tbuckley/cabot-search huggingface dataset:
The POOR Get POORer: A Hypothesis for the Pathogenesis of Ventilator-induced Lung Injury
Authors: Donald P. Gaver, Gary F. Nieman, Louis A. Gatto, Maurizio Cereda, Nader M. Habashi, Jason H. T. Bates
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Protective ventilation strategies for the injured lung currently revolve around the use of low Vt, ostensibly to avoid volutrauma, together with positive end-expiratory pressure to increase the fraction of open lung and reduce atelectrauma. Protective ventilation is currently applied in a one-size-fits-all manner, and although this practical approach has reduced acute respiratory distress syndrome deaths, mortality is still high and improvements are at a standstill. Furthermore, how to minimize ventilator-induced lung injury (VILI) for any given lung remains controversial and poorly understood. Here we present a hypothesis of VILI pathogenesis that potentially serves as a basis upon which minimally injurious ventilation strategies might be developed. This hypothesis is based on evidence demonstrating that VILI begins in isolated lung regions manifesting a Permeability-Originated Obstruction Response (POOR) in which alveolar leak leads to surfactant dysfunction and increases local tissue stresses. VILI progresses topographically outward from these regions in a POOR-get-POORer fashion unless steps are taken to interrupt it. We propose that interrupting the POOR-get-POORer progression of lung injury relies on two principles: 1) open the lung to minimize the presence of heterogeneity-induced stress concentrators that are focused around the regions of atelectasis, and 2) ventilate in a patient-dependent manner that minimizes the number of lung units that close during each expiration so that they are not forced to rerecruit during the subsequent inspiration. These principles appear to be borne out in both patient and animal studies in which expiration is terminated before derecruitment of lung units has enough time to occur.
Nonalcoholic Steatohepatitis Is the Most Rapidly Increasing Indication for Liver Transplantation in the United States
Authors: Zobair M. Younossi, Maria Stepanova, Janus Ong, Greg Trimble, Saleh AlQahtani, Issah Younossi, Aijaz Ahmed, Andrei Racila, Linda Henry
Journal: Clinical Gastroenterology and Hepatology (2020)
Abstract 11440: Fragmented QRS as a Novel Non-Invasive Predictor for Lethal Arrhythmic Events in Hypertrophic Cardiomyopathy
Authors: Yuko Wada, Takeshi Aiba, Taka-aki Matsuyama, Kohei Ishibashi, Ikutaro Nakajima, Koji Miyamoto, Yuko Yamada, Hideo Okamura, Takashi Noda, Kazuhiro Satomi, Yoshiaki Morita, Hideaki Kanzaki, Toshihisa Anzai, Masaharu Ishihara, Kengo F Kusano, Satoshi Yasuda, Shiro Kamakura, Hatsue Ishibashi-Ueda, Wataru Shimizu, Hisao Ogawa
Journal: Circulation (2013)

Presence of fragmented QRS complex (frgQRS) of ECG has been recognized as a potential predictor of lethal ventricular arrhythmias in ischemic heart disease or cardiomyopathies, however the prognost...
Collodion babies: A 15-year retrospective multicenter study in The Netherlands—Evaluation of severity scores to predict the underlying disease
Authors: Edwin Cuperus, Marieke C. Bolling, Marlies de Graaf, Peter C. van den Akker, Marielle E. van Gijn, Marleen E.H. Simon, Vigfús Sigurdsson, Suzanne G.M.A. Pasmans
Journal: Journal of the American Academy of Dermatology (2020)
PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma?
Authors: Mustafa Khasraw, David A. Reardon, Michael Weller, John H. Sampson
Journal: Clinical Cancer Research (2020)

Abstract Glioblastoma (WHO grade IV glioma) is the most common malignant primary brain tumor in adults. Survival has remained largely static for decades, despite significant efforts to develop new effective therapies. Immunotherapy and especially immune checkpoint inhibitors and programmed cell death (PD)-1/PD-L1 inhibitors have transformed the landscape of cancer treatment and improved patient survival in a number of different cancer types. With the exception of few select cases (e.g., patients with Lynch syndrome) the neuro-oncology community is still awaiting evidence that PD-1 blockade can lead to meaningful clinical benefit in glioblastoma. This lack of progress in the field is likely to be due to multiple reasons, including inherent challenges in brain tumor drug development, the blood–brain barrier, the unique immune environment in the brain, the impact of corticosteroids, as well as inter- and intratumoral heterogeneity. Here we critically review the clinical literature, address the unique aspects of glioma immunobiology and potential immunobiological barriers to progress, and contextualize new approaches to increase the efficacy of PD-1/PD-L1 inhibitors in glioblastoma that may identify gaps and testable relevant hypotheses for future basic and clinical research and to provide a novel perspective to further stimulate preclinical and clinical research to ultimately help patients with glioma, including glioblastoma, which is arguably one of the greatest areas of unmet need in cancer. Moving forward, we need to build on our existing knowledge by conducting further fundamental glioma immunobiology research in parallel with innovative and methodologically sound clinical trials.
TME-activatable theranostic nanoplatform with ATP burning capability for tumor sensitization and synergistic therapy
Authors: Yuanli Luo, Bin Qiao, Ping Zhang, Chao Yang, Jin Cao, Xun Yuan, Haitao Ran, Zhigang Wang, Lan Hao, Yang Cao, Jianli Ren, Zhiyi Zhou
Journal: Theranostics (2020)

Adenosine triphosphate (ATP), as a key substance for regulating tumor progression in the tumor microenvironemnt (TME), is an emerging target for tumor theranostics. Herein, we report a minimalist but versatile nanoplatform with simultaneously TME-responsive drug release, TME-enhanced imaging, ATP-depletion sensitized chemotherapy and photothermal therapy for intelligent tumor theranostics. Methods: The Fe3+ and tannic acid (TA) coordination were self-deposited on doxorubicin (Dox) in a facile method to prepare Dox-encapsulated nanoparticles (DFTNPs). Results: When irradiated by a near infrared laser, the DFTNPs could elevate the temperature in the tumor region efficiently. Subsequently, the Dox could be released by the disassembly of Fe3+/TA in the TME to initiate chemotherapy. Particularly, the smart nanoagent not only enabled ATP-depletion and enhanced the therapeutic effect of chemotherapy, but also acted as photothermal transduction agent for photothermal therapy. Moreover, the nanoagent also acted as T1-weighted MR imaging,photoacoustic imaging and photothermal imaging contrast agent. The mice treated by DFTNPs plus laser showed a complete tumor eradication in 14d observation. Conclusion: This as-prepared versatile nanoplatform offers new insights toward the application of smart nanoagents for improved tumor theranostics.
Vicarious Trauma: The Hazard and Joy of Caring for Refugees
Authors: Gabriel E. Fabreau
Journal: Annals of Internal Medicine (2020)

On Being a Doctor16 June 2020Vicarious Trauma: The Hazard and Joy of Caring for RefugeesGabriel E. Fabreau, MD, MPHGabriel E. Fabreau, MD, MPHUniversity of Calgary, Calgary, Alberta, Canada (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-0151 Audio Reading - “Vicarious Trauma: The Hazard and Joy of Caring for Refugees” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Vicarious Trauma: The Hazard and Joy of Caring for Refugees” by Gabriel E. Fabreau, MD, MPH Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I knew I was in trouble when I found myself crying inexplicably at a stoplight or in the hospital on teaching rounds. The chilling stories from refugees prompted ever more hideous nightmares. Most troubling, the optimism that had fueled my passion for refugee health was becoming eclipsed by a disillusionment with humanity.“Why do we try so hard to help people heal and recover when humans themselves are capable of such cruelty?” I wondered.At the Mosaic Refugee Health Clinic—a specialized, multidisciplinary clinic that cares for recently arrived refugees and asylum seekers in Calgary—there is a look I have seen ... Author, Article, and Disclosure InformationAffiliations: University of Calgary, Calgary, Alberta, Canada (G.E.F.)Corresponding Author: Gabriel Fabreau, MD, MPH, TRW 3E28, 3280 Hospital Drive NW, Calgary, AB T2T4Z6, Canada; e-mail, [email protected]ca. PreviousarticleNextarticle Advertisement Audio Reading - “Vicarious Trauma: The Hazard and Joy of Caring for Refugees” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Vicarious Trauma: The Hazard and Joy of Caring for Refugees” by Gabriel E. Fabreau, MD, MPH Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 16 June 2020Volume 172, Issue 12Page: 830-831KeywordsEmotionsFatigueFearGratitudeHealth care providersMemoryNauseaRefugee healthSafetySuicide ePublished: 16 June 2020 Issue Published: 16 June 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
At the Heart of Safe and Successful Pregnancies in Cancer Survivors
Authors: Melissa M. Hudson, Matthew J. Ehrhardt
Journal: JACC CardioOncology (2020)

OBJECTIVE  To examine the influence of the glycemic index (GI) of foods consumed after evening exercise on postprandial glycemia, metabolic and inflammatory markers, and nocturnal glycemic control in type 1 diabetes.  RESEARCH DESIGN AND METHODS  On two evenings (∼1700 h), 10 male patients (27 ± 5 years of age, HbA1c 6.7 ± 0.7% [49.9 ± 8.1 mmol/mol]) were administered a 25% rapid-acting insulin dose with a carbohydrate bolus 60 min before 45 min of treadmill running. At 60 min postexercise, patients were administered a 50% rapid-acting insulin dose with one of two isoenergetic meals (1.0 g carbohdyrate/kg body mass [BM]) matched for macronutrient content but of either low GI (LGI) or high GI (HGI). At 180 min postmeal, the LGI group ingested an LGI snack and the HGI group an HGI snack (0.4 g carbohdyrate/kg BM) before returning home (∼2300 h). Interval samples were analyzed for blood glucose and lactate; plasma glucagon, epinephrine, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α); and serum insulin, cortisol, nonesterified fatty acid, and β-hydroxybutyrate concentrations. Interstitial glucose was recorded for 20 h postlaboratory attendance through continuous glucose monitoring.  RESULTS  Following the postexercise meal, an HGI snack induced hyperglycemia in all patients (mean ± SD glucose 13.5 ± 3.3 mmol/L) and marked increases in TNF-α and IL-6, whereas relative euglycemia was maintained with an LGI snack (7.7 ± 2.5 mmol/L, P   CONCLUSIONS  Consuming LGI food with a reduced rapid-acting insulin dose following evening exercise prevents postprandial hyperglycemia and inflammation and provides hypoglycemia protection for ∼8 h postexercise; however, the risk of late nocturnal hypoglycemia remains.
Nucleolus‐Targeted Photodynamic Anticancer Therapy Using Renal‐Clearable Carbon Dots
Authors: Wen Pang, Pengfei Jiang, Shihui Ding, Zhouzhou Bao, Ningtao Wang, Hongxia Wang, Junle Qu, Dan Wang, Bobo Gu, Xunbin Wei
Journal: Advanced Healthcare Materials (2020)

Abstract Photodynamic therapy (PDT), which utilizes light excited photosensitizers (PSs) to generate reactive oxygen species (ROS) and consequently ablate cancer cells or diseased tissue, has attracted a great deal of attention in the last decades due to its unique advantages. In order to further enhance PDT effect, PSs are functionalized to target specific sub‐cellular organelles, but most PSs cannot target nucleolus, which is demonstrated as a more efficient and ideal site for cancer treatment. Here, an effective carbon dots (C‐dots) photosensitizer with intrinsic nucleolus‐targeting capability, for the first time, is synthesized, characterized, and employed for in vitro and in vivo image‐guided photodynamic anticancer therapy with enhanced treatment performance at a low dose of PS and light irradiation. The C‐dots possess high ROS generation efficiency and fluorescence quantum yield, excellent in vitro and in vivo biocompatibility, and rapid renal clearance, endowing it with a great potential for future translational research.
Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity
Authors: Jian Xu, Rong-Jian Liu, Shaylyn Fahey, Luciana Frick, James Leckman, Flora Vaccarino, Ronald S. Duman, Kyle Williams, Susan Swedo, Christopher Pittenger
Journal: American Journal of Psychiatry (2020)

Pediatric obsessive-compulsive disorder (OCD) sometimes appears rapidly, even overnight, often after an infection. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or PANDAS, describes such a situation after infection with Streptococcus pyogenes. PANDAS may result from induced autoimmunity against brain antigens, although this remains unproven. Pilot work suggests that IgG antibodies from children with PANDAS bind to cholinergic interneurons (CINs) in the striatum. CIN deficiency has been independently associated with tics in humans and with repetitive behavioral pathology in mice, making it a plausible locus of pathology. The authors sought to replicate and extend earlier work and to investigate the cellular effects of PANDAS antibodies on cholinergic interneurons.Binding of IgG to specific neurons in human and mouse brain slices was evaluated ex vivo after incubation with serum from 27 children with rigorously characterized PANDAS, both at baseline and after intravenous immunoglobulin (IVIG) treatment, and 23 matched control subjects. Binding was correlated with symptom measures. Neural activity after serum incubation was assessed in mouse slices using molecular markers and electrophysiological recording.IgG from children with PANDAS bound to CINs, but not to several other neuron types, more than IgG from control subjects, in three independent cohorts of patients. Post-IVIG serum had reduced IgG binding to CINs, and this reduction correlated with symptom improvement. Baseline PANDAS sera decreased activity of striatal CINs, but not of parvalbumin-expressing GABAergic interneurons, and altered their electrophysiological responses, in acute mouse brain slices. Post-IVIG PANDAS sera and IgG-depleted baseline sera did not alter the activity of striatal CINs.These findings provide strong evidence for striatal CINs as a critical cellular target that may contribute to pathophysiology in children with rapid-onset OCD symptoms, and perhaps in other conditions.
Home Noninvasive Positive Pressure Ventilation for Chronic Obstructive Pulmonary Disease—Reply
Authors: Michael E. Wilson, M. Hassan Murad, Zhen Wang
Journal: JAMA (2020)

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Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children
Authors: Anne H. Rowley
Journal: Nature reviews. Immunology (2020)

A new multisystem inflammatory syndrome apparently related to infection with SARS-CoV-2 has recently been reported in older children (known as MIS-C), manifested by severe abdominal pain, cardiac dysfunction and shock. Here, I discuss the similarities and differences between MIS-C and Kawasaki disease, focusing on their epidemiology, aetiology and pathophysiological mechanisms. In this Comment, Anne Rowley discusses what we know so far about the recently described multisystem inflammatory syndrome in older children associated with SARS-CoV-2 infection and how it differs from Kawasaki disease.
Autoantibody Profiles of Cancer-Testis Genes in Non-Small Cell Lung Cancer
Authors: D. Djureinovic, Cecilia Hellström, Tea Dodig-Crnkovic, F. Ponten, M. Bergqvist, G. Holgersson, Jochen M. Schwenk, P. Micke
Journal: Journal of Thoracic Oncology (2017)
Heterozygous IKKβ activation loop mutation results in a complex immunodeficiency syndrome
Authors: Jordan Abbott, Angelica C. Ehler, Divya Jayaraman, Paul R. Reynolds, Kanao Otsu, Laurie Manka, Erwin W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2020)

The importance of NF-κB to human immune signaling is demonstrated by the large number of monogenetic diseases that arise from defects in the NF-κB subunits and the proteins that regulate them. Hypomorphic variants in IKBKG and N-terminal variants in NFKBIA cause X-linked and dominant ectodermal dysplasia with combined immunodeficiency (EDA-ID), respectively. Biallelic loss of IKBKB (the gene coding the protein IKKβ) causes a severe form of combined immunodeficiency. Monoallelic deficiency of individual NF-κB subunits is associated with common variable immunodeficiency and autoimmunity, and defects in proteins that carry out posttranslational modifications of NF-κB pathway proteins cause immunodeficiency, severe inflammatory disease, or both.
Very early-life exposure to microbiota-induced TNF drives the maturation of neonatal pre-cDC1
Authors: Arnaud Köhler, Sandrine Delbauve, Justine Smout, David Torres, Véronique Flamand
Journal: Gut (2020)

Induction of immune protection against pathogens is particularly crucial during the neonatal period dominated by anti-inflammatory and tolerance immunity. The preclinical study was carried out to determine whether environmental factors such as microbiota may influence early life immunity by impacting the development and the functional maturation of precursors of type 1 conventional dendritic cells (pre-cDC1), endowed with regulatory properties.Pre-cDC1 phenotype and cytokine expression in the spleen of neonates from antibiotic-treated mothers were established. The role of myeloid-derived tumour necrosis factor (TNF) was tested in vitro and in vivo. RNA sequencing analysis on neonatal sorted pre-cDC1 was performed. The early life protective CD8+ T-cell response against Listeria monocytogenes was monitored.We observed that first exposure to microbiota promotes TNF secretion by monocytes and macrophages shortly after birth. We demonstrated that this myeloid-derived inflammatory cytokine is crucial to induce the maturation of these neonatal regulatory pre-cDC1. Myeloid TNF signalling acts on C1q and β-catenin pathway and modifies the fatty acid metabolism in neonatal pre-cDC1. Furthermore, we showed that during neonatal L. monocytogenes infection, microbiota-associated myeloid TNF promotes the capacity of these pre-cDC1 to induce protective CD8+ T-cell responses, by modulating their ability to secrete interleukin-10 (IL-10) and IL-12p40.Our findings emphasise the role of microbiota-derived TNF to kick-start the differentiation and the functional maturation of the neonatal splenic pre-cDC1 compartment. They bring a better understanding of potential mechanisms underlying some microbiota-linked immune dysfunction in early life.
FRI0522 OPIOIDS PRESCRIPTION AT DISCHARGE IN HOSPITALIZED PATIENTS: AN ANALYSIS FROM A RHEUMATOLOGY WARD OF A SWISS TERTIARY HOSPITAL
Authors: A. Dumusc, F. Valerio, T. Hügle
Journal: Annals of the Rheumatic Diseases (2020)

Background: Opioids prescription for non-cancer pain has come under intense scrutiny as opioids abuse has become a major public health issue. Chronic opioid use is common among patients with rheumatic diseases. There are data showing that opioids are associated with a higher mortality in osteoarthritis patients receiving joint replacement. However, more data are needed on opioids use and prescription in rheumatology inpatients [1]. Objectives: To evaluate inpatient characteristics on opioid prescription at discharge from our rheumatology ward in 2017 and 2019. Methods: We prospectively recorded analgesics prescription patterns of paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), weak opioids (tramadol/codeine) and strong opioids at discharge for all patients hospitalized in the Rheumatology Department from May to October 2017 and from October to December 2019. Statistical analyses consisted of descriptive statistics and univariate/multivariate logistic regression. P≤0.05 was considered statistically significant. Results: We analysed 240 hospital inpatient stays of 223 patients (mean age 64 years). At discharge, 25% of patients were respectively on weak opioids (tramadol/codeine) and 23% were on strong opioids, at a fixed dosage. Overall, a minority of patients were on opioids monotherapy (20% for weak opioids and 22% for strong opioids), the majority receiving combined treatments with WHO class I analgesics. The highest rate of opioids prescription at discharge was observed in patients hospitalized for severe low back pain (40%) and osteoporotic fracture (30%). At discharge, all patients transferred to a nursing home and 35% of patients transferred to a transitional care unit were on opioids compared to only 16% of the patients discharged home. The majority of patients being on opioids when transferred to a transitional care unit were prescribed opioids when discharged home (86%). Opioids prescription at discharge was negatively associated with home discharge in multivariate analysis (0.23, 0.09 to 0.55, adjusted OR, 95%CI), Table 1. There was no significant association between inpatient stay length and opioids prescription at discharge. Between 2017 and 2019, we observed a non-significant decrease in opioids prescription at discharge (absolute difference -4.7%). Conclusion: Analysis of opioids prescription from a Swiss rheumatology service of a tertiary hospital show frequent opioids prescription at inpatients discharge, mainly for non-inflammatory disorders. Opioids prescription negatively predict home discharge. References: [1] Kim, S.C., Solomon, D.H. Towards defining the safer use of opioids in rheumatology. Nat Rev Rheumatol 16, 71–72 (2020). Disclosure of Interests: Alexandre Dumusc: None declared, Flore Valerio: None declared, Thomas Hügle Grant/research support from: Abbvie, Novartis, Consultant of: Abbvie, Pfizer, Novartis, Roche, Lilly, BMS