tbuckley/cabot-search huggingface dataset:
Abstract 12913: Trabectedin Related Reversible Cardiogenic Shock: A Rare Side Effect of Anti-neoplastic Drug
Authors: Samir Jha, Jimmy Wang, Roshan Jha, Jerel M Zoltick
Journal: Circulation (2020)

Trabectedin, an alkylating agent, is used as palliative chemotherapy of soft-tissue sarcoma after failure of first-line treatment. It is labeled as a low cardiac risk profile. We present a case of a lady with metastatic synovial sarcoma with a pre-treatment normal echocardiography, who received 3 cycles of Trabectedin, and presented in cardiogenic shock which reversed back to normal function with vasopressor, diuresis and inotrope support. Case report: A 66-year-old female with metastatic synovial sarcoma of lungs (post right upper lobectomy and chemotherapy), with positive mediastinal and hilar nodes improvement, was transferred in with hypotension and respiratory distress. She was recently started on trabectedin as palliative chemotherapy, about 2 months prior to this admission, received 3 cycles, the last cycle was 4 days prior to admission. There was an elevation of high-sensitivity troponin (peaked to 2000) which trended down. With metastatic disease and ongoing thrombocytopenia (post-chemotherapy), cardiac catheterization was not deemed appropriate, managed medically with inotrope, and pressor support for cardiogenic shock. A nuclear stress test done after weaning off all intravenous medicine showed an LVEF of 55% without any area of ischemic defect. As no other precipitants were identified and with reversibility of cardiac function over time, we considered these events were related to trabectedin toxicity. Discussion: For the use of Trabectedin, there is no specific caution for patients with cardiac disease or risk factors hence labeled as low cardiac risk profile by comprehensive analysis. This case highlights a rare but life-threatening side effect of this drug. It is important to balance the potential of an increase in progression-free survival with chemotherapy versus a life-threatening adverse effect which may counter-effect the mortality benefit and highlights a need for close serial monitoring.
Legends of allergy and immunology: Robert P. Schleimer
Authors: Atsushi Kato, Whitney W. Stevens, Bruce S. Bochner
Journal: Allergy (2021)

AK reports a consultant fee from Astellas Pharma and a gift for his research from Lyra Therapeutics. WWS served on advisory boards for GlaxoSmithKline, GenenTech, and Bristol Myers Squibb. BSB receives publication-related royalty payments from Elsevier and UpToDate. He receives remuneration for consulting services (GlaxoSmithKline, Sanofi/Regeneron) and for serving on the scientific advisory board of Third Harmonic Bio, Inc. and Allakos, Inc. He also own stock in Allakos. BSB is a co-inventor on existing Siglec-8–related patents and thus may be entitled to a share of royalties received by Johns Hopkins University during development and potential sales of such products. BSB is a co-founder of Allakos, Inc. which makes him subject to certain restrictions under university policy. The terms of this arrangement are being managed by Johns Hopkins University and Northwestern University in accordance with their conflict of interest policies.
Association Between Atopic Dermatitis and Educational Attainment in Denmark
Authors: Sigrun Alba Johannesdottir Schmidt, Aurélie Mailhac, Bianka Darvalics, Amy Mulick, Mette S. Deleuran, Henrik T. Sørensen, Jette Lindorff Riis, Sinéad M. Langan
Journal: JAMA Dermatology (2021)

Atopic dermatitis (AD) may affect academic performance through multiple pathways, including poor concentration associated with itching, sleep deprivation, or adverse effects of medications. Because educational attainment is associated with health and well-being, any association with a prevalent condition such as AD is of major importance.
Abstract 16122: Comparative Risk of Incident Coronary Heart Disease Across Multiple Chronic Inflammatory Diseases
Authors: Arjun Sinha, Adovich Rivera, Simran Chadha, Sameer Prasada, Anna Pawlowski, Edward B Thorp, Matthew Deberge, Rosalind Ramsey-Goldman, Yvonne Lee, Chad Achenbach, Donald M Lloyd-jones, Matthew J Feinstein
Journal: Circulation (2020)

Introduction: Inflammation plays an important role in the pathogenesis of coronary heart disease (CHD). Chronic inflammatory diseases (CIDs) may serve as models to provide insights into the relationships between immune dysfunction, inflammation, and CHD. To investigate this further, we analyzed the risk of incident CHD across different CIDs. Methods: We created a cohort of individuals with CIDs and non-CID controls (frequency-matched on demographics and CHD risk factors), free of baseline CHD, receiving regular outpatient care in a large medical system from 2000 to 2019. CIDs included psoriasis, rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and inflammatory bowel disease (IBD). CHD was defined as myocardial infarction (MI), angina, or coronary revascularization. We used adjusted hazards models to determine incident CHD risk for each CID relative to controls. We also analyzed incident CHD risk by severity of inflammation (baseline C-reactive protein) or immune dysfunction (baseline CD4 T cell level in HIV). Results: Of 18,129 individuals with CIDs and 18,988 controls, there were 1,011 incident CHD events over a median of 3.5 years. After adjusting for demographics and CHD risk factors, CHD risk was significantly elevated in SLE [hazard ratio (HR) 2.85, 95% confidence interval (CI) 2.19-3.71, p&lt;0.01], SSc (HR 2.14, 95% CI 1.54-2.99, p&lt;0.01), HIV (HR 1.38, 95% CI 1.12-1.69, p&lt;0.01), and RA (HR 1.22, 95% CI 1.00-1.49, p=0.05). Findings were similar with MI as the lone outcome. When CIDs were categorized by inflammation or immune dysfunction, there was a pattern of higher CHD risk with higher levels of inflammation/immune dysfunction across CIDs (Figure). Conclusions: Our results show that SLE, SSc, HIV, and RA were associated with significantly elevated risks of incident CHD and MI. Higher levels of inflammation or immune dysfunction were associated with heightened CHD risk within CIDs.
Abstract PO-058: Acute total body ionizing radiation induces long-term cardiac effects and immediate changes in oxidative carbonylation of cardiac troponin T in the rat
Authors: Elliot Rosen
Journal: Clinical Cancer Research (2021)

Abstract Radiation-induced heart disease represents a significant health risk in the event of an accidental radiation exposure as well as to cancer patients who receive acute doses of irradiation as part of radiation therapy. We utilized the Wistar-Kyoto and spontaneously hypertensive rat models, previously shown to demonstrate drug-induced cardiomyopathy, to evaluate the acute and long-term effects of sub-lethal total body irradiation at two, four, and fifty-two weeks. We examined irreversible oxidative protein carbonylation in the heart immediately following irradiation. Both males and females sustained reduced growth and anemic conditions over a one-year period as reflected by reduced body weight and low red blood cell count. Increased inflammation was detected via elevated IL-6 serum levels selectively in males at four weeks. Serum cardiac troponin T and I analyses revealed signs of cardiomyopathy at earlier timepoints, but high variability was observed, especially at one year. Echocardiography at two weeks following 5.0 Gy treatment revealed inflammation and a decrease in cardiac output in the short term, but significant differences were not observed at the one-year timepoint. Cardiac output was decreased in both males and females after two weeks, and statistically significant in females. Following 10.0 Gy irradiation, the heart tissue showed an increase in total protein oxidative carbonylation accompanied by DNA damage indicated γ-H2AX. Using proteomic analyses, several novel proteins showed a marked carbonylation profile including those associated with mitochondrial homeostasis and cardiac contractility, most notably, cardiac troponin T. Overall, we present findings of acute oxidative protein, DNA damage, and long-term cardiomyopathy in the irradiated animals, along with oxidative proteomic markers of acute damage. Citation Format: Elliot Rosen. Acute total body ionizing radiation induces long-term cardiac effects and immediate changes in oxidative carbonylation of cardiac troponin T in the rat [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-058.
Abstract IA-025: Exploiting Redox Biology for Selectively Targeting Cancer Cells
Authors: Douglas R Spitz
Journal: Clinical Cancer Research (2021)

Abstract Relative to normal cells, cancer cells have been shown to demonstrate fundamental alterations in oxidative metabolism leading to increased steady-state levels of superoxide, hydrogen peroxide, and labile iron pools. Alterations in cancer cell oxidative metabolism in turn lead to disruptions in many redox sensitive signaling and gene expression pathways that impact cell growth, differentiation, genomic instability, and cancer progression. Cancer cells adapt to this altered metabolic state by activating many signaling and gene expression pathways that allow them to survive and continue to progress to malignancy. The current talk will discuss how pharmacological ascorbate and superoxide dismutase mimics can be used to target the oxidative metabolic frailties of cancer versus normal cells to enhance therapeutic outcomes to radio-chemo-therapies both in pre-clinical and clinical trials. The long-term goal is to utilize a detailed mechanistic understanding of alterations in cancer versus normal cell oxidative metabolism and redox biology to develop rapidly implementable new strategies that can enhance tumor responses while protecting normal tissues during standard radio-chemo-therapy protocols. (Supported by P01 CA217797, R01 CA182804, T32 CA078586). Citation Format: Douglas R Spitz. Exploiting Redox Biology for Selectively Targeting Cancer Cells [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-025.
Remote Research and Clinical Trial Integrity During and After the Coronavirus Pandemic
Authors: Mary M. McDermott, Anne B. Newman
Journal: JAMA (2021)

Remote Research and Clinical Trial Integrity During and After the Coronavirus PandemicApproximately 1 year ago, in March 2020, clinical trials were suddenly and severely disrupted by the COVID-19 pandemic.Pandemic-related restrictions that limited or prevented in-person visits resulted in unprecedented obstacles to clinical trial enrollment, data collection, and intervention delivery for many clinical trials. 1 As of April 21, 2021, ClinicalTrials.govlisted 1773 suspended clinical trials, with many trials identifying the COVID-19 pandemic as the primary reason for suspension.Ongoing trials that were not suspended are likely to be experiencing challenges with enrollment and fidelity to aspects of study protocols that require in-person contact, including interventions and outcome assessment.Many clinical trial investigators replaced in-person interactions with alternative approaches conducted remotely. 2A survey of 245 clinical trial investigators reported that the proportion of participant interactions conducted remotely increased from 9% in January 2020 to 57% in May 2020. 2 Remote interactions with participants implemented in response to the pandemic included mailings or drop-off of devices, such as physical activity monitors or pulse oximeters for outcome measurements, and mail delivery or drop-off of pills or devices for trial interventions. 3,44][5] These remote activities facilitated clinical trial progress during the pandemic.Embedded trials build data collection for a clinical trial into essential clinical care and represent another alternative to in-person clinical trial interactions.An example is the ongoing Pragmatic Evaluation of Events And Benefits of Lipid-lowering in Older Adults (PREVENTABLE) trial (NCT04262206), in which 20 000 participants 75 years or older are randomized to atorvastatin 40 mg daily or placebo and followed up with the electronic health record for outcomes of disability-free survival and cardiovascular events.Medications are mailed to participants' homes.Outcomes that are not part of routine clinical care, including detailed cognitive assessments and physical performance testing, are collected at participants' homes by trained research staff.A visit to a research laboratory is required to collect blood for a biorepository of red blood cells and DNA.An example of a fully remote trial was a randomized, double-blind, clinical trial conducted in St Louis, Missouri, that evaluated whether fluvoxamine, compared with placebo, improved outcomes in 152 outpatients newly diagnosed with COVID-19. 4Eligibility screening was conducted by email and telephone and COVID diagnosis was confirmed using electronic health record
Real-world use of thrombopoietin receptor agonists in older patients with primary immune thrombocytopenia
Authors: Francesca Palandri, Elena Rossi, Daniela Bartoletti, Antonietta Ferretti, Marco Ruggeri, Elisa Lucchini, Valentina Carrai, Wilma Barcellini, Andrea Patriarca, Elena Rivolti, Ugo Consoli, Silvia Cantoni, Esther Natalie Oliva, Federico Chiurazzi, Giovanni Caocci, Gaetano Giuffrida, Alessandra Borchiellini, Giuseppe Auteri, Erminia Baldacci, Giuseppe Carli, Daniela Nicolosi, Emanuele Sutto, Monica Carpenedo, Michele Cavo, Maria Gabriella Mazzucconi, Francesco Zaja, Valerio De Stefano, Francesco Rodeghiero, Nicola Vianelli
Journal: Blood (2021)
Covid-19: Failed response in Brazil has led to humanitarian catastrophe, says MSF
Authors: Zosia Kmietowicz
Journal: BMJ (2021)

This review is the summary of a workshop on small airways disease, which took place in Porquerolles, France in November 2011. The purpose of this workshop was to review the evidence on small airways (bronchiolar) involvement under various pathophysiological circumstances, excluding asthma and chronic obstructive pulmonary disease. Histopathological patterns associated with small airways disease were reviewed, including cellular and obliterative bronchiolitis. Many pathophysiological conditions have been associated with small airways disease including airway infections, connective tissue diseases and inflammatory bowel diseases, bone marrow and lung transplantation, common variable immunodeficiency disorders, diffuse panbronchiolitis, and diseases related to environmental exposures to pollutants, allergens and drugs. Pathogenesis, clinical presentation, a computed tomography scan and pulmonary function test findings are reviewed, and therapeutic options are described with the objective of providing an integrative approach to these disorders.
Estimating and mitigating the risk of COVID-19 epidemic rebound associated with reopening of international borders in Vietnam: a modelling study
Authors: Quang D Pham, Robyn M Stuart, Thuong V Nguyen, Quang C Luong, Quang D Tran, Thai Q Pham, Lan T Phan, Tan Q Dang, Duong N Tran, Hung T Do, Dina Mistry, Daniel J Klein, Romesh G Abeysuriya, Assaf P Oron, Cliff C Kerr
Journal: The Lancet Global Health (2021)

Vietnam has emerged as one of the world's leading success stories in responding to COVID-19. After a prolonged period of little to no transmission, there was an outbreak of unknown source in July, 2020, in the Da Nang region, but the outbreak was quickly suppressed. We aimed to use epidemiological, behavioural, demographic, and policy data from the COVID-19 outbreak in Da Nang to calibrate an agent-based model of COVID-19 transmission for Vietnam, and to estimate the risk of future outbreaks associated with reopening of international borders in the country.
THE IMPACT OF THE COVID-19 PANDEMIC ON A MULTI-CENTER CLINICAL - ADAPTING IN REAL-TIME TO MAINTAIN TRIAL INTEGRITY
Authors: Osama Dasa, Eileen Handberg, George Spoko, Chrisandra L Shufelt, Janet Wei, André Rogatko, Rhonda Cooper-DeHoff, C. Noel Bairey Merz, Carl Pepine
Journal: Journal of the American College of Cardiology (2021)
Reply to Phillpotts and Webster
Authors: Hirofumi Kogure, Yousuke Nakai, Hiroyuki Isayama
Journal: Endoscopy (2021)

See also: Multicenter randomized trial of endoscopic papillary large balloon dilation without sphincterotomy versus endoscopic sphincterotomy for removal of bile duct stones: MARVELOUS trialEndoscopy 2020; 52(09): 736-744DOI: 10.1055/a-1145-3377 See also: The role of endoscopic papillary large balloon dilatation without sphincterotomyEndoscopy 2021; 53(05): 559-559DOI: 10.1055/a-1308-2160
Evaluation of the Cancer Transition Theory in the US, Select European Nations, and Japan by Investigating Mortality of Infectious- and Noninfectious-Related Cancers, 1950-2018
Authors: Omer Gersten, Magali Barbieri
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Despite cancer being a leading cause of death worldwide, scant research has been carried out on the validity of the cancer transition theory, the idea that as nations develop, they move from a situation where infectious-related cancers are prominent to one where noninfectious-related cancers dominate. <h3>Objective</h3> To examine whether cancer transitions exist in the US, select European countries, and Japan. <h3>Design, Setting, and Participants</h3> In this cross-sectional study, annual cause-of-death data from the 1950s to 2018 for the US, England and Wales, France, Sweden, Norway, and Japan were extracted from the Human Mortality Database and the World Health Organization (WHO). Statistical analysis was performed from April 2020 to February 2021. <h3>Main Outcomes and Measures</h3> Age-standardized death rates for all ages and both sexes combined were estimated for cancers of the stomach, cervix, liver, lung, pancreas, esophagus, colorectum, breast, and prostate. <h3>Results</h3> The results of the analysis show that for all countries in this study except for Japan, mortality from infectious-related cancers has declined steadily throughout the period, so that by the end of the period, for Norway, England and Wales, Sweden, and the US, rates were approximately 20 deaths per 100 000 population. Regarding noninfectious-related cancers, at the beginning of the period, all countries exhibited an increasing trend in rates, with England and Wales having the greatest peak of 215.1 deaths per 100 000 population (95% CI 213.7-216.6 deaths per 100 000 population) in 1985 followed by a decline, with most of the other countries reaching a peak around 1990 and declining thereafter. Furthermore, there is a visible crossover in the trends for infectious-related and noninfectious-related cancers in Japan and Norway. This crossover occurred in 1988 in Japan, when the rates for both types of cancers stood at 116 per 100 000 population (95% CI, 115.0-116.5 per 100 000 population), and in 1955 in Norway, when they passed each other at 100 per 100 000 population (95% CI, 96.4-105.3 per 100 000 population). <h3>Conclusions and Relevance</h3> In this cross-sectional study, the findings suggest that cancer mortality patterns parallel the epidemiological transition, which states that as nations develop, they move from a stage where infectious diseases are prominent to one where noninfectious diseases dominate. An implication is that the epidemiological transition theory as originally formulated continues to be relevant, despite some researchers arguing that there should be additional stages beyond the original 3.
Synergistic enhancement of tendon-to-bone healing via anti-inflammatory and pro-differentiation effects caused by sustained release of Mg<sup>2+</sup>/curcumin from injectable self-healing hydrogels
Authors: Baojun Chen, Yongping Liang, Jing Zhang, Lang Bai, Meiguang Xu, Qian Han, Xuezhe Han, Jintao Xiu, Meng Li, Xiaoling Zhou, Baolin Guo, Zhanhai Yin
Journal: Theranostics (2021)

Poor healing response after rotator cuff reconstruction is multifactorial, with the inflammatory microenvironment and deficiency of stem cell differentiation factors at the lesion site being most relevant. However, there is a lack of effective tissue engineering strategies that can simultaneously exert anti-inflammatory and pro-differentiation effects to promote rotator cuff healing. Methods: In this study, we synthesized and characterized a novel active drug delivery vector that successfully overcame the challenge of simultaneous high-efficiency loading and controlled release of Mg2+ and curcumin. The anti-inflammatory and pro-differentiation effects of the composite hydrogel were evaluated in vitro and in vivo. Moreover, healing of the rotator cuff tendon-to-bone interface was studied by histology, immunofluorescence, and biomechanical tests. Results: The composite hydrogel exhibited excellent biocompatibility and injectability, good adhesiveness, and rapid self-healing. The released curcumin showed obvious anti-inflammatory and antioxidation effects, which protected stem cells and tendon matrix. Furthermore, released Mg2+ promoted stem cell aggregation and chondrogenesis. Moreover, biomechanical tests and histological results of a rat rotator cuff tear model at 8 weeks after surgery indicated that the composite hydrogel significantly enhanced tendon-to-bone healing. Conclusions: The composite hydrogel mediated sustained in situ release of curcumin and Mg2+ to effectively promote rotator cuff tendon-to-bone healing via anti-inflammatory and pro-differentiation effects. Therefore, this composite hydrogel offers significant promise for rotator cuff repair.
Fucosylated lipid nanocarriers loaded with antibiotics efficiently inhibit mycobacterial propagation in human myeloid cells
Authors: Verónica Durán, Elena Grabski, Constantin Hozsa, Jennifer Becker, Hanzey Yasar, João T. Monteiro, Bibiana Costa, Nicole Koller, Yvonne Lueder, Bettina Wiegmann, Gudrun Brandes, Volkhard Kaever, Claus-Michael Lehr, Bernd Lepenies, Robert Tampé, Reinhold Förster, Berislav Bošnjak, Marcus Furch, Theresa Graalmann, Ulrich Kalinke
Journal: Journal of Controlled Release (2021)

Antibiotic treatment of tuberculosis (TB) is complex, lengthy, and can be associated with various adverse effects. As a result, patient compliance often is poor, thus further enhancing the risk of selecting multi-drug resistant bacteria. Macrophage mannose receptor (MMR)-positive alveolar macrophages (AM) constitute a niche in which Mycobacterium tuberculosis replicates and survives. Therefore, we encapsulated levofloxacin in lipid nanocarriers functionalized with fucosyl residues that interact with the MMR. Indeed, such nanocarriers preferentially targeted MMR-positive myeloid cells, and in particular, AM. Intracellularly, fucosylated lipid nanocarriers favorably delivered their payload into endosomal compartments, where mycobacteria reside. In an in vitro setting using infected human primary macrophages as well as dendritic cells, the encapsulated antibiotic cleared the pathogen more efficiently than free levofloxacin. In conclusion, our results point towards carbohydrate-functionalized nanocarriers as a promising tool for improving TB treatment by targeted delivery of antibiotics.