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Article ; Online: Intravital Microscopy Evidence That Methylene Blue Should Be a Vasopressor-Sparing Agent in Sepsis Vasoplegia.

Mestriner, Fabiola Leslie Antunes Cardoso / Dantas, Pedro Brüch / Barbosa, Jéssyca Michelon / Evora, Paulo Roberto B / Becari, Christiane

Brazilian journal of cardiovascular surgery

2024 Volume 39, Issue 3, Page(s) e20230066

Abstract: Microvasculature failure is expected in sepsis and at higher amine concentrations. Therefore, special attention focused individually on microcirculation is needed. Here, we present that methylene blue can prevent leukocytes from adhering to the ... ...

Abstract	Microvasculature failure is expected in sepsis and at higher amine concentrations. Therefore, special attention focused individually on microcirculation is needed. Here, we present that methylene blue can prevent leukocytes from adhering to the endothelium in a rat model of lipopolysaccharide-induced endotoxemia. As hypothesis evidence, an intravital microscopy image is presented.
MeSH term(s)	Rats ; Animals ; Methylene Blue/pharmacology ; Methylene Blue/therapeutic use ; Vasoconstrictor Agents ; Vasoplegia/drug therapy ; Sepsis/drug therapy ; Intravital Microscopy
Chemical Substances	Methylene Blue (T42P99266K) ; Vasoconstrictor Agents
Language	English
Publishing date	2024-04-03
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2031026-2
ISSN	1678-9741 ; 1678-9741
ISSN (online)	1678-9741
ISSN	1678-9741
DOI	10.21470/1678-9741-2023-0066
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Article ; Online: Indigo Carmine Hemodynamic Studies to Treat Vasoplegia Induced by Compound 48/80 in a Swine Model of Anaphylaxis.

Albuquerque, Agnes Afrodite S / Celotto, Andrea Carla / Becari, Christiane / Prandi, Marelaine / Barbosa, Jessyca M / Moreira, Francisco / Jordani, Maria Cecília / Evora, Paulo Roberto B

Brazilian journal of cardiovascular surgery

2022 Volume 37, Issue 1, Page(s) 20–28

Abstract: Introduction: There are many reasons to believe that the nitric oxide/guanosine 3'5' - cyclic monophosphate (or NO/cGMP) pathway on vasoplegic states is underestimated. To study indigo carmine (IC) as an alternative to methylene blue was the ... ...

Abstract	Introduction: There are many reasons to believe that the nitric oxide/guanosine 3'5' - cyclic monophosphate (or NO/cGMP) pathway on vasoplegic states is underestimated. To study indigo carmine (IC) as an alternative to methylene blue was the investigation rationale. Methods: The IC (3mg/kg intravenous infusion) study protocol included five experimental groups; 1) Control group - saline was injected at 0 and 10 minutes; 2) IC group - IC was injected at 0 and saline at 10 minutes; 3) compound 48/80 (C48/80) group - C48/80 was injected at 0 minute and saline at 10 minutes; 4) C48/80 + IC group - C48/80 was injected at 0 minute and IC at 10 minutes; and 5) IC + C48/80 group - IC was injected at 0 minute and C48/80 at 10 minutes. The studies were carried out by registering and measuring hemodynamic and blood gasometric parameters, including continuous cardiac output. Results: 1) The effects of the drugs (IC and C48/80) were more evident in the first 20 minutes of recording; 2) hypotensive responses were more pronounced in the C48/80 groups; 3) IC isolated or applied before C48/80 caused transient pulmonary hypertension; and 4) after the first 20 minutes, the pressure responses showed stability with apparent hypotension more pronounced in the C48/80 groups. Clinical observations showed significant hemodynamic instability and catastrophic anaphylactic reactions (agitation, pulmonary hypertension, severe bronchospasm, urticaria, high-intensity cyanosis, violent gastric hypersecretion, and ascites). Conclusion: A global results analysis showed differences between groups only in the first 20 minutes of the experiments.
MeSH term(s)	Anaphylaxis/drug therapy ; Animals ; Hemodynamics ; Humans ; Indigo Carmine/adverse effects ; Nitric Oxide ; Swine ; Vasoplegia ; p-Methoxy-N-methylphenethylamine/adverse effects
Chemical Substances	Nitric Oxide (31C4KY9ESH) ; p-Methoxy-N-methylphenethylamine (4091-50-3) ; Indigo Carmine (D3741U8K7L)
Language	English
Publishing date	2022-03-10
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2183753-3
ISSN	1678-9741 ; 1678-9741
ISSN (online)	1678-9741
ISSN	1678-9741
DOI	10.21470/1678-9741-2020-0622
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Article: Honeymoon Period in Newborn Rats With CDH Is Associated With Changes in the VEGF Signaling Pathway.

Miura da Costa, Karina / Fabro, Alexandre Todorovic / Becari, Christiane / Figueira, Rebeca Lopes / Schmidt, Augusto F / Ruano, Rodrigo / Sbragia, Lourenço

Frontiers in pediatrics

2021 Volume 9, Page(s) 698217

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2021-07-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2021.698217
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Article ; Online: Incidence of hospital acquired pressure injury in critically ill patients with COVID-19 in prone position admitted to the intensive care unit.

Sato, Lucas / Heck, Letícia Olandin / Bimbatti, Karina de Fátima / Petroski-Moraes, Bruno Cesar / Becari, Christiane / Basile-Filho, Anibal / Auxiliadora-Martins, Maria / Gonçalves Menegueti, Mayra

Medicine

2023 Volume 102, Issue 18, Page(s) e33615

Abstract: Critical patients have conditions that may favor the occurrence of hospital-acquired pressure injury (HAPI). The objective of this study was to identify the incidence and factors associated with the occurrence of HAPI in patients with coronavirus disease ...

Abstract	Critical patients have conditions that may favor the occurrence of hospital-acquired pressure injury (HAPI). The objective of this study was to identify the incidence and factors associated with the occurrence of HAPI in patients with coronavirus disease 2019 admitted to the intensive care unit (ICU) who used the prone position. Retrospective cohort study carried out in an ICU of a tertiary university hospital. Two hundred four patients with positive real-time polymerase chain reactions were evaluated, of which 84 were placed in the prone position. All patients were sedated and submitted to invasive mechanical ventilation. Of the prone patients, 52 (62%) developed some type of HAPI during hospitalization. The main place of occurrence of HAPI was the sacral region, followed by the gluteus and thorax. Of the patients who developed HAPI, 26 (50%) had this event in places possibly associated with the prone position. The factors associated with the occurrence of HAPI in patients prone to coronavirus disease 2019 were the Braden Scale and the length of stay in the ICU. The incidence of HAPI in prone patients was extremely high (62%), which denotes the need to implement protocols in order to prevent the occurrence of these events.
MeSH term(s)	Humans ; COVID-19/epidemiology ; Retrospective Studies ; Pressure Ulcer/epidemiology ; Pressure Ulcer/prevention & control ; Critical Illness/epidemiology ; Incidence ; Prone Position ; Hospitalization ; Intensive Care Units ; Hospitals
Language	English
Publishing date	2023-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000033615
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Article ; Online: Effect of methylene blue on hemodynamic response in the early phase of septic shock: A case series.

Luis-Silva, Fabio / Menegueti, Mayra Gonçalves / Sato, Lucas / Peres, Leandro Moreira / Dos Reis Sepeda, Corina / Petroski-Moraes, Bruno C / Donadel, Mariana Dermínio / Gallo, Gabriela Bortoleto / Jordani, Maria Cecília / Mestriner, Fabiola / Becari, Christiane / Basile-Filho, Anibal / Evora, Paulo R B / Martins-Filho, Olindo Assis / Auxiliadora-Martins, Maria

Medicine

2023 Volume 102, Issue 4, Page(s) e32743

Abstract: Rationale: Methylene blue (MB) has been used to increase blood pressure in septic shock, acting on the activity of guanylate cyclase and nitric oxide synthase.: Patience concerns: The aim of this study is to demonstrate the benefit of MB in early ... ...

Abstract	Rationale: Methylene blue (MB) has been used to increase blood pressure in septic shock, acting on the activity of guanylate cyclase and nitric oxide synthase. Patience concerns: The aim of this study is to demonstrate the benefit of MB in early phase of septic shock.Diagnoses: We report 6 cases of patients with septic shock with up to 72 hours of evolution. Interventions: We used MB after fluid replacement, use of norepinephrine and vasopressin. Patients received a loading dose of MB and maintenance for 48 hours. Outcomes: All patients presented a reduction in the dose of vasopressors and lactate levels soon after the administration of the loading dose of MB, an effect that was maintained with the maintenance dose for 48 hours. Interleukin 6 and interleukin 8 were elevated at the beginning of the septic condition, with a progressive and marked reduction after the beginning of MB infusion, demonstrating a role of MB in reducing the inflammatory activity. Lessons: This case series suggests that MB used early in the treatment of septic shock may be useful in reducing vasopressor dose and lactate levels. Further studies are still required to further validate these findings.
MeSH term(s)	Humans ; Methylene Blue/pharmacology ; Methylene Blue/therapeutic use ; Shock, Septic ; Hemodynamics ; Blood Pressure/physiology ; Vasoconstrictor Agents/therapeutic use ; Norepinephrine/therapeutic use ; Lactates
Chemical Substances	Methylene Blue (T42P99266K) ; Vasoconstrictor Agents ; Norepinephrine (X4W3ENH1CV) ; Lactates
Language	English
Publishing date	2023-01-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000032743
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Article ; Online: Isolation and primary culture of human abdominal aorta smooth muscle cells from brain-dead donors: an experimental model for vascular diseases.

Corsi, Carlos Alexandre Curylofo / Sares, Claudia Tarcila Gomes / Mestriner, Fabiola / Michelon-Barbosa, Jéssyca / Dugaich, Vinicius Flora / Martins, Timna Varela / Násare, Alex Martins / Rosales, Roberta Ribeiro Costa / Jordani, Maria Cecília / Alves-Filho, José Carlos / Dos Reis, Rodolfo Borges / Ribeiro, Mauricio Serra / Becari, Christiane

Cell and tissue banking

2023 Volume 25, Issue 1, Page(s) 187–194

Abstract: Primary cell cultures are essential tools for elucidating the physiopathological mechanisms of the cardiovascular system. Therefore, a primary culture growth protocol of cardiovascular smooth muscle cells (VSMCs) obtained from human abdominal aortas was ... ...

Abstract	Primary cell cultures are essential tools for elucidating the physiopathological mechanisms of the cardiovascular system. Therefore, a primary culture growth protocol of cardiovascular smooth muscle cells (VSMCs) obtained from human abdominal aortas was standardized. Ten abdominal aorta samples were obtained from patients diagnosed with brain death who were organ and tissue donors with family consent. After surgical ablation to capture the aorta, the aortic tissue was removed, immersed in a Custodiol® solution, and kept between 2 and 8 °C. In the laboratory, in a sterile environment, the tissue was fragmented and incubated in culture plates containing an enriched culture medium (DMEM/G/10% fetal bovine serum, L-glutamine, antibiotics and antifungals) and kept in an oven at 37 °C and 5% CO
MeSH term(s)	Humans ; Aorta, Abdominal ; Brain Death/metabolism ; Brain Death/pathology ; Muscle, Smooth, Vascular/metabolism ; Vascular Diseases/metabolism ; Vascular Diseases/pathology ; Models, Theoretical ; Myocytes, Smooth Muscle ; Brain ; Cells, Cultured
Language	English
Publishing date	2023-05-05
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2170897-6
ISSN	1573-6814 ; 1389-9333
ISSN (online)	1573-6814
ISSN	1389-9333
DOI	10.1007/s10561-023-10091-3
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Article ; Online: Epilepsy and hypertension: The possible link for sudden unexpected death in epilepsy?

Szczurkowska, Patrycja J / Polonis, Katarzyna / Becari, Christiane / Hoffmann, Michał / Narkiewicz, Krzysztof / Chrostowska, Marzena

Cardiology journal

2019 Volume 28, Issue 2, Page(s) 330–335

Abstract: Epilepsy affects about 50 million people worldwide. Sudden unexpected death in epilepsy (SUDEP) is the main cause of death in epilepsy accounting for up to 17% of all deaths in epileptic patients, and therefore remains a major public health problem. ... ...

Abstract	Epilepsy affects about 50 million people worldwide. Sudden unexpected death in epilepsy (SUDEP) is the main cause of death in epilepsy accounting for up to 17% of all deaths in epileptic patients, and therefore remains a major public health problem. SUDEP likely arises from a combination and interaction of multiple risk factors (such as being male, drug resistance, frequent generalized tonic-clonic seizures) making risk prediction and mitigation challenging. While there is a general understanding of the physiopathology of SUDEP, mechanistic hypotheses linking risk factors with a risk of SUDEP are still lacking. Identifying cross-talk between biological systems implicated in SUDEP may facilitate the development of improved models for SUDEP risk assessment, treatment and clinical management. In this review, the aim was to explore an overlap between the pathophysiology of hypertension, cardiovascular disease and epilepsy, and discuss its implication for SUDEP. Presented herein, evidence in literature in support of a cross-talk between the renin-angiotensin system (RAS) and sympathetic nervous system, both known to be involved in the development of hypertension and cardiovascular disease, and as one of the underlying mechanisms of SUDEP. This article also provides a brief description of local RAS in brain neuroinflammation and the role of centrally acting RAS inhibitors in epileptic seizure alleviation.
MeSH term(s)	Death, Sudden ; Epilepsy ; Humans ; Hypertension ; Male ; Risk Factors ; Sudden Unexpected Death in Epilepsy
Language	English
Publishing date	2019-09-30
Publishing country	Poland
Document type	Journal Article ; Review
ZDB-ID	2488680-4
ISSN	1898-018X ; 1897-5593
ISSN (online)	1898-018X
ISSN	1897-5593
DOI	10.5603/CJ.a2019.0095
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Article ; Online: Cytokine storm in individuals with severe COVID-19 decreases endothelial cell antioxidant defense via downregulation of the Nrf2 transcriptional factor.

Rodrigues, Daniel / Machado, Mirele R / Alves, Juliano V / Fraga-Silva, Thais F C / Martins, Ronaldo B / Campos, Ligia C B / Francisco, Daniely F / Couto, Ariel E S / Bonato, Vânia L D / Arruda, Eurico / Becari, Christiane / Auxiliadora-Martins, Maria / Louzada-Júnior, Paulo / Costa, Rafael M / Tostes, Rita C

American journal of physiology. Heart and circulatory physiology

2023 Volume 325, Issue 2, Page(s) H252–H263

Abstract: The cytokine storm in SARS-CoV-2 infection contributes to the onset of inflammation and target-organ damage. The endothelium is a key player in COVID-19 pathophysiology and it is an important target for cytokines. Considering that cytokines trigger ... ...

Abstract	The cytokine storm in SARS-CoV-2 infection contributes to the onset of inflammation and target-organ damage. The endothelium is a key player in COVID-19 pathophysiology and it is an important target for cytokines. Considering that cytokines trigger oxidative stress and negatively impact endothelial cell function, we sought to determine whether serum from individuals with severe COVID-19 decreases endothelial cells' main antioxidant defense, i.e., the antioxidant transcriptional factor Nrf2. Human umbilical vein endothelial cells (HUVECs) were incubated with serum from patients with severe COVID-19 at different time points and the effects on redox balance and Nrf2 activity were determined. Serum from individuals with COVID-19 increased oxidant species, as indicated by higher DHE (dihydroethydine) oxidation, increased protein carbonylation, and induced mitochondrial reactive oxygen species (ROS) generation and dysfunction. Serum from patients with COVID-19, but not serum from healthy individuals, induced cell death and diminished nitric oxide (NO) bioavailability. In parallel, Nrf2 nuclear accumulation and the expression of Nrf2-targeted genes were decreased in endothelial cells exposed to serum from individuals with COVID-19. In addition, these cells exhibited higher expression of Bach-1, a negative regulator of Nrf2 that competes for DNA binding. All events were prevented by tocilizumab, an IL-6 receptor blocker, indicating that IL-6 is key to the impairment of endothelial antioxidant defense. In conclusion, endothelial dysfunction related to SARS-CoV-2 infection is linked to decreased endothelial antioxidant defense via IL-6-dependent mechanisms. Pharmacological activation of Nrf2 may decrease endothelial cell damage in individuals with severe COVID-19.
MeSH term(s)	Humans ; Antioxidants/pharmacology ; Antioxidants/metabolism ; NF-E2-Related Factor 2/metabolism ; Down-Regulation ; Cytokine Release Syndrome ; Interleukin-6/metabolism ; Cells, Cultured ; COVID-19 ; SARS-CoV-2/metabolism ; Oxidative Stress ; Human Umbilical Vein Endothelial Cells/metabolism ; Reactive Oxygen Species/metabolism ; Cytokines/metabolism
Chemical Substances	Antioxidants ; NF-E2-Related Factor 2 ; Interleukin-6 ; Reactive Oxygen Species ; Cytokines
Language	English
Publishing date	2023-06-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00096.2023
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Article ; Online: Inhibition of IL-6 signaling prevents serum-induced umbilical cord artery dysfunction from patients with severe COVID-19.

Almeida, Cellyne R / Lima, Júlia F / Machado, Mirele R / Alves, Juliano V / Couto, Ariel E S / Campos, Ligia C B / Avila-Mesquita, Carolina D / Auxiliadora-Martins, Maria / Becari, Christiane / Louzada-Júnior, Paulo / Tostes, Rita C / Lobato, Núbia S / Costa, Rafael M

American journal of physiology. Regulatory, integrative and comparative physiology

2023 Volume 324, Issue 4, Page(s) R435–R445

Abstract: Coronavirus disease 2019 (COVID-19) infection has a negative impact on the cytokine profile of pregnant women. Increased levels of proinflammatory cytokines seem to be correlated with the severity of the disease, in addition to predisposing to ... ...

Abstract	Coronavirus disease 2019 (COVID-19) infection has a negative impact on the cytokine profile of pregnant women. Increased levels of proinflammatory cytokines seem to be correlated with the severity of the disease, in addition to predisposing to miscarriage or premature birth. Proinflammatory cytokines increase the generation of reactive oxygen species (ROS). It is unclear how interleukin-6 (IL-6) found in the circulation of patients with severe COVID-19 might affect gestational health, particularly concerning umbilical cord function. This study tested the hypothesis that IL-6 present in the circulation of women with severe COVID-19 causes umbilical cord artery dysfunction by increasing ROS generation and activating redox-sensitive proteins. Umbilical cord arteries were incubated with serum from healthy women and women with severe COVID-19. Vascular function was assessed using concentration-effect curves to serotonin in the presence or absence of pharmacological agents, such as tocilizumab (antibody against the IL-6 receptor), tiron (ROS scavenger), ML171 (Nox1 inhibitor), and Y27632 (Rho kinase inhibitor). ROS generation was assessed by the dihydroethidine probe and Rho kinase activity by an enzymatic assay. Umbilical arteries exposed to serum from women with severe COVID-19 were hyperreactive to serotonin. This effect was abolished in the presence of tocilizumab, tiron, ML171, and Y27632. In addition, serum from women with severe COVID-19 increased Nox1-dependent ROS generation and Rho kinase activity. Increased Rho kinase activity was abolished by tocilizumab and tiron. Serum cytokines in women with severe COVID-19 promote umbilical artery dysfunction. IL-6 is key to Nox-linked vascular oxidative stress and activation of the Rho kinase pathway.
MeSH term(s)	Female ; Humans ; Pregnancy ; 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt ; Arteries/metabolism ; COVID-19 ; Cytokines ; Interleukin-6 ; Reactive Oxygen Species/metabolism ; rho-Associated Kinases ; Serotonin ; Umbilical Cord
Chemical Substances	1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt (4X87R5T106) ; 2-acetylphenothiazine ; Cytokines ; Interleukin-6 ; Reactive Oxygen Species ; rho-Associated Kinases (EC 2.7.11.1) ; Serotonin (333DO1RDJY) ; Y 27632 (138381-45-0) ; IL6 protein, human
Language	English
Publishing date	2023-02-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00154.2022
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Article ; Online: Assessment of physicians' knowledge about brain death and organ donation and associated factors.

Fernandes Vasconcelos, Tauana / Gonçalves Menegueti, Mayra / Corsi, Carlos Alexandre Curylofo / Michelon-Barbosa, Jéssyca / Sato, Lucas / Basile-Filho, Anibal / Becari, Christiane / Dantas, Rosana Aparecida Spadoti / Auxiliadora-Martins, Maria

Medicine

2022 Volume 101, Issue 38, Page(s) e30793

Abstract: Precocity and assertiveness when diagnosing brain death are essential for identifying potential donors. To assess the knowledge of physicians about brain death and organ donation, cross-sectional web-based survey was carried out with physicians from ... ...

Abstract	Precocity and assertiveness when diagnosing brain death are essential for identifying potential donors. To assess the knowledge of physicians about brain death and organ donation, cross-sectional web-based survey was carried out with physicians from different specialties. The knowledge about brain death and organ donation was assessed by a questionnaire with 12 multiple-choice or multiple-answer questions (possible range from 0 to 12). The nonparametric Mann-Whitney and Kruskal-Wallis tests were performed to verify the association between the physicians' knowledge and others variables. The project was approved by the Research Ethics Committee of the Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, under number 4.022.657, and all patients agreed to participate and provided free prior-informed consent. Three hundred sixty physicians were included in this study, most of them have postgraduate (55%) and 59.2% were intensive care physicians. The median of responses was 5 (obtained range from 0 to 10). The participants were classified in 2 groups: with satisfactory knowledge (scores above 5) or without satisfactory knowledge (scores equal/below 5). There was better performance among participants who: completed graduation between 6 and 10 years (P < .012); were intensive care physicians (P < .002); had participated in training courses (P < .001); and those who had worked in intensive care unit (ICU) from 6 to 10 years (P < .023); had performed over 10 brain death protocols (P < .001), and felt safe to talk to family members about brain death (P < .001). The results showed that the participants had low knowledge about diagnosis of brain death and organ donation protocols despite the majority working in ICUs. Be an intensive care physician, had large time experience in ICU, and had performed brain death protocols were associated with unsatisfactory knowledge concerning the subject.
MeSH term(s)	Attitude of Health Personnel ; Brain Death/diagnosis ; Cross-Sectional Studies ; Health Knowledge, Attitudes, Practice ; Humans ; Intensive Care Units ; Physicians ; Surveys and Questionnaires ; Tissue and Organ Procurement
Language	English
Publishing date	2022-10-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000030793
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