tbuckley/cabot-search huggingface dataset:
Results of NOPHO ALL2008 treatment for patients aged 1–45 years with acute lymphoblastic leukemia
Authors: N Toft, H Birgens, J Abrahamsson, L Griškevičius, H Hallböök, M Heyman, T W Klausen, ÓG Jónsson, K Palk, K Pruunsild, P Quist-Paulsen, G Vaitkeviciene, K Vettenranta, A Åsberg, T L Frandsen, H V Marquart, H O Madsen, U Norén-Nyström, K Schmiegelow
Journal: Leukemia (2017)
Abstract 385: Broccoli Sprout Extracts Prevents Diabetic Cardiomyopathy in <i>db/db</i> Mice: The Importance of Up-regulated Nrf2 Expression and Function
Authors: Zheng xu, Yi Tan, Jian Sun, Lu Cai
Journal: Circulation Research (2016)

This study was to define whether consumption of broccoli sprout extracts (BSE) can be used as natural sulforaphane (SFN) supplement to systemically up-regulate NFE2-related factor 2 (Nrf2) for the prevention of diabetic cardiomyopathy (DCM). Five-months-old db/db and age-matched wild type (WT) mice were fed BSE or SFN by gavage every other day for 3 months. Both db/db and WT mice were divided into four groups: vehicle (0.1 ml/10g), BSE-low dose (delivery SFN 0.5 mg/kg), BSE-high dose (delivery SFN 1.0 mg/kg), and SFN (0.5 mg/kg) as a positive control. After 3 months treatment, cardiac function was evaluated by echocardiography. Cardiac hypertrophy, fibrosis, inflammation, and oxidative stress damage were assessed by Western blot, real-time PCR, and histopathological examination. Both BSE and SFN significantly prevented diabetes-induced cardiac dysfunction, hypertrophy, and fibrosis (increased accumulation of collagen and expression of connective tissue growth factor). BSE and SFN also prevented diabetes-induced cardiac inflammation and oxidative injury. Like SFN, the positive control of Nrf2 activator, BSE significantly up-regulated Nrf2 expression and transcription activity, reflected by increased Nrf2 nuclear accumulation and the expression of its downstream genes at both mRNA and protein levels. These results indicated that the effect of BSE-high dose is similar to those of SFN, suggesting that BSE can be used as SFN nature supplement to up-regulate Nrf2 expression and function for the prevention of DCM in type 2 diabetes. Since BSE is a health supplement, the potential for its clinical application for diabetic patients is highly promised.
PTH-053 Colonoscopy: the doctors’ gold standard, but is it the patients’? a study of choice of colonic investigation made by fully informed patients
Authors: H Ojidu, J Lewandowski, H Palmer, J Hampton, T Blakeborough, O Epstein, M McAlindon
Journal: Gut (2017)

Introduction  Informed consent requires information about the nature, the risks, the benefits of the investigation proposed and the alternatives. [Brooks et al., Endoscopy 2005] Optical colonoscopy (OC) is widely accepted as the gold standard colonic investigative modality, but it is uncomfortable, incurs the risks of intubation and sedation and diagnostic yield is only 10% in symptomatic patients. [Gavin et al., Gut 2013] Alternatives include CT colonography (CTC) and colon capsule endoscopy (CCE) which are better tolerated and safer. The aim of this study was to determine the choices made by a cohort randomly selected from the population when provided with information about all three tests.  Method  Members of the public were invited to take part in the study outside a local shopping centre. They were provided with written literature explaining the nature, and a summary table of the advantages and disadvantages, of each test and were free to ask questions of the research team. Patient tolerance and acceptability data was obtained from earlier studies of our patient population. [Ojidu et al., submitted to BSG 2017] The risk of serious complications (perforation, bleeding and radiation exposure), diagnostic yield and expected incidence of incidental pathology (polyps or extraluminal findings on CTC) were derived from published literature and patients were advised of the possible need for OC (if a non-invasive test identified a polyp or tumour) or further investigation if CTC identified extraluminal pathology, which they were told may or may not be important. They were asked to choose which test they would prefer for the investigation of two clinical scenarios: new symptoms and a positive faecal occult blood test in the bowel cancer screening programme (BCSP).  Results  100 subjects (median age (range) 42.5 years (19-92), 38% male) chose OC, CTC and CCE in 45%, 37% and 18% respectively to investigate new symptoms and 71%, 22% and 7% for the BCSP. Thus 55% of patients having symptoms investigated preferred an alternative to OC compared to 29% of those undergoing screening (p  Conclusion  Over half of a non-select cohort of the lay public prefer non-invasive colonic investigation of symptoms when fully informed about the modalities available, which should therefore be offered in clinical practice. Almost one third would prefer the same approach in the BCSP, which should be considered if compliance is to be optimised.  Disclosure of Interest  None Declared
Why It Is So Hard to Talk About Overuse in Pediatrics and Why It Matters
Authors: Shawn L. Ralston, Alan R. Schroeder
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Cutaneous lupus erythematosus: quality of life and related factors in a cohort of 260 patients from A Coruña, Spain
Authors: M.P. Arévalo-Bermúdez, S. Pita-Fernández, S. Paradela, E. Fonseca
Journal: British Journal of Dermatology (2017)

Dermatological disease has a significant impact on quality of life (QoL). However, information is scarce for cutaneous lupus erythematosus (CLE) in this regard. Thus, the manifestation of and co-morbidities associated with CLE were assessed in the current study to determine factors predictive of QoL impairment. A descriptive cross-sectional study was performed on predominantly Caucasian patients with CLE, recruited at our institution between April 2013 and August 2016 (α = 0.050; precision ± 6.5%).

This article is protected by copyright. All rights reserved.
単一細胞トランスクリプトーム:単一細胞トランスクリプトームのreference component analysisからヒト大腸腫瘍における細胞の不均一性が明らかになる
Authors: LI Huipeng, Courtois Elise T, Sengupta Debarka, Tan Yuliana, Prabhakar Shyam, Robson Paul, Chen Kok Hao, Goh Jolene Jie Lin, Choi Paul Jongjoon, Kong Say Li, Hillmer Axel M, Tan Iain Beehuat, Chua Clarinda, Hon Lim Kiat, Tan Wah Siew, Wong Mark, Wee Lawrence J K
Journal: Nature Genetics (2017)
Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation as Alternative to Matched Sibling or Unrelated Donor Transplantation for Hodgkin Lymphoma: A Registry Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation
Authors: Carmen Martínez, Jorge Gayoso, Carmen Canals, Hervé Finel, Karl Peggs, Alida Dominietto, Luca Castagna, Boris Afanasyev, Stephen Robinson, Didier Blaise, Paolo Corradini, Maija Itälä-Remes, Arancha Bermúdez, Edouard Forcade, Domenico Russo, Michael Potter, Grant McQuaker, Ibrahim Yakoub-Agha, Christof Scheid, Adrian Bloor, Silvia Montoto, Peter Dreger, Anna Sureda
Journal: Journal of Clinical Oncology (2017)

Purpose To compare the outcome of patients with Hodgkin lymphoma who received post-transplantation cyclophosphamide-based haploidentical (HAPLO) allogeneic hematopoietic cell transplantation with the outcome of patients who received conventional HLA-matched sibling donor (SIB) and HLA-matched unrelated donor (MUD). Patients and Methods We retrospectively evaluated 709 adult patients with Hodgkin lymphoma who were registered in the European Society for Blood and Marrow Transplantation database who received HAPLO (n = 98), SIB (n = 338), or MUD (n = 273) transplantation. Results Median follow-up of survivors was 29 months. No differences were observed between groups in the incidence of acute graft-versus-host disease (GVHD). HAPLO was associated with a lower risk of chronic GVHD (26%) compared with MUD (41%; P = .04). Cumulative incidence of nonrelapse mortality at 1 year was 17%, 13%, and 21% in HAPLO, SIB, and MUD, respectively, and corresponding 2-year cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. On multivariable analysis, relative to SIB, nonrelapse mortality was similar in HAPLO ( P = .26) and higher in MUD ( P = .003), and risk of relapse was lower in both HAPLO ( P = .047) and MUD ( P < .001). Two-year overall survival and progression-free survival were 67% and 43% for HAPLO, 71% and 38% for SIB, and 62% and 45% for MUD, respectively. There were no significant differences in overall survival or progression-free survival between HAPLO and SIB or MUD. The rate of the composite end point of extensive chronic GVHD and relapse-free survival was significantly better for HAPLO (40%) compared with SIB (28%; P = .049) and similar to MUD (38%; P = .59). Conclusion Post-transplantation cyclophosphamide-based HAPLO transplantation results in similar survival outcomes compared with SIB and MUD, which confirms its suitability when no conventional donor is available. Our results also suggest that HAPLO results in a lower risk of chronic GVHD than MUD transplantation.
International Surviving Sepsis Campaign guidelines 2016: the perspective from low-income and middle-income countries
Authors: Gentle S Shrestha, Arthur Kwizera, Ganbold Lundeg, John I Baelani, Luciano C P Azevedo, Rajyabardhan Pattnaik, Rashan Haniffa, Srdjan Gavrilovic, Nguyen Thi Hoang Mai, Niranjan Kissoon, Rakesh Lodha, David Misango, Ary Serpa Neto, Marcus J Schultz, Arjen M Dondorp, Jonarthan Thevanayagam, Martin W Dünser, A K M Shamsul Alam, Ahmed M Mukhtar, Madiha Hashmi, Suchitra Ranjit, Akaninyene Otu, Charles Gomersall, Jacinta Amito, Nicolas Nin Vaeza, Jane Nakibuuka, Pierre Mujyarugamba, Elisa Estenssoro, Gustavo A Ospina-Tascón, Sanjib Mohanty, Mervyn Mer
Journal: The Lancet Infectious Diseases (2017)
Comparison of the BTA textitstattextsuperscriptTM Test with Voided Urine Cytology and Bladder Wash Cytology in the Diagnosis and Monitoring of Bladder Cancer
Authors: Herbert Leyh, Michael Marberger, Pierre Conort, Cora Sternberg, Vito Pansadoro, Francesco Pagano, Pierfrancesco Bassi, Laurent Boccon-Gibod, Vincent Ravery, Uwe Treiber, Laura Ishak
Journal: European Urology (1999)
ADDENBROOKE'S HOSPITAL, CAMBRIDGE: CASES OF TRACHEOTOMY: IN LARYNGITIS; FOR FOREIGN BODY IN THE LARYNX; AND IN TETANUS
Authors: G. M. Humphry
Journal: BMJ (1856)

ASSOCITION MEDICAL JOUR0AL(MAR01 1, 1"& log cels sufIrea from the effusion, their fibrous wals be- came ofrened and broken down; and here and there, this state of things could be observed.The bronchi which suffered from the pressure of the tubeces, in contact with their outsides, presented nothing abnormal in their mucous coats.Neither fatty epithelium, casts, nor tubercle-cells were found in them.The epithe- lium of the ultimate bronchi of the affected air-cells was invariably broken down, and contained many free oil globuls.No diseased blood-vessels were observed.The kid- necscontained tubercles and cysts, and were very large and RXMAs.The interesting features in this case were, the relation between the pathological condition of the lungs,
Colchicine: an ancient drug with novel applications
Authors: B. Dasgeb, D. Kornreich, K. McGuinn, L. Okon, I. Brownell, D.L. Sackett
Journal: British Journal of Dermatology (2017)

Colchicine is a treatment for gout that has been used for more than a millennium. It is the treatment of choice for familial Mediterranean fever and its associated complication, amyloidosis. The 2009 U.S. Food and Drug Administration approval of colchicine as a new drug had research consequences. Recent investigations with large cohorts of patients with gout who have been taking colchicine for years have demonstrated novel applications within oncology, immunology, cardiology and dermatology. Some emerging dermatological uses include the treatment of epidermolysis bullosa acquisita, leucocytoclastic vasculitis, aphthous stomatitis and others. In this work we relate the history and the new horizon of this ancient medicine.
General intelligence does not help us understand cognitive evolution
Authors: David M Shuker, Louise Barrett, Thomas E Dickins, Thom C Scott-Phillips, Robert A Barton
Journal: Behavioral and Brain Sciences (2017)

Abstract Burkart et al. conflate the domain-specificity of cognitive processes with the statistical pattern of variance in behavioural measures that partly reflect those processes. General intelligence is a statistical abstraction, not a cognitive trait, and we argue that the former does not warrant inferences about the nature or evolution of the latter.
Human Papillomavirus Vaccination Rates in Young Cancer Survivors
Authors: James L. Klosky, Melissa M. Hudson, Yanjun Chen, James A. Connelly, Karen Wasilewski-Masker, Can-Lan Sun, Liton Francisco, Laura Gustafson, Kathryn M. Russell, Gina Sabbatini, Jessica S. Flynn, Jocelyn M. York, Anna R. Giuliano, Leslie L. Robison, F. Lennie Wong, Smita Bhatia, Wendy Landier
Journal: Journal of Clinical Oncology (2017)

Cancer survivors are at high risk for human papillomavirus (HPV)-related morbidities; we estimated the prevalence of HPV vaccine initiation in cancer survivors versus the US population and examined predictors of noninitiation.Participants included 982 cancer survivors (9 to 26 years of age; 1 to 5 years postcompletion of therapy); we assessed HPV vaccine initiation, sociodemographic and clinical characteristics, and vaccine-specific health beliefs; age-, sex-, and year-matched US population comparisons were from the National Immunization Survey-Teen and the National Health Interview Survey (2012-2015).The mean age at the time of the study was 16.3 ± 4.7 years; the mean time off therapy was 2.7 ± 1.2 years; participants were 55% male and 66% non-Hispanic white; 59% had leukemia/lymphoma. Vaccine initiation rates were significantly lower in cancer survivors versus the general population (23.8%; 95% CI, 20.6% to 27.0% v 40.5%; 95% CI, 40.2% to 40.7%; P < .001); survivors were more likely to be HPV vaccine-naïve than general population peers (odds ratio [OR], 1.72; 95% CI, 1.41 to 2.09; P < .001). Initiation in adolescent survivors (ages 13 to 17 years) was 22.0% (95% CI, 17.3% to 26.7%), significantly lower than population peers (42.5%; 95% CI, 42.2% to 42.8%; P < .001). Initiation in young adult survivors and peers (ages 18 to 26 years) was comparably low (25.3%; 95% CI, 20.9% to 29.7% v 24.2%; 95% CI, 23.6% to 24.9%). Predictors of noninitiation included lack of provider recommendation (OR, 10.8; 95% CI, 6.5 to 18.0; P < .001), survivors' perceived lack of insurance coverage for HPV vaccine (OR, 6.6; 95% CI, 3.9 to 11.0; P < .001), male sex (OR, 2.9; 95% CI, 1.7 to 4.8; P < .001), endorsement of vaccine-related barriers (OR, 2.7; 95% CI, 1.6 to 4.6; P < .001), and younger age (9 to 12 years; OR, 3.7; 95% CI, 1.8-7.6; P < .001; comparison, 13 to 17 years).HPV vaccine initiation rates in cancer survivors are low. Lack of provider recommendation and barriers to vaccine receipt should be targeted in vaccine promotion efforts.
NHS expands overseas GP recruitment drive despite slow progress so far
Authors: Abi Rimmer
Journal: BMJ (2017)

NHS England has expanded its international programme to recruit GPs from overseas, despite the scheme recruiting only 38 doctors since last year.

On Tuesday 22 August NHS England announced that it was intending to recruit 601 overseas doctors into general practice in 2017-18 and at least 2000 doctors over the next three years.1

The initial target for the programme, set out in April 2016 in the General Practice Forward View , was to recruit 500 GPs by 2020-21.2

Figures from NHS England, shared with The BMJ last month, showed that the programme had recruited only 28 GPs to Lincolnshire and 10 GPs to Essex, the first …
術後腹膜癒着を予防するための戦略としてのゲニピン架橋のゼラチン微小球体:in vitroおよびin vivo特性化【Powered by NICT】
Authors: De Clercq Kaat, Schelfhout Charlotte, Bracke Marc, De Wever Olivier, Van Bockstal Mieke, Ceelen Wim, Remon Jean Paul, Vervaet Chris
Journal: Biomaterials (2016)
Cytokine release syndrome (CRS) in patients treated with NY-ESO-1<sup>c259</sup> TCR.
Authors: Crystal Mackall, Sandra P. D'Angelo, Mihaela C. Cristea, Kunle Odunsi, Elliot Norry, Lini Pandite, Tom Holdich, Gabor Kari, Indu R. Ramachandran, Lilliam Ribeiro, Gwendolyn Binder-Scholl, Rafael G. Amado
Journal: Journal of Clinical Oncology (2016)

3040 Background: Cytokine release syndrome (CRS) is observed with adoptive T-cell therapies (ACT) with varying frequency. CRS can be life threatening and may require steroids, which hinder the effectiveness of ACT. CRS prevalence and severity within the context NY-ESO-1C259T across 5 studies in 4 tumor types were examined: synovial sarcoma (SS), ovarian cancer (OC), myeloma and melanoma. Methods: A review of CRS including evaluation of concurrent AEs and reported symptoms, cytokine levels and CRP was performed in pts treated with NY-ESO-1C259T. AEs that are known manifestations of CRS were summarized for each pt. diagnosed with CRS. CRP was measured by the hospital laboratory. Serum cytokines were measured by Luminex. Results: Of 53 pts treated with NY-ESO-1C259T, 7 were diagnosed with CRS (Table). 2/7 pts received immunomodulatory treatment for mitigation of CRS: methylprednisolone 2 mg/kg x 2 doses with prednisone taper (n=1, G3) and Tocilizumab 4 mg/kg x 1 dose (n=1 G4). Diagnosis of CRS was made within the first 2 wks in all 7 pts and resolved within 32 days after the T-cell infusions. Onset of CRS coincided with T-cell expansion. Elevated IL-6 and IL-8 were observed during CRS. Timing of the increase of IL-6 and IL-8 suggests involvement in the effector phase of CRS instead of its induction. IL-5, IL-15, INF-γ and GM-CSF showed no discernable pattern associated with CRS. Conclusions: CRS was observed in 13% of pts treated with NY-ESO-1C259T. Symptoms manifest in the first 2 wks and have been effectively managed with supportive care measures. Two pts required immunomodulatory therapy. While there are differences in the pt. populations, incidence of CRS with NY-ESO-1C259T appears to be of lower frequency and severity than reported with CD19 CAR-T therapy. Data summary. Trial/Patient SS 205 SS 207 SS 208 SS 261 SS 264 OC 101 OC 203 Grade CRS/duration (days) 2/3 1/8 3/24 3/11 4/11 3/10 2/7 Responder Y N Y N Y N × Fever/Rash/Diarrhea Y/Y/Y Y/NR/Y Y/Y/Y Y/NR/Y Y/Y/NR Y/Y/Y Y/Y/NR CNS symptoms NR Y Y NR NR Y Y Dyspnea/hypoxia NR NR NR Y Y Y NR Hypotension Y NR NR NR Y Y Y Fatigue N N Y Y NR Y NR CRP (mg/L) 261 157 198 175 182 ND 143 IL-6 peak/IL-8 (pg/mL) 385/129 114/671 72/226 ND 987/394 80/150 ND × too early to assess response; NR – not reported; ND – not done
Fevipiprant, an oral prostaglandin DP<sub>2</sub>receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids
Authors: Eric D. Bateman, Alfredo G. Guerreros, Florian Brockhaus, Björn Holzhauer, Abhijit Pethe, Richard A. Kay, Robert G. Townley
Journal: European Respiratory Journal (2017)

Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP 2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS). Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d .) or twice-daily (2, 25, 75 or 150 mg b.i.d .) fevipiprant (n=782), montelukast 10 mg q.d . (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.d . Fevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d . and 75 mg b.i.d . groups, with no clinically meaningful differences between q.d . and b.i.d . Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments. Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted.
H PMA共重合体抱合体による癌細胞への細胞増殖抑制薬とP‐糖蛋白質阻害剤の同時送達による多剤耐性の克服【Powered by NICT】
Authors: Sivak Ladislav, Subr Vladimir, Tomala Jakub, Rihova Blanka, Strohalm Jiri, Etrych Tomas, Kovar Marek
Journal: Biomaterials (2017)
Immune checkpoint inhibitors (ICI): A meta-analysis of immune-related adverse events (irAE) from cancer clinical trials.
Authors: Badi Edmond El Osta, Fengjiao Hu, Ramses F. Sadek, Rohini Chintalapally, Shou-Ching Tang
Journal: Journal of Clinical Oncology (2016)

e14562 Background: irAE occur as a result of autoimmunity triggered by ICI during cancer treatment. We hypothesize that more patients (pts) will develop any grade irAE if treated with ICI targeting immune and regulatory T-cells (CTLA-4) than those treated with ICI targeting immune cells without T regulatory (PD-1) and those targeting non-immune cells having the least pts to develop irAE (PD-L1). Methods: We reviewed all ICI cancer clinical trials (104; 201 arms) that reported irAE and were published on PubMed or presented at an ASCO meeting (only if not published on PubMed) during 2005-2015. 127 arms from 81 trials met the inclusion criteria for this meta-analysis. We collected and compared arm-specific data including ICI target, number of pts with irAE any grade (A), grade 3+ (B) and grade 5, specific irAE A and B, response rate, evaluable pts for irAE and for response. R package “meta” was used for the meta-analysis to calculate and compare % of pts with irAE and response rates. Results: 116 (91%) arms used ICI monotherapy and 11 (9%) arms used combination of ICI to treat 11400 pts. 122 (96%) arms included solid tumors. 102 (80%) arms were phase 1/2. See Table below. Higher % of pts with irAE A was observed with ICI CTLA-4 followed by ICI PD-1 then ICI PD-L1 (P <0.0001). ICI CTLA-4 had higher % of pts with irAE B than others; no significant difference in % of pts with irAE B was observed with ICI PD-1 and PD-L1. Conclusions: Our meta-analysis supported our mechanistic-driven hypothesis that ICI targeting less immune cells caused less pts to develop any grade irAE. We encourage investigators to report % pts with irAE in ICI combination trials in order to balance their toxicity and efficacy profiles. ICI Arms that met inclusion criteria Evaluable pts for irAE Evaluable pts for response % pts with irAE, any grade % pts with irAE, grade 3+ % pts with irAE grade 5 Overall re sponse rate CTLA-4 56 4284 3160 54% 19% 1.4% 10.6% PD-1 35 4074 3636 26% 3.8%* 0.8% 27.5% PD-L1 25 2448 491 13.7% 5%* 1.1% 17.6% PD-1 + CTLA-4 8 495 1242 NR+ NR 1.8% 47.8% PD-L1 + CTLA-4 3 99 60 NR NR 1.8% 28.6% Total / P 127 11400 8589 P <0.0001 P <0.0001 P =0.34 P <0.0001 * p = 0.33+: not reported