tbuckley/cabot-search huggingface dataset:
AB0246 Impact of treat to target strategy with complementary ultrasound on real world radiographic outcomes in early rheumatoid arthritis over the past decade
Authors: K Kobayashi, K Minegishi, S Ohno, H Nakajima
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Treatment for rheumatoid arthritis (RA) has changed over the past decade. Early diagnosis and prompt agressive treatment based on treat to target strategy, as well as complementary ultrasound have been adopted and proven to improve patient clinical and radiological outcomes in clinical trials. <h3>Objectives</h3> The aim of this study was to compare radiographic progression of early RA patients starting their first DMARD 10 years ago vs more recently in daily clinical practice. <h3>Methods</h3> We reviewed the medical records of consecutive patients with symptom of 3 years duration who fulfilled the 1987 ACR classification criteria or the 2010 ACR/EULAR classification criteria in a single center retrospectively. In the first cohort (2000s), 70 patients (55.3±13.3y.o, Female 77%) who were diagnosed with RA during 2003–2005 were included. in the second cohort (2010s), 71 patients (54.5±17.3y.o,Female90%) who were diagnosed with RA during 2013–2015 were included. Radiographs of hands were assessed at baseline and one year after according to the van der Heijde modified Sharp score (range 0–280) without clinical information and chronological orders of radiographs in the individual patients. <h3>Results</h3> Mean changes in radiographic joint damage for joint space narrowing score, erosion score, total radiographic score were higher in 2000s than 2010s (0.92±2.70 vs 0.28±1.86; p=0.010, 0.54±1.35 vs 0.35±0.99; p=0.390, 1.45±3.54 vs 0.68±2.55; p=0.015, respectively). Radiographic progression defined as total radiographic score &gt;0 and &gt;5 were 31.4% vs 22.5% and 8.6% vs 8.5% between 2000s and 2010s (p=0.230 and p=0.970, respectively). Methotrexate (MTX) was frequently used for initial treatment in 2010s than 2000s (86% vs55%, p≤0.001), and initial dose and maximum dose of MTX were higher in 2010s than 2000s (9.13±2.09 mg/week vs 4.67±1.54 mg/week; p≤0.001 and 12.04±3.73 mg/week vs 8.13±1.88 mg/week; p≤0.001, respectively). The mean duration from symptom onset to diagnosis was earlier in 2010s than 2000s (5.75±5.04 months vs 7.85.±6.85 months, p=0.001). CRP at baseline and 1 year after were lower in 2010s than in 2000s (2.74±1.90 mg/dL vs 3.35±3.94 mg/dl; p=0.001 and 0.60±1.19 mg/dL vs 1.20±1.99 mg/dl; p=0.03 respectively). There were no significant differences in sex, age, positive rate of RF and ACPA, the Sharp score at baseline, steroid use, and biological agents use between two cohorts. <h3>Conclusions</h3> In recent 10 years, early diagnosis with complementary ultrasound and appropriate MTX use based on treat to target strategy led to prevent joint destruction of RA patients in daily clinical practice. <h3>Disclosure of Interest</h3> None declared
FRI0411 Coadministration of bosentan has no effect on the pharmacokinetics of nintedanib
Authors: S Wind, G Simons, J Bertulis, C Coeck
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Nintedanib is a potent intracellular inhibitor of tyrosine kinases that has been approved for the treatment of idiopathic pulmonary fibrosis and is being investigated as a treatment for interstitial lung disease associated with systemic sclerosis (SSc-ILD). Bosentan is a dual endothelin receptor antagonist used in the treatment of pulmonary arterial hypertension, which is a common comorbidity of SSc-ILD. <h3>Objectives</h3> To ascertain the effect of bosentan on the pharmacokinetics of nintedanib. <h3>Methods</h3> In an open-label, single-centre study, healthy male subjects aged ≥18 and ≤55 years with a body mass index (BMI) ≥18.5 and ≤29.9 kg/m<sup>2</sup> received a single dose of nintedanib 150 mg alone (period 1) followed by bosentan 125 mg twice daily (bid) for 8 days (bosentan loading dose phase on days 1–6) with a single dose of nintedanib 150 mg on day 7 (period 2). The primary endpoints were the maximum plasma concentration (C<sub>max</sub>) of nintedanib and the area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC<sub>0-tz</sub>) of nintedanib. The secondary endpoint was the AUC from time 0 extrapolated to infinity (AUC<sub>0–∞</sub>) for nintedanib. <h3>Results</h3> Thirteen subjects (12 White; mean [SD] age 35.0 [9.8] years and BMI 24.5 [2.5] kg/m<sup>2</sup>) were treated. All subjects completed the planned observation period. Based on C<sub>max</sub>, AUC<sub>0-tz</sub> and AUC<sub>0–∞</sub>, exposure to nintedanib was similar after a single dose of nintedanib given alone or in combination with multiple doses of bosentan 125 mg bid (Table). Adverse events were reported in 4 subjects (30.8%) on nintedanib alone (period 1), 4 subjects (30.8%) on bosentan 125 mg bid (days 1–6 of period 2) and 2 subjects (15.4%) after administration of bosentan with nintedanib (days 7 and 8 of period 2). All adverse events were mild in intensity. <h3>Conclusions</h3> Coadministration of bosentan 125 mg bid had no effect on the pharmacokinetics of a single dose of nintedanib 150 mg. <h3>Disclosure of Interest</h3> S. Wind Employee of: Boehringer Ingelheim Pharma GmbH &amp; Co. KG, G. Simons Employee of: Boehringer Ingelheim Pharma GmbH &amp; Co. KG, J. Bertulis Employee of: Boehringer Ingelheim Pharma GmbH &amp; Co. KG, C. Coeck Employee of: Boehringer Ingelheim Pharma GmbH &amp; Co. KG
Prevention of reflux after esophagectomy with endoscopic negative pressure therapy using a new double-lumen open-pore film drainage with an intestinal feeding tube
Authors: Gunnar Loske, Tobias Schorsch, Christian Müller
Journal: Endoscopy (2017)

Reflux after Ivor Lewis esophagectomy has a deleterious effect on anastomotic wound healing and is a risk for pulmonary aspiration [1]. We report endoscopic negative pressure therapy, using a novel double-lumen open-pore film drainage method, for prevention of postoperative reflux.
SAT0679 Are adult trajectories of weight over a lifetime linked to foot problems years later?
Authors: AB Dufour, E Losina, HB Menz, MP LaValley, MT Hannan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Obesity and foot problems are common in older adults and associated with many negative health outcomes. Better understanding of the consequences of patterns of weight change may lead to better prediction and dealing with foot pain and foot disorders. <h3>Objectives</h3> This study identified longitudinal trajectories of weight in a population-based study and examined the association of these groups with current foot problems. <h3>Methods</h3> We used 28 measures of weight over 57 years to identify trajectories of weight in 2445 members of the Framingham Foot Study using k-means longitudinal cluster analysis. Foot examinations (2002–2008) recorded presence of foot pain, hallux valgus, claw toes, hammer toes and overlapping toes on each foot. Associations between weight group membership and foot problems at time of foot exam, adjusted for age and sex, were examined using logistic regression with generalized estimating equation correction for two feet per subject. The reference group used for analysis was the group with the lowest weight trajectory ("E"). <h3>Results</h3> We found 5 trajectories of weight, representing relatively constant patterns over time, with weight increasing from groups E to A. Those in group "E" were more likely to be older, while the youngest were in group "A" group. "E" had the lowest prevalence of foot pain (14%) while group "A" had the highest (22%). Similarly, group "A" had the lowest prevalence of hallux valgus, while group "E" had the highest (36%) (Table 1). Compared to group "E", other groups were more likely to have foot pain (ORs 1.57–3.50, Table 2) and less likely to have hallux valgus (ORs 0.73–0.99). For claw toes, all but one group were more likely to have claw toes compared to group "E". Groups "A" and "D" were more likely to have hammer toes (ORs 2.40 and 1.35, respectively) compared to group "E". We found no associations between overlapping toes and group membership. <h3>Conclusions</h3> Trajectories with higher weight over a lifetime had increased odds of foot pain and claw toes, and decreased odds of hallux valgus later in life. These results provide evidence that having lower weight over one9s lifetime can reduce the likelihood of foot problems later in life. <h3>Disclosure of Interest</h3> None declared
Upregulation of Cystathionine-β-Synthase in Colonic Epithelia Reprograms Metabolism and Promotes Carcinogenesis
Authors: Ches'Nique M. Phillips, John R. Zatarain, Michael E. Nicholls, Craig Porter, Steve G. Widen, Ketan Thanki, Paul Johnson, Muhammad U. Jawad, Mary P. Moyer, James W. Randall, Judith L. Hellmich, Manjit Maskey, Suimin Qiu, Thomas G. Wood, Nadiya Druzhyna, Bartosz Szczesny, Katalin Módis, Csaba Szabo, Celia Chao, Mark R. Hellmich
Journal: Cancer Research (2017)

Abstract The trans-sulfuration enzyme cystathionine-β-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells. Differentially expressed metabolites (65 increased and 20 decreased) clustered into the glycolytic pathway, nucleotide sugars, intermediates of the pentose phosphate pathway, and lipogenesis, including primarily phospholipids, sphingolipids, and bile acids. CBS upregulation induced broad changes in the NCM356 cell transcriptome with over 350 differentially expressed genes. These genes overlapped significantly with gene sets related to glycolysis, hypoxia, and a colon cancer cell phenotype, including genes regulated by NF-κB, KRAS, p53, and Wnt signaling, genes downregulated after E-cadherin knockdown, and genes related to increased extracellular matrix, cell adhesion, and epithelial-to-mesenchymal transition. The CBS-induced switch to an anabolic metabolism was associated with increased NCM356 cell bioenergetics, proliferation, invasion through Matrigel, resistance to anoikis, and CBS-dependent tumorigenesis in immunocompromised mice. Genetic ablation of CBS in CBS heterozygous mice (CBS+/−) reduced the number of mutagen-induced aberrant colonic crypt foci. Taken together, these results establish that activation of the CBS/H2S axis promotes colon carcinogenesis. Cancer Res; 77(21); 5741–54. ©2017 AACR.
Review: In older patients with chronic disease, transitional care reduces mortality and readmissions
Authors: Henry S. Sacks
Journal: Annals of Internal Medicine (2017)

Source Citation Le Berre M, Maimon G, Sourial N, Guériton M, Vedel I. Impact of transitional care services for chronically ill older patients: a systematic evidence review. J Am Geriatr Soc. 2017;65:1597-608. 28403508
Challenges of developing small-molecule kinase inhibitors for brain tumors and the need for emphasis on free drug levels
Authors: Timothy P Heffron
Journal: Neuro-Oncology (2017)

Despite biological rationale and significant clinical study, the pursuit of small-molecule kinase inhibitors for the treatment of brain cancers has had very limited success. This Advance-in-Brief discusses the need for drugs to achieve free brain penetration to engage their targets where CNS tumors reside. This need to achieve free, as opposed to total, drug concentrations in the brain may be a contributing factor to why so many small-molecule kinase inhibitors have not realized success in the neuro-oncology setting. For kinase targets of interest for brain cancer, either the vast majority of small-molecule inhibitors have data suggesting that free brain penetration would be limited or there are inadequate data to suggest that free brain penetration could be expected. Therefore, kinase targets of interest in the treatment of brain cancers may be inadequately assessed due to a lack of freely brain-penetrant inhibitors available for clinical study. Encouraging recent drug discovery efforts that focused on achieving free brain penetration for cancers in the CNS are highlighted. Still, further efforts are needed to enable thorough clinical evaluation of biological hypotheses.
Abstract 19266: Derivation of Risk Score in Predicting Deterioration in Left Ventricular Ejection Fraction in Patients With Low-flow Significant Aortic Stenosis and Initially Preserved Ejection Fraction
Authors: Benjamin Y Tan, Nicholas J Ngiam, Glenn Lee, Yiong-Huak Chan, Kian-Keong Poh
Journal: Circulation (2015)

Introduction: Low-flow significant aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF&gt;50%) is associated with worse clinical outcomes. In classical severe AS, guidelines have indicated that deterioration of LVEF to &lt;50% is a Class I indication for aortic valve replacement. However, predictors of LVEF deterioration in patients with low-flow AS have not been studied. We developed a model, based on clinical and echocardiographic parameters to predict LVEF deterioration to &lt;50%. Methods: Consecutive subjects (n=162) with low-flow (stroke volume index &lt;35mg/ml) significant AS and paired echocardiographic studies (&gt;180 days apart) were studied. Significant predictors of LVEF deterioration on univariate analyses were fit into a multivariable logistic regression. A risk score was then developed by converting the B-coefficients into weights, and its performance in predicting the LVEF deterioration to &lt;50% was evaluated. Results: There were 50 patients (30.9%) with significant deterioration of LVEF to &lt;50% from baseline. A risk score was developed based on five clinical and echocardiographic predictors (History of hypertension (p=0.008) – 1 point, initial LVEF &lt;65% (p=0.012) – 2 points, Tissue Doppler S’ velocity &lt;7.3cm/s (p=0.049) – 1 point, End-systolic wall stress &gt;70g/cm2 (p=0.001) – 2 points, and left ventricular mass index &gt;100g/m2 (p=0.010) – 1 point). The risk score performed well under receiver operating characteristic curve (AUC=0.78, 95%CI 0.72-0.85, p&lt;0.001). A score of 4 points or more was the optimal cut-off, predicting most cases (98%, 48 out of 50). Conclusions: Despite preserved LVEF, subclinical myocardial dysfunction may represent an important comorbidity in patients with low-flow AS, which may accelerate inappropriate left ventricular remodelling. The risk score may be used to identify patients at risk of significant LVEF deterioration, thereby allowing for closer monitoring and earlier surgical intervention.
AB1212-HPR Dynamics of articular syndrome in rheumatoid arthritis against correction of progesterone insufficiency
Authors: M Salokhiddinov, A Ahmedov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> According to the literature, sex hormones manifest themselves as immune modulators that inhibit the ones and stimulate other immune functions. Studies have shown that patients with RA, decrease of estradiol and particularly progesterone in the blood serum is found in the women of reproductive age. According to the literature, progesterone has a close relationship with T-cell immunity. A value of T-cell deficiency plays an important role in the cause of the autoimmune process <h3>Objectives</h3> To study of progesterone correction in RA patients.The aim of this study was to evaluate the effectiveness of progesterone deficiency correction in patients with rheumatoid arthritis based on the analysis of articular syndrome <h3>Methods</h3> The study involved 40 patients with a documented diagnosis of RA, women of reproductive age. The study group consisted of 30 patients who had correction of progesterone deficiency background in the pathogenetic therapy. The control group consisted of 10 female patients who are on the pathogenetic therapy. We used the following criteria: disease activity and severity of the articular syndrome with determining of the number of tender and swollen joints, indices of DAS and HAQ. Statistical analysis of the results of research used the method of parametrics of Student criterion <h3>Results</h3> Among the patients studied disease duration ranged from 3 months to 19 years (mean age 10±7,2 years), 20 patients (50%), from 5 to 10 years – 15 (37.5%), and more than 10 years – 5 patients (12.5%). X-ray picture of joint damage in the majority of patients corresponded to stage 2–3 – 87.5% (35 patients). Less common muscular disorders (7.5%), mainly in patients taking long-term GC, myalgia and muscle malnutrition were detected in 7.5% and 25% of patients, respectively. In addition to the articular syndrome, the most frequent complaints of general weakness (75%), irritability, sleep disorders and attention (50%), anxiety and anxiety (75%), low-grade temperature (10%) <h3>Conclusions</h3> Progesterone deficiency correction in RA patients against pathogenic therapy has improved performance of articular syndrome and improves quality of life, such as vitality, general health and social function as well as it contributes to the positive dynamics of mental health <h3>References</h3> McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis New Engl. J. Med. 2011;365:2205–19. Wells G et al. Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann. Rheum. Dis. 2009;68:954–60. Ware JE, Sherbourne CD. The MOS 36-Item short-form health survey. Med. Care. Med Care. 1992;30(6):473–83. <h3>Disclosure of Interest</h3> None declared
THU0557 Venous vessel wall thickness in lower extremity is increased in male behcet's disease patients without vascular involvement
Authors: F Alibaz-Oner, A Mutis, R Ergelen, Z Erturk, T Ergun, H Direskeneli
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Vascular involvement is seen in up to 40% of the patients with Behcet9s Disease (BD), especially in young males and is one of the major causes of mortality and morbidity. Lower extremity vein thrombosis due to vascular inflammation is the most frequent form of vascular involvement in BD. Recently, assessment of vessel wall thickness (VWT) and venous dilatation by US is suggested to be valuable in patients with vascular inflammation. <h3>Objectives</h3> In this study, we investigated whether vessel wall thickness or dilatation is present in young male BD patients prone to venous vascular disease. <h3>Methods</h3> Fifteen male patients with BD without major organ involvement followed in Marmara University Behcet9s Clinics, 14 healthy male controls and 14 male patients with Ankylosing Spondylitis (AS) were included the study. Bilateral lower extremity venous doppler ultrasonography (US) was performed by an experienced radiologist blinded to cases. No patient was under immunosuppressive treatment. Bilateral common femoral vein (CFV) wall thickness and great/small saphenous vein dilatations were examined. Behçet Syndrome Activity Score (BSAS) was used for the general assessment of disease activity. <h3>Results</h3> The mean disease duration was 9.1±6.3 years in patients with BD. BSAS score was 28.9±19. Bilateral CFV wall thickness was significantly higher in BD patients compared to healthy controls and AS (p=0.001, p=0.002, respectively for right CFV; p=0.001, p&lt;0.001, respectively for left CFV) (Table 1). The width of great and small saphenous veins were also higher in patients with BD, but without reaching statistical significance. There were no correlations between BSAS and wall thickness of any vessel. <h3>Conclusions</h3> In preliminary results of our study, an increased venous vessel wall thickness in lower extremity was shown in male BD patients without vascular involvement. As a similar change was not observed in controls, we think, increased VWT might be an early sign of venous inflammation in patients with BD rather than a result of non-specific systemic inflammation. Further studies with a larger group of patients is planned. <h3>Disclosure of Interest</h3> None declared
Correction: Corrigendum: Can we deliver randomized trials of focal therapy in prostate cancer?
Authors: Hashim U. Ahmed, Viktor Berge, David Bottomley, William Cross, Rakesh Heer, Richard Kaplan, Tom Leslie, Chris Parker, Clare Relton, Richard Stephens, Matthew R. Sydes, Lindsay Turnbull, Jan van der Meulen, Andrew Vickers, Timothy Wilt, Mark Emberton
Journal: Nature Reviews Clinical Oncology (2017)
New Ultrasound Techniques Promise Further Advances in AKI and CKD
Authors: Travis D. Hull, Anupam Agarwal, Kenneth Hoyt
Journal: Journal of the American Society of Nephrology (2017)

AKI and CKD are important clinical problems because they affect many patients and the associated diagnostic and treatment paradigms are imperfect. Ultrasound is a cost-effective, noninvasive, and simple imaging modality that offers a multitude of means to improve the diagnosis, monitoring, and treatment of both AKI and CKD, especially considering recent advances in this technique. Ultrasound alone can attenuate AKI and prevent CKD by stimulating the splenic cholinergic anti-inflammatory pathway. Additionally, microbubble contrast agents are improving the sensitivity and specificity of ultrasound for diagnosing kidney disease, especially when these agents are conjugated to ligand-specific mAbs or peptides, which make the dynamic assessment of disease progression and response to treatment possible. More recently, drug-loaded microbubbles have been developed and the load release by ultrasound exposure has been shown to be a highly specific treatment modality, making the potential applications of ultrasound even more promising. This review focuses on the multiple strategies for using ultrasound with and without microbubble technology for enhancing our understanding of the pathophysiology of AKI and CKD.