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1.
J Med Microbiol ; 70(7)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34259621

RESUMO

Introduction. Contamination of specimens and overuse of broad spectrum antibiotics contribute to false positives and false negatives, respectively. Therefore, useful and applicable biomarkers of bacteremia are still required.Hypothesis/Gap Statement. IL-6 can be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection.Aim. We aimed to evaluate the diagnostic efficiency of neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating Gram-negative (G-) bacteria from Gram-positive (G+) bacteria and fungi in febrile patients.Methodology. A total of 567 patients with fever were evaluated. Serum levels of IL-6, PCT, NLR and CRP were compared among a G- group (n=188), a G+ group (n=168), a fungal group (n=38) and a culture negative group (n=173). Sensitivity, specificity, Yuden's index and area under the Receiver operating characteristic (ROC) curve (AUC) were obtained to analyse the diagnostic abilities of these biomarkers in discriminating bloodstream infection caused by different pathogens.Results. Serum IL-6 and PCT in the G- group increased significantly when compared with both the G+ group and fungal group (P <0.05). AUC of IL-6 (0.767, 95 % CI:0.725-0.805) is higher than AUC of PCT (0.751, 95 % CI:0.708-0.796) in discriminating the G- group from G+ group. When discriminating the G- group from fungal group, the AUC of IL-6 (0.695, 95 % CI:0.651-0.747) with a cut-off value of 464.3 pg ml-1 was also higher than the AUC of PCT (0.630, 95 % CI:0.585-0.688) with a cut-off value of 0.68 ng ml-1. Additionally, AUC of NLR (0.685, 95 % CI:0.646-0.727) in discriminating the fungal group from G+ group at the cut-off value of 9.03, was higher than AUC of IL-6, PCT and CRP.Conclusion. This study suggests that IL-6 could be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. In addition, NLR is valuable to discriminate fungal infections from Gram-positive infections in febrile patients with a bloodstream infection.


Assuntos
Biomarcadores/sangue , Febre/sangue , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Positivas/sangue , Micoses/sangue , Adolescente , Adulto , Idoso , Contagem de Células Sanguíneas , Proteína C-Reativa/análise , Calcitonina/sangue , Análise Discriminante , Febre/diagnóstico , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Humanos , Interleucina-6/sangue , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico , Neutrófilos/citologia , Curva ROC , Estudos Retrospectivos , Adulto Jovem
2.
Acta Med Indones ; 53(2): 194-201, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34251348

RESUMO

Coronavirus disease 19 (COVID-19) which is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has been a problem worldwide, particularly due to the high rate of transmission and wide range of clinical manifestations. Acute respiratory distress syndrome (ARDS) and multiorgan failure are the most common events observed in severe cases and can be fatal. Cytokine storm syndrome emerges as one of the possibilities for the development of ARDS and multiorgan failure in severe cases of COVID-19. This case report describes a case of a 53-year-old male patient who has been diagnosed with COVID-19. Further evaluation in this patient showed that there was a marked increase in IL-6 level in blood accompanied with hyperferritinemia, which was in accordance with the characteristic of cytokine storm syndrome. Patient was treated with tocilizumab, a monoclonal antibody and is an antagonist to IL-6 receptor. The binding between tocilizumab and IL-6 receptors effectively inhibit and manage cytokine storm syndrome. Although this case report reported the efficacy of tocilizumab in managing cytokine storm syndrome, tocilizumab has several adverse effects requiring close monitoring. Further clinical randomized control trial is required to evaluate the efficacy and safety of tocilizumab administration in participants with various clinical characteristics and greater number of subjects.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/complicações , Síndrome da Liberação de Citocina/tratamento farmacológico , Biomarcadores/sangue , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , SARS-CoV-2
3.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203838

RESUMO

The phosphatidylinositol 3-kinase (PI3K) family of enzymes plays a determinant role in inflammation and autoimmune responses. However, the implication of the different isoforms of catalytic subunits in these processes is not clear. Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that entails innate and adaptive immune response elements in which PI3K is a potential hub for immune modulation. In a mouse transgenic model with T-cell-specific deletion of p110α catalytic chain (p110α-/-ΔT), we show the modulation of collagen-induced arthritis (CIA) by this isoform of PI3K. In established arthritis, p110α-/-ΔT mice show decreased prevalence of illness than their control siblings, higher IgG1 titers and lower levels of IL-6 in serum, together with decreased ex vivo Collagen II (CII)-induced proliferation, IL-17A secretion and proportion of naive T cells in the lymph nodes. In a pre-arthritis phase, at 13 days post-Ag, T-cell-specific deletion of p110α chain induced an increased, less pathogenic IgG1/IgG2a antibodies ratio; changes in the fraction of naive and effector CD4+ subpopulations; and an increased number of CXCR5+ T cells in the draining lymph nodes of the p110α-/-ΔT mice. Strikingly, T-cell blasts in vitro obtained from non-immunized p110α-/-ΔT mice showed an increased expression of CXCR5, CD44 and ICOS surface markers and defective ICOS-induced signaling towards Akt phosphorylation. These results, plus the accumulation of cells in the lymph nodes in the early phase of the process, could explain the diminished illness incidence and prevalence in the p110α-/-ΔT mice and suggests a modulation of CIA by the p110α catalytic chain of PI3K, opening new avenues of intervention in T-cell-directed therapies to autoimmune diseases.


Assuntos
Artrite Experimental/enzimologia , Artrite Experimental/patologia , Domínio Catalítico , Classe Ia de Fosfatidilinositol 3-Quinase/química , Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo , Linfócitos T/enzimologia , Animais , Anticorpos/sangue , Artrite Experimental/sangue , Artrite Experimental/imunologia , Biomarcadores/metabolismo , Proliferação de Células , Classe Ia de Fosfatidilinositol 3-Quinase/genética , Modelos Animais de Doenças , Deleção de Genes , Imunidade , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Interleucina-6/sangue , Linfonodos/patologia , Camundongos Endogâmicos C57BL , Transdução de Sinais
4.
Front Immunol ; 12: 619906, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194420

RESUMO

The role of sMAdCAM, an important gut immune migratory marker, remains unexplored in COVID-19 pathogenesis considering recent studies positing the gut as a sanctuary site for SARS-CoV-2 persistence. Thus, assimilating profiles of systemic inflammatory mediators with sMAdCAM levels may provide insights into the progression of COVID-19 disease. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. A cohort (n = 84) of SARS-C0V-2 infected individuals included a group of in-patients (n = 60) at various stages of disease progression together with convalescent individuals (n = 24) recruited between April and June 2020 from Mumbai, India. Follow-up of 35 in-patients at day 7 post diagnosis was carried out. Th1/Th2/Th17 cytokines along with soluble MAdCAM (sMAdCAM) levels in plasma were measured. Also, anti-viral humoral response as measured by rapid antibody test (IgG, IgM), Chemiluminescent Immunoassay (IgG), and antibodies binding to SARS-CoV-2 proteins were measured by Surface Plasmon Resonance (SPR) from plasma. IL-6 and sMAdCAM levels among in-patients inversely correlated with one another. When expressed as a novel integrated marker-sMIL index (sMAdCAM/IL-6 ratio)-these levels were incrementally and significantly higher in various disease states with convalescents exhibiting the highest values. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association response units of receptor binding domain and fold change in binding to spike respectively as measured by SPR. Our results highlight key systemic and gut homing parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19.


Assuntos
COVID-19/imunologia , Moléculas de Adesão Celular/sangue , Interleucina-6/sangue , Mucoproteínas/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Estudos de Coortes , Citocinas/sangue , Progressão da Doença , Feminino , Humanos , Intestinos/imunologia , Masculino , Pessoa de Meia-Idade , Ressonância de Plasmônio de Superfície , Adulto Jovem
5.
Int J Med Sci ; 18(13): 2789-2798, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220307

RESUMO

Coronavirus disease 2019 (COVID-19) has spread widely in the communities in many countries. Although most of the mild patients could be cured by their body's ability to self-heal, many patients quickly progressed to severe disease and had to undergo treatment in the intensive care unit (ICU). Thus, it is very important to effectively predict which patients with mild disease are more likely to progress to severe disease. A total of 72 patients hospitalized with COVID-19 in Shandong Provincial Public Health Clinical Center and 1141 patients included in the published papers were enrolled in this study. We determined that the combination of interleukin-6 (IL-6), Neutrophil (NEUT), and Natural Killer (NK) cells had the highest prediction accuracy (with 75% sensitivity and 95% specificity) for progression of COVID-19 infection. A binomial regression equation that accounted for a multiple risk score for the combination of IL-6, NEUT, and NK was also established. The multiple risk score is a good indicator for early stratification of mild patients into risk categories, which is very important for adjusting the treatment plan and preventing death.


Assuntos
Biomarcadores/análise , COVID-19/etiologia , Idoso , Biomarcadores/sangue , Contagem de Células Sanguíneas , COVID-19/epidemiologia , Comorbidade , Progressão da Doença , Humanos , Interleucina-6/sangue , Células Matadoras Naturais , Pessoa de Meia-Idade , Neutrófilos , Estudos Retrospectivos
6.
Sci Rep ; 11(1): 14471, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262116

RESUMO

Early detection of severe forms of COVID-19 is absolutely essential for timely triage of patients. We longitudinally followed-up two well-characterized patient groups, hospitalized moderate to severe (n = 26), and ambulatory mild COVID-19 patients (n = 16) at home quarantine. Human D-dimer, C-reactive protein (CRP), ferritin, cardiac troponin I, interleukin-6 (IL-6) levels were measured on day 1, day 7, day 14 and day 28. All hospitalized patients were SARS-CoV-2 positive on admission, while all ambulatory patients were SARS-CoV-2 positive at recruitment. Hospitalized patients had higher D-dimer, CRP and ferritin, cardiac troponin I and IL-6 levels than ambulatory patients (p < 0.001, p < 0.001, p = 0.016, p = 0.035, p = 0.002 respectively). Hospitalized patients experienced significant decreases in CRP, ferritin and IL-6 levels from admission to recovery (p < 0.001, p = 0.025, and p = 0.001 respectively). Cardiac troponin I levels were high during the acute phase in both hospitalized and ambulatory patients, indicating a potential myocardial injury. In summary, D-dimer, CRP, ferritin, cardiac troponin I, IL-6 are predictive laboratory markers and can largely determine the clinical course of COVID-19, in particular the prognosis of critically ill COVID-19 patients.


Assuntos
COVID-19/sangue , COVID-19/diagnóstico , Assistência Ambulatorial , Biomarcadores/sangue , Proteína C-Reativa/análise , Diagnóstico Precoce , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Seguimentos , Hospitalização , Humanos , Interleucina-6/sangue , Estudos Longitudinais , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Medicina de Precisão , Prognóstico , Quarentena , SARS-CoV-2 , Índice de Gravidade de Doença , Troponina I/sangue
7.
BMC Med ; 19(1): 163, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34256745

RESUMO

BACKGROUND: Few studies had described the health consequences of patients with coronavirus disease 2019 (COVID-19) especially in those with severe infections after discharge from hospital. Moreover, no research had reported the health consequences in health care workers (HCWs) with COVID-19 after discharge. We aimed to investigate the health consequences in HCWs with severe COVID-19 after discharge from hospital in Hubei Province, China. METHODS: We conducted an ambidirectional cohort study in "Rehabilitation Care Project for Medical Staff Infected with COVID-19" in China. The participants were asked to complete three physical examinations (including the tests of functional fitness, antibodies to SARS-CoV-2 and immunological indicators) at 153.4 (143.3, 164.8), 244.3 (232.4, 259.1), and 329.4 (319.4, 339.3) days after discharge, respectively. Mann-Whitney U test, Kruskal-Wallis test, t test, one-way ANOVA, χ2, and Fisher's exact test were used to assess the variance between two or more groups where appropriate. RESULTS: Of 333 HCWs with severe COVID-19, the HCWs' median age was 36.0 (31.0, 43.0) years, 257 (77%) were female, and 191 (57%) were nurses. Our research found that 70.4% (114/162), 48.9% (67/137), and 29.6% (37/125) of the HCWs with severe COVID-19 were considered to have not recovered their functional fitness in the first, second, and third functional fitness tests, respectively. The HCWs showed improvement in muscle strength, flexibility, and agility/dynamic balance after discharge in follow-up visits. The seropositivity of IgM (17.0% vs. 6.6%) and median titres of IgM (3.0 vs. 1.4) and IgG (60.3 vs. 45.3) in the third physical examination was higher than that in the first physical examination. In the third physical examination, there still were 42.1% and 45.9% of the HCWs had elevated levels of IL-6 and TNF-α, and 11.9% and 6.3% of the HCWs had decreased relative numbers of CD3+ T cells and CD4+ T cells. CONCLUSION: The HCWs with severe COVID-19 showed improvement in functional fitness within 1 year after discharge, active intervention should be applied to help their recovery if necessary. It is of vital significance to continue monitoring the functional fitness, antibodies to SARS-CoV-2 and immunological indicators after 1 year of discharge from hospital in HCWs with severe COVID-19.


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19 , COVID-19 , Teste de Esforço , Pessoal de Saúde/estatística & dados numéricos , SARS-CoV-2/imunologia , Adulto , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/fisiopatologia , COVID-19/reabilitação , Teste Sorológico para COVID-19/métodos , Teste Sorológico para COVID-19/estatística & dados numéricos , China/epidemiologia , Teste de Esforço/métodos , Teste de Esforço/estatística & dados numéricos , Feminino , Seguimentos , Estado Funcional , Humanos , Interleucina-6/sangue , Masculino , Alta do Paciente/estatística & dados numéricos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue
9.
J Int Soc Sports Nutr ; 18(1): 42, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090451

RESUMO

OBJECTIVE: Systemic elevations in pro-inflammatory cytokines are a marker of non-functional over reaching, and betaine has been shown to reduce the secretion of pro-inflammatory cytokines in vitro. The aim of this study was to investigate the effects of betaine supplementation on tumor necrosis factor alpha (TNF-α), interleukins-1 beta (IL-1ß), - 6 (IL-6) and the complete blood cell (CBC) count in professional youth soccer players during a competitive season. METHODS: Twenty-nine soccer players (age, 15.5 ± 0.3 years) were randomly divided into two groups based on playing position: betaine group (BG, n = 14, 2 g/day) or placebo group (PG, n = 15). During the 14-week period, training load was matched and well-being indicators were monitored daily. The aforementioned cytokines and CBC were assessed at pre- (P1), mid- (P2), and post- (P3) season. RESULTS: Significant (p < 0.05) group x time interactions were found for TNF-α, IL-1ß, and IL-6. These variables were lower in the BG at P2 and P3 compared to P1, while IL-1ß was greater in the PG at P3 compared to P1 (p = 0.033). The CBC count analysis showed there was significant group by time interactions for white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), and mean corpuscular hemoglobin concentration (MCHC). WBC demonstrated increases at P3 compared to P2 in PG (p = 0.034); RBC was less at P3 compared to P1 in BG (p = 0.020); Hb was greater at P2 compared to P1, whilst it was less at P3 compared to P3 for both groups. MCHC was greater at P3 and P2 compared to P1 in BG, whereas MCHC was significantly lower at P3 compared to P2 in the PG (p = 0.003). CONCLUSION: The results confirmed that 14 weeks of betaine supplementation prevented an increase in pro-inflammatory cytokines and WBC counts. It seems that betaine supplementation may be a useful nutritional strategy to regulate the immune response during a fatiguing soccer season.


Assuntos
Betaína/administração & dosagem , Comportamento Competitivo/fisiologia , Citocinas/sangue , Suplementos Nutricionais , Futebol/fisiologia , Adolescente , Biomarcadores/sangue , Contagem de Células Sanguíneas , Método Duplo-Cego , Índices de Eritrócitos , Hemoglobinometria , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue
10.
Medicine (Baltimore) ; 100(22): e26131, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087864

RESUMO

ABSTRACT: To evaluate the development of coronavirus disease 2019 (COVID-19), the roles of interleukin 6 (IL-6) and procalcitonin (PCT) were assessed to diagnose severe COVID-19.Between January and February 2020, 100 consecutive patients with confirmed COVID-19 were included and divided into common (n = 56), severe (n = 28), and critical (n = 16) groups.IL-6 and PCT levels were assayed and compared among groups. IL-6 levels were significantly different among groups (common, 23.93±9.64 pg/mL; severe, 69.22 ±â€Š22.98 pg/mL; critical, 160.34 ±â€Š26.15 pg/mL; P < .05), and there was also a significant difference in the levels of PCT among groups (common, 0.23 ±â€Š0.13 ng/mL; severe, 0.38 ±â€Š0.16 ng/mL; critical, 0.73 ±â€Š0.36 ng/mL; P < .05). Further analysis showed that patients in the critical group had the highest levels of IL-6 and PCT, and those in the common group had the lowest levels (all P < .05).IL-6 and PCT are associated with the severity of COVID-19, and thus have potential value in the diagnosis of COVID-19.


Assuntos
COVID-19/sangue , Interleucina-6/sangue , Pró-Calcitonina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto Jovem
11.
PLoS One ; 16(6): e0253894, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34185801

RESUMO

OBJECTIVE: To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. METHODS: A search with standardized descriptors and synonyms was performed on November 28th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters-including serum interleukin-6 levels-from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. DATA SYNTHESIS: The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases. CONCLUSIONS: This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.


Assuntos
Biomarcadores/sangue , COVID-19/patologia , Síndrome da Liberação de Citocina/diagnóstico , Proteína C-Reativa/análise , COVID-19/complicações , COVID-19/mortalidade , COVID-19/virologia , Síndrome da Liberação de Citocina/etiologia , Ferritinas/sangue , Humanos , Interleucina-6/sangue , Leucócitos/citologia , Leucócitos/metabolismo , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
12.
Medicine (Baltimore) ; 100(25): e26426, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160431

RESUMO

INTRODUCTION: Esophagectomy is a major surgery with a high degree of catabolic and post-surgical inflammatory response accompanied by high morbidity and significant mortality. Post-surgical nutritional support via enteral administration of ω-3 fatty acids has been seen to be effective although its bad tolerance. There are few clinical trials with parenteral ω-3 fatty acids in these patients. We propose to investigate the effect of combining a parenteral fish oil lipid emulsion with the standard enteral nutrition (EN) support. MATERIALS AND METHODS: Prospective, single-center, randomized, double-blind study in esophagectomized patients, and treated after surgery with parenteral lipid emulsions of ω-3 fatty acids or a mixture of ω-6 long-chain triglycerides/short-chain triglycerides 50%. These emulsions will be added to the standard nutritional support in continuous infusion until 5 days of treatment have been completed. Patients will be randomized 1:1:1 in Group A receiving 0.4 g/kg/d of fish-oil lipid emulsion and 0.4 g/kg/d of a lipid emulsion mixture of ω-6 long-chain fatty acids (LCT) plus medium-chain fatty acids (MCT) (total dose of 0.8 g/kg/d of lipid emulsion); Group B receiving 0.8 g/kg/d of fish oil lipid emulsion and Group C receiving 0.8 g/kg/d of LCT/MCT emulsion.The main objective is to determine whether 5 days administration of intravenous ω-3 fatty acid lipid emulsion is effective in normalizing interleukin-6 levels compared with LCT/MCT emulsions, and whether a 0.8 g/kg/d dose is more effective than 0.4 g/kg/d. Secondary outcomes include other inflammatory markers such as C-reactive protein, tumor necrosis factor alpha and interleukin-10, and parameters of morbidity, safety, nutrition and mortality.Samples will be collected at the time when surgery is indicated and on days 0, 1, 3, 5 and 21 to determine inflammatory, nutritional, hepatic and safety parameters. In addition, clinical follow-up will be continued throughout the hospital admision and up to 1 year after surgery. DISCUSSION: Studies of ω-3 fatty acids administered parenterally in esophagectomized patients are scarce. This study proposes to investigate the effect of combining fish-oil lipid emulsions administered parenterally with EN support. Potential benefits include fast incorporation of lipids to the cellular membranes and to the inflammatory cascade, and the use of only 1 pharmaconutrient. TRIAL REGISTRATION: FAR-NP-2017-01 EudraCT number: 2016-004978-17.https://reec.aemps.es/reec/public/detail.html searching the EudraCT number. VERSION IDENTIFIER: Version 2, 08/06/2017.


Assuntos
Esofagectomia/reabilitação , Emulsões Gordurosas Intravenosas/administração & dosagem , Óleos de Peixe/administração & dosagem , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/terapia , Adulto , Terapia Combinada/métodos , Método Duplo-Cego , Nutrição Enteral , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Feminino , Humanos , Interleucina-6/sangue , Interleucina-6/imunologia , Masculino , Nutrição Parenteral/métodos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/imunologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Sci Rep ; 11(1): 13134, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162948

RESUMO

COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48-72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50-60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with viremia were older (p = 0.006), had poorer baseline oxygenation (PaO2/FiO2; p < 0.001), more severe lymphopenia (p < 0.001) and higher LDH (p < 0.001), IL-6 (p = 0.021), C-reactive protein (CRP; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant viremia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35% specificity. Relevant viremia predicted death during hospitalization (OR 9.2 [3.8-22.6] for Roche, OR 10.3 [3.6-29.3] for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant viremia (HR = 9.87 [4.13-23.57] for TFS viremia and HR = 7.09 [3.3-14.82] for Roche viremia) as the best markers to predict mortality. Viremia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. Viremia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 and better predictive accuracy.


Assuntos
COVID-19/sangue , RNA Viral/sangue , SARS-CoV-2/genética , Viremia/sangue , Idoso , Biomarcadores/sangue , COVID-19/mortalidade , COVID-19/virologia , Cuidados Críticos , Feminino , Hospitalização , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , Espanha , Viremia/virologia
14.
J Int Soc Sports Nutr ; 18(1): 50, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34154603

RESUMO

BACKGROUND: Acute capsaicinoid and capsinoid supplementation has endurance and resistance exercise benefits; however, if these short-term performance benefits translate into chronic benefits when combined with resistance training is currently unknown. This study investigated changes of chronic Capsiate supplementation on muscular adaptations, inflammatory response and performance in untrained men. METHODS: Twenty untrained men were randomized to ingest 12 mg Capsiate (CAP) or placebo in a parallel, double-blind design. Body composition and performance were measured at pre-training and after 6 weeks of resistance training. An acute resistance exercise session test was performed pre and post-intervention. Blood samples were collected at rest and post-resistance exercise to analyze Tumor necrosis factor- (TNF-), Soluble TNF- receptor (sTNF-r), Interleukin-6 (IL-6) and Interleukin-10 (IL-10). RESULTS: Exercise and CAP supplementation increased fat-free mass in comparison to baseline by 1.5 kg (P < 0.001), however, the majority of the increase (1.0 kg) resulted from an increase in total body water. The CAP change scores for fat-free mass were significantly greater in comparison to the placebo (CAP ∆%= 2.1 ± 1.8 %, PLA ∆%= 0.7 ± 1.3 %, P = 0.043) and there was a significant difference between groups in the bench press exercise (P = 0.034) with greater upper body strength change score for CAP (∆%= 13.4 ± 9.1 %) compared to placebo (∆%= 5.8 ± 5.2 %), P = 0.041. CAP had no effect on lower body strength and no supplementation interactions were observed for all cytokines in response to acute resistance exercise (P > 0.05). CONCLUSION: Chronic Capsiate supplementation combined with resistance training during short period (6 weeks) increased fat-free mass and upper body strength but not inflammatory response and performance in young untrained men.


Assuntos
Capsaicina/análogos & derivados , Mediadores da Inflamação/sangue , Força Muscular/efeitos dos fármacos , Treinamento de Força/métodos , Adulto , Desempenho Atlético , Composição Corporal/efeitos dos fármacos , Água Corporal/efeitos dos fármacos , Água Corporal/metabolismo , Capsaicina/administração & dosagem , Capsaicina/farmacologia , Método Duplo-Cego , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Receptores do Fator de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
15.
Int J Biol Sci ; 17(8): 2124-2134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34131411

RESUMO

The efficacy of tocilizumab on the prognosis of severe/critical COVID-19 patients is still controversial so far. We aimed to delineate the inflammation characteristics of severe/critical COVID-19 patients and determine the impact of tocilizumab on hospital mortality. Here, we performed a retrospective cohort study which enrolled 727 severe or critical inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China), among which 50 patients received tocilizumab. This study confirmed that most recovered patients manifested relatively normal inflammation levels at admission, whereas most of the deceased cases presented visibly severe inflammation at admission and even progressed into extremely aggravated inflammation before their deaths, proved by some extremely high concentrations of interleukin-6, procalcitonin, C-reactive protein and neutrophil count. Moreover, based on the Cox proportional-hazards models before or after propensity score matching, we demonstrated that tocilizumab treatment could lessen mortality by gradually alleviating excessive inflammation and meanwhile continuously enhancing the levels of lymphocytes within 14 days for severe/critical COVID-19 patients, indicating potential effectiveness for treating COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/tratamento farmacológico , Inflamação/tratamento farmacológico , SARS-CoV-2 , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/mortalidade , COVID-19/fisiopatologia , Comorbidade , Feminino , Humanos , Inflamação/sangue , Interleucina-6/sangue , Tempo de Internação/estatística & dados numéricos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pró-Calcitonina/sangue , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos
16.
Sci Prog ; 104(2_suppl): 368504211026119, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34187224

RESUMO

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a vast number of infections and deaths that deeply affect the world. When the virus encounters the host cell, it binds to angiotensin-converting enzyme 2, then the S protein of the virus is broken down by the transmembrane protease serine 2 with the help of furin, allowing the virus to enter the cell. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome, may play a major role in the pathology of COVID-19. Therefore, the aim of this study is to investigate the relationship between circulating furin levels, disease severity, and inflammation in patients with SARS-CoV-2. A total of 52 SARS-CoV-2 patients and 36 healthy control participants were included in this study. SARS- CoV-2 patients were scored by the disease activity score. Serum furin, presepsin, and interleukin-6 (IL-6) levels were assessed using an enzyme-linked immunosorbent assay. The mean furin, presepsin, and IL-6 levels were significantly higher in the peripheral blood of SARS-CoV-2 compared to the controls (p < 0.001). There were close positive relationship between serum furin and IL-6, furin and presepsin, and furin and disease severity (r = 0.793, p < 0001; r = 0.521, p < 0.001; and r = 0,533, p < 0.001, respectively) in patients with SARS-CoV-2. These results suggest that furin may contribute to the exacerbation of SARS-CoV-2 infection and increased inflammation, and could be used as a predictor of disease severity in COVID-19 patients.


Assuntos
COVID-19/sangue , COVID-19/patologia , Furina/sangue , Interleucina-6/sangue , Receptores de Lipopolissacarídeos/sangue , Fragmentos de Peptídeos/sangue , SARS-CoV-2 , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo
17.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072601

RESUMO

The high mortality rate in septic shock patients is likely due to environmental and genetic factors, which influence the host response to infection. Two genome-wide association studies (GWAS) on 832 septic shock patients were performed. We used integrative bioinformatic approaches to annotate and prioritize the sepsis-associated single nucleotide polymorphisms (SNPs). An association of 139 SNPs with death based on a false discovery rate of 5% was detected. The most significant SNPs were within the CISH gene involved in cytokine regulation. Among the 139 SNPs associated with death and the 1311 SNPs in strong linkage disequilibrium with them, we investigated 1439 SNPs within non-coding regions to identify regulatory variants. The highest integrative weighted score (IW-score) was obtained for rs143356980, indicating that this SNP is a robust regulatory candidate. The rs143356980 region is located in a non-coding region close to the CISH gene. A CRISPR-Cas9-mediated deletion of this region and specific luciferase assays in K562 cells showed that rs143356980 modulates the enhancer activity in K562 cells. These analyses allowed us to identify several genes associated with death in patients with septic shock. They suggest that genetic variations in key genes, such as CISH, perturb relevant pathways, increasing the risk of death in sepsis patients.


Assuntos
Elementos Facilitadores Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Choque Séptico/etiologia , Choque Séptico/mortalidade , Proteínas Supressoras da Sinalização de Citocina/genética , Alelos , Biomarcadores , Biologia Computacional/métodos , Humanos , Interleucina-6/sangue , Anotação de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Prognóstico , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Curva ROC , Sequências Reguladoras de Ácido Nucleico , Reprodutibilidade dos Testes , Choque Séptico/metabolismo
18.
Virol J ; 18(1): 117, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088317

RESUMO

BACKGROUND: To date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. We determined the levels of inflammatory cytokines in patients with COVID-19 and their relationships with ARDS and extrapulmonary MOD. METHODS: The clinical and laboratory data of 94 COVID-19 patients with and without ARDS were analyzed. The levels of inflammatory cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α [TNF-α]) were measured on days 1, 3, and 5 following admission. Seventeen healthy volunteers were recruited as controls. Correlations in the levels of inflammatory cytokines with clinical and laboratory variables were analyzed, furthermore, we also explored the relationships of different cytokines with ARDS and extrapulmonary MOD. RESULTS: The ARDS group had higher serum levels of all 4 inflammatory cytokines than the controls, and these levels steadily increased after admission. The ARDS group also had higher levels of IL-6, IL-8, and IL-10 than the non-ARDS group, and the levels of these cytokines correlated significantly with coagulation parameters and disseminated intravascular coagulation (DIC). The levels of IL-6 and TNF-α correlated with the levels of creatinine and urea nitrogen, and were also higher in ARDS patients with acute kidney injury (AKI). All 4 inflammatory cytokines had negative correlations with PaO2/FiO2. IL-6, IL-8, and TNF-α had positive correlations with the APACHE-II score. Relative to survivors, non-survivors had higher levels of IL-6 and IL-10 at admission, and increasing levels over time. CONCLUSIONS: The cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients. The levels of IL-6, IL-8, and IL-10 correlated with DIC, and the levels of IL-6 and TNF-α were associated with AKI. Relative to survivors, patients who died within 28 days had increased levels of IL-6 and IL-10.


Assuntos
COVID-19/sangue , Síndrome da Liberação de Citocina/sangue , Citocinas/sangue , Síndrome do Desconforto Respiratório/sangue , Injúria Renal Aguda/diagnóstico , Idoso , Nitrogênio da Ureia Sanguínea , COVID-19/patologia , Creatinina/sangue , Síndrome da Liberação de Citocina/diagnóstico , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/patologia , Feminino , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Síndrome do Desconforto Respiratório/patologia , Estudos Retrospectivos , SARS-CoV-2 , Fator de Necrose Tumoral alfa/sangue
19.
PLoS One ; 16(6): e0252818, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34111164

RESUMO

Most deaths from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in older subjects. We assessed the utility of serum inflammatory markers interleukin-6 (IL-6), C reactive protein (CRP), and ferritin (Roche, Indianapolis, IN), and SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies (Diazyme, Poway, CA). In controls, non-hospitalized subjects, and hospitalized subjects assessed for SARS-CoV-2 RNA (n = 278), median IgG levels in arbitrary units (AU)/mL were 0.05 in negative subjects, 14.83 in positive outpatients, and 30.61 in positive hospitalized patients (P<0.0001). Neutralizing antibody levels correlated significantly with IgG (r = 0.875; P<0.0001). Having combined values of IL-6 ≥10 pg/mL and CRP ≥10 mg/L occurred in 97.7% of inpatients versus 1.8% of outpatients (odds ratio 3,861, C statistic 0.976, P = 1.00 x 10-12). Antibody or ferritin levels did not add significantly to predicting hospitalization. Antibody testing in family members and contacts of SARS-CoV-2 RNA positive cases (n = 759) was invaluable for case finding. Persistent IgM levels were associated with chronic COVID-19 symptoms. In 81,624 screened subjects, IgG levels were positive (≥1.0 AU/mL) in 5.21%, while IgM levels were positive in 2.96% of subjects. In positive subjects median IgG levels in AU/mL were 3.14 if <30 years of age, 4.38 if 30-44 years of age, 7.89 if 45-54 years of age, 9.52 if 55-64 years of age, and 10.64 if ≥65 years of age (P = 2.96 x 10-38). Our data indicate that: 1) combined IL-6 ≥10 pg/mL and CRP ≥10 mg/L identify SARS-CoV-2 positive subjects requiring hospitalization; 2) IgG levels were significantly correlated with neutralizing antibody levels with a wide range of responses; 3) IgG levels have significant utility for case finding in exposed subjects; 4) persistently elevated IgM levels are associated with chronic symptoms; and 5) IgG levels are significantly higher in positive older subjects than their younger counterparts.


Assuntos
COVID-19/sangue , Inflamação/sangue , Adulto , Fatores Etários , Idoso , Envelhecimento , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Proteína C-Reativa/análise , Proteína C-Reativa/imunologia , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/imunologia , Feminino , Ferritinas/sangue , Ferritinas/imunologia , Hospitalização , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Inflamação/diagnóstico , Inflamação/epidemiologia , Inflamação/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação
20.
BMC Infect Dis ; 21(1): 566, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34126960

RESUMO

BACKGROUND: Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 (COVID-19). We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with interleukin 6 (IL-6) levels and with disease severity and mortality in COVID-19. METHODS: We prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1 ± 14.1 years, 70 males) for severely-symptomatic COVID-19. Fifty-two subjects with SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and 206 subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at admission and focused on respiratory outcome during hospitalization. RESULTS: Severely-symptomatic COVID-19 patients had lower 25OHD levels (18.2 ± 11.4 ng/mL) than mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3 ± 8.5 ng/mL and 25.4 ± 9.4 ng/mL, respectively, p < 0.0001 for both comparisons). 25OHD and IL-6 levels were respectively lower and higher in severely-symptomatic COVID-19 patients admitted to intensive care Unit [(ICU), 14.4 ± 8.6 ng/mL and 43.0 (19.0-56.0) pg/mL, respectively], than in those not requiring ICU admission [22.4 ± 1.4 ng/mL, p = 0.0001 and 16.0 (8.0-32.0) pg/mL, p = 0.0002, respectively]. Similar differences were found when comparing COVID-19 patients who died in hospital [13.2 ± 6.4 ng/mL and 45.0 (28.0-99.0) pg/mL] with survivors [19.3 ± 12.0 ng/mL, p = 0.035 and 21.0 (10.5-45.9) pg/mL, p = 0.018, respectively). 25OHD levels inversely correlated with: i) IL-6 levels (ρ - 0.284, p = 0.004); ii) the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98-1.00, p = 0.011] regardless of age, gender, presence of at least 1 comorbidity among obesity, diabetes, arterial hypertension, creatinine, IL-6 and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count; iii) mortality (RR 0.97, 95%CI, 0.95-0.99, p = 0.011) regardless of age, gender, presence of diabetes, IL-6 and C-reactive protein and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count. CONCLUSION: In our COVID-19 patients, low 25OHD levels were inversely correlated with high IL-6 levels and were independent predictors of COVID-19 severity and mortality.


Assuntos
COVID-19/sangue , COVID-19/mortalidade , SARS-CoV-2/genética , Índice de Gravidade de Doença , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/epidemiologia , Calcifediol/administração & dosagem , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Unidades de Terapia Intensiva , Interleucina-6/sangue , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Admissão do Paciente , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Vitaminas/administração & dosagem
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