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  1. Article ; Online: Pulmonary pathology of ARDS in COVID-19: A pathological review for clinicians.

    Batah, Sabrina Setembre / Fabro, Alexandre Todorovic

    Respiratory medicine

    2020  Volume 176, Page(s) 106239

    Abstract: COVID-19 has quickly reached pandemic levels since it was first reported in December 2019. The virus responsible for the disease, named SARS-CoV-2, is enveloped positive-stranded RNA viruses. During its replication in the cytoplasm of host cells, the ... ...

    Abstract COVID-19 has quickly reached pandemic levels since it was first reported in December 2019. The virus responsible for the disease, named SARS-CoV-2, is enveloped positive-stranded RNA viruses. During its replication in the cytoplasm of host cells, the viral genome is transcribed into proteins, such as the structural protein spike domain S1, which is responsible for binding to the cell receptor of the host cells. Infected patients have initially flu-like symptoms, rapidly evolving to severe acute lung injury, known as acute respiratory distress syndrome (ARDS). ARDS is characterized by an acute and diffuse inflammatory damage into the alveolar-capillary barrier associated with a vascular permeability increase and reduced compliance, compromising gas exchange and causing hypoxemia. Histopathologically, this condition is known as diffuse alveolar damage which consists of permanent damage to the alveoli epithelial cells and capillary endothelial cells, with consequent hyaline membrane formation and eventually intracapillary thrombosis. All of these mechanisms associated with COVID-19 involve the phenotypic expression from different proteins transcription modulated by viral infection in specific pulmonary microenvironments. Therefore, this knowledge is fundamentally important for a better pathophysiological understanding and identification of the main molecular pathways associated with the disease evolution. Evidently, clinical findings, signs and symptoms of a patient are the phenotypic expression of these pathophysiological and molecular mechanisms of SARS-CoV-2 infection. Therefore, no findings alone, whether molecular, clinical, radiological or pathological axis are sufficient for an accurate diagnosis. However, their intersection and/or correlation are extremely critical for clinicians establish the diagnosis and new treatment perspectives.
    MeSH term(s) COVID-19/complications ; COVID-19/pathology ; Humans ; Respiratory Distress Syndrome/pathology ; Respiratory Distress Syndrome/virology ; SARS-CoV-2/pathogenicity
    Language English
    Publishing date 2020-11-19
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1003348-8
    ISSN 1532-3064 ; 0954-6111
    ISSN (online) 1532-3064
    ISSN 0954-6111
    DOI 10.1016/j.rmed.2020.106239
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The role of

    Forgerini, Marcela / Urbano, Gustavo / De Nadai, Tales Rubens / Batah, Sabrina Setembre / Fabro, Alexandre Todorovic / De Carvalho Mastroianni, Patrícia

    Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques

    2023  Volume 26, Page(s) 11136

    Abstract: Purpose: ...

    Abstract Purpose:
    MeSH term(s) Humans ; Cytochrome P-450 CYP2C9/genetics ; Case-Control Studies ; Gastrointestinal Hemorrhage/chemically induced ; Gastrointestinal Hemorrhage/genetics ; Aspirin/adverse effects ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Genotype ; Anticoagulants ; Vitamin K Epoxide Reductases/genetics
    Chemical Substances Cytochrome P-450 CYP2C9 (EC 1.14.13.-) ; Aspirin (R16CO5Y76E) ; Anti-Inflammatory Agents, Non-Steroidal ; Anticoagulants ; CYP2C9 protein, human (EC 1.14.13.-) ; VKORC1 protein, human (EC 1.17.4.4) ; Vitamin K Epoxide Reductases (EC 1.17.4.4)
    Language English
    Publishing date 2023-01-30
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1422972-9
    ISSN 1482-1826 ; 1482-1826
    ISSN (online) 1482-1826
    ISSN 1482-1826
    DOI 10.3389/jpps.2023.11136
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  3. Article ; Online: Pulmonary pathology of ARDS in COVID-19: A pathological review for clinicians

    Batah, Sabrina Setembre / Fabro, Alexandre Todorovic

    Respir Med

    Abstract: COVID-19 has quickly reached pandemic levels since it was first reported in December 2019. The virus responsible for the disease, named SARS-CoV-2, is enveloped positive-stranded RNA viruses. During its replication in the cytoplasm of host cells, the ... ...

    Abstract COVID-19 has quickly reached pandemic levels since it was first reported in December 2019. The virus responsible for the disease, named SARS-CoV-2, is enveloped positive-stranded RNA viruses. During its replication in the cytoplasm of host cells, the viral genome is transcribed into proteins, such as the structural protein spike domain S1, which is responsible for binding to the cell receptor of the host cells. Infected patients have initially flu-like symptoms, rapidly evolving to severe acute lung injury, known as acute respiratory distress syndrome (ARDS). ARDS is characterized by an acute and diffuse inflammatory damage into the alveolar-capillary barrier associated with a vascular permeability increase and reduced compliance, compromising gas exchange and causing hypoxemia. Histopathologically, this condition is known as diffuse alveolar damage which consists of permanent damage to the alveoli epithelial cells and capillary endothelial cells, with consequent hyaline membrane formation and eventually intracapillary thrombosis. All of these mechanisms associated with COVID-19 involve the phenotypic expression from different proteins transcription modulated by viral infection in specific pulmonary microenvironments. Therefore, this knowledge is fundamentally important for a better pathophysiological understanding and identification of the main molecular pathways associated with the disease evolution. Evidently, clinical findings, signs and symptoms of a patient are the phenotypic expression of these pathophysiological and molecular mechanisms of SARS-CoV-2 infection. Therefore, no findings alone, whether molecular, clinical, radiological or pathological axis are sufficient for an accurate diagnosis. However, their intersection and/or correlation are extremely critical for clinicians establish the diagnosis and new treatment perspectives.
    Keywords covid19
    Publisher Elsevier; PMC
    Document type Article ; Online
    DOI 10.1016/j.rmed.2020.106239
    Database COVID19

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  4. Article: Genetic Variants in

    Forgerini, Marcela / Urbano, Gustavo / de Nadai, Tales Rubens / Batah, Sabrina Setembre / Fabro, Alexandre Todorovic / Mastroianni, Patrícia de Carvalho

    Frontiers in pharmacology

    2021  Volume 12, Page(s) 671835

    Abstract: Objective: ...

    Abstract Objective:
    Language English
    Publishing date 2021-07-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2021.671835
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  5. Article ; Online: A methanolic extract of Eclipta prostrata (L.) L. decreases inflammation in a murine model of chronic allergic asthma via inhibition of the NF-kappa-B pathway.

    Morel, Lucas Junqueira de Freitas / Carmona, Fabio / Guimarães, Camila Carla / Moreira, Letícia Gabriela Quieroz / Leão, Patricia Dos Santos / Crevelin, Eduardo José / Batah, Sabrina Setembre / Fabro, Alexandre Todorovic / França, Suzelei de Castro / Borges, Marcos de Carvalho / Pereira, Ana Maria Soares

    Journal of ethnopharmacology

    2023  Volume 318, Issue Pt B, Page(s) 116930

    Abstract: Ethnopharmacological relevance: Eclipta prostrata (L.) L. is a medicinal plant used by many ethnic groups in Brazil to treat respiratory diseases, hepatitis and the bites of venomous animals. A methanolic extract of E. prostrata (MEEP), the major ... ...

    Abstract Ethnopharmacological relevance: Eclipta prostrata (L.) L. is a medicinal plant used by many ethnic groups in Brazil to treat respiratory diseases, hepatitis and the bites of venomous animals. A methanolic extract of E. prostrata (MEEP), the major components of which are wedelolactone (WED) and demethylwedelolactone (DMW), exhibited anti-inflammatory activity in acute asthma models but the effects on lung inflammation and the mechanisms of action of MEEP in a chronic asthma model are not known.
    Aim of the study: To study the effects of MEEP in vivo using a chronic ovalbumin (OVA)-induced allergic asthma model in mice.
    Materials and methods: The identities of WED and DMW in MEEP were confirmed and the concentrations determined by liquid chromatography and tandem mass spectrometry. Male Balb/c mice were sensitized and challenged with OVA and experimental animals were treated with MEEP (100, 250 or 500 mg/kg) while control animals were treated with dexamethasone (2 mg/kg) or normal saline. Bronchial hyperresponsiveness, total and differential cell counts in bronchoalveolar lavage (BAL), and the production of Th2 cytokines in lung homogenates were assessed. Lung inflammation and mucus production were evaluated by histological analysis while nuclear factor kappa-B (NF-κB) activation was assessed immunohistochemically.
    Results: Concentrations of WED and DMW in MEEP were 5.12% and 1.04%, respectively. Treatments with MEEP (250 or 500 mg/kg) significantly decreased bronchial hyperresponsiveness, reduced total cell and eosinophil counts in BAL and IL-4 concentrations in lung homogenate, and inhibited NF-κB activation. Treatment with MEEP at 500 mg/kg reduced the level of IL-5 in lung homogenates but did not decrease IL-13 concentration or mucus production.
    Conclusions: MEEP attenuated bronchial hyperresponsiveness and decreased lung and airway inflammation in a chronic asthma model in mice. The mechanism of action involves inhibition of NF-κB activation, most likely associated with the presence of the coumestans WED and DMW. These results support the ethnopharmacological evidence for the use of E. prostrata against asthma and other respiratory inflammatory diseases.
    MeSH term(s) Animals ; Mice ; NF-kappa B/metabolism ; Eclipta ; Methanol/therapeutic use ; Disease Models, Animal ; Bronchoalveolar Lavage Fluid ; Asthma/pathology ; Lung ; Hypersensitivity/pathology ; Inflammation/drug therapy ; Bronchial Hyperreactivity/drug therapy ; Ovalbumin/pharmacology ; Mice, Inbred BALB C
    Chemical Substances NF-kappa B ; Methanol (Y4S76JWI15) ; Ovalbumin (9006-59-1)
    Language English
    Publishing date 2023-07-23
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2023.116930
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  6. Article ; Online: Sexual dimorphism in the murine model of extraparenchymal neurocysticercosis.

    Moreira, Carlos Alexandre Aguiar / Murayama, Luis Henrique Vallesquino / Martins, Tatiane de Camargo / Oliveira, Vinicius Tadeu / Generoso, Diego / Machado, Vania Maria de Vasconcelos / Batah, Sabrina Setembre / Fabro, Alexandre Todorovic / Bazan, Rodrigo / Zanini, Marco Antônio / Sciutto, Edda / Fleury, Agnès / Hamamoto Filho, Pedro Tadao

    Parasitology research

    2023  Volume 122, Issue 9, Page(s) 2147–2154

    Abstract: Neurocysticercosis is a heterogeneous disease, and the patient's sex seems to play a role in this heterogeneity. Hosts' sexual dimorphism in cysticercosis has been largely explored in the murine model of intraperitoneal Taenia crassiceps cysticercosis. ... ...

    Abstract Neurocysticercosis is a heterogeneous disease, and the patient's sex seems to play a role in this heterogeneity. Hosts' sexual dimorphism in cysticercosis has been largely explored in the murine model of intraperitoneal Taenia crassiceps cysticercosis. In this study, we investigated the sexual dimorphism of inflammatory responses in a rat model of extraparenchymal neurocysticercosis caused by T. crassiceps. T. crassiceps cysticerci were inoculated in the subarachnoid space of Wistar rats (25 females, 22 males). Ninety days later, the rats were euthanized for histologic, immunohistochemistry, and cytokines studies. Ten animals also underwent a 7-T magnetic resonance imaging (MRI). Female rats presented a higher concentration of immune cells in the arachnoid-brain interface, reactive astrogliosis in the periventricular region, in situ pro-inflammatory cytokine (interleukin [IL]-6) and anti-inflammatory cytokine (IL-10), and more intense hydrocephalus on MRI than males. Intracranial hypertension signals were not observed during the observational period. Overall, these results suggest sexual dimorphism in the intracranial inflammatory response that accompanied T. crassiceps extraparenchymal neurocysticercosis.
    MeSH term(s) Male ; Mice ; Female ; Rats ; Animals ; Neurocysticercosis/diagnostic imaging ; Neurocysticercosis/pathology ; Disease Models, Animal ; Sex Characteristics ; Rats, Wistar ; Cysticercosis ; Taenia ; Cytokines ; Interleukin-6 ; Mice, Inbred BALB C
    Chemical Substances Cytokines ; Interleukin-6
    Language English
    Publishing date 2023-07-10
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 284966-5
    ISSN 1432-1955 ; 0932-0113 ; 0044-3255
    ISSN (online) 1432-1955
    ISSN 0932-0113 ; 0044-3255
    DOI 10.1007/s00436-023-07913-4
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  7. Article ; Online: Effects of early exercise on cardiac function and lipid metabolism pathway in heart failure.

    de Souza, Sérgio Luiz Borges / Mota, Gustavo Augusto Ferreira / da Silva, Vitor Loureiro / Vileigas, Danielle Fernandes / Sant'Ana, Paula Grippa / Gregolin, Cristina Schmitt / Figueira, Rebeca Lopes / Batah, Sabrina Setembre / Fabro, Alexandre Todorovic / Murata, Gilson Masahiro / Bazan, Silmeia Garcia Zanati / Okoshi, Marina Politi / Cicogna, Antonio Carlos

    Journal of cellular and molecular medicine

    2023  Volume 27, Issue 19, Page(s) 2956–2969

    Abstract: We employed an early training exercise program, immediately after recovery from surgery, and before severe cardiac hypertrophy, to study the underlying mechanism involved with the amelioration of cardiac dysfunction in aortic stenosis (AS) rats. As ET ... ...

    Abstract We employed an early training exercise program, immediately after recovery from surgery, and before severe cardiac hypertrophy, to study the underlying mechanism involved with the amelioration of cardiac dysfunction in aortic stenosis (AS) rats. As ET induces angiogenesis and oxygen support, we aimed to verify the effect of exercise on myocardial lipid metabolism disturbance. Wistar rats were divided into Sham, trained Sham (ShamT), AS and trained AS (AST). The exercise consisted of 5-week sessions of treadmill running for 16 weeks. Statistical analysis was conducted by anova or Kruskal-Wallis test and Goodman test. A global correlation between variables was also performed using a two-tailed Pearson's correlation test. AST rats displayed a higher functional capacity and a lower cardiac remodelling and dysfunction when compared to AS, as well as the myocardial capillary rarefaction was prevented. Regarding metabolic properties, immunoblotting and enzymatic assay raised beneficial effects of exercise on fatty acid transport and oxidation pathways. The correlation assessment indicated a positive correlation between variables of angiogenesis and FA utilisation, as well as between metabolism and echocardiographic parameters. In conclusion, early exercise improves exercise tolerance and attenuates cardiac structural and functional remodelling. In parallel, exercise attenuated myocardial capillary and lipid metabolism derangement in rats with aortic stenosis-induced heart failure.
    MeSH term(s) Rats ; Animals ; Rats, Wistar ; Lipid Metabolism ; Physical Conditioning, Animal ; Heart Failure/metabolism ; Aortic Valve Stenosis
    Language English
    Publishing date 2023-08-31
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2074559-X
    ISSN 1582-4934 ; 1582-4934 ; 1582-1838
    ISSN (online) 1582-4934
    ISSN 1582-4934 ; 1582-1838
    DOI 10.1111/jcmm.17908
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  8. Article: SARS-Cov-2 pneumonia phenotyping on imaging exams of patients submitted to minimally invasive autopsy.

    Koenigkam-Santos, Marcel / Wada, Danilo Tadao / Benatti, Maira Nilson / Siyuan, Li / Batah, Sabrina Setembre / Cetlin, Andrea Antunes / de Menezes, Marcelo Bezerra / Fabro, Alexandre Todorovic

    Annals of translational medicine

    2022  Volume 10, Issue 3, Page(s) 140

    Abstract: Background: Correlation between pathology and imaging of the new SARS-Cov-2 disease (COVID-19) is scarce. This study aimed to characterize SARS-Cov-2 pneumonia on imaging of patients submitted to minimally invasive autopsy (MIA).: Methods: This ... ...

    Abstract Background: Correlation between pathology and imaging of the new SARS-Cov-2 disease (COVID-19) is scarce. This study aimed to characterize SARS-Cov-2 pneumonia on imaging of patients submitted to minimally invasive autopsy (MIA).
    Methods: This unicentric retrospective observational study included 46 consecutive patients with confirmed COVID-19 who underwent MIA. All clinical chest images were reviewed and classified for the presence and grade of viral pneumonia, as well as disease evolution. On CT, phenotypes were described as consistent with mild, moderate, or severe viral pneumonia, with or without radiological signs of organizing pneumonia (OP). In severe pneumonia, CT could also be classified as diffuse progressive OP or radiological diffuse alveolar damage (DAD). Specific features on CT were noted, including fibroproliferative signs that could indicate potential or initial fibrosis.
    Results: MIA showed a heterogeneous panel of alterations, with a high prevalence of OP and acute fibrinous and organizing pneumonia (AFOP). Also, signs of interstitial fibrosis corresponded to the most prevalent pathological feature. Initial chest radiography (CXR) findings were mainly consistent with moderate or severe viral pneumonia. Most patients showed stability or improvement (reduction of opacities) on imaging. CTs were performed on 15 patients. Consolidations were found in most patients, frequently showing features consistent with an OP phenotype. Fibroproliferative changes were also prevalent on CT.
    Conclusions: In this study, SARS-Cov-2 pneumonia showed heterogeneous radiological and pathological patterns. Signs of organization and potential or initial fibrosis were prevalent on both imaging and pathology. Imaging phenotyping may help to predict post-infection fibrosing interstitial pneumonitis in COVID-19.
    Language English
    Publishing date 2022-02-24
    Publishing country China
    Document type Journal Article
    ZDB-ID 2893931-1
    ISSN 2305-5847 ; 2305-5839
    ISSN (online) 2305-5847
    ISSN 2305-5839
    DOI 10.21037/atm-21-4354
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  9. Article ; Online: Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas' cardiomyopathy.

    Tanaka, Denise Mayumi / Fabricio, Camila Godoy / Marin-Neto, José A / de Barros Filho, Antônio Carlos Leite / de Oliveira, Luciano Fonseca Lemos / Mejia, Jorge / Almeida, Rafael Ribeiro / de Souza Vieira, Raquel / Lopes, Carla Duque / Batah, Sabrina Setembre / Moreira, Henrique Turin / de Lourdes Higuchi, Maria / Neto, Edecio Cunha / Fabro, Alexandre Todorovic / Nekolla, Stephan G / Romano, Minna Moreira Dias / Simões, Marcus Vinícius

    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology

    2023  Volume 30, Issue 6, Page(s) 2327–2337

    Abstract: Background: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce ... ...

    Abstract Background: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters.
    Methods and results: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm
    Conclusions: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.
    MeSH term(s) Cricetinae ; Animals ; Female ; Chagas Cardiomyopathy/diagnostic imaging ; Pentoxifylline/pharmacology ; Pentoxifylline/therapeutic use ; Stroke Volume ; Ventricular Function, Left ; Tomography, X-Ray Computed ; Chagas Disease ; Inflammation ; Perfusion
    Chemical Substances Pentoxifylline (SD6QCT3TSU)
    Language English
    Publishing date 2023-05-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1212505-2
    ISSN 1532-6551 ; 1071-3581
    ISSN (online) 1532-6551
    ISSN 1071-3581
    DOI 10.1007/s12350-023-03270-y
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  10. Article ; Online: COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.

    Barreto, Ester A / Cruz, Amanda S / Veras, Flavio P / Martins, Ronaldo / Bernardelli, Rafaella S / Paiva, Isadora M / Lima, Thais M / Singh, Youvika / Guimarães, Raphael C / Damasceno, Samara / Pereira, Nayara / Alves, João Manoel / Gonçalves, Tiago T / Forato, Julia / Muraro, Stéfanie P / Souza, Gabriela F / Batah, Sabrina Setembre / Proenca-Modena, José L / Mori, Marcelo A /
    Cunha, Fernando Q / Louzada-Junior, Paulo / Cunha, Thiago M / Nakaya, Helder I / Fabro, Alexandre / de Oliveira, Renê D R / Arruda, Eurico / Réa, Rosângela / Réa Neto, Álvaro / Fernandes da Silva, Miguel M / Leiria, Luiz Osório

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 21, Page(s) e2217119120

    Abstract: Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes ... ...

    Abstract Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones.
    MeSH term(s) Humans ; COVID-19/complications ; SARS-CoV-2 ; Gluconeogenesis ; Blood Glucose ; Retrospective Studies ; Hepatocytes ; Hyperglycemia/complications ; Glucose
    Chemical Substances Blood Glucose ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-05-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2217119120
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