tbuckley/cabot-search huggingface dataset:
Abstract 18407: Identifying Patients With Acute Heart Failure who Require a Critical Care Admission: ASCEND-HF Insights
Authors: Ismail R Raslan, Cynthia M Westerhout, Justin A Ezekowitz, Adrian F Hernandez, Randall C Starling, Christopher M O’Connor, Paul W Armstrong, Sean v Diepen
Journal: Circulation (2015)

Background: The benefit of critical care unit (CCU) admission in acute heart failure (AHF) remains unclear. The risk factors for in-hospital events best managed in a CCU including the need for CCU restricted therapies (including invasive and non-invasive mechanical ventilation, mechanical circulatory support devices, and intravenous vasopressors or vasodilators) have not yet been formulated. The purpose of this study was to develop a clinical prediction model for adverse outcomes or CCU restricted therapies in patients with AHF. Methods: Using data from the ASCEND-HF trial, patients with AHF who did not require critical care related therapies within the preceding 12 hours of randomization were selected. The primary outcome was an in-hospital composite of the requirement of CCU specific therapies, death, myocardial infarction, cardiogenic shock, resuscitated sudden cardiac death, or ventricular arrhythmias requiring intervention. Model discrimination and calibration were evaluated using the c-index and the Hosmer-Lemeshow test, respectively. Results: The study cohort included 4772 patients and the primary composite outcome occurred in 547 (11.5%) patients. A total of 11 variables were independent predictors of the primary composite outcome as follows (Figure): chronic respiratory disease, prior ACE inhibitor, angiotensin receptor blocker or aldosterone antagonist use, Asian race, body mass index, diastolic blood pressure, respiratory rate, resting dyspnea, hemoglobin, sodium, and blood urea nitrogen. The simplified clinical prediction model demonstrated modest discrimination (c-index= 0.66) and good calibration (Hosmer-Lemeshow Goodness of Fit=7.017, p=0.535). Conclusions: In an international dataset of patients with AHF, we derived a clinical prediction describing patients who are likely to need a CCU. This model may be useful as a triage tool to identify patients with AHF who may benefit from admission to a higher acuity CCU.
Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis
Authors: Selena Ferrian, Candace C Liu, Erin F McCaffrey, Rashmi Kumar, Theodore S Nowicki, David W Dawson, Alex Baranski, John A Glaspy, Antoni Ribas, Sean C Bendall, Michael Angelo
Journal: Cell Reports Medicine (2021)

Immune checkpoint blockade using PD-1 inhibition is an effective approach for treating a wide variety of cancer subtypes. While lower gastrointestinal (GI) side effects are more common, upper gastrointestinal adverse events are rarely reported. Here, we present a case of nivolumab-associated autoimmune gastritis. To elucidate the immunology underlying this condition, we leverage multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to identify the presence and proportion of infiltrating immune cells from a single section of biopsy specimen. Using MIBI-TOF, we analyze formalin-fixed, paraffin-embedded human gastric tissue with 28 labels simultaneously. Our analyses reveal a gastritis characterized by severe mucosal injury, interferon gamma (IFN-γ)-producing gastric epithelial cells, and mixed inflammation that includes CD8 and CD4 T cell infiltrates with reduced expression of granzyme B and FOXP3, respectively. Here, we provide a comprehensive multiplexed histopathological mapping of gastric tissue, which identifies IFN-γ-producing epithelial cells as possible contributors to the nivolumab-associated gastritis.
Abstract 14376: The Impact of Mitral Regurgitation on Left Ventricular Energy Loss by Vector Flow Mapping in Patients With Heart Failure
Authors: Yuko Soyama, Nobuyuki Kagiyama, Justin Vader, Masataka Sugahara, John Gorcsan
Journal: Circulation (2018)

Background: Vector Flow Mapping (VFM) is a novel method to characterize flow mechanics using color flow Doppler and speckle tracking. Accordingly, VFM can quantify left ventricular (LV) energy loss...
Prevalence and outcomes of acute pancreatitis in COVID-19: a meta-analysis
Authors: Feng Yang, Yuting Huang, Tian Li, Yunting Fu, Chenyu Sun, Yecheng Xu, John Windsor, Deliang Fu
Journal: Gut (2021)

The study by Pandanaboyana et al 1 showed that acute pancreatitis (AP) patients with COVID-19 had a significantly higher mortality than those without COVID-19. Nevertheless, a similar trend of mortality was found by another observational cohort study.2 The true prevalence and outcomes of AP in patients with COVID-19 are not known. The aim of this study was to conduct a meta-analysis to determine the pooled prevalence and clinical outcomes of AP in patients with COVID-19.

PubMed, Embase, Scopus and Cochrane library were searched for outcome studies of adult patients with AP and COVID-19 published before 15 September 2021 (online supplemental file 1). Excluded were studies that either did not use the revised Atlanta criteria for AP diagnosis or reported patients with COVID-19 with a prior history of pancreatitis. Patients were divided into three groups: group I—AP with COVID-19, group II—AP without COVID-19 and group III—COVID-19 without AP. The primary endpoint was mortality (both in-hospital or 30-day). Secondary endpoints were pooled prevalence of AP and other clinical outcomes. The overall pooled prevalence and mortality were assessed for group I with a random-effects model and Freeman–Tukey …
Mental health: Intentions are good but investment is lacking, says WHO
Authors: Jacqui Wise
Journal: BMJ (2021)

The World Health Organization’s triennial assessment of mental health services shows that the world has missed most of the 2020 targets endorsed by the World Health Assembly in 2013.1

The 136 page Mental Health Atlas , which includes data from 171 countries, shows that despite the increased attention given to mental health in recent years there is a global shortfall in investment in mental health services.

“It is extremely concerning that, despite the evident and increasing need for mental health services, which has become …
P36.02 A Case of Recurrent Giant Malignant Solitary Fibrous Tumour of the Pleura: An Elephant in the Room?
Authors: S. Ricciardi, N. Daddi, G. Tallini, G. Dolci, F. Antonacci, E. Salvaterra, C. Parisi, M. Pantaleo, P. Solli
Journal: Journal of Thoracic Oncology (2021)
Stillbirth rate in UK’s poorest areas is twice that in affluent ones, finds audit
Authors: Jacqui Wise
Journal: BMJ (2021)

Babies born to women who live in the most deprived areas of the UK are twice as likely to be stillborn and are at a 73% excess risk of neonatal death when compared with babies born in the most affluent areas, and the poverty gap is widening, a surveillance report has found.1

The report produced by MBRRACE-UK (Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK) looked at perinatal deaths (including late fetal losses, stillbirths, and neonatal deaths) from gestational age of 22 weeks among babies born in the UK between 1 January and 31 December 2019.

The results showed that perinatal deaths are declining overall. Between 2013 and 2019 numbers of stillbirths across the UK fell by more than 20%, representing around 610 fewer stillbirths in 2019, and neonatal mortality by 12%, representing around 160 fewer neonatal deaths in 2019.

However, stillbirth rates among babies of black ethnicity were more than …
Extent of resection in glioblastoma: a 10-year local survival analysis
Authors: Theodore Hirst, Patrick McAleavey, Tom Flannery
Journal: Neuro-Oncology (2021)

Abstract Aims The impact on extent of resection (EOR) in glioblastoma has been well documented. It is clear that gross-total resection (GTR) confers best overall survival (OS), however the minimum EOR required to confer a survival benefit over biopsy is debated. Recent studies favour partial resection (PR) over biopsy for IDH-wildtype, MGMT-unmethylated tumours. We describe our experiences locally with these principles in mind. Method Retrospective evaluation of a single surgeon cohort. All patients over 18 years old, undergoing a surgical treatment for histologically confirmed GBM in the stated period were included. We collected information on demographics, tumour volume, EOR, complications, adjuvant therapies, molecular profile, and OS. We used log rank tests and Cox Proportional Hazards Models to identify factors associated with OS. Results The patient and tumour characteristics of our cohort were similar to those documented in the literature. The mean age was 56.6 years. 72 patients underwent biopsy and 202 had debulking surgery. Median OS was 11 months. Of those debulked, gross-total resection was achieved in 41 patients (20%); associated median OS was 29 months. Patients receiving partial resection (defined as EOR &amp;lt;80%) had no clear survival benefit over patients undergoing biopsy (median OS 6 vs 5 months) but had a higher rate of post-op neurological deficit (3% vs 12%). Tumour molecular profile appeared to influence survival outcome in a manner comparable to worldwide experience. Conclusion In our experience, partial resection is not a justifiable surgical aim in the typical glioblastoma cohort. The limited benefit that it may confer over biopsy appears to be outweighed by the risk of neurological deficit that affects quality and probably quantity of life. This finding applies to our glioblastoma population in general as well as those specifically with an MGM-unmethylated tumour.
Abstract 977: Mesenchymal Stem Cell Therapy Prevents Ischemia/Reperfusion Injury and Promotes Tissue Regeneration
Authors: Eddie Manning, Shashikumar Salgar, Mireya Hernandez, Dania Mateu, Roberto Vazquez-Padron, Sen Li, James Mathew, Si Pham
Journal: Circulation (2007)

Ischemic heart disease, especially myocardial infarction, is an important cause of heart failure. However, therapeutic potential of mesenchymal stem cells (MSC) for myocardial or pulmonary ischemia reperfusion (IR) injury is not well studied. Interleukin-10 (IL-10) is an anti-inflammatory cytokine. In this study MSC and IL-10 engineered MSC were tested for their ability to prevent IR injury and promote tissue repair. Methods: Bone marrow cells from Lewis rat were cultured in plastic tissue culture flasks for 72 hours; cells in suspension were discarded and the adherent cells (MSC) were expanded. MSC were transduced with r vIL-10-retrovirus and selected on neomycin (1mg/ml for 7 days). Experimental design: following 120 minutes of left lung ischemia, Group A, rats received vIL10 transduced MSC (∼15 x 10 6 ; i.v.); Group B, rats received empty vector engineered MSC; Group C, received MSC; and Group D, received saline. Group E received no ischemia or MSC. Left lung ischemia was performed by clamping left pulmonary artery/vein/bronchus at end inspiration. At 24h, 72 h, &amp; 7 days following ischemia, blood was collected from left and right pulmonary veins, separately. Results : Mean blood oxygenation (PaO2/FIO2 ratio, mmHg) at day 7 was significantly (P&lt;0.05) reduced following IR injury in Group B (161± 77) and Group D (181± 64), compared to MSC-vIL10 (404± 32; Group A) &amp; MSC (294±103;Group C) treated animals. In Group E, PaO2/FIO2 was 440± 42mm Hg. Significant improvement in lung oxygenation with MSC and vIL-10 therapy was observed as early as 3 days. MSC produced vIL-10 (∼5ng/ml) ex vivo . HP of lungs demonstrated reduced PMN cells with MSC therapy. Inflammatory mediators IL-1a, MCP-1, MIP-1a, and IL1-b protein levels were markedly increased in the injured lung; their analysis in MSC treated groups are underway. I.V. injected Tg GFP+MSC trafficked to the lung &amp; other tissues. VEGF &amp; HGF mRNA in MSC was 66% &amp; 43% of β-actin, respectively. Ex vivo expanded MSC were CD34-, CD45+ (5%), CD29+ (92%), CD80-, CD86+ (10%), CD90+ (∼90%), MHC Class I low &amp; MHC Class II-. Conclusions: Autologous MSC therapy prevented IR injury and served as an excellent vehicle to deliver cytokine. MSC therapy to prevent IR injury and enhance tissue regeneration in cardiopulmonary diseases seems promising.
P47.08 A Phase II, Single-arm, Multicenter, Efficacy of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With EGFR Mutated NSCLC
Authors: S. Park, J.S. Lee, S. Kim, H.T. Kim, K.H. Lee, D. Kim, M. Ahn
Journal: Journal of Thoracic Oncology (2021)
M<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.svg"><mml:msup><mml:mrow/><mml:mn>3</mml:mn></mml:msup></mml:math>Net: A multi-scale multi-view framework for multi-phase pancreas segmentation based on cross-phase non-local attention
Authors: Taiping Qu, Xiheng Wang, Chaowei Fang, Li Mao, Juan Li, Ping Li, Jinrong Qu, Xiuli Li, Huadan Xue, Yizhou Yu, Zhengyu Jin
Journal: Medical Image Analysis (2021)
Abstract 99: Remodeling of calcium influx pathways in models of cancer associated fibroblasts in breast cancer
Authors: Greg Monteith, Francisco Sadras, Teneale Stewart, Melanie Robitaille, Priyakshi Kalita-de Croft, Patsy Soon, Jodi Saunus, Sunil Lakhani, Sarah Roberts-Thomson
Journal: Cancer Research (2019)

Abstract Calcium (Ca2+) influx pathways are remodelled in a variety of disease states, and alterations in the expression of specific Ca2+ permeable ion channels are a feature of some breast cancer subtypes. However, no studies have yet assessed possible alterations in Ca2+ influx pathways in the context of cancer-associated fibroblasts (CAFs), which are important in the tumor microenvironment and disease progression. The aim of this study was to identify possible changes in the nature of Ca2+ influx in CAFs and to define the role of Ca2+ signaling in the induction of breast CAFs. Levels of mRNA for voltage-gated and store-operated Ca2+ entry (SOCE) components were assessed in paired normal and CAF patient samples using qRT-PCR. The immortalised human mammary fibroblast cell line HMF3S, was treated with transforming growth factor beta (TGFβ) to induce a CAF phenotype (HMF3S-CAF) as confirmed by the expression of alpha smooth muscle actin (αSMA). HMF3S-CAF and HMF3S were also compared for expression of Ca2+ channels using qRT-PCR and functional store operated Ca2+ entry (SOCE) using a Fluorescence Imaging Plate Reader (FLIPR) Ca2+ assay. Specific Ca2+ channel subtypes were pharmacologically inhibited during TGFβ treatment to assess their role in CAF induction. Ca2+channel levels were altered in CAF patient samples compared to their paired controls and also in TGFβ-treated HMF3S cells. Voltage-gated Ca2+channel inhibitors significantly decreased TGFβ-mediated CAF activation. These data suggest that Ca2+ signaling is remodeled in CAFs and that the Ca2+ signal is important in breast CAF induction. Citation Format: Greg Monteith, Francisco Sadras, Teneale Stewart, Melanie Robitaille, Priyakshi Kalita-de Croft, Patsy Soon, Jodi Saunus, Sunil Lakhani, Sarah Roberts-Thomson. Remodeling of calcium influx pathways in models of cancer associated fibroblasts in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 99.
MA02.03 MET-Driven Acquired Resistance (AR) in Fusion-Positive Non-Small Cell Lung Cancer (NSCLC)
Authors: J. Lee, M. Rosenzweig, A. Piper-Vallillo, P. Vanderlaan, K. Tolba, T. Li, J. Riess, J. Venstrom, G. Oxnard, A. Schrock, D. Costa, S. Ou
Journal: Journal of Thoracic Oncology (2021)
IL12 integrated into the CAR exodomain converts CD8+ T cells to poly-functional NK-like cells with superior killing of antigen-loss tumors
Authors: Andreas Hombach, Markus Barden, Lisa Hannappel, Markus Chmielewski, Gunter Rappl, Agapios Sachinidis, Hinrich Abken
Journal: Molecular Therapy (2021)

Chimeric antigen receptor (CAR)-redirected T cell therapy often fails to control tumors in the long term due to selecting cancer cells that downregulated or lost CAR targeted antigen. To reprogram the functional capacities specifically of engineered CAR T cells, we inserted IL12 into the extracellular moiety of a CD28-ζ CAR; both the CAR endodomain and IL12 were functionally active, as indicated by antigen-redirected effector functions and STAT4 phosphorylation, respectively. The IL12-CAR reprogrammed CD8+ T cells toward a so far not recognized natural killer (NK) cell-like signature and a CD94+CD56+CD62Lhigh phenotype closely similar, but not identical, to NK and cytokine induced killer (CIK) cells. In contrast to conventional CAR T cells, IL12-CAR T cells acquired antigen-independent, human leukocyte antigen E (HLA-E) restricted cytotoxic capacities eliminating antigen-negative cancer cells in addition to eliminating cancer cells with CAR cognate antigen. Simultaneous signaling through both the CAR endodomain and IL12 were required for inducing maximal NK-like cytotoxicity; adding IL12 to conventional CAR T cells was not sufficient. Antigen-negative tumors were attacked by IL12-CAR T cells, but not by conventional CAR T cells. Overall, we present a prototype of a new family of CARs that augments tumor recognition and elimination through expanded functional capacities by an appropriate cytokine integrated into the CAR exodomain.
Update of Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non–Small Cell Lung Cancer in the US
Authors: Apar Kishor Ganti, Alyssa B. Klein, Ion Cotarla, Brian Seal, Engels Chou
Journal: JAMA Oncology (2021)

Updated estimates of non-small cell lung cancer (NSCLC) in the US are needed.To calculate the most recent epidemiologic estimates of NSCLC in the US.This cross-sectional epidemiological analysis used the most recently released data from US cancer registries. The population-based US Cancer Statistics (USCS) database (2010-2017), comprised of the Surveillance, Epidemiology, and End Results (SEER) program and the National Program of Cancer Registries (NPCR) (collectively, SEER-NPCR) provided the NSCLC incidence estimate. The SEER-18 database provided data for incidence, prevalence, survival, and initial treatment by NSCLC stage. Adults aged 18 years or older diagnosed with NSCLC identified by International Classification of Diseases for Oncology, Third Edition, morphology codes were included.Annual age-adjusted NSCLC incidence per 100 000 persons; annual prevalence per 100 000 persons; survival rate; initial treatment. Due to database release delays, incidence data were available through 2017, and other parameters through 2016. The analysis was conducted from June 2020 to July 2020.There were 1.28 million new NSCLC cases recorded during 2010 to 2017 in the US (SEER-NPCR: 53% male; 67% ≥ 65 years). From 2010 to 2017, NSCLC incidence per 100 000 decreased from 46.4 to 40.9 overall (age <65 years: 15.5 to 13.5; age ≥65 years: 259.9 to 230.0); the incidence of stage II, IIIA, and IIIB NSCLC was stable, and stage IV decreased slightly from 21.7 to 19.6, whereas stage I incidence increased from 10.8 to 13.2. From 2010 to 2016, NSCLC prevalence per 100 000 increased from 175.3 to 198.3 (nationwide projection of SEER-18); prevalence increased among younger patients (77.5 to 87.9) but decreased among older patients (825.1 to 812.4). Period survival analysis found that 26.4% of patients survived 5 years, which is higher than previously reported. The proportion of stage I NSCLC treated with radiation as single initial treatment rose markedly from 14.7% in 2010 to 25.7% in 2016. Patients with stage IV NSCLC aged 65 years or older were most likely to be untreated (38.3%).The findings of this cross-sectional epidemiological analysis suggest that the increased incidence of stage I NSCLC at diagnosis likely reflected improved evaluation of incidental nodules. A smaller proportion of patients aged 65 years or older with stage IV NSCLC were treated. Earlier detection and availability of effective treatments may underlie increased overall NSCLC prevalence, and higher than previously reported survival.
Bone marrow mesenchymal stem cell-derived exosomal miR-34c-5p ameliorates RIF by inhibiting the core fucosylation of multiple proteins
Authors: Xuemei Hu, Nan Shen, Anqi Liu, Weidong Wang, Lihua Zhang, Zhigang Sui, Qingzhu Tang, Xiangning Du, Ning Yang, Wantao Ying, Biaojie Qin, Zhitong Li, Lin Li, Nan Wang, Hongli Lin
Journal: Molecular Therapy (2021)

Renal interstitial fibrosis (RIF) is an incurable pathological lesion in chronic kidney diseases. Pericyte activation is the major pathological characteristic of RIF. Fibroblast and macrophage activation are also involved in RIF. Studies have revealed that core fucosylation (CF), an important post-translational modification of proteins, plays a key role in pericyte activation and RIF by regulating multiple profibrotic signaling pathways as a hub-like target. Here, we reveal that mesenchymal stem cell (MSC)-derived exosomes reside specifically in the injured kidney and deliver microRNA (miR)-34c-5p to reduce cellular activation and RIF by inhibiting CF. Furthermore, we showed that the CD81-epidermal growth factor receptor (EGFR) ligand-receptor complex aids the entry of exosomal miR-34c-5p into pericytes, fibroblasts, and macrophages. Altogether, our findings reveal a novel role of MSC-derived exosomes in inhibiting multicellular activation via CF and provide a potential intervention strategy for renal fibrosis.
P24.11 Cell-Free Tumor DNA (ctDNA) Utility in Detection and Monitoring EGFR Mutations in Non-Small Cell Lung Cancer (NSCLC)
Authors: J. Agulnik, G. Kasymjanova, A. Papadakis, D. Small, L. Sakr, C. Pepe, H. Wang, V. Cohen
Journal: Journal of Thoracic Oncology (2021)
Persistence of Abnormally-Spliced, Functionally-Dead BCR-ABL Variants Is a Critical Obstacle to Achieve Sustained Complete Molecular Response in CML Patients: Results of a Quantitative, Highly-Sensitive, Deep Sequencing Study
Authors: Junichiro Yuda, Toshihiro Miyamoto, Jun Odawara, Yoshikane Kikushige, Yasuyuki Ohkawa, Koichi Akashi
Journal: Blood (2014)
Long-term outcomes of adult pulmonary Langerhans cell histiocytosis: a prospective cohort
Authors: Amira Benattia, Emmanuelle Bugnet, Anouk Walter-Petrich, Constance de Margerie-Mellon, Véronique Meignin, Agathe Seguin-Givelet, Gwenaël Lorillon, Sylvie Chevret, Abdellatif Tazi
Journal: European Respiratory Journal (2021)

Background The long-term outcomes of adult pulmonary Langerhans cell histiocytosis (PLCH), particularly survival, are largely unknown. Two earlier retrospective studies reported a high rate of mortality, which contrasts with our clinical experience. Methods To address this issue, all patients with newly diagnosed PLCH referred to the French national reference centre for histiocytoses between 2004 and 2018 were eligible for inclusion. The primary outcome was survival, which was defined as the time from inclusion to lung transplantation or death from any cause. Secondary outcomes included the cumulative incidences of chronic respiratory failure (CRF), pulmonary hypertension (PH), malignant diseases and extrapulmonary involvement in initially isolated PLCH. Survival was estimated using the Kaplan–Meier method. Results 206 patients (mean age 39±13 years, 60% female, 95% current smokers) were prospectively followed for a median duration of 5.1 years (IQR 3.2–7.6 years). Of these, 12 patients (6%) died. The estimated rate of survival at 10 years was 93% (95% CI 89–97%). The cumulative incidences of CRF and/or PH were &lt;5% at both 5 and 10 years, and 58% of these patients died. 27 malignancies were observed in 23 patients. The estimated standardised incidence ratio of lung carcinoma was 17.0 (95% CI 7.45–38.7) compared to an age- and sex-matched French population. Eight (5.1%) of the 157 patients with isolated PLCH developed extrapulmonary involvement. Conclusion The long-term prognosis of PLCH is significantly more favourable than has previously been reported. Patients must be closely monitored after diagnosis to detect severe complications early.