance. <h3>Conclusions</h3> The studies of high methodological quality that evaluate the efficacy of RTX in pSS do not find significant improvement in the primary outcome variables, such as ESSDAI, glandular involvement and other objective parameters of dryness. However, open and retrospective studies find significant improvement in activity parameters, systemic manifestations, glandular involvement and improvement of certain objective tests of dryness. <h3>Disclosure of Interest</h3> None declared
Guidance for full-thickness suturing in endoscopic sleeve gastroplasty – preliminary exploration using laparoscopy
Authors: Lei Peng, Xuan Li, Guoxin Zhang
Journal: Endoscopy (2019)

Endoscopic sleeve gastroplasty (ESG) is a new endoscopic weight loss procedure that creates a sleeve along the gastric greater curvature using a full-thickness endoscopic suturing device [1] [2] [3]. However, there is no specific guide for full-thickness suturing in ESG.
Evading the STING: LKB1 Loss Leads to STING Silencing and Immune Escape in KRAS-Mutant Lung Cancers
Authors: Carminia Maria Della Corte, Lauren Averett Byers
Journal: Cancer Discovery (2019)

Abstract Summary: Mutations in STK11 (LKB1) are a major cause of primary resistance to immunotherapy in non–small cell lung cancer. Kitajima and colleagues dissect the underlying mechanism of this immune-resistant phenotype, demonstrating that LKB1 loss leads directly to suppression of stimulator of interferon genes (STING) and insensitivity to cytoplasmic double-strand DNA detection. Therapies that reactivate LKB1 or theSTING pathway may boost anticancer immune response in cancers with resistance to immune-checkpoint blockade. See related article by Kitajima et al., p. 34.
Clinical and Hematological Risk Factors for Postpartum Hemorrhage: A 2 Years Population Based Cohort Study in France
Authors: Claire Salomon, Claire De Moreuil, Jacob Hannigsberg, Christophe Trémouilhac, Guillaume Drugmanne, Florence Gatineau, Frédérique Falchier, Delphine Briend, Jean-François Abgrall, Emmanuelle Le Moigne, Karine Lacut, Brigitte Pan-Petesch
Journal: Blood (2018)
SAT0621 Clinical significance of interleukin-18 and interleukin -6 on disease course of adult-onset still’s disease
Authors: M.G. Ahmed
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Innate pro inflammatory cytokines interleukin (IL)−6 and IL-18 are critical for perpetuating the inflammatory processes in adult-onset Still's disease (AOSD),<sup>1</sup> and macrophage activation syndrome (MAS).<sup>2</sup> <h3>Objectives</h3> To assess the role of IL-6 and IL-18 in the pathogenesis of (AOSD) and MAS, and to investigate the clinical significance of serum cytokine profile with IL-6 and IL-18 in (AOSD) and MAS, <h3>Methods</h3> we analysed the serum IL-6 and IL-18 in patients with (AOSD) and compared them with the clinical features of (AOSD) 51 patients with (AOSD) including 17 patients with MAS were analysed. Levels of IL-6 and IL-18 were quantified in serum by enzyme linked immune sorbent assay. Results were compared with clinical features of (AOSD). <h3>Results</h3> Two distinct Adult Still's disease patient subsets based on their serum IL-6 and IL-18 levels were identified: an IL-18 dominant (IL-18/IL-6 1000) and an IL-6 dominant (IL-18/IL-6 1000). The IL-6 dominant subset had a significantly greater number of joints with active disease and higher serum levels of matrix metalloproteinase-3, whereas the IL-18-dominant subset was more likely to develop MAS. The cut off value of serum IL-18 to predict the development of MAS was 52000 pg/ml with 87.3% of sensitivity and 79.3% of specificity. The patients with IL-18 dominant pattern were likely to have monophasic or polycyclic disease course, whereas the patients with IL-6 dominant pattern were likely to have persistent disease course. Serum IL-18 levels in patients achieved remission decreased to the levels&lt;1,000 pg/mL in inactive phase and normalised in remission phase. In contrast, serum IL-18 levels in patients experienced relapse during withdrawal of steroid within 12 months after disease onset demonstrated a sustained elevation of serum IL-18 levels&gt;1,000 pg/mL during the inactive phase <h3>Conclusions</h3> Two subsets of patients with (AOSD), one which is prone for arthritis and another with prone for MAS, can be identified on the basis of their serum IL-6 and IL-18 levels. These two subsets appear to be characterised by certain distinct clinical features. Monitoring the cytokine profile with IL-18 and IL-6 might be useful to predict disease course. Furthermore, serum IL-18 levels reflect the biological activities of the immune system in (AOSD) and may predict the development of MAS and the prognosis of Adult Still's disease <h3>References</h3> [1] Choi JH, Suh CH, Lee YM, Suh YJ, Lee SK, Kim SS, et al. Serum cytokine profiles in patients with adult onset Still's disease. J. Rheumatol2003;30:2422–2427. [2] Schulert GS, Grom AA. Macrophage activation syndrome and cytokine-directed therapies. Best Practice &amp; Research: Clinical Rheumatology2014;28:277–292. <h3>Disclosure of Interest</h3> None declared
Abstract MP20: Cardiovascular Protection by the Mediterranean Diet Differs Across Socioeconomic Groups: Prospective Findings From The MOLI-SANI Study
Authors: Marialaura Bonaccio, Augusto Di Castelnuovo, George Pounis, Simona Costanzo, Mariarosaria Persichillo, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello
Journal: Circulation (2016)

Introduction: Low socioeconomic status is associated with poor health outcomes and unhealthy behaviors. The traditional Mediterranean diet (MD) has been related to reduced risk of major chronic diseases and mortality and exhibits a socioeconomic gradient. Hypothesis: The association of the MD with cardiovascular risk (CVD) may differ across different socioeconomic status groups. Methods: Population-based cohort study on 18,710 individuals apparently free at enrollment from CVD and diabetes, randomly recruited from the general population of the MOLI-SANI study (Italy). The cohort was followed up for a median of 4.3 years (81,367 person-years). Food intake was recorded by the EPIC food frequency questionnaire. Adherence to the MD was appraised by the Greek Mediterranean diet score. Household income (Euros/year) and educational levels were used as socioeconomic status indicators. Incident CVD events were identified from the hospital discharge records based on ICD-9 codes. Results: We identified 252 CVD events (CHD n=207, stroke n=45). A 2-point increase in the MD score was associated with 16% reduced risk (2% to 28%). The protective effect of the MD differed across educational levels and household income categories (p for interaction=0.042 and 0.0081 respectively) with subjects in the highest category of either education or income reporting a significant reduction of CVD risk in respect to the lowest (HR=0.40;0.23-0.69 and HR=0.38; 0.22-0.64 respectively). In multivariable analysis further controlled for adherence to the MD, nutrient intake varied across socioeconomic strata with those with higher status reporting higher intake of antioxidants and polyphenols (see Table). Conclusions: The protective effect of the MD on CVD risk was only evident within high socioeconomic status groups. At comparable levels of adherence to the MD, differences in dietary antioxidant and polyphenol intakes were apparent across population strata. These nutritional gaps may partly explain the observed socioeconomic pattern of protection.