tbuckley/cabot-search huggingface dataset:
Association of Whole-Body Computed Tomography With Mortality Risk in Children With Blunt Trauma
Authors: James A. Meltzer, Melvin E. Stone, Srinivas H. Reddy, Ellen J. Silver
Journal: JAMA Pediatrics (2018)

<h3>Importance</h3> Although several studies have demonstrated an improvement in mortality for injured adults who receive whole-body computed tomography (WBCT), it is unclear whether children experience the same benefit. <h3>Objective</h3> To determine whether emergent WBCT is associated with lower mortality among children with blunt trauma compared with a selective CT approach. <h3>Design, Setting, and Participants</h3> A retrospective, multicenter cohort study was conducted from January 1, 2010, to December 31, 2014, using data from the National Trauma Data Bank on children aged 6 months to 14 years with blunt trauma who received an emergent CT scan in the first 2 hours after emergency department arrival. Data analysis was conducted from February 2 to December 29, 2017. <h3>Exposures</h3> Patients were classified as having WBCT if they received CT head, CT chest, and CT abdomen/pelvis scans in the first 2 hours and as having a selective CT if they did not receive all 3 scans. <h3>Main Outcomes and Measures</h3> The primary outcome was in-hospital mortality in the 7 days after ED arrival. To adjust for potential confounding, propensity score weighting was used. Subgroup analyses were performed for those with the highest mortality risk (ie, occupants and pedestrians involved in motor vehicle crashes, children with a Glasgow Coma Scale score lower than 9, children with hypotension, and those admitted to the intensive care unit). <h3>Results</h3> Of the 42 912 children included in the study (median age [interquartile range], 9 [5-12] years; 27 861 [64.9%] boys), 8757 (20.4%) received a WBCT. Overall, 405 (0.9%) children died within 7 days. After adjusting for the propensity score, children who received WBCT had no significant difference in mortality compared with those who received selective CT (absolute risk difference, −0.2%; 95% CI, −0.6% to 0.1%). All subgroup analyses similarly showed no significant association between WBCT and mortality. <h3>Conclusions and Relevance</h3> Among children with blunt trauma, WBCT, compared with a selective CT approach, was not associated with lower mortality. These findings do not support the routine use of WBCT for children with blunt trauma.
The efficacy and feasibility of the beforehand-endoloop technique for colorectal endoscopic submucosal dissection
Authors: Tatsuma Nomura, Shinya Sugimoto, Takaaki Morikawa, Noriyuki Horiki
Journal: Endoscopy (2018)

Intraoperative perforation of colorectal endoscopic submucosal dissection (ESD) often occurs. Therefore, techniques to close intraoperative perforations safely are important. Various methods for suturing mucosal defects to prevent postoperative bleeding and perforation have been reported [1] [2]. To solve these problems, we report a technique we have developed, named the “beforehand-endoloop technique.”
184P Clinico-radiological pattern of response to nivolumab in stage IV NSCL: A real life experience over two years
Authors: M. Perna, V. Scotti, C. Muntoni, C. Moroni, F. Giannelli, D. Cozzi, F. Mazzoni, V. Bonti, D. Lavacchi, L. Livi
Journal: Journal of Thoracic Oncology (2018)
Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector
Authors: Chengzhong Wang, Ramsey Najm, Qin Xu, Dah-eun Jeong, David Walker, Maureen E. Balestra, Seo Yeon Yoon, Heidi Yuan, Gang Li, Zachary A. Miller, Bruce L. Miller, Mary J. Malloy, Yadong Huang
Journal: Nature Medicine (2018)
Abstract 12826: Cardiovascular Mortality and Heart Failure Risk Score For Patients After ST-Segment Elevation Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention: Data From the Leiden MISSION! Infarct Registry
Authors: M. L Antoni, Georgette E Hoogslag, Helèn Boden, Su S Liem, Eric Boersma, Kim Fox, Martin J Schalij, Jeroen J Bax, Victoria Delgado
Journal: Circulation (2011)

Introduction:  Risk scores developed for the prediction of an adverse outcome in patients after ST-segment elevation myocardial infarction (STEMI) have mostly addressed patients treated with thrombolysis and evaluated solely all-cause mortality as primary endpoint. Primary percutaneous coronary interventions (PCI) in STEMI patients have improved the outcome significantly and may have changed the relative contribution of different risk factors.   Methods:  The patient population comprised 1484 consecutive patients admitted with STEMI treated with primary PCI. Clinical, angiographic and echocardiographic data that were obtained during the hospitalization were used to derive a risk score for the prediction of short-term (30-days) and long-term (1- and 4-years) cardiovascular mortality and hospitalization for heart failure.   Results:  During a median follow-up duration of 30 months, 87 patients (6%) died from cardiovascular mortality or were hospitalized for heart failure. Multivariate Cox regression analyses identified age ≥70 years, Killip class ≥2, diabetes, left anterior descending coronary artery as culprit vessel, three vessel disease, peak cardiac troponin T level ≥3.5μ g/l, left ventricular ejection fraction ≤40% and heart rate at discharge ≥70bpm as relevant factors for the construction of the risk score. The discriminatory power of the model as assessed with the areas under the receiver operating characteristic curves was good (0.84, 0.83, 0.81 at 30-days, 1- and 4-years, respectively) and patients could be allocated to low (1%), intermediate (6%), or high (24%) risk categories.   Conclusions:  In conclusion, eight parameters which are readily available during the hospitalization of STEMI patients treated with primary PCI can accurately stratify patients into low, intermediate and high risk categories.
Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma
Authors: David S. Hong, Kathleen Moore, Manish Patel, Stefan C. Grant, Howard A. Burris, William N. William, Suzanne Jones, Funda Meric-Bernstam, Jeffrey Infante, Lisa Golden, Wei Zhang, Ricardo Martinez, Sameera Wijayawardana, Richard Beckmann, Aimee Bence Lin, Cathy Eng, Johanna Bendell
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Prexasertib, a checkpoint kinase 1 inhibitor, demonstrated single-agent activity in patients with advanced squamous cell carcinoma (SCC) in the dose-escalation portion of a phase I study (NCT01115790). Monotherapy prexasertib was further evaluated in patients with advanced SCC. Patients and Methods: Patients were given prexasertib 105 mg/m2 as a 1-hour infusion on day 1 of a 14-day cycle. Expansion cohorts were defined by tumor and treatment line. Safety, tolerability, efficacy, and exploratory biomarkers were analyzed. Results: Prexasertib was given to 101 patients, including 26 with SCC of the anus, 57 with SCC of the head and neck (SCCHN), and 16 with squamous cell non–small cell lung cancer (sqNSCLC). Patients were heavily pretreated (49% ≥3 prior regimens). The most common treatment-related adverse event was grade 4 neutropenia (71%); 12% of patients had febrile neutropenia. Median progression-free survival was 2.8 months [90% confidence interval (CI), 1.9–4.2] for SCC of the anus, 1.6 months (90% CI, 1.4–2.8) for SCCHN, and 3.0 months (90% CI, 1.4–3.9) for sqNSCLC. The clinical benefit rate at 3 months (complete response + partial response + stable disease) across tumors was 29% (23% SCC of the anus, 28% SCCHN, 44% sqNSCLC). Four patients with SCC of the anus had partial or complete response [overall response rate (ORR) = 15%], and three patients with SCCHN had partial response (ORR = 5%). Biomarker analyses focused on genes that altered DNA damage response or increased replication stress. Conclusions: Prexasertib demonstrated an acceptable safety profile and single-agent activity in patients with advanced SCC. The prexasertib maximum-tolerated dose of 105 mg/m2 was confirmed as the recommended phase II dose. Clin Cancer Res; 24(14); 3263–72. ©2018 AACR.
PD-1 blockade using pembrolizumab in adolescent and young adult patients with advanced bone and soft tissue sarcoma.
Authors: Tahlia Scheinberg, Anna Lomax, Martin HN Tattersall, David Morgan Thomas, Geoffrey Brian McCowage, Michael James Sullivan, Vivek Bhadri
Journal: Journal of Clinical Oncology (2017)

3060 Background: Sarcomas represent 1015% of cancers in adolescent and young adult (AYA) patients, and survival for those with metastatic disease or after relapse is poor. Immunotherapy with checkpoint inhibition has improved outcomes in multiple tumour types, but there are limited data on the efficacy of immunotherapy in advanced sarcomas, particularly within the AYA population. Methods: We retrospectively reviewed AYA patients with advanced bone and soft tissue sarcoma who received self-funded pembrolizumab at Chris OBrien Lifehouse and Childrens Hospital Westmead. Initial response was evaluated after cycle three or four using RECIST v1.1 criteria. Results: Fourteen AYA patients with sarcoma received pembrolizumab 2mg/kg IV every 3 weeks from May 2015 to December 2016. Median age was 24 (14  35), male to female was 7:7, ECOG PS was 0  1 in 6 patients, 2 in 6 patients and 3  4 in 2 patients. Malignancy type included three patients with osteosarcoma (OS), five patients with Ewing sarcoma (ES), two patients with synovial sarcoma (SS), two patients with alveolar soft part sarcoma (ASPS), and one patient with each of embryonal rhabdomyosarcoma (RMS) and clear cell sarcoma (CCS). The median number of pembrolizumab doses was four (range 1  16), with one patient still receiving treatment at the time of last follow up. Treatment was generally very well tolerated with no G3-4 toxicity. One patient with ES had an excellent, sustained response; of the two patients with ASPS one had a radiological partial response with an excellent clinical response and one patient achieved stable disease. Three patients (two ES, one RMS) died of disease prior to first scheduled assessment and thus their response was not evaluable. The remaining 8 patients had progressive disease. Conclusions: Our data suggest further evaluation of the role of pembrolizumab in AYA patients with advanced sarcoma is warranted.
A rare case of gastric wall abscess arising after endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic mass
Authors: Weiquan Wu, Jing Du, Jian-min Yang, Bin Zhou, Guo-chun Lou
Journal: Endoscopy (2018)

A 55-year-old man was admitted to our hospital because of a 7-month history of upper abdominal pain. The magnetic resonance imaging (MRI) scan showed a solid mass occupying the body and tail of the pancreas ([Fig. 1 a]). To make a more definitive diagnosis, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was carried out with a 22-gauge needle (EchoTip Ultra HD; Wilson-Cook Medical Inc., Winston Salem, North Carolina, USA). In total, five passes were completed using a fanning technique. Pathological examination of the collected tissue revealed severe atypical epithelial cells, and adenocarcinoma was suspected ([Fig. 1 b]). Combined with MRI images, we clinically diagnosed pancreatic adenocarcinoma.
Correlation of consistent blood-based gene expression with change in CTLA4 in two large independent clinical studies of patients with advanced melanoma treated with tremelimumab.
Authors: Philip Adam Friedlander, Karl Wassman, Chrisann Kyi, William K. Oh, Nina Bhardwaj
Journal: Journal of Clinical Oncology (2017)

6 Background: We previously reported 16-gene pre- and 8-gene post-treatment response predictive gene signatures in whole blood that were trained in one cohort (N=210) of advanced melanoma patients treated with tremelimumab and validated in an independent test dataset (N=150) for both response and survival.(SITC 2016 Annual Meeting Poster Submission ID: 214348.) Methods: A correlation matrix was calculated for the change between pre- and post-treatment gene expression for all 169 genes in two independent clinical trials. The genes were ranked by their relationship with CTLA4. Comparison was made between the training and test datasets. Reliable biological signals exceeded technical variance of +/- 0.5 fold change. Results: Correlation of the change in gene expression relative to CTLA4 between the 169 genes in two independent datasets was consistent as to fold change and ranking. The literature describes the genes in the Table as playing a role in anti-CTLA4 and PD-1 immunotherapy. We found only ICOS to be predictive of gene response in our 16-gene pre- and 8-gene post-treatment algorithms. Conclusions: Several genes, such as CTLA4, CD28, CXCR3, IL32, FOXP3, CD25, CCR5, and IFNG, are consistently upregulated one to three fold from anti-CTLA4 immunotherapy but are not predictive of response. ClinicalTrials.gov NCT00257205. [Table: see text]
Medical schools should be prioritising nutrition and lifestyle education
Authors: Kate Womersley, Katherine Ripullone
Journal: British Journal of Sports Medicine (2018)

Would you expect a junior doctor to be confident giving basic advice and care for the most common and fatal diseases? Of course you would. The National Institute for Health and Care Excellence guidelines state that a first line intervention for diabetes, obesity, and high cholesterol is to give ‘lifestyle advice’—but this phrase is so vague that it is left up to doctors and patients to define it and, potentially, ignore it.

In 2008 and 2009, more than 75% of American junior physicians felt inadequately trained to counsel patients on diet and physical activity.1 The picture is reportedly similar in the UK.2 In Tomorrow’s Doctors, the General Medical Council requires qualifying medical students to understand the role of diet in health promotion and disease prevention, which includes being nutritionally competent. Internationally, this knowledge is lacking in medical training. Just 27% of US medical schools provided the agreed minimum of 25 hours of nutrition education in 2008.3 A recent study of European medical schools was slightly more optimistic, suggesting that nutrition education was a requirement in 68.8% of …
Sentinel node biopsy in patients with microinvasive breast cancer: A systematic review and meta-analysis.
Authors: Helene Gojon, David Fawunmi, Antonis Valachis
Journal: Journal of Clinical Oncology (2013)

1119 Background: The aim of this meta-analysis is to evaluate the role of sentinel lymph node biopsy (SLNB) in patients with microinvasive breast cancer. Methods: We searched MEDLINE and ISI Web of Science to identify studies including patients with microinvasive breast cancer who underwent SLNB and reported the rate of sentinel-node positivity. We performed proportion meta-analysis using either fixed or random-effects model based on the between-study heterogeneity. Results: A total of 23 studies including 952 patients met the eligibility criteria. The summary estimate for the sentinel-node (SN) positivity rate was 3.1% (95% Confidence Interval (CI): 2.0%-4.4%), 4.1 % (95% CI 2.8%-5.6%), and 2.8% (95% CI : 1.6%-4.5%) for macrometastasis, micrometastasis and isolated tumor cells (ITC) respectively. Significant between-study heterogeneity was observed only in the meta-analysis of ITC positivity rate. Conclusions: The amount of positive sentinel node in patients with proven microinvasive breast cancer is relatively low. As a result, the indications for SLNB in these patients should be probably individualized.
12P Cigarette smoke promotes proliferation of non-small cell lung cancer (NSCLC) via enhancing glucose uptake and glycolysis
Authors: I-S. Hsieh, F-J. Cheng, C-Y. Tu, C-H. Chen, T-C. Hsia, B-W. Wang, Y-L. Yeh, W-C. Huang
Journal: Journal of Thoracic Oncology (2018)
Platelets expressing IgG receptor FcγRIIA/CD32A determine the severity of experimental anaphylaxis
Authors: Héloïse Beutier, Béatrice Hechler, Ophélie Godon, Yu Wang, Caitlin M. Gillis, Luc de Chaisemartin, Aurélie Gouel-Chéron, Stéphanie Magnenat, Lynn E. Macdonald, Andrew J. Murphy, Sylvie Chollet-Martin, Dan Longrois, Christian Gachet, Pierre Bruhns, Friederike Jönsson
Journal: Science Immunology (2018)

Platelets are key regulators of vascular integrity; however, their role in anaphylaxis, a life-threatening systemic allergic reaction characterized by the loss of vascular integrity and vascular leakage, remains unknown. Anaphylaxis is a consequence of inappropriate cellular responses triggered by antibodies to generally harmless antigens, resulting in a massive mediator release and rapidly occurring organ dysfunction. Human platelets express receptors for immunoglobulin G (IgG) antibodies and can release potent mediators, yet their contribution to anaphylaxis has not been previously addressed in mouse models, probably because mice do not express IgG receptors on platelets. We investigated the contribution of platelets to IgG-dependent anaphylaxis in human IgG receptor-expressing mouse models and a cohort of patients suffering from drug-induced anaphylaxis. Platelet counts dropped immediately and markedly upon anaphylaxis induction only when they expressed the human IgG receptor FcγRIIA/CD32A. Platelet depletion attenuated anaphylaxis, whereas thrombocythemia substantially worsened its severity. FcγRIIA-expressing platelets were directly activated by IgG immune complexes in vivo and were sufficient to restore susceptibility to anaphylaxis in resistant mice. Serotonin released by activated platelets contributed to anaphylaxis severity. Data from a cohort of patients suffering from drug-induced anaphylaxis indicated that platelet activation was associated with anaphylaxis severity and was accompanied by a reduction in circulating platelet numbers. Our findings identify platelets as critical players in IgG-dependent anaphylaxis and provide a rationale for the design of platelet-targeting strategies to attenuate the severity of anaphylactic reactions.
Effects of in vitro ATRA treatment on human MDSC expansion and function.
Authors: Richard P. Tobin, Kimberly R Jordan, Dana Davis, Martin McCarter
Journal: Journal of Clinical Oncology (2017)

125 Background: Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of immature immunosuppressive myeloid cells that are expanded in tumor bearing hosts. Melanoma patients with high frequencies of MDSCs have decreased overall survival and an increased risk of death and disease progression, as well as impaired responses to ipilimumab. Targeting MDSCs to decease their frequency or suppressive activity may provide an effective means to improve the efficacy of anti-cancer therapies. All-trans retinoic acid (ATRA) is a vitamin A derivative currently used to treat APL that may target MDSCs. ATRA differentiates immature myeloid cells into macrophages, dendritic cells, or granulocytes. ATRA has been tested as an MDSC targeting agent in two completed caner clinical trials and is being investigated in several other open and completed trials. Methods: We purified myeloid cells from LRS chambers collected from normal donors. The purified cells were treated with GM-CSF+IL-6, GM-CSF+IL-4, or melanoma conditioned media with or without ATRA. After 5 days of incubation, PCR was used to determine the expression of immunoregulatory genes. Additionally, we used a MLR to determine the effect of ATRA on MDSC’s T cell suppressive function. Results: Here we report that in vitro ATRA treatment decreases the expression of ARG1, NOX1, INOS, and PD-L1. Further, we report that ATRA treatment improved T cell proliferation. Conclusions: Controlling MDSC suppressive function and accumulation may provide a mechanism to improve the efficacy of many current cancer therapies. Here we show that ATRA reduces the expression of the immunosuppressive genes ARG1, NOX1, INOS, and PD-L1 in MDSCs. Additionally, we show that treatment of MDSCs with ATRA decreases MDSC’s ability to suppress T cell proliferation. These results indicate that ATRA may improve the efficacy of conventional and immnunotherapeutic treatments.
Is Optimism Associated With Healthier Cardiovascular-Related Behavior?
Authors: Julia K. Boehm, Ying Chen, Hayami Koga, Maya B. Mathur, Loryana L. Vie, Laura D. Kubzansky
Journal: Circulation Research (2018)

Optimistic people have reduced risk for cardiovascular disease and cardiovascular-related mortality compared with their less optimistic peers. One explanation for this is that optimistic people may be more likely to engage in healthy behavior like exercising frequently, eating fruits and vegetables, and avoiding cigarette smoking. However, researchers have not formally determined the extent or direction of optimism's association with health behaviors. Moreover, it is unclear whether optimism temporally precedes health behaviors or whether the relationship is because of shared common causes. We conducted random effects meta-analyses examining optimism's association with 3 health behaviors relevant for the prevention of cardiovascular disease. PubMed and PsycINFO databases were searched for studies published through November 2017 reporting on optimism's relationship with physical activity, diet, and cigarette smoking. We identified 34 effect sizes for physical activity (n=90 845), 15 effect sizes for diet (n=47 931), and 15 effect sizes for cigarette smoking (n=15 052). Findings suggested that more optimistic individuals tended to engage in healthier behaviors compared with less optimistic individuals, but effect sizes were modest (ractivity=0.07, P<0.0001; rdiet=0.12, P<0.0001; and rsmoking=0.07, P=0.001). Most evidence was cross-sectional (≥53% of effect sizes) and did not consider sociodemographic characteristics (<53% of effect sizes) or psychological distress (<27% of effect sizes) as potential confounders. Optimism is associated with healthier behaviors that protect against cardiovascular disease, although most evidence was relatively low quality. Additional longitudinal and experimental research is required to determine whether optimism causally contributes to healthy behaviors and whether optimism could be an effective target for preventing cardiovascular disease.
Stimulation of entorhinal cortex–dentate gyrus circuitry is antidepressive
Authors: Sanghee Yun, Ryan P. Reynolds, Iraklis Petrof, Alicia White, Phillip D. Rivera, Amir Segev, Adam D. Gibson, Maiko Suarez, Matthew J. DeSalle, Naoki Ito, Shibani Mukherjee, Devon R. Richardson, Catherine E. Kang, Rebecca C. Ahrens-Nicklas, Ivan Soler, Dane M. Chetkovich, Saïd Kourrich, Douglas A. Coulter, Amelia J. Eisch
Journal: Nature Medicine (2018)
94P Lung cancer recurrence in patients with preoperative circulating tumor DNA and elevated tumor markers
Authors: S. Isaksson, A.M. George, M. Jönsson, H. Cirenajwis, H. Brunnström, P. Jönsson, J. Staaf, L.H. Saal, M. Planck
Journal: Journal of Thoracic Oncology (2018)