tbuckley/cabot-search huggingface dataset:
Pharmaco-Immunomodulatory Therapy in COVID-19
Authors: John G. Rizk, Kamyar Kalantar-Zadeh, Mandeep R. Mehra, Carl J. Lavie, Youssef Rizk, Donald N. Forthal
Journal: Drugs (2020)

The severe acute respiratory syndrome coronavirus 2 associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival. Immune modulators have the potential to inhibit cytokines and treat the cytokine storm. A literature search using PubMed, Google Scholar, and ClinicalTrials.gov was conducted through 8 July 2020 using the search terms 'coronavirus', 'immunology', 'cytokine storm', 'immunomodulators', 'pharmacology', 'severe acute respiratory syndrome 2', 'SARS-CoV-2', and 'COVID-19'. Specific immune modulators include anti-cytokines such as interleukin (IL)-1 and IL-6 receptor antagonists (e.g. anakinra, tocilizumab, sarilumab, siltuximab), Janus kinase (JAK) inhibitors (e.g. baricitinib, ruxolitinib), anti-tumor necrosis factor-α (e.g. adalimumab, infliximab), granulocyte–macrophage colony-stimulating factors (e.g. gimsilumab, lenzilumab, namilumab), and convalescent plasma, with promising to negative trials and other data. Non-specific immune modulators include human immunoglobulin, corticosteroids such as dexamethasone, interferons, statins, angiotensin pathway modulators, macrolides (e.g. azithromycin, clarithromycin), hydroxychloroquine and chloroquine, colchicine, and prostaglandin D2 modulators such as ramatroban. Dexamethasone 6 mg once daily (either by mouth or by intravenous injection) for 10 days may result in a reduction in mortality in COVID-19 patients by one-third for patients on ventilators, and by one-fifth for those receiving oxygen. Research efforts should focus not only on the most relevant immunomodulatory strategies but also on the optimal timing of such interventions to maximize therapeutic outcomes. In this review, we discuss the potential role and safety of these agents in the management of severe COVID-19, and their impact on survival and clinical symptoms.
Silver Alert: Lost-and-Found Dad
Authors: Marianne Parshley
Journal: Annals of Internal Medicine (2020)

On Being a Doctor21 July 2020Silver Alert: Lost-and-Found DadMarianne Parshley, MDMarianne Parshley, MDProvidence Medical Group, Portland, Oregon (M.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-2905 Audio Reading - “Silver Alert: Lost-and-Found Dad” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Silver Alert: Lost-and-Found Dad” by Marianne Parshley, MD 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 leaned against the wall next to the gas fireplace in the hospital lobby; propped my crutches next to me; and put my head back against the cool tile, seeking calm. Where the hell was my father in this hillside maze of a health care campus that was so brimming with people, many of whom were dedicated to helping others?That cold, rainy November morning 1 week after my knee surgery, I had picked up Mom for an annual visit with her internist. In his lifelong role as her caregiver, Dad came, too; however, she wanted him to remain in ... Author, Article, and Disclosure InformationAffiliations: Providence Medical Group, Portland, Oregon (M.P.)Corresponding Author: Marianne Parshley, MD, PMG Gateway Internal Medicine, Suite 100, 1321 NE 99th Avenue, Portland, OR 97220; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Silver Alert: Lost-and-Found Dad” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Silver Alert: Lost-and-Found Dad” by Marianne Parshley, MD 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 Cited byAnalysis of Silver Alert Reporting System Activations for Missing Adults With Dementia in Texas, 2017 to 2022 21 July 2020Volume 173, Issue 2Page: 155-156KeywordsCaregiversCognitive impairmentComputed axial tomographyDementiaEmergency departmentFearHealth careKneesResearch laboratoriesSafety ePublished: 21 July 2020 Issue Published: 21 July 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Homeless people with mental illness in India and COVID-19
Authors: Shalini S Naik, Guru S Gowda, Prakrithi Shivaprakash, Bhaskaran Aandi Subramaniyam, Narayana Manjunatha, Krishna Prasad Muliyala, V Senthil Kumar Reddi, Channaveerachari Naveen Kumar, Suresh Bada Math, Bangalore N Gangadhar
Journal: The Lancet Psychiatry (2020)
Extraperitoneal Radical Prostatectomy with the Senhance Robotic Platform: First 40 Cases
Authors: Zeljko Kastelan, Tvrtko Hudolin, Tomislav Kulis, Luka Penezic, Stefano Gidaro, Mirko Bakula, Toni Zekulic, Nikola Knezevic
Journal: European Urology (2020)
The Textbook of Pharmaceutical Medicine
Authors: A Herxheimer
Journal: BMJ (1994)

Queen's University of Belfast, £25, pp 579 ISBN 0-85389-489-2

In Britain pharmaceutical medicine is now recognised as a distinct medical specialty: a diploma in the subject was created in 1976, a journal launched in 1984, and a Faculty of Pharmaceutical Medicine founded by the Royal College of Physicians in 1990. Pharmaceutical physicians have major responsibilities to their employers and to regulatory authorities as well as to medicine and to patients. They need much special knowledge and experience to cope with urgent and often conflicting demands. Perhaps only hard working and …
Vital corner of diagnostic challenge: eosinophilic granulomatosis with polyangiitis or COVID-19 pneumonia?
Authors: Emine Duran, Levent Kilic, Gamze Durhan, Ahmet Çağkan Inkaya, Gulay Sain Guven, Gul Karakaya, Orhan Macit Ariyurek, Omer Karadag
Journal: Annals of the Rheumatic Diseases (2020)

Figure 1 (A) Axial thorax CT image shows focal ground-glass opacities (B) Mucosal thickening and opacities are seen in ethmoid and maxillary sinuses.(C) Bilateral ground-glass opacifications that almost completely disappeared with corticosteroid on axial CT scans of the chest lung window (before and after treatment).(D) Lymph nodes that disappeared (red arrows) after treatment on axial CT scans of the chest mediastinal window (before and after treatment).
Estimation of Viral Aerosol Emissions From Simulated Individuals With Asymptomatic to Moderate Coronavirus Disease 2019
Authors: Michael Riediker, Dai-Hua Tsai
Journal: JAMA Network Open (2020)

Individuals with asymptomatic or mild coronavirus disease 2019 (COVID-19) have been reported to frequently transmit the disease even without direct contact. The severe acute respiratory syndrome coronavirus 2 has been found at very high concentrations in swab and sputum samples from such individuals. To estimate the virus levels released from individuals with asymptomatic to moderate COVID-19 into different aerosol sizes by normal breathing and coughing, and to determine what exposure could result from this in a room shared with such individuals. This mathematical modeling study combined the size-distribution of exhaled breath microdroplets for coughing and normal breathing with viral swab and sputum concentrations as approximation for lung lining liquid to obtain an estimate of emitted virus levels. Viral data were obtained from studies published as of May 20, 2020. The resulting emission data fed a single-compartment model of airborne concentrations in a room of 50 m3, the size of a small office or medical examination room. Modeling was used to estimate the viral load emitted by individuals breathing normally or coughing, and the concentrations expected in the simulated room at different ventilation rates. The mean estimated viral load in microdroplets emitted by simulated individuals while breathing regularly was 0.0000049 copies/cm3, with a range of 0.0000000049 to 0.637 copies/cm3. The corresponding estimates for simulated coughing individuals were a mean of 0.277 copies/cm3 per cough, with a range of 0.000277 to 36 030 copies/cm3 per cough. The estimated concentrations in a room with an individual who was coughing frequently were very high, with a maximum of 7.44 million copies/m3 from an individual who was a high emitter. However, regular breathing from an individual who was a high emitter was modeled to result in lower room concentrations of up to 1248 copies/m3. In this modeling study, breathing and coughing were estimated to release large numbers of viruses, ranging from thousands to millions of virus copies per cubic meter in a room with an individual with COVID-19 with a high viral load, depending on ventilation and microdroplet formation process. The estimated infectious risk posed by a person with typical viral load who breathes normally was low. The results suggest that only few people with very high viral load pose an infection risk in poorly ventilated closed environments. These findings suggest that strict respiratory protection may be needed when there is a chance to be in the same small room with an individual, whether symptomatic or not, especially for a prolonged period.
Downregulation of LAPTM4B Contributes to the Impairment of the Autophagic Flux via Unopposed Activation of mTORC1 Signaling During Myocardial Ischemia/Reperfusion Injury
Authors: Shanshan Gu, Jiliang Tan, Qiang Li, Shenyan Liu, Jian Ma, Yanjun Zheng, Jinlong Liu, Wei Bi, Ping Sha, Xuxia Li, Meng Wei, Nan Cao, Huang-Tian Yang
Journal: Circulation Research (2020)

Impaired autophagic flux contributes to ischemia/reperfusion (I/R)-induced cardiomyocyte death, but the underlying molecular mechanisms remain largely unexplored.To determine the role of LAPTM4B (lysosomal-associated transmembrane protein 4B) in the regulation of autophagic flux and myocardial I/R injury.LAPTM4B was expressed in murine hearts but downregulated in hearts with I/R (30 minutes/2 hours) injury and neonatal rat cardiomyocytes with hypoxia/reoxygenation (6 hours/2 hours) injury. During myocardial reperfusion, LAPTM4B-knockout (LAPTM4B-/-) mice had a significantly increased infarct size and lactate dehydrogenase release, whereas adenovirus-mediated LAPTM4B-overexpression was cardioprotective. Concomitantly, LAPTM4B-/- mice showed higher accumulation of the autophagy markers LC3-II (microtubule-associated protein 1A/1B-light chain 3), but not P62, in the I/R heart, whereas they did not alter chloroquine-induced further increases of LC3-II and P62 in both sham and I/R hearts. Conversely, LAPTM4B-overexpression had opposite effects. The hypoxia/reoxygenation-reduced viability of neonatal rat cardiomyocytes, ratio of autolysosomes/autophagosomes, and function of lysosomes were further decreased by LAPTM4B-knockdown but reversed by LAPTM4B-overexpression. Moreover, the LAPTM4B-overexpression-mediated benefits were abolished by knockdown of lysosome-associated membrane protein-2 (an autophagosome-lysosome fusion protein) in vivo and by the autophagy inhibitor bafilomycin A1 in vivo. In contrast, rapamycin (Rapa) successfully restored the impaired autophagic flux in LAPTM4B-/- mice and the subsequent myocardial I/R injury. Mechanistically, LAPTM4B regulated the activity of mTORC1 (mammalian target of rapamycin complex 1) via interacting with mTOR through its EC3 (extracelluar) domain. Thus, mTORC1 was overactivated in LAPTM4B-/- mice, leading to the repression of TFEB (transcription factor EB), a master regulator of lysosomal and autophagic genes, during myocardial I/R. The mTORC1 inhibition or TFEB-overexpression rescued the LAPTM4B-/--induced impairment in autophagic flux and I/R injury, whereas TFEB-knockdown abolished the LAPTM4B-overexpression-mediated recovery of autophagic flux and cardioprotection.The downregulation of LAPTM4B contributes to myocardial I/R-induced impairment of autophagic flux via modulation of the mTORC1/TFEB pathway. Graphic Abstract: A graphic abstract is available for this article.
A Phase I Study of DLYE5953A, an Anti-LY6E Antibody Covalently Linked to Monomethyl Auristatin E, in Patients with Refractory Solid Tumors
Authors: Sara M. Tolaney, Khanh T. Do, Joseph P. Eder, Patricia M. LoRusso, Colin D. Weekes, Sarat Chandarlapaty, Ching-Wei Chang, Shang-Chiung Chen, Denise Nazzal, Eva Schuth, Flavia Brunstein, Montserrat Carrasco-Triguero, Walter C. Darbonne, Jennifer M. Giltnane, William M. Flanagan, S. Renee Commerford, Alexander Ungewickell, Geoffrey I. Shapiro, Shanu Modi
Journal: Clinical Cancer Research (2020)

DLYE5953A is an antibody-drug conjugate consisting of an anti-LY6E antibody covalently linked to the cytotoxic agent monomethyl auristatin E. This study characterized the safety, pharmacokinetics, immunogenicity, potential biomarkers, and antitumor activity of DLYE5953A in patients with metastatic solid tumors.This was a phase I, open-label, 3+3 dose-escalation, and dose-expansion study of DLYE5953A administered intravenously every 21 days (Q3W) in patients with locally advanced or metastatic solid malignancies.Sixty-eight patients received DLYE5953A (median, four cycles; range, 1-27). No dose-limiting toxicities were identified during dose escalation (0.2-2.4 mg/kg; n = 20). The recommended phase II dose (RP2D) of 2.4 mg/kg Q3W was based on overall safety and tolerability. Dose-expansion cohorts for HER2-negative metastatic breast cancer (HER2-negative MBC; n = 23) and non-small cell lung cancer (NSCLC; n = 25) patients were enrolled at the RP2D. Among patients receiving DLYE5953A 2.4 mg/kg (n = 55), the most common (≥30%) related adverse events (AEs) included alopecia, fatigue, nausea, and peripheral neuropathy. Grade ≥3 related AEs occurred in 14 of 55 (26%) patients, with neutropenia being the most common (13%). DLYE5953A demonstrated linear total antibody pharmacokinetics at doses of ≥0.8 mg/kg with low unconjugated monomethyl auristatin E levels in blood. Partial response was confirmed in eight of 68 (12%) patients, including three of 29 patients with MBC (10%) and five of 25 patients with NSCLC (20%) at the RP2D. Stable disease was the best response for 37 of 68 (54%) patients.DLYE5953A administered at 2.4 mg/kg has acceptable safety. Preliminary evidence of antitumor activity in patients with HER2-negative MBC and NSCLC supports further investigation of LY6E as a therapeutic target.
Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing
Authors: Stephen C. Cunnane, Eugenia Trushina, Cecilie Morland, Alessandro Prigione, Gemma Casadesus, Zane B. Andrews, M. Flint Beal, Linda H. Bergersen, Roberta D. Brinton, Suzanne de la Monte, Anne Eckert, Jenni Harvey, Ross Jeggo, Jack H. Jhamandas, Oliver Kann, Clothide Mannoury la Cour, William F. Martin, Gilles Mithieux, Paula I. Moreira, Michael P. Murphy, Klaus-Armin Nave, Tal Nuriel, Stéphane H. R. Oliet, Frédéric Saudou, Mark P. Mattson, Russell H. Swerdlow, Mark J. Millan
Journal: Nature Reviews Drug Discovery (2020)
Long-Term Outcome of Patients Receiving Extracorporeal Photopheresis for Acute and Chronic Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies: Results from an Observational Study on 106 Patients
Authors: Mauricette Michallet, Mohamad Sobh, Alexandre Deloire, Daniela Revesz, Youcef Chelgoum, Mohamed El-Hamri, Fiorenza Barraco, Helene Labussiere-Wallet, Franck Emmanuel Nicolini, Olivier Hequet
Journal: Blood (2017)
Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
Authors: Alexandre B Cavalcanti, Fernando G Zampieri, Regis G Rosa, Luciano C P Azevedo, Viviane C Veiga, Alvaro Avezum, Lucas P Damiani, Aline Marcadenti, Letícia Kawano-Dourado, Thiago Lisboa, Debora L M Junqueira, Pedro G M de Barros E Silva, Lucas Tramujas, Erlon O Abreu-Silva, Ligia N Laranjeira, Aline T Soares, Leandro S Echenique, Adriano J Pereira, Flávio G R Freitas, Otávio C E Gebara, Vicente C S Dantas, Remo H M Furtado, Eveline P Milan, Nicole A Golin, Fábio F Cardoso, Israel S Maia, Conrado R Hoffmann Filho, Adrian P M Kormann, Roberto B Amazonas, Monalisa F Bocchi de Oliveira, Ary Serpa-Neto, Maicon Falavigna, Renato D Lopes, Flávia R Machado, Otavio Berwanger
Journal: New England Journal of Medicine (2020)

Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited.We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed.A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent.Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).
THU0641-HPR ILLITERACY IS NOT AN OBSTACLE FOR ASSIMILATION OF A PATIENT EDUCATION SESSION ON METHOTREXATE SELF-INJECTION IN RA PATIENTS A PROSPECTIVE PILOT STUDY
Authors: S. Afilal, H. Rkain, B. Berchane, J. Moulay Berkchi, S. Fellous, T. Fatima Zahrae, A. Ilham, N. Alami, T. Latifa, N. Hajjaj-Hassouni, F. Allali
Journal: Annals of the Rheumatic Diseases (2020)

Background: Patient education for RA patients has been shown to improve adherence and self-management of this chronic disease. Objectives: To assess the impact of illiteracy on assimilation of a patient education session on methotrexate self-injection in RA patients. Methods: Prospective pilot study that included 27 consecutive patients (81.5% female, mean age 44.4 years, illiteracy rate 40.7%) with RA (median duration of progression of 4 years, mean delay in referral for specialist of 6 months, median duration of methotrexate use of 1 year). The patients benefited from an individual patient education session to learn how to self-inject with methotrexate subcutaneously. The patient education session was supervised by a nurse and a rheumatologist. A 10-question dichotomous questionnaire was then administered to patients to assess the level of uptake of messages passed during the patient education session. The prevalence of correct answers was compared between illiterate and non-illiterate patients. Results: The mean duration of patient education session is 13 min. Table I illustrates the results of the correct responses prevalence and the comparison of correct response rates between illiterate and non-illiterate patients. Table 1. Prevalence of correct responses and comparison of correct response rates between illiterate and non-illiterate patients. Questions N=27 Illiterate P Yes (N=11 ) No (N=16 ) 1.Do I always have to self-inject on the same day of the week? (%) 96,3 90,9 100 NS 2.Should Methotrexate be protected from light and away from children? (%) 96,3 100 93,7 NS 3.Can I self-inject anywhere on my thigh and belly 5 cm from the navel? (%) 85,2 100 75 NS 4.Is it important to change the injection sites? (%) 70,4 72,7 68,75 NS 5.Do I need to pinch the skin before self-injection? (%) 92,6 100 87,5 NS 6.Can I always use the same needle for each injection? (%) 81,5 90,9 75 NS 7.Do I have to wear gloves to inject Methotrexate? (%) 81,5 90,9 75 NS 8.Do I have to apply an antiseptic product (alcohol, Betadine) to the injection site before self-injecting? (%) 88,9 90,9 87,5 NS 9.Can I use the rest of the MTX ampoule for the next injection? (%) 74,1 81,8 68,7 NS 10.Do I tell my doctor if I have side effects? (%) 100 100 100 NS Conclusion: This study suggests that illiteracy does not affect the assimilation of information given during a patient education session. These preliminary results should encourage the development of patient education programs in our context where illiteracy rate is high. Disclosure of Interests: None declared
High Frequency of Both, Short and Long-Term Post-Transfusion Microchimerism Among the Regularly-Transfused Thalassemic Patient Population
Authors: Spiros Matsagos, Alexandra Kourakli, Constantina Argyropoulou, Panagiota Spyropoulou, Vasileios Lazaris, Evgenia Verigou, Panagiota Triantafyllou, Paraskevi Katsaouni, Maria Likouresi, Eleni Fragopanagou, Evangelia Tzouvara, Maria Tiniakou, Chrysoula Alepi, Argiris Symeonidis
Journal: Blood (2017)
Abstract 15448: Reversible Endothelial Membrane Perforation for Targeted Drug/Gene Delivery Using Ultrasound and Microbubbles
Authors: Brandon Helfield, Xucai Chen, Simon Watkins, Flordeliza S Villanueva
Journal: Circulation (2019)

Introduction: Ultrasound (US)-stimulated microbubbles (MBs) are emerging as non-viral gene delivery vehicles for the treatment of cardiovascular disease. The MB-cell interactions that facilitate nu...