tbuckley/cabot-search huggingface dataset:
Association of Twice-Daily Radiotherapy With Subsequent Brain Metastases in Adults With Small Cell Lung Cancer
Authors: Haiyan Zeng, Rui Li, Chen Hu, Guoqin Qiu, Hong Ge, Huiming Yu, Kaixian Zhang, Miaomiao Hu, Peng Zeng, Dan Xiao, Chuanwang Miao, Chuqing Wei, Meng Ni, Jingyi Shen, Hui Li, Jinbo Yue, Heming Lu, Bingjie Fan, Hui Zhu, Xudong Hu, Feng-Ming (Spring) Kong, Jinming Yu, Shuanghu Yuan
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Although thoracic twice-daily radiotherapy (TDRT) is one of the standards of care for small cell lung cancer, its association with brain metastases remains unknown. <h3>Objective</h3> To investigate the association of TDRT vs once-daily radiotherapy (ODRT) with brain metastases after prophylactic cranial irradiation in patients with small cell lung cancer. <h3>Design, Setting, and Participants</h3> In this multicenter cohort study, data on 778 consecutive patients with small cell lung cancer who had undergone thoracic radiotherapy (609 received ODRT and 169 received TDRT), chemotherapy, and prophylactic cranial irradiation were retrieved from the databases of 8 hospitals in China between July 1, 2003, and June 30, 2016. A 1:1 propensity score matching approach was used to control for confounding between the ODRT and TDRT groups. Confounding covariates included 8 demographic variables and 8 treatment-related covariates. Data analysis was conducted from November 1, 2017, to May 31, 2018, and reanalyzed for revision. <h3>Exposures</h3> The ODRT group received 50 to 66 Gy given in 25 to 33 fractions. The TDRT group received 45 Gy given in 30 fractions. <h3>Main Outcomes and Measures</h3> The primary end point was brain metastases. Secondary end points included progression-free survival and overall survival. <h3>Results</h3> Of the 778 patients (median age, 55 years [interquartile range, 48-61 years]), 204 were women and 574 were men. At a median follow-up of 23.6 months (interquartile range, 14.2-38.2 months), 131 patients (16.8%) experienced brain metastases. The rate of brain metastasis at 3 years in the TDRT group was significantly higher than in the ODRT group (26.0% vs 16.9%; hazard ratio, 1.55; 95% CI, 1.06-2.26;<i>P</i> = .03). Of the 338 matched patients (169 in the ODRT group vs 169 in the TDRT group), 60 (17.8%) experienced brain metastases, with a rate at 3 years of 14.9% in the ODRT group vs 26.0% in the TDRT group (hazard ratio, 1.71; 95% CI, 1.02-2.88;<i>P</i> = .04). Progression-free survival was similar in both the whole cohort and the matched cohort. Median overall survival in the ODRT group tended to be significantly longer than in the TDRT group after matching (47.2 vs 32.8 months; hazard ratio, 1.41; 95% CI, 0.99-2.01;<i>P</i> = .06). <h3>Conclusions and Relevance</h3> In this study, patients with small cell lung cancer who received thoracic TDRT appeared to have a higher risk of brain metastases than those who received ODRT, which supports the need for further prospective randomized clinical trials, especially in China and other parts of Asia.
DIAGNOSTIC ACCURACY OF ENDOFASTER COMPARED TO HISTOLOGY FOR CHRONIC ATROPHIC GASTRITIS USING NARROW BAND IMAGING (NBI) TARGETED BIOPSIES: A REAL-TIME PROSPECTIVE STUDY
Authors: G Esposito, M Cazzato, G Galli, L Conti, E Lahner, E Di Giulio, B Annibale
Journal: Endoscopy (2019)

NISO Biomed EndoFaster is a new device that within 15 seconds measures the gastric pH of the gastric juice through its aspiration from the gastric cavity during routine endoscopy. The aim of this study was to compare the diagnostic accuracy of NISO Biomed EndoFaster in comparison of histological examination as gold standard for chronic atrophic gastritis using narrow band imaging (NBI) targeted biopsies.
A l'aube de l'anastomose gastro jéjunale endoscopique, les résultats des prothèses duodénales dans les sténoses malignes gastroduodénales sont-ils si décevants? Expérience d'un centre français d'endoscopie interventionnelle à propos de 220 cas
Authors: JP Ratone, F Caillol, C Zemmour, E Bories, C Pesenti, V Lestelle, S Godat, S Hoibian, A Proux, G Capodano, M Giovannini
Journal: Endoscopy (2019)

Le développement d'une sténose maligne gastroduodénale peut compliquer l'évolution naturelle de plusieurs cancers en particulier l'adénocarcinome (ADK) du pancréas. Bien que l'utilisation des prothèses duodénales auto-expansibles (PDAE) ait améliorer la qualité de vie des patients, cette efficacité nous semblait imparfaite et nous avons voulu rapporter nos résultats dans cette indication quel que soit le cancer primitif. Le but principal était d'évaluer le niveau d'ingestion orale avant et après la pose de la PDAE à l'aide du «Gastric Outlet Obstruction Scoring System» (GOOSS: 0, aucun aliment ou boisson, 1, alimentation liquide; 2, alimentation mixée; 3, alimentation en morceaux ou normal). Les objectifs secondaires étaient le temps médian de perméabilité de la prothèse, le pourcentage de ré-interventions, l'incidence cumulée de perméabilité (évaluant le risque d'avoir une nouvelle procédure duodénale au cours du temps), le taux de complications, la médiane de survie et l'identification de sous-groupes dans lesquels l'efficacité était meilleure ou plus prolongée.
EULAR recommendations for the management of antiphospholipid syndrome in adults
Authors: Maria G Tektonidou, Laura Andreoli, Marteen Limper, Zahir Amoura, Ricard Cervera, Nathalie Costedoat-Chalumeau, Maria Jose Cuadrado, Thomas Dörner, Raquel Ferrer-Oliveras, Karen Hambly, Munther A Khamashta, Judith King, Francesca Marchiori, Pier Luigi Meroni, Marta Mosca, Vittorio Pengo, Luigi Raio, Guillermo Ruiz-Irastorza, Yehuda Shoenfeld, Ljudmila Stojanovich, Elisabet Svenungsson, Denis Wahl, Angela Tincani, Michael M Ward
Journal: Annals of the Rheumatic Diseases (2019)

The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2-3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2-3 or INR 3-4 is recommended, considering the individual's bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3-4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research.
Abstract 13422: Novel Calcium Therapy for Preserving Cardiac Conduction During Myocardial Inflammation
Authors: Sharon George, Patrick Calhoun, Robert Gourdie, James Smyth, Steven Poelzing
Journal: Circulation (2016)

Introduction: Diseases like ischemia, myocarditis and heart failure are associated with myocardial inflammation and elevated cytokines such as Tumor Necrosis Factor α (TNFα). TNFα modulates gap junctional coupling (GJC) which may then alter cardiac conduction velocity (CV) . Yet, the relationship between TNFα and GJC is controversial. TNFα also modulates extracellular edema, and edema slows CV via an alternative mode of intercellular communication called ephaptic coupling (EpC). However, the relationship between TNFα, CV, GJC, and EpC remains poorly understood. Hypothesis: TNFα modulates cardiac conduction velocity (CV) by altering EpC. Methods: CV was quantified from optically mapped guinea pig ventricles. The width of the candidate cardiac ephapse called the perinexus (WP) was measured by transmission electron microscopy. Connexin43 (Cx43) expression, phosphorylation and distribution around the myocyte was determined by western blotting and confocal immunofluorescence. Results: TNFα anisotropically slowed conduction at 90 minutes relative to time controls (0.21±0.01 vs 0.24±0.01m/s). While TNFα increased WP and reduced EpC (24.2±1.12 vs 18.6±0.86 nm), TNFα did not significantly modify total Cx43 expression or phosphorylation, although Cx43 localization at the intercalated disc was reduced relative to time controls (81% vs 86%). Physiologically elevating calcium concentration in the presence of TNFα (TNFα + 2.5mM calcium) restored CV to time control values within 15 mins and further improved conduction above time control values at 90 mins. This CV increase correlated with restoration of WP to control values at both 0 and 90 mins. Interestingly, at 90 mins, TNFα + 2.5mM calcium also increased total Cx43 expression as well as intercalated disc localization relative to 90mins of TNFα alone(86%). Conclusions: TNFα reduces CV by increasing WP and redistributing Cx43. With TNFα, 2.5mM calcium acutely (15 mins) improves CV presumably by increasing EpC, and over 90 mins, improves CV above control values possibly by the increase in both EpC and GJC . Taken together, the data suggests that physiologic ionic modulation could be an effective therapy to prevent cardiac arrhythmias.
ENDOSCOPIC HISTOACRYL INJECTION IS SAFE AND EFFECTIVE MODAILTY FOR HEMOSTASIS OF BOTH ACUTE VARICEAL AND NON-VARICEAL BLEEDING
Authors: JS Moon, JH Choi, YM Kang, JH Park, YS Kim, SH Ryu, TY Park
Journal: Endoscopy (2019)

Histoacryl is one of the materials that can be used as a sclerosing agent and is known to be effective in endoscopic hemostasis of acute gastric variceal bleeding. In addition, it can be applied to hemostasis of ulcer bleeding with relatively simple manipulation and is also effective. We reviewed patients who had undergone treatment endoscopically with Histoacryl and assessed the effectiveness and side effects according to each disease.
A QUANTITATIVE INSIGHT ON PRECLINICAL AND CLINICAL YEAR LEBANESE MEDICAL STUDENTS' KNOWLEDGE AND ATTITUDE TOWARDS COLORECTAL CANCER SCREENING
Authors: M Hussein Kamareddine, W Alam, Y Ghosn, G Jabbour, S Khoury, G Cortas, K Bedran, S Farhat
Journal: Endoscopy (2019)

Colorectal cancer is one of the leading cancers worldwide, with early screening leading to a large reduction in mortality and morbidity, yet screening efforts in Lebanon remain inadequate and a large number of cases present in advanced stages. Health care providers in training, such as medical students, play an important role in raising awareness and educating the public on the importance of CRC screening. Assessing these students' knowledge and attitudes is the aim of this study.
Functional CRISPR knockout screens for modifiers of sensitivity to trastuzumab emtansine
Authors: B. Lipert, K.N. Siemens, A. Khan, H.R. Barker, P. Tsai, T.W. Ketela, S.K. Bohlander, C.G. Print, S.M.F. Jamieson, F.W. Hunter
Journal: Annals of Oncology (2019)

Background: Therapies targeting HER2 amplification are a success of modern oncology, yet resistance to these agents remains a major challenge. For example, the mertansine- (DM1-) armed antibody-drug conjugate trastuzumab emtansine (T-DM1; Kadcyla) extends the survival of HER2-positive metastatic breast cancer patients after failure of prior trastuzumab-based therapy. However, T-DM1 provides objective responses in less than half of patients and its effectiveness is limited by both acquired and intrinsic resistance. Methods: We employed whole-genome CRISPR knockout screens using the GeCKOv2 sgRNA library in two trastuzumab-refractory breast cancer cell lines (MDA-MB-361 and MDA-MB-453) to identify and characterise genomic modifiers of sensitivity to T-DM1 and free DM1 in vitro. Genome-scale knockout libraries developed resistance to T-DM1 and DM1 after eight and thirteen weeks of escalating drug treatment, respectively. Positive and negative selection screen hits were identified by sequencing and bioinformatics analysis using MaGECK and PinAPL-Py. In parallel, we undertook RNA sequencing analysis of the DM1 and T-DM1 resistant cells to identify transcriptional adaptations to therapy. Results: Fourteen genes, highly enriched for positive or negative selection after T-DM1 or DM1 treatment, were selected to assess the impact of individual knockout on T-DM1 sensitivity. This confirmed the role of the putative lysosomal DM1 transporter SLC46A3, in T-DM1 resistance, and identified a set of genes potentially involved in T-DM1 activity. This study revealed consistent changes for both drugs with the genes involved in mitosis and cell cycle regulation highly overrepresented among differentially expressed transcripts. Adaptation to T-DM1 alone involved upregulation of genes related to proteolysis, acidification of vacuoles, intracellular trafficking of vesicles and maturation of lysosomes. Conclusions: A panel of 550 candidate genes from both the genome-wide knockout screen and transcriptomic profiling informed the generation of a custom sgRNA library for secondary in vitro and in vivo validation screens. Finally, the predictive utility of these genes is being explored in clinical datasets. Legal entity responsible for the study: The University of Auckland. Funding: Roche. Disclosure: All authors have declared no conflicts of interest.
REVISITING REPORTING OF PERFORMANCE MEASURES FOR LOWER GASTROINTESTINAL ENDOSCOPY FROM A TERTIARY REFERRAL CENTER FROM ROMANIA: STILL A LONG WAY TO GO...
Authors: D Bobeica, T Draghici, T Voiosu, A Bengus, M Rimbas, B Mateescu, A Voiosu
Journal: Endoscopy (2019)

Standardized reporting and quality benchmarking for colonoscopy are essential marks of a high-quality Endoscopic unit. We previously reported suboptimal key performance measures in colonoscopy practices in a single tertiary referral center. This is a reassessment of the key performance measures 6 months after announcing the results of the former audit to the colonoscopists in the unit.
Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry
Authors: J. Mazieres, A. Drilon, A. Lusque, L. Mhanna, A.B. Cortot, L. Mezquita, A.A. Thai, C. Mascaux, S. Couraud, R. Veillon, M. Van den Heuvel, J. Neal, N. Peled, M. Früh, T.L. Ng, V. Gounant, S. Popat, J. Diebold, J. Sabari, V.W. Zhu, S.I. Rothschild, P. Bironzo, A. Martinez-Marti, A. Curioni-Fontecedro, R. Rosell, M. Lattuca-Truc, M. Wiesweg, B. Besse, B. Solomon, F. Barlesi, R.D. Schouten, H. Wakelee, D.R. Camidge, G. Zalcman, S. Novello, S.I. Ou, J. Milia, O. Gautschi
Journal: Annals of Oncology (2019)
HIGH-RISK LESIONS ARE A STRONGER PREDICTOR FOR INTERVAL CANCER THAN LOW ADENOMA DETECTION RATE
Authors: E Waldmann, H Sinkovec, G Heinze, D Penz, B Majcher, A Hinterberger, M Trauner, M Ferlitsch
Journal: Endoscopy (2019)

Although endoscopic screening reached high quality standards, interval cancers still occur in a significant number of patients and the underlying risk factors are poorly understood. After index colonoscopy patients with high-risk adenomas (≥2 polyps or ≥10 mm or high-grade dysplasia or villous or tubulovillous histology) should undergo surveillance colonoscopy after 3 years, patients with low-risk adenomas after 10 years.
Loss of Adaptive Myelination Contributes to Methotrexate Chemotherapy-Related Cognitive Impairment
Authors: Anna C. Geraghty, Erin M. Gibson, Reem A. Ghanem, Jacob J. Greene, Alfonso Ocampo, Andrea K. Goldstein, Lijun Ni, Tao Yang, Rebecca M. Marton, Sergiu P. Paşca, Michael E. Greenberg, Frank M. Longo, Michelle Monje
Journal: Neuron (2019)
Rate of breast-conserving surgery vs mastectomy in developing countries
Authors: A. Kr, S. Sp, R. Kumar
Journal: Annals of Oncology (2019)

Background: Worldwide, breast conservation has become increasingly accepted as the surgical management of breast cancer in clinical practice. Cancer care in India is also evolving tremendously with many cancer treatment centres following evidence-based practice hence the rates of breast conservation are expected to increase. Here, we are reporting the rate of breast-conserving surgery (BCS) at our centre. Methods: A retrospective study of 401 patients who underwent breast cancer surgery at a tertiary care centre in South India from January 2015 to August 2017 were analysed to study the rate of BCS. All early breast cancers (EBC) were offered BCS. For large operable breast cancer (LOBC) and locally advanced breast cancer (LABC), neoadjuvant chemotherapy (NACT) followed by BCS was offered to these patients who wish to conserve their breast. Results: The mean age was 45 years. A total of 163 patients underwent BCS. Yearly, BCS rates were 38.8% in 2015, 36.7% in 2016 and 46.5% in 2017. Majority had EBC 310 (77.3%) of which 62.7% of T1 lesions (n = 51) had BCS, and 45.7% of T2 lesions (n = 258) had BCS of which 5 patients had to undergo NACT to preserve their breast whereas 100% Tis patient (n = 1) had mastectomy. Fifty patients had LOBC and only 2 (4%) patients had upfront BCS whereas 9 of them had to undergo NACT (18%). cT4 lesions had NACT followed by BCS in 2 patients. Conclusions: The rates of BCS have been increasing in India over the past few years. The majority of the women presented with EBC which makes them suitable for BCS. Legal entity responsible for the study: Manipal Hospital. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
The E3 ligase VHL promotes follicular helper T cell differentiation via glycolytic-epigenetic control
Authors: Yangyang Zhu, Yanxia Zhao, Le Zou, Danfeng Zhang, Daisuke Aki, Yun-Cai Liu
Journal: The Journal of Experimental Medicine (2019)

Follicular helper T (Tfh) cells are essential for germinal center formation and effective humoral immunity, which undergo different stages of development to become fully polarized. However, the detailed mechanisms of their regulation remain unsolved. Here we found that the E3 ubiquitin ligase VHL was required for Tfh cell development and function upon acute virus infection or antigen immunization. VHL acted through the hypoxia-inducible factor 1α (HIF-1α)-dependent glycolysis pathway to positively regulate early Tfh cell initiation. The enhanced glycolytic activity due to VHL deficiency was involved in the epigenetic regulation of ICOS expression, a critical molecule for Tfh development. By using an RNA interference screen, we identified the glycolytic enzyme GAPDH as the key target for the reduced ICOS expression via m6A modification. Our results thus demonstrated that the VHL-HIF-1α axis played an important role during the initiation of Tfh cell development through glycolytic-epigenetic reprogramming.
Les polypes gastriques: particularités cliniques, endoscopiques et histologiques
Authors: D Cherif, S Bizid, MK Temani, B Ben Slimane, M Ghanem, H Ben Abdallah, MR Bouali, N Abdelli
Journal: Endoscopy (2019)

Les polypes gastriques sont souvent des lésions asymptomatiques découvertes fortuitement au cours de l'endoscopie digestive haute.
UNDERWATER RESECTION OF DUODENAL SUBMUCOSAL TUMOR AND ENDOSCOPIC FULL THICKNESS SUTURING
Authors: A Granata, M Amata, D Ligresti, I Tarantino, L Barresi, M Traina
Journal: Endoscopy (2019)

A 61-year-old man was referred to our institute for subepithelial lesion of the duodenal bulb. Echographic imaging showed a 15-millimeter in diameter, homogeneous, hypoechoic lesion of the fourth layer of the inferior wall of the duodenal bulb. The EUS-guided fine needle aspiration showed a gastrointestinal stromal tumor (GIST). The increasing in size of the GIST with respect to the previous examination indicated resection, which remains the only modality that can offer a permanent cure of GISTs, and avoid tumor rupture and injuries to the pseudocapsule.
ENDOSCOPIC PYLOROMYOTOMY (G-POEM), EFFICACITY EVALUATION AFTER ONE YEAR, IN REFRACTORY GASTROPARESIS: A FRENCH MULTICENTRIC STUDY
Authors: O Ragi, J Jacques, J Branche, S Leblanc, G Vanbiervliet, R Legros, M Pioche, J Rivory, S Chaussade, V Vitton, M Barthet, JM Gonzalez
Journal: Endoscopy (2019)

Long term results of G-POEM for refractory gastroparesis are lacking. Here we report the results of the largest multicenter study with long term follow up about G-POEM for refractory gastroparesis.
Erdheim–Chester disease: expanding the spectrum of cutaneous manifestations
Authors: A. Kobic, K.K. Shah, A.R. Schmitt, G. Goyal, R.S. Go, R. Guo, K.L. Rech, J.C. Sartori‐Valinotti
Journal: British Journal of Dermatology (2019)

BackgroundErdheim–Chester disease (ECD) is a rare condition and there is limited information available regarding its cutaneous manifestations.
Efficacité de la sphinctérotomie endoscopique dans l'empierrement cholédocien
Authors: S Lajouad, M Kadiri, M Acharki, I Serraj, M Salihoun, N Kabbaj
Journal: Endoscopy (2019)

La sphinctérotomie endoscopique est une méthode efficace dans la prise en charge de la lithiase de la voie biliaire principale (VBP). Le but de notre travail est de déterminer les caractéristiques épidémiologiques, cholangiographiques et la corrélation; entre la taille la nature des calculs et l'abord thérapeutique. Ainsi que les résultats du traitement endoscopique de la lithiase de la VBP.
Abstract 11654: Association of Pulmonary Vein Diameters With Atrial Fibrillation Recurrence Following Ablation
Authors: Yuliya Mints, Esra Gucuk Ipek, Mohammadali Habibi, Jonathan Chrispin, Joseph E Marine, Jack Rickard, David Spragg, Stefan Zimmerman, Hugh Calkins, Saman Nazarian
Journal: Circulation (2015)

Background: Pulmonary vein (PV) isolation is commonly used for treatment of drug-refractory symptomatic atrial fibrillation (AF). Previous studies have reported contradictory results regarding the association of PV structure and AF recurrence following ablation. We sought to examine the association of PV diameter with AF recurrence following ablation. Methods: We conducted a retrospective cohort study of 132 patients with AF that had undergone initial PV isolation. Cardiac magnetic resonance angiography was performed prior to ablation, and pulmonary vein and left atrial dimensions were measured. In the presence of a left common PV trunk, the diameter of the superior vein branch was measured after the ostium. Recurrence of AF was documented using scheduled (6 and 12 months) and symptom-prompted electrocardiography. Results: The average age was 59.7±9.8 years. Of all patients 78.8% were male, 88.6% were Caucasian, and 45.5% had persistent AF. Atrial fibrillation recurrence was noted in 48 (36%) of patients at 1 year. Due to significant co-linearity among PV diameters within the same individual, the left superior PV (LSPV) diameter was used as a surrogate for all veins. In a multivariable Cox proportional hazards model adjusting for left atrial volume, AF persistence, age, and gender, LSPV diameter &gt; 90 th percentile (22 mm) was independently associated with AF recurrence (Figure, Hazard Ratio 1.89 ± 0.57, p=0.035). Conclusion: Increased PV diameter is associated with AF recurrence following PV isolation. Tools to improve the efficiency and permanence of electrical isolation for large diameter PVs will likely improve procedural efficacy. Figure. The hazard ratio plot demonstrates that as the LSPV diameter increases, the hazard ratio of AF recurrence after PVI increases.