tbuckley/cabot-search huggingface dataset:
The PRIMETEST trial: Interim analysis of a phase II trial for primary retroperitoneal lymph node dissection (RPLND) in stage II A/B seminoma patients without adjuvant treatment.
Authors: Peter Albers, Andreas Hiester, Robert Grosse Siemer, Achim Lusch
Journal: Journal of Clinical Oncology (2019)

507 Background: We thought to evaluate progression-free survival of stage II A/B seminoma patients (pts) undergoing primary retroperitoneal lymph node dissection (RPLND) without adjuvant treatment. Aim is to present interim data of a feasibility study and a phase II trial. Methods: Prior to the phase II study, 9 patients have been treated within a pilot feasibility study. After IRB approval, additional 12 patients from 3/2016 to 9/2018 within the prospective phase II trial were accrued. All patients received primary retroperitoneal lymph node dissection (open or daVinci assisted) for stage IIA/B seminoma without adjuvant treatment. The data was analyzed for peri- and postoperative outcome including recurrence free survival. The trial will have to accrue 30 pts and was designed to exclude a &gt; 30% recurrence to standard treatment. Results: Since 5.2014 twenty-two patients with seminomateous germ cell tumor have been included in both studies, including one patient with an atypical inguinal recurrence and one patient with a 6 cm marker negative recurrence (clinical stage IIC). Primary RPLND was performed in 4 patients with initial CSIIA. 14 and 4 patients experiences a recurrence under surveillance and after carboplatin adjuvant treatment, respectively. Mean tumor size was 2.6 cm with a mean OR time of 134 min and a mean blood loss of 70 cc. One patient after DaVinci RPLND developed a ureteral stricture requiring ileal ureter substitute. The mean follow-up is 24 month (range 1-51 months), 17/22 patients (77%) are free of recurrence. 5/22 (23%) developed a recurrence (4x outside field and 1x inside field) with a mean time to recurrence of 4.5 months. All patients received salvage treatment (4x CTX and 1x radiotherapy) and are currently recurrence free. Conclusions: Primary RPLND in stage IIA/B seminoma patients is an experimental treatment approach in order to reduce long term toxicity and secondary malignancies. Interim results of this strategy justifies continuation of the study. This kind of surgery should only be performed within clinical trials in high volume referral centers. Clinical trial information: NCT 2015053664.
Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: A randomized, double-blind, phase 3 trial (CheckMate 238)
Authors: J. Weber, M. Mandala, M. Del Vecchio, H. Gogas, A.M. Arance, L.C. Cowey, S. Dalle, M. Schenker, V. Chiarion-Sileni, I. Márquez-Rodas, J-J. Grob, M. Butler, M.R. Middleton, M. Maio, V. Atkinson, P. Queirolo, V. de Pril, A. Qureshi, J. Larkin, P.A. Ascierto
Journal: Annals of Oncology (2017)
Feasibility and economic assessment of chromocolonoscopy for detection of proximal serrated neoplasia within a population-based colorectal cancer screening programme (CONSCOP): an open-label, randomised controlled non-inferiority trial
Authors: Chris Hurt, Rajeswari Ramaraj, Angela Farr, Meleri Morgan, Namor Williams, Ceri J Philips, Geraint T Williams, Georgina Gardner, Catherine Porter, Julian Sampson, Sharon Hillier, Hayley Heard, Sunil Dolwani
Journal: The Lancet. Gastroenterology & hepatology (2019)
Therapeutic power of radiofrequency induced intravesical hyperthermia-chemotherapy (RIHTC) in high-risk non-muscle-invasive bladder cancer NMIBC in respect of recurrence rate over 2 years: International, multi-institutional cohort study.
Authors: Gerson Lüdecke, Larissa Schäfer, Ofer Nativ, Ulrich Witzsch, Herbert Hanitzsch, Florian Hasner, Rami Issa, Alfred Witjes, Wolfgang Weidner
Journal: Journal of Clinical Oncology (2015)

e15513 Background: High-risk NMIBC patients can't get the indicated BCG treatment worldwide actually. As an alternative we have proven the RIHTC treatment in an international, multi-institutional cohort study prospectively. Treatments have been performed under unique treatment protocols in all study centers and follow-up has been checked for up to 12 years to evaluate effectiveness in respect to recurrence rate in NMIBC. Methods: We treated 271 high-risk patients (pTis, pT1 G3, non complete resected NMIBC and BCG failures) with the ablative RIHTC protocol. 8 treatments weekly with twice 40 mg Mitomycin C over 60 minutes per cycle, followed by a bladder resection 3 weeks after the last RIHTC. If tumor free status was achieved we continued with 6 maintenance treatments every 6 weeks with twice 20 mg Mitomycin C over 60 minutes. Follow-up controls were performed for 2 years every 3 months by cystoscopy and cytology and thereafter every 6 months respectively. Results: The study population was 67.3 years in mean, male to female ratio 3 to 1. Follow-up in mean for 2.2 years (range 28 days to 12.9 years). NMIBC patients who completed the treatment with induction and maintenance the overall recurrence rate after 2 years was 19.4% only. BCG failure patients with BCG-resistance stay tumor-free in 41.7% whereas early BCG-relapse patients remained recurrence-free in 66.7% over 2 years. BCG naive high-risk NMIBC patients impressed with a recurrence-free rate of 81.6% over 2 years. Conclusions: In respect to the actual situation that BCG is not available over the world with certainty for high-risk NMIBC, RIHTC is able to ensure a save and powerful treatment with a long lasting recurrence free survival with a 80.6% success rate over 2 years. In case of high-risk NMIBC with a BCG treatment indication RIHTC achieved a nearly 100% more effective recurrence free survival as BCG demonstrated in meta-analysis alone.
Inflammatory and non-inflammatory triggers of acute coronary syndromes
Authors: Mehmet Eyuboglu
Journal: Annals of the Rheumatic Diseases (2019)

Inflammatory and non-inflammatory triggers of acute coronary syndromesInflammation plays an important role in the pathogenesis of acute coronary syndromes (ACS). 1 However, ACS include different clinical conditions that can present as an acute cardiac event, and it may also be seen in various clinical settings independent of underlying cardiovascular status and traditional risk factors. 2 Recently, Westerlind et al 3 reported that siblings of patients with rheumatoid arthritis (RA) are at increased risk of ACS that could not be explained by traditional cardiovascular risk factors.This article provides excellent information regarding importance of inflammation and its hereditary role in the pathophysiology of ACS.Nevertheless, because of many clinical conditions may be the underlying cause of ACS and myocardial infarction (MI), there are some important points to be discussed to clarify the findings of the present article.ACS and MI may also occur as an acute cardiac event in the absence of significant coronary artery disease (CAD) and inflammation.This type of MI is known as type 2 MI, and may occur in the context of a mismatch between myocardial oxygen supply and demand due to various diseases. 4Therefore, ACS is not only triggered by atherosclerotic plaque disruption, it may occur due to non-cardiovascular reasons, and this situation should be taken into consideration while defining ACS.Additionally, inflammation also seems to play a role in the mechanism of ACS secondary to non-atherosclerotic spontaneous coronary artery dissection. 5ence, it would be worth to know the CAD severity and the underlying mechanism of ACS of the study groups in the study by Westerlind et al, 3 to comment on the relationship between index event and patients' clinical conditions.In conclusion, rheumatoid diseases and inflammation have important roles in the pathophysiology of CAD and ACS.However, ACS and MI do not occur only due to atherosclerotic plaque disruption.Non-cardiovascular and non-atherosclerotic reasons also may trigger ACS and MI in various clinical conditions.Hence, the underlying mechanism of ACS should be clearly stated to claim a relationship between siblings of patients with RA and an increased risk of ACS.
Abstract P426: Association Between Neighborhood Characteristics, Personal Resilience, and Arterial Stiffness Among Blacks: Results From the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity
Authors: Jeong Hwan Kim, Matthew L Topel, Tené T Lewis, Peter Baltrus, Chang Liu, Yi-An Ko, Mahasin Mujahid, Viola Vaccarino, Mario Sims, Mohamed Mubasher, Ahsan Khan, Kiran Ejaz, Charles Searles, Sandra B Dunbar, Priscilla Pemu, Herman Taylor, Arshed A Quyyumi
Journal: Circulation (2019)

Introduction: Arterial stiffness is associated with cardiovascular (CV) risk factors and adverse cardiovascular events. While inter-racial differences in arterial stiffness have been reported, factors contributing to intra-racial differences within Blacks are less known. We examined whether neighborhood characteristics and personal resilience factors were associated with arterial stiffness among Blacks. Hypothesis: More desirable neighborhood characteristics and greater personal resilience are associated with reduced arterial stiffness. Methods: We examined 385 Black adults (age 53 ± 10, 40% male) without known CV disease living in Atlanta, GA. Arterial stiffness was measured as augmentation index (AIX) and pulse wave velocity (PWV) using applanation tonometry (Sphygmocor Inc). Perceived residential neighborhood characteristics in 7 domains: aesthetic quality, walking environment, safety, food access, social cohesion, activity with neighbors, and violence were determined. Personal resilience was also assessed using standard questionnaires on experience of discrimination, environmental mastery, purpose in life, optimism, resilient coping, and depressive symptoms. Multiple linear regression models were used to examine the differences of arterial stiffness between the highest and the lowest tertiles of neighborhood characteristics and personal resilience factors after adjustment for age, gender, systolic blood pressure, body mass index, household income, education, marital status, and employment status. Results: Higher composite scores of neighborhood characteristics were associated with lower AIX (β=-3.42, 95% CI [-6.42 to -0.41], P=0.026; highest vs lowest tertiles). Specifically, higher scores of safety (β=-4.26, 95% CI [-7.34 to -1.17], P=0.007) and social cohesion (β=-4.62 [-7.64 to -1.61], P=0.003) were associated with lower AIX (highest vs lowest tertiles for both). For factors of personal resilience, higher scores in purpose in life (β=-4.89 [-7.88 to -1.90], P=0.001) and resilient coping (β=-3.26 [-6.36 to -0.15], P=0.040) were significantly associated with lower AIX (highest vs lowest tertiles for both). There were no significant associations between PWV and scores of neighborhood characteristics or personal resilience factors. Conclusion: In a study examining the impact of neighborhood and markers of resilience on arterial stiffness in an exclusively Black cohort, we found that better neighborhood characteristics and personal resilience factors were associated with lower pulse wave reflections (AIX).
Investigating and re-evaluating the role of glycogen synthase kinase 3 beta kinase as a molecular target for cardioprotection by using novel pharmacological inhibitors
Authors: Panagiota-Efstathia Nikolaou, Kerstin Boengler, Panagiotis Efentakis, Konstantina Vouvogiannopoulou, Anastasia Zoga, Nicholas Gaboriaud-Kolar, Vassilios Myrianthopoulos, Pavlos Alexakos, Nikolaos Kostomitsopoulos, Ioannis Rerras, Anna Tsantili-Kakoulidou, Alexios Leandros Skaltsounis, Andreas Papapetropoulos, Efstathios K Iliodromitis, Rainer Schulz, Ioanna Andreadou
Journal: Cardiovascular Research (2019)

Glycogen synthase kinase 3 beta (GSK3β) link with the mitochondrial Permeability Transition Pore (mPTP) in cardioprotection is debated. We investigated the role of GSK3β in ischaemia (I)/reperfusion (R) injury using pharmacological tools.Infarct size using the GSK3β inhibitor BIO (6-bromoindirubin-3'-oxime) and several novel analogues (MLS2776-MLS2779) was determined in anaesthetized rabbits and mice. In myocardial tissue GSK3β inhibition and the specificity of the compounds was tested. The mechanism of protection focused on autophagy-related proteins. GSK3β localization was determined in subsarcolemmal (SSM) and interfibrillar mitochondria (IFM) isolated from Langendorff-perfused murine hearts (30'I/10'R or normoxic conditions). Calcium retention capacity (CRC) was determined in mitochondria after administration of the inhibitors in mice and in vitro. The effects of the inhibitors on mitochondrial respiration, reactive oxygen species (ROS) formation, ATP production, or hydrolysis were measured in SSM at baseline. Cyclosporine A (CsA) was co-administered with the inhibitors to address putative additive cardioprotective effects. Rabbits and mice treated with MLS compounds had smaller infarct size compared with control. In rabbits, MLS2776 and MLS2778 possessed greater infarct-sparing effects than BIO. GSK3β inhibition was confirmed at the 10th min and 2 h of reperfusion, while up-regulation of autophagy-related proteins was evident at late reperfusion. The mitochondrial amount of GSK3β was similar in normoxic SSM and IFM and was not altered by I/R. The inhibitors did not affect CRC or respiration, ROS and ATP production/hydrolysis at baseline. The co-administration of CsA ensured that cardioprotection was CypD-independent.Pharmacological inhibition of GSK3β attenuates infarct size beyond mPTP inhibition.
CD40 Ligand-Modified Chimeric Antigen Receptor T Cells Enhance Antitumor Function by Eliciting an Endogenous Antitumor Response
Authors: Nicholas F. Kuhn, Terence J. Purdon, Dayenne G. van Leeuwen, Andrea V. Lopez, Kevin J. Curran, Anthony F. Daniyan, Renier J. Brentjens
Journal: Cancer Cell (2019)
Abstract P378: A Novel Risk Prediction Score for Incident Heart Failure Among Patients With Diabetes
Authors: Matthew W Segar, Kershaw V Patel, Jarett D Berry, Ambarish Pandey
Journal: Circulation (2019)

Introduction: Diabetes is a well-established risk factor for heart failure (HF). However, risk prediction models for incident HF in patients with diabetes are lacking. Accordingly, we aim to develop a novel risk-prediction model for HF in a diabetes cohort using a hybrid machine learning method for variable selection and CoxPH approach for risk prediction. Methods: We used data from the ACCORD trial that included patients with prevalent diabetes at baseline and had adjudicated HF events on follow up. The data was divided in to 80/20% training and testing (n = 6,896/1,725, respectively) and 152 baseline variables were included. A random survival forest (RSF) of 1000 trees was constructed to identify the top 20 predictors. Finally, a 5-year incident HF risk score was developed using the 9 variables selected by backward CoxPH regression. Results: The study included 8,621 participants (Mean age: 63 y, 62% male) without prevalent HF. The RSF model for incident HF with top 20 predictors derived from the training cohort had superior discrimination than the CoxPH model in the testing cohort ( C -index 0.80 vs. 0.78; P &lt; 0.001). The top 9 variables identified included age, waist circumference, BP, serum creatinine, HDL, prior MI, prior CABG, and EKG QTC duration and T-axis. The weighted risk score based on the nine clinical variables was used to create a composite HF risk score ranging from -6 to 36. A 1-unit increment in the risk score was associated with a 27% higher risk of HF at 5 years. A graded increment in the 5-year HF incidence was noted across quintiles of the HF risk score ranging from 1.2% in the lowest to 9.8% in the highest quintile (Figure). The HF risk score demonstrated good discrimination with an overall C -index of 75.2. Conclusions: In conclusion, an RSF model in a clinical diabetes cohort outperformed conventional CoxPH in the identification of important risk factors of incident HF. Additionally, the diabetes-HF prediction model using common clinical variables demonstrated good discrimination and risk stratification in the overall cohort.
The Innate Immune Sensor Sting Regulates Intestinal Inflammation and GVHD after Allogeneic Hematopoietic Stem Cell Transplantation in Knock-out and Human Allele Knock-in Recipient Mice
Authors: Cameron S. Bader, Henry Barreras, Casey O. Lightbourn, Sabrina Copsel, Jeonghyun Ahn, Glen N. Barber, Lei Jin, Robert B. Levy
Journal: Blood (2018)
Cell plasticity associated to taxane-resistance in preclinical cell models and in circulating tumor cells from metastatic castration-resistant prostate cancer patients.
Authors: Ruth Montalbo, Natalia Jiménez, Maria Mila, Òscar Reig, Iván Victoria, Aleix Prat, Mercedes Marin, Begona Mellado
Journal: Journal of Clinical Oncology (2019)

238 Background: Treatment resistance is associated with tumor cells molecular plasticity. In metastatic castration resistant prostate cancer (mCRPC), alterations in androgen receptor (AR) have been described as predictors of shorter response to hormonal treatments. Previously, we associated epithelial to mesenchymal transition (EMT) phenotype with chemotherapy resistance. However, other molecular changes responsible of such resistance should be elucidated. Here, we investigate the effect of taxanes on cell plasticity through in vitro models and in circulating tumor cells (CTCs) from mCRPC patients. Methods: Molecular differences due to taxane-exposure were evaluated in cell models of mCRPC (PC-3 and DU-145 resistant to taxanes). Global gene expression (GE) analysis was performed using Affimetrix GeneChip Human Gene 2.0 arrays. GE related with AR axis, EMT and neuroendocrine (NE) phenotypes was validated by quantitative (qRT-PCR). Clinical validation was performed in CTCs from 24 mCRPC patients collected prior and post taxane-treatment. CTCs enrichment was achieved by Isoflux technology through a personalized combination of EpCAM, CDH2 and PSCA antibodies. Results: GE analysis revealed a different deregulation pattern related to the EMT, NE and AR-related phenotypes in resistant CRPC-cells compared to parental cells. Docetaxel resistance was more associated to an EMT phenotype while cabazitaxel resistance to NE patterns. GE patterns in CTCs at post taxane-treatment showed a common upregulation of AR-related genes compared to pre-treatment collected samples. Moreover, most patients experienced upregulation of EMT and NE markers after treatment, which was more pronounced after docetaxel than cabazitaxel therapy. Conclusions: GE changes related to taxane-resistance observed in pre-clinical models also occur in CTCs. This supports the great value of CTCs to evaluate cell plasticity due to taxanes treatment. Further investigation is ongoing to better characterize cellular plasticity and to improve personalized therapeutic strategies that would enhance better clinical outcomes in mCRPC.
Pyloric gland adenoma in the duodenal bulb: case report of a giant laterally spreading tumor treated with endoscopic submucosal dissection
Authors: Qi-Shan Zeng, Lian-Song Ye, Chun-Cheng Wu, Jian-Rong Liu, Qiong-Ying Zhang, Shuai Bai, Bing Hu
Journal: Endoscopy (2019)

A 55-year-old man underwent gastroduodenoscopy because of epigastric pain. Abdominal computed tomography revealed a uniformly enhanced mass (10 × 8 mm) within the duodenum, with no enlargement of lymph nodes ([Fig. 1]). A laterally spreading tumor, with a diameter of about 60 mm, was detected within the duodenal bulb ([Fig. 2]). The lesion involved the pylorus ring and had a positive lifting sign. Considering the difficulty of endoscopic resection of such a giant lesion in the duodenal bulb, surgical resection was proposed, but the patient refused. Therefore, a standard endoscopic submucosal dissection was performed ([Video 1]).
Abstract P356: Association Between Acculturation and Diet Quality Varies by Acculturation Construct and Heritage: Results From the Hispanic Community Health Study/Study on Latinos
Authors: Josiemer Mattei, Martha Tamez, Daniela Sotres-Alvarez, Anna Maria Siega-Riz, Linda C Gallo, Linda Van Horn, Martha Daviglus, Denise C Vidot, Tali Elfassy, Robert C Kaplan
Journal: Circulation (2019)

Introduction: Inconsistencies remain on the reported associations between measures of acculturation and diet quality, particularly among Hispanics/Latinos. Hypothesis: We hypothesized that associations between acculturation and diet quality would differ according to the acculturation measure used and by country of origin (heritage). Methods: Baseline data were analyzed from 16,275 Hispanic/Latino adults aged 18-74y enrolled in the population-based Hispanic Community Health Study/Study of Latinos cohort. Dietary intake was assessed with two 24-hour recalls. Diet quality was measured via the Alternate Healthy Eating Index (AHEI; range 0-110: lowest to highest quality and categorized into tertiles). Acculturation questions on language preference, US vs. foreign-born, years living in the US, and the Short Acculturation Scale for Hispanics (SASH) language and social subscales (higher score = more English use or US orientation) were interviewer-administered. Results: Adjusting for demographic, socioeconomic, and behavioral factors, each acculturation measure (except SASH-social) was independently and inversely associated with AHEI among overall Hispanics/Latinos (i.e. higher US acculturation = lower AHEI). There were significant interactions (at p&lt;0.10) between acculturation measures and heritage, and thus multivariable-adjusted models were stratified by heritage. Analyses by heritage found higher adjusted odds ratios (AOR; 95% CI) for the top tertile (vs. lowest) of AHEI for being foreign-born (vs. US born) in Mexicans [2.36 (1.54, 3.64)] and for each point of the SASH-social subscale in Puerto Ricans [2.20 (1.21, 4.00)]. Conversely, lower AOR for the top tertile (vs. lowest) of AHEI were observed for living &lt;10y in the US (vs. &gt;10y) in Puerto Ricans [0.01 (0.001, 0.19)], and for each point of the SASH-language subscale in Mexicans [0.79 (0.64, 0.97)] and Puerto Ricans [0.69 (0.50, 0.97)]. Higher AOR for the middle tertile (vs. lowest) of AHEI was noted for foreign-born and living &lt;10y in the US in Central Americans, while lower AOR was noted for living &lt;10y in the US in South Americans. Conclusions: In conclusion, acculturation measures associated with diet quality are specific to Hispanic/Latino heritage and should be carefully selected in diet and health studies.
Canadian Retrospective Multicentric Study Comparing the Combination of Bortezomib, Cyclophosphamide and Dexamethasone (Cybord) Versus Bortezomib, Thalidomide and Dexamethasone (VTD) Versus Bortezomib and Dexamethasone (Vd) in Patients with Newly Diagnosed Multiple Myeloma Eligible for Autologous Hematopoietic Stem Cell Transplantation (HCT)
Authors: Eric Yamga, Richard Leblanc, Jean-Samuel Boudreault
Journal: Blood (2018)