tbuckley/cabot-search huggingface dataset:
Immune-related adverse events (irAEs) and survival (OS) in metastatic non-small cell lung cancer (mNSCLC) patients (pts) treated with immunotherapy
Authors: M. Meliàn Sosa, C. Puchades, J.A. Mendez, A. Torres, C. Rodrigo, G. Gimeno, E. Rama, A. Martínez-Castillo, J. Caballero Daroqui, J. Gomez Codina, O. Juan-Vidal, D. Lorente
Journal: Annals of Oncology (2018)
Stage 2 enrollment complete: Sitravatinib in combination with nivolumab in NSCLC patients progressing on prior checkpoint inhibitor therapy
Authors: T.A. Leal, A.I. Spira, C. Blakely, K. He, D. Berz, D. Richards, J. Uyeki, A. Savage, T. Roque, E. Massarelli, R.M. Jotte, I. Chen, J. Christensen, P. Olson, V. Tassell, L. Horn
Journal: Annals of Oncology (2018)
P1.01-09 Pembrolizumab Plus Ipilimumab or Placebo in 1L Metastatic NSCLC with PD-L1 Tumor Proportion Score (TPS) ≥50%: KEYNOTE-598
Authors: M. Boyer, J. Mclean, L. Xu, A. Samkari, D. Carbone
Journal: Journal of Thoracic Oncology (2018)
Mental health funding to rise by at least £2bn a year by 2023-24, chancellor announces
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The government will increase funding for mental health services by at least £2bn a year in real terms by 2023-24 as a key part of its long term plan for the NHS, the chancellor of the exchequer, Philip Hammond, has announced

In a speech to parliament to deliver his budget on Monday 29 October, Hammond said that the funding boost would pay for “comprehensive” 24 hour mental health support in every major hospital emergency department in the UK. It would also provide more mental health ambulances, more “safe havens” in the community, and a crisis hotline, he said.

The chancellor also announced …
Primary and Secondary Breast Angiosarcoma
Authors: Thibaut Cassou-Mounat, Laurence Champion, Laurence Bozec, Valerie Laurence, Virginie Huchet, Marie Luporsi, Nina Jehanno
Journal: Clinical Nuclear Medicine (2018)

Breast angiosarcoma is a rare and aggressive tumor. The role of F-FDG PET/CT in breast angiosarcoma is poorly known. We report a series of 13 lesions in 11 patients with histologically proven primary or secondary breast angiosarcoma who underwent FDG PET/CT at the initial assessment in our institution. All breast lesions showed FDG avidity. Visually and statistically, we observed a significant difference of SUVmax uptake foci between primary and secondary breast angiosarcoma (Wilcoxon test P < 0.0046) and a significantly poorer prognosis for high SUVmax than those with low SUVmax (P = 0.049) regardless of primary or secondary origins.
Abstract P368: Neighborhoods and Subclinical Cardiovascular Disease
Authors: Todd R Sponholtz, Ramachandran S Vasan
Journal: Circulation (2018)

Background: Research on the health impact of the built environment has focused on health behaviors such as diet and exercise, and conditions such as obesity and diabetes. Few studies have examined its influence on downstream outcomes such as cardiovascular disease. We investigated the proportional variance in the 10-year and 30-year Framingham risk score (FRS) attributable to neighborhoods in the Framingham Heart Study. Methods: Offspring- and Generation 3 cohort members’ homes at the time of exam 7 (Offspring, 1998-2001) or exam 1 (Generation 3, 2002-2005) were geocoded to 2000 Census block groups. We evaluated Framingham Offspring and Generation 3 cohort participants inhabiting private residences in block groups within Massachusetts containing the residences of 5 or more participants. Analyses of the 10-year FRS were further restricted to participants aged 30-74 at the time of the relevant exam and those of the 30-year FRS to participants 20-59 years old. Cardiovascular risk was determined on the bases of sex, age, systolic blood pressure, anti-hypertensive medication, smoking, diabetes, total cholesterol, and HDL. The outcomes were the standardized residuals of log-transformed FRS regressed on age and sex. We analyzed the percentage of variance of FRS explained at the block-group level and 95% confidence intervals using multilevel linear regression. An empty model was first used to estimate the total variance and the following factors were then added singly to evaluate their influence on the group-level FRS variance explained by education, body mass index, waist circumference, physical activity score, and depression (CES-D score ≥16). Analyses were repeated stratified by sex. Results: The analysis of 10-year FRS included a total of 2,882 participants in 188 census block groups. The block-group-level variance explained for this outcome was 1.77% (95% CI=0.69, 4.44). Upon the addition of BMI to the model, the variance explained dropped to 1.11% (95% CI=0.28%, 4.30%). None of the other covariates had a substantial impact. Among 1,363 women in 117 block groups, the block level group explained a total of 2.03% of the FRS variance at the block level group (95% CI=0.61, 6.56), which dropped to 0.64% (95% CI=0.03, 13.82) when BMI was added to the model. Results were somewhat stronger in analysis of the 30-year FRS. The group-level FRS variance explained by census blocks was 3.56% (95% CI=1.75, 7.12) among 2096 participants in 156 neighborhoods. Similar to the 10-year CVD risk score, the variance explained among women (959 in 97 block groups) was higher (6.06%, 95% CI=2.75, 12.83), but null among males. Conclusions: In this relatively homogenous suburban white population, census block groups explained a small percentage of the variance in CVD risk. The explained variance was higher among women (19% non-working vs. 5% of males), and largely explained by the clustering of obesity.
Abstract P026: Early Repolarization Pattern is Associated With Increased Left Ventricular Mass and Left Ventricular Hypertrophy: Results From the Dallas Heart Study
Authors: David A McNamara, Ari Bennett, Jarett D Berry, Mark S Link
Journal: Circulation (2018)

Introduction: Recent studies have shown an association between early repolarization pattern (ERP) ECG morphology and sudden cardiac death. The role of left ventricular mass (LVM) as a potential mediator of ERP has not been well explored. Methods: Participants in the Dallas Heart Study who underwent an ECG and cardiac MRI (CMR) were assessed for ERP, defined as J-point elevation ≥1 mm in any 2 contiguous leads. We compared participants with and without ERP by age, gender, race/ethnicity, established cardiovascular risk factors of diabetes, hypertension and hyperlipidemia, lean body mass and percent body fat, and CMR-derived LVM, LVM/body surface area, and LVH defined by standard criteria, using Student’s T-tests and chi-squared tests where appropriate. Results: Of the 3,015 participants in our study, 276 (9.2%) had ERP. Participants with ERP were younger (43±9 vs 44±10 yrs, p=0.04), more prevalent in blacks than non-blacks (14 vs 5.0%, p&lt;0.00001), and in men than women (18 vs 2.0%, p&lt;0.00001). Baseline cardiovascular risk factors were not significantly different. Participants with ERP demonstrated higher lean body mass (59±10 vs 52±11 kg, p&lt;0.00001) and lower percent body fat (27±8 vs 36±9%, p&lt;0.00001). The presence of ERP was associated with greater LVM, increased LVM/body surface area, and the presence of LVH in the overall population and in analyses stratified by sex (Table 1). Conclusion: In a large, multi-ethnic cohort, ERP is associated with increased total LVM, increased LVM/body surface area, and LVH. These novel associations may provide insight into the biology of ERP. Further studies investigating the relationship of LVM and LVH with ERP are warranted.
Sorafenib Reduced Significantly Heptopulmonary Shunt in a Large Hepatocelullar Carcinoma
Authors: Philippe d'Abadie, Ivan Borbath, Pierre Goffette, Nadia Amini, Renaud Lhommel
Journal: Clinical Nuclear Medicine (2018)

An 81-year-old man with a large hepatocellular carcinoma was referred in our institution for Y radioembolization (RE). The preliminary arteriography using Tc-macroaggregate albumin demonstrated an important hepatopulmonary shunt. It was an exclusion criterion for RE due to high risks of lung radiations. Then, the patient was treated with sorafenib during 4 months, stopped because of grade 3 toxicity. A second liver arteriography was performed, and Tc-macroaggregate albumin imaging showed an important reduction of the lung shunt. Transient therapy with sorafenib permitted to close the lung shunt and was a bridge for RE.
“Cell-addictive” dual-target traceable nanodrug for Parkinson's disease treatment via flotillins pathway
Authors: YanHui Li, ZiXuan Chen, ZhiGuo Lu, QingHu Yang, LinYing Liu, ZhaoTan Jiang, LiQun Zhang, Xin Zhang, Hong Qing
Journal: Theranostics (2018)

α-synclein (αS) aggregation is a representative molecular feature of the pathogenesis of Parkinson's disease (PD).Epigallocatechin gallate (EGCG) can prevent αS aggregation in vitro.However, the in vivo effects of PD treatment are poor due to the obstacles of EGCG accumulation in dopaminergic neurons, such as the blood brain barrier and high binding affinities between EGCG and membrane proteins.Therefore, the key to PD treatment lies in visual examination of EGCG accumulation in dopaminergic neurons.Methods: DSPE-PEG-B6, DSPE-PEG-MA, DSPE-PEG-phenylboronic acid, and superparamagnetic iron oxide nanocubes were self-assembled into tracing nanoparticles (NPs).EGCG was then conjugated on the surface of the NPs through the formation of boronate ester bonds to form a "cell-addictive" dual-target traceable nanodrug (B6ME-NPs).B6ME-NPs were then used for PD treatment via intravenous injection.Results: After treatment with B6ME-NPs, the PD-like characteristics was alleviated significantly.First, the amount of EGCG accumulation in PD lesions was markedly enhanced and traced via magnetic resonance imaging.Further, αS aggregation was greatly inhibited.Finally, the dopaminergic neurons were considerably increased.Conclusion: Due to their low price, simple preparation, safety, and excellent therapeutic effect on PD, B6ME-NPs are expected to have potential application in PD treatment.
MDM2-Recruiting PROTAC Offers Superior, Synergistic Antiproliferative Activity via Simultaneous Degradation of BRD4 and Stabilization of p53
Authors: John Hines, Schan Lartigue, Hanqing Dong, Yimin Qian, Craig M. Crews
Journal: Cancer Research (2018)

Abstract Although the number of proteins effectively targeted for posttranslational degradation by PROTAC has grown steadily, the number of E3 ligases successfully exploited to accomplish this has been limited to the few for which small-molecule ligands have been discovered. Although the E3 ligase MDM2 is bound by the nutlin class of small-molecule ligands, there are few nutlin-based PROTAC. Because a nutlin-based PROTAC should both knockdown its target protein and upregulate the tumor suppressor p53, we examined the ability of such a PROTAC to decrease cancer cell viability. A nutlin-based, BRD4-degrading PROTAC, A1874, was able to degrade its target protein by 98% with nanomolar potency. Given the complementary ability of A1874 to stabilize p53, we discovered that the nutlin-based PROTAC was more effective in inhibiting proliferation of many cancer cell lines with wild-type p53 than was a corresponding VHL-utilizing PROTAC with similar potency and efficacy to degrade BRD4. This is the first report of a PROTAC in which the E3 ligase ligand and targeting warhead combine to exert a synergistic antiproliferative effect. Our study highlights the untapped potential that may be unlocked by expanding the repertoire of E3 ligases that can be recruited by PROTAC. Significance: These findings present the first BRD4-targeting MDM2-based PROTAC that possesses potent, distinct, and synergistic biological activities associated with both ends of this heterobifunctional molecule.
Abstract 17383: Pre-Renal Transplant Diastolic Dysfunction is an Independent Predictor of Post Transplant Major Cardiac Events
Authors: Meron Teshome, Addis A Asfaw, Ibtihaj Fughhi, Rami Doukky
Journal: Circulation (2017)

Introduction: Cardiac structural and functional abnormalities are common in patients with end-stage renal disease. In these patients, diastolic dysfunction is an independent predictor of cardiovasc...
Abstract 14797: Impact of Normalized Pulmonary Vein Flow Pattern After Percutaneous Mitral Valve Repair
Authors: Yukiko Mizutani, Shunsuke Kubo, Song Guangyuan, Justin Cox, Asma Hussaini, Moody Makar, Mamoo Nakamura, Robert Siegel, Trent Alfred, Saibal Kar
Journal: Circulation (2015)

Background: Systolic reverse pulmonary venous flow (PVF) assessed with pulsed Doppler echocardiography is a valuable marker of severe mitral regurgitation (MR). However, the relationship between PVF pattern after MR reduction by percutaneous mitral valve repair with MitraClip system and clinical outcome is not well established. We hypothesized that normalized PVF after MitraClip procedure was associated with successful MR reduction and clinical outcome. Method: 146 consecutive patients with symptomatic MR who implanted the MitraClip were studied. The patients were divided into 2 groups on the basis of post-procedural left upper PVF pattern; the normalized group (n = 77) and the non-normalized group (n = 69). The normalized PVF was defined as a ratio of peak systolic to diastolic flow velocity ≧1. Results: In baseline characteristics, the normalized PVF was independently associated with age &lt;75 (liner regression coefficient [B] = 0.521, 95% confidence interval [CI] = 0.146 - 0.822, P = 0.016) and degenerative MR (B = 0.969, 95% CI 0.049 - 0.383, P &lt;.0001). The normalized group demonstrated significantly higher residual MR ≦2 rate than non-normalized group (100% vs. 97.3%, P = 0.003). At a mean of 2.9 ± 1.9 years follow up, the rate of freedom from the composite endpoint (defined as surgery or 2nd MitraClip procedure for mitral valve dysfunction or all cause death) was significantly higher in the normalized group. Mutivariable Cox regression analysis demonstrated that normalized PVF was an independent post-procedural parameter of freedom from composite endpoint (hazard ratio =0.571, 95%CI 0.339 - 0.948, P = 0.03). Conclusion: The normalized PVF after the MitraClip procedure was associated with successful MR reduction and a long-term clinical outcome. Prospective data should be used to validate this.
Abstract 19375: Platelet Activation Plays an Important Role in Regulation of Aortic Valve Calcification in Calcific Aortic Valve Disease
Authors: Zuzana Motovska, Richard Fojt, Jiri Jarkovsky, Zbynek Straka, Petr Widimsky, Jan Pirk
Journal: Circulation (2016)

Background: The most significant predictor of valve disease progression is the load of calcium in aortic valve. Dickkopf-1 (DKK-1) might be along the causal pathway in regulation of valvular calcif...
Multiple transmissions of de novo mutations in families
Authors: Hákon Jónsson, Patrick Sulem, Gudny A. Arnadottir, Gunnar Pálsson, Hannes P. Eggertsson, Snaedis Kristmundsdottir, Florian Zink, Birte Kehr, Kristjan E. Hjorleifsson, Brynjar Ö. Jensson, Ingileif Jonsdottir, Sigurdur Einar Marelsson, Sigurjon Axel Gudjonsson, Arnaldur Gylfason, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Simon N. Stacey, Olafur Th. Magnusson, Unnur Thorsteinsdottir, Gisli Masson, Augustine Kong, Bjarni V. Halldorsson, Agnar Helgason, Daniel F. Gudbjartsson, Kari Stefansson
Journal: Nature Genetics (2018)
Occult Cerebral Abscess Revealed by FDG PET/CT in a Case of Unresponsive Wakefulness Syndrome
Authors: Caroline Bund, Hugo Andres Coca, Stéphane Kremer, Julien Pottecher, Izzie-Jacques Namer
Journal: Clinical Nuclear Medicine (2018)

A 51-year-old woman developed profound coma complicating subarachnoid hemorrhage after aneurysmal rupture. An external ventricular drain was inserted. FDG PET/CT was performed for prognostication purposes and showed global cortical hypometabolism. This was consistent with the clinical findings of an unresponsive wakefulness syndrome. During the follow-up, ventriculitis was diagnosed. Because of no clinical improvement under focused, high-dose antimicrobial treatment, a second FDG PET/CT was performed. It showed an improved diffuse cortical fixation and an intense intraventricular hyperfixation, suggestive of intraventricular abscess. A third functional imaging, performed to monitor treatment, showed progressive metabolic recovery with especially uptake in frontoparietal areas over time.
Abstract 20257: Decline in Chest Compression Release Velocity Over Time is Associated With Out-of-Hospital Cardiac Arrest Outcomes
Authors: Samuel Beger, John Sutter, Chengcheng Hu, Daniel W Spaite, Annemarie Silver, Robyn McDannold, Margaret Mullins, Tyler F Vadeboncoeur, Bentley J Bobrow
Journal: Circulation (2016)

Background: High chest compression release velocity (CCRV) has been independently associated with improved outcomes after out-of-hospital cardiac arrest (OHCA). We assessed the change in CCRV over ...
THU0466 Sexual dysfunction and depression in behcet`s disease – are there differences regarding patient’s origin
Authors: T. Xenitidis, A.-C. Pecher, T. Schmalen, M. Henes, J.C. Henes
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Behcet's disease (BD) is a systemic vasculitis of veins and arteries characterised by oral and genital ulcers (aphthae), skin lesions and uveitis. BD is more common in Middle Eastern countries and Asia but also occurs in Caucasian people. <h3>Objectives</h3> Aim of this study was to evaluate the prevalence of sexual dysfunction (SD) in patients with BD as well as analysing differences between patients from different origins. Additionally we investigated the prevalence of depression in both ethnic groups. <h3>Methods</h3> This prospective, monocentric study included 106 patients with BD. The International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI) were used for assessing sexual dysfunction and the Beck Depression Inventory (BDI) was used for depression assessment. <h3>Results</h3> The mean age of our group was 40.5 years. Half of the patients had Middle Eastern and half Caucasian origin. SD was found in 24.5% of all subjects. Only 6.9% of the male patient's group showed signs of SD, while half of the women's group was suffering from SD (p&lt;0.001). The prevalence for SD was significantly higher in women with Middle Eastern origin compared to women with Caucasian origin (75% vs. 33,3%, p=0.024). Genital ulcers affected 73.6% of all patients. Depression was found in 36.7% of all subjects. Both SD and depression correlated positively in males (p=0.017) and females (p=0.013). <h3>Conclusions</h3> SD and depression are very common problems in BD and should be addressed by the treating physician. Both manifestations are intensifying each other. <h3>Disclosure of Interest</h3> None declared
THU0236 Ankylosing spondylitis related factors predict the presence of cardiac conduction disturbances – a swedish longitudinal cohort study
Authors: K. Bengtsson, E. Klingberg, A. Deminger, L.T. Jacobsson, L. Bergfeldt, H. Forsblad-d’Elia
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Despite a well-known association between ankylosing spondylitis (AS) and cardiac conduction disturbances (from here CCD), it's not clear which factors that predict their presence. <h3>Objectives</h3> To describe electrocardiographic (ECG) alterations in a cohort of patients with AS and if AS related factors at baseline predict the presence of CCD at 5 year follow-up. <h3>Methods</h3> In total 210 patients diagnosed with AS at 3 rheumatology clinics from Western Sweden participated 2009 in an observational longitudinal cohort study with a planned follow-up after 5 years. , At follow-up 2014 physical examination, ECG, questionnaires, laboratory tests and radiographic examinations were repeated in 172 patients (82%). CCD was defined in the presence of AV block I (PQ duration ≥220 ms), AV block Ix (PQ duration 200–219 ms), AV block II-III, right and left bundle branch block (RBBB and LBBB)), left anterior and posterior fascicular block (LAFB and LPFB) and pacemaker. Descriptive statistics and logistic regression analyses were performed in order to find predictors at baseline for the presence of CCD at follow-up. Baseline characteristics with a p-value&lt;0.2 in univariate analyses (dependent variable <i>present CCD</i> (yes=1, no=0)) were included as independent variables in a forward stepwise multiple logistic regression analysis. <h3>Results</h3> In total 23 of the 172 patients (13.4%) had CCD at 5 year follow-up. Eight had developed a new CCD out of which 2 had required pacemaker implantation, 3 had a more aggravated CCD, whereas 10 patient had an unchanged and 2 a less pronounced . CCD compared with 2009 CCD and some of the patient characteristics are presented in table 1. (None had LPFB or AV block II-III). According to multiple logistic regression analysis, male sex (Odds ratio (OR) (95% CI) 4.7 (1.1–20.6)), increasing age (OR 1.1 (1.0–1.1) per 1 year), a history of anterior uveitis (OR 6.4 (1.1–36.2)), higher ASDAS-CRP (OR 3.6 (1.6–7.9)) and existing CCD at baseline (OR 42.4 (8.9–202.2)) were predictors for the presence of CCD at follow-up. Data are expressed as mean ±SD or number (%). <sup>#</sup> Missing data in 13 patients (10 without CCD and 3 with CCD) who did not underwent echocardiography at baseline. DMARDs; disease-modifying anti-rheumatic drugs. ASDAS-CRP; ankylosing spondylitis disease activity score using C-reactive protein. <h3>Conclusions</h3> The presence of CCD in AS is dynamic. AS related factors, represented by baseline ASDAS-CRP and a history of anterior uveitis, predicted their presence at 5 year follow-up. <h3>Disclosure of Interest</h3> None declared
Why junior doctors need more autonomy
Authors: Rose Penfold
Journal: BMJ (2018)

To tackle low morale, strategies to reduce workload are only partly feasible or desirable, writes <b>Rose Penfold</b>: we must also empower doctors in training to give them more control over tasks and working environment. Her essay was the winning entry in a competition run by Doctors for the NHS and <i>The BMJ</i>
Ibrutinib Alone or in Combination with Rituximab Produces Superior Progression Free Survival (PFS) Compared with Bendamustine Plus Rituximab in Untreated Older Patients with Chronic Lymphocytic Leukemia (CLL): Results of Alliance North American Intergroup Study A041202
Authors: Jennifer A. Woyach, Amy S. Ruppert, Nyla A. Heerema, Weiqiang Zhao, Allison M Booth, Wei Ding, Nancy L. Bartlett, Danielle M. Brander, Paul Barr, Kerry A. Rogers, Sameer A. Parikh, Steven Coutre, Arti Hurria, Gerard Lozanski, Sreenivasa Nattam, Richard A. Larson, Harry P. Erba, Mark R. Litzow, Carolyn Owen, Jim Atkins, Jeremy S. Abramson, Richard F. Little, Scott E. Smith, Richard M. Stone, Sumithra J Mandrekar, John C. Byrd
Journal: Blood (2018)
Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis
Authors: Yinghong Wang, Diana H. Wiesnoski, Beth A. Helmink, Vancheswaran Gopalakrishnan, Kati Choi, Hebert L. DuPont, Zhi-Dong Jiang, Hamzah Abu-Sbeih, Christopher A. Sanchez, Chia-Chi Chang, Edwin R. Parra, Alejandro Francisco-Cruz, Gottumukkala S. Raju, John R. Stroehlein, Matthew T. Campbell, Jianjun Gao, Sumit K. Subudhi, Dipen M. Maru, Jorge M. Blando, Alexander J. Lazar, James P. Allison, Padmanee Sharma, Michael T. Tetzlaff, Jennifer A. Wargo, Robert R. Jenq
Journal: Nature Medicine (2018)