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Article ; Online: Use of Tocilizumab for COVID-19-Induced Cytokine Release Syndrome: A Cautionary Case Report.

Radbel, Jared / Narayanan, Navaneeth / Bhatt, Pinki J

2020 Volume 158, Issue 1, Page(s) e15–e19

Abstract: Novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in Wuhan, China. Since then, COVID-19 has become a pandemic affecting more than 4.1 million people worldwide. Patients with COVID-19 have a wide spectrum of manifestations, one being ...

Abstract	Novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in Wuhan, China. Since then, COVID-19 has become a pandemic affecting more than 4.1 million people worldwide. Patients with COVID-19 have a wide spectrum of manifestations, one being cytokine release syndrome (CRS) and its fatal correlate, secondary hemophagocytic lymphohistiocytosis (sHLH). Anti-cytokine therapy such as tocilizumab, an IL-6 receptor antagonist, is a potential treatment for COVID-19; however, data regarding the efficacy of this anti-IL-6 therapy are currently lacking. We report two cases of patients who received a diagnosis of COVID-19 complicated by CRS and were treated with tocilizumab. Both patients progressed to sHLH despite treatment with tocilizumab, and one developed viral myocarditis, challenging the safety and clinical usefulness of tocilizumab in the treatment of COVID-19-induced CRS. These cases highlight the need for clinical trials to determine optimal patient selection and timing for the use of tocilizumab during this disease process.
MeSH term(s)	Adult ; Aged ; Anti-Infective Agents/administration & dosage ; Anti-Inflammatory Agents/administration & dosage ; Antibodies, Monoclonal, Humanized/administration & dosage ; Azithromycin/administration & dosage ; Betacoronavirus/isolation & purification ; C-Reactive Protein/analysis ; COVID-19 ; Clinical Deterioration ; Coronavirus Infections/complications ; Coronavirus Infections/diagnosis ; Coronavirus Infections/physiopathology ; Coronavirus Infections/therapy ; Cytokine Release Syndrome/blood ; Cytokine Release Syndrome/therapy ; Cytokine Release Syndrome/virology ; Fatal Outcome ; Female ; Humans ; Hydroxychloroquine/administration & dosage ; Hypoxia/etiology ; Hypoxia/therapy ; Lymphohistiocytosis, Hemophagocytic/blood ; Lymphohistiocytosis, Hemophagocytic/therapy ; Lymphohistiocytosis, Hemophagocytic/virology ; Male ; Myocarditis/therapy ; Myocarditis/virology ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/etiology ; Pneumonia, Viral/physiopathology ; Pneumonia, Viral/therapy ; Respiration, Artificial/methods ; SARS-CoV-2 ; Shock, Septic/etiology ; Shock, Septic/therapy
Chemical Substances	Anti-Infective Agents ; Anti-Inflammatory Agents ; Antibodies, Monoclonal, Humanized ; Hydroxychloroquine (4QWG6N8QKH) ; Azithromycin (83905-01-5) ; C-Reactive Protein (9007-41-4) ; tocilizumab (I031V2H011)
Keywords	covid19
Language	English
Publishing date	2020-04-25
Publishing country	United States
Document type	Case Reports
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1016/j.chest.2020.04.024
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Article ; Online: The New Usual Care.

Radbel, Jared / Boutsikaris, Daniel

Emergency medicine clinics of North America

2017 Volume 35, Issue 1, Page(s) 11–23

Abstract: Recent literature continues to refine which components of the early goal-directed therapy (EGDT) algorithm are necessary. Given it utilizes central venous pressure, continuous central venous oxygen saturation, routine blood transfusions, and inotropic ... ...

Abstract	Recent literature continues to refine which components of the early goal-directed therapy (EGDT) algorithm are necessary. Given it utilizes central venous pressure, continuous central venous oxygen saturation, routine blood transfusions, and inotropic medications, this algorithm can be timely, invasive, costly, and potentially harmful. New trials highlight early recognition, early fluid resuscitation, appropriate antibiotic treatment, source control, and the application of a multidisciplinary evidence-based approach as essential components of current sepsis management. This article discusses the landmark sepsis trials that have been published over the past several decades and offers recommendations on what should currently be considered 'usual care'.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Catheterization, Central Venous ; Clinical Protocols/standards ; Evidence-Based Medicine ; Fluid Therapy ; Humans ; Sepsis/diagnosis ; Sepsis/therapy
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2017-01-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	605637-4
ISSN	1558-0539 ; 0733-8627
ISSN (online)	1558-0539
ISSN	0733-8627
DOI	10.1016/j.emc.2016.08.007
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Article ; Online: Disease-modifying treatment of chemical threat agent-induced acute lung injury.

Radbel, Jared / Laskin, Debra L / Laskin, Jeffrey D / Kipen, Howard M

Annals of the New York Academy of Sciences

2020 Volume 1480, Issue 1, Page(s) 14–29

Abstract: Acute respiratory distress syndrome (ARDS) is a highly morbid lung pathology induced by exposure to chemical warfare agents, including vesicants, phosgene, chlorine, and ricin. In this review, we describe the pathology associated with the development of ... ...

Abstract	Acute respiratory distress syndrome (ARDS) is a highly morbid lung pathology induced by exposure to chemical warfare agents, including vesicants, phosgene, chlorine, and ricin. In this review, we describe the pathology associated with the development of ARDS in humans and experimental models of acute lung injury following animal exposure to these high-priority threat agents. Potential future approaches to disease-modifying treatment used in preclinical animal studies, including antioxidants, anti-inflammatories, biologics, and mesenchymal stem cells, are also described. As respiratory pathologies, including ARDS, are the major cause of morbidity and mortality following exposure to chemical threat agents, understanding mechanisms of disease pathogenesis is key to the development of efficacious therapeutics beyond the primary intervention principle, which remains mechanical ventilation.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/therapeutic use ; Antioxidants/therapeutic use ; Chemical Warfare Agents/poisoning ; Humans ; Respiration, Artificial ; Respiratory Distress Syndrome/chemically induced ; Respiratory Distress Syndrome/metabolism ; Respiratory Distress Syndrome/pathology ; Respiratory Distress Syndrome/therapy
Chemical Substances	Anti-Inflammatory Agents ; Antioxidants ; Chemical Warfare Agents
Keywords	covid19
Language	English
Publishing date	2020-07-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	211003-9
ISSN	1749-6632 ; 0077-8923
ISSN (online)	1749-6632
ISSN	0077-8923
DOI	10.1111/nyas.14438
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Article ; Online: Multi-feature Multi-Scale CNN-Derived COVID-19 Classification from Lung Ultrasound Data.

Che, Hui / Radbel, Jared / Sunderram, Jag / Nosher, John L / Patel, Vishal M / Hacihaliloglu, Ilker

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

2021 Volume 2021, Page(s) 2618–2621

Abstract: The global pandemic of the novel coronavirus disease 2019 (COVID-19) has put tremendous pressure on the medical system. Imaging plays a complementary role in the management of patients with COVID-19. Computed tomography (CT) and chest X-ray (CXR) are the ...

Abstract	The global pandemic of the novel coronavirus disease 2019 (COVID-19) has put tremendous pressure on the medical system. Imaging plays a complementary role in the management of patients with COVID-19. Computed tomography (CT) and chest X-ray (CXR) are the two dominant screening tools. However, difficulty in eliminating the risk of disease transmission, radiation exposure and not being cost-effective are some of the challenges for CT and CXR imaging. This fact induces the implementation of lung ultrasound (LUS) for evaluating COVID-19 due to its practical advantages of noninvasiveness, repeatability, and sensitive bedside property. In this paper, we utilize a deep learning model to perform the classification of COVID-19 from LUS data, which could produce objective diagnostic information for clinicians. Specifically, all LUS images are processed to obtain their corresponding local phase filtered images and radial symmetry transformed images before fed into the multi-scale residual convolutional neural network (CNN). Secondly, image combination as the input of the network is used to explore rich and reliable features. Feature fusion strategy at different levels is adopted to investigate the relationship between the depth of feature aggregation and the classification accuracy. Our proposed method is evaluated on the point-of-care US (POCUS) dataset together with the Italian COVID-19 Lung US database (ICLUS-DB) and shows promising performance for COVID-19 prediction.
MeSH term(s)	COVID-19 ; Humans ; Lung/diagnostic imaging ; Neural Networks, Computer ; SARS-CoV-2
Language	English
Publishing date	2021-12-10
Publishing country	United States
Document type	Journal Article
ISSN	2694-0604
ISSN (online)	2694-0604
DOI	10.1109/EMBC46164.2021.9631069
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Article ; Online: Novel method to assess resident alveolar macrophage efferocytosis of apoptotic neutrophils by flow cytometry.

Radbel, Jared / Meshanni, Jaclynn A / Gardner, Carol R / Le-Hoang, Oanh / Cervelli, Jessica / Laskin, Jeffrey D / Gow, Andrew J / Laskin, Debra L

Toxicology and applied pharmacology

2022 Volume 460, Page(s) 116359

Abstract: Macrophage efferocytosis of apoptotic neutrophils (PMNs) plays a key role in the resolution of inflammation. In these studies, we describe a novel flow cytometric method to assess efferocytosis of apoptotic PMNs. Resident alveolar macrophages and PMNs ... ...

Abstract	Macrophage efferocytosis of apoptotic neutrophils (PMNs) plays a key role in the resolution of inflammation. In these studies, we describe a novel flow cytometric method to assess efferocytosis of apoptotic PMNs. Resident alveolar macrophages and PMNs were collected from lungs of mice exposed to inhaled ozone (0.8 ppm, 3 h) followed by lipopolysaccharide (3 mg/kg, i.v.) to induce acute lung injury. PMNs were labeled with PKH26 or DilC
MeSH term(s)	Mice ; Animals ; Neutrophils/metabolism ; Macrophages, Alveolar/metabolism ; Flow Cytometry ; Phagocytosis ; Inflammation/metabolism ; Apoptosis
Chemical Substances	PKH 26
Language	English
Publishing date	2022-12-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	204477-8
ISSN	1096-0333 ; 0041-008X
ISSN (online)	1096-0333
ISSN	0041-008X
DOI	10.1016/j.taap.2022.116359
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Article ; Online: Use of Tocilizumab for COVID-19-Induced Cytokine Release Syndrome

Radbel, Jared / Narayanan, Navaneeth / Bhatt, Pinki J.

Chest

2020 Volume 158, Issue 1, Page(s) e15–e19

Keywords	Critical Care and Intensive Care Medicine ; Pulmonary and Respiratory Medicine ; Cardiology and Cardiovascular Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1016/j.chest.2020.04.024
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Asthma and COVID: What Are the Important Questions?

Panettieri, Reynold A / Carson, Jeffrey / Horton, Daniel / Barrett, Emily / Roy, Jason / Radbel, Jared

The journal of allergy and clinical immunology. In practice

2020 Volume 8, Issue 8, Page(s) 2487–2488

MeSH term(s)	Asthma/diagnosis ; COVID-19 ; Humans ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-06-22
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2020.06.008
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Article ; Online: Impaired energy metabolism and altered functional activity of alveolar type II epithelial cells following exposure of rats to nitrogen mustard.

Sunil, Vasanthi R / Vayas, Kinal N / Radbel, Jared / Abramova, Elena / Gow, Andrew / Laskin, Jeffrey D / Laskin, Debra L

Toxicology and applied pharmacology

2022 Volume 456, Page(s) 116257

Abstract: Nitrogen mustard (NM) is a cytotoxic vesicant known to cause acute lung injury which progresses to fibrosis. Alveolar Type II cells are primarily responsible for surfactant production; they also play a key role in lung repair following injury. Herein, we ...

Abstract	Nitrogen mustard (NM) is a cytotoxic vesicant known to cause acute lung injury which progresses to fibrosis. Alveolar Type II cells are primarily responsible for surfactant production; they also play a key role in lung repair following injury. Herein, we assessed the effects of NM on Type II cell activity. Male Wistar rats were administered NM (0.125 mg/kg) or PBS control intratracheally. Type II cells, lung tissue and BAL were collected 3 d later. NM exposure resulted in double strand DNA breaks in Type II cells, as assessed by expression of γH2AX; this was associated with decreased expression of the DNA repair protein, PARP1. Expression of HO-1 was upregulated and nitrotyrosine residues were noted in Type II cells after NM exposure indicating oxidative stress. NM also caused alterations in Type II cell energy metabolism; thus, both glycolysis and oxidative phosphorylation were reduced; there was also a shift from a reliance on oxidative phosphorylation to glycolysis for ATP production. This was associated with increased expression of pro-apoptotic proteins activated caspase-3 and -9, and decreases in survival proteins, β-catenin, Nur77, HMGB1 and SOCS2. Intracellular signaling molecules important in Type II cell activity including PI3K, Akt2, phospho-p38 MAPK and phospho-ERK were reduced after NM exposure. This was correlated with dysregulation of surfactant protein production and impaired pulmonary functioning. These data demonstrate that Type II cells are targets of NM-induced DNA damage and oxidative stress. Impaired functioning of these cells may contribute to pulmonary toxicity caused by mustards.
MeSH term(s)	Rats ; Male ; Animals ; Mechlorethamine/toxicity ; Rats, Wistar ; Acute Lung Injury/chemically induced ; Alveolar Epithelial Cells ; Oxidative Stress ; Energy Metabolism ; Surface-Active Agents/adverse effects
Chemical Substances	Mechlorethamine (50D9XSG0VR) ; Surface-Active Agents
Language	English
Publishing date	2022-09-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	204477-8
ISSN	1096-0333 ; 0041-008X
ISSN (online)	1096-0333
ISSN	0041-008X
DOI	10.1016/j.taap.2022.116257
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Article: Observational study of the use of recombinant tissue-type plasminogen activator in COVID-19 shows a decrease in physiological dead space.

Orfanos, Sarah / El Husseini, Ibrahim / Nahass, Thomas / Radbel, Jared / Hussain, Sabiha

ERJ open research

2020 Volume 6, Issue 4

Abstract: COVID19-induced ARDS is partly explained by the presence of microthrombi, motivating the use of thrombolytics. This study shows that thrombolytics decrease dead space ventilation in COVID-19 ARDS patients. ...

Abstract	#COVID19-induced ARDS is partly explained by the presence of microthrombi, motivating the use of thrombolytics. This study shows that thrombolytics decrease dead space ventilation in COVID-19 ARDS patients.
Keywords	covid19
Language	English
Publishing date	2020-10-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2827830-6
ISSN	2312-0541
ISSN	2312-0541
DOI	10.1183/23120541.00455-2020
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Article: Use of Tocilizumab for COVID-19-Induced Cytokine Release Syndrome: A Cautionary Case Report

Radbel, Jared / Narayanan, Navaneeth / Bhatt, Pinki J

Chest

Abstract	Novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in Wuhan, China. Since then, COVID-19 has become a pandemic affecting more than 4.1 million people worldwide. Patients with COVID-19 have a wide spectrum of manifestations, one being cytokine release syndrome (CRS) and its fatal correlate, secondary hemophagocytic lymphohistiocytosis (sHLH). Anti-cytokine therapy such as tocilizumab, an IL-6 receptor antagonist, is a potential treatment for COVID-19; however, data regarding the efficacy of this anti-IL-6 therapy are currently lacking. We report two cases of patients who received a diagnosis of COVID-19 complicated by CRS and were treated with tocilizumab. Both patients progressed to sHLH despite treatment with tocilizumab, and one developed viral myocarditis, challenging the safety and clinical usefulness of tocilizumab in the treatment of COVID-19-induced CRS. These cases highlight the need for clinical trials to determine optimal patient selection and timing for the use of tocilizumab during this disease process.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #125382
Database	COVID19

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