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1.
Saudi Med J ; 42(9): 994-1001, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34470838

RESUMO

OBJECTIVES: To analyze the prognostic value of serum presepsin value in community-acquired pneumonia focal sepsis using sepsis-3 criteria and its relationship with other biomarkers and clinical severity scores. METHODS: For this prospective observational study, 176 patients above 18 years old, diagnosed with community-acquired pneumonia, pneumonia focal sepsis and septic shock were included. It was performed in a tertiary hospital between May 2020 and December 2020. Blood samples were obtained from patients for presepsin levels at the time of diagnosis in the emergency room. The serum presepsin levels of 3 groups were statistically compared with each other. RESULTS: The sepsis group had significantly higher serum presepsin levels than the pneumonia group (p=0.004).The septic shock group had serum presepsin levels than sepsis group; however, the difference was not statistically significant (p=0.25). Non survivor patients had significantly higher serum presepsin levels than survivors (p=0.001). Significant correlation determined between serum presepsin level and procalcitonin, C-reactive protein, lactate, pneumonia severity index, and quick sequential organ failure assessment (qSOFA). CONCLUSION: Serum presepsin level is a new biomarker that can be used an indicator of sepsis and mortality in community-acquired pneumonia. However, for determining the prognosis of sepsis, there was no superiority detected over other biomarkers and clinical severity scores.


Assuntos
Fragmentos de Peptídeos/sangue , Pneumonia , Sepse , Adulto , Biomarcadores/sangue , Humanos , Receptores de Lipopolissacarídeos , Pneumonia/diagnóstico , Prognóstico , Sepse/diagnóstico
3.
Ann R Coll Surg Engl ; 103(8): 604-611, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34464565

RESUMO

INTRODUCTION: A novel hyperinflammatory syndrome has emerged in the paediatric population: paediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 (PIMS-TS). Up to 50% of patients develop shock with cardiac dysfunction but presentation with acute abdominal pain is common and difficult to distinguish from appendicitis. METHOD: Prospective case series of PIMS-TS patients presenting to a single UK tertiary paediatric centre. RESULTS: As of 16 September 2020, 89 patients have presented with PIMS-TS to our institution; 19 (21.3%) were referred for surgical review. Pyrexia and acute abdominal pain were seen in all 19 patients. Diarrhoea was reported in 14 (73%) and vomiting in 12 (63%). On examination, eight (42%) had right abdominal tenderness, of which five had right iliac fossa (RIF) peritonism. C-reactive protein (CRP) was universally raised: median 176 (15-463)mg/l. Abdominal imaging was performed in 17 (89%), with 11 undergoing abdominal ultrasonography (65%) and 8 abdominal computed tomography (47%); two required both. Findings included nonspecific features of inflammation in the RIF. Eight patients (42%) had an abnormal echocardiogram at admission. Two (10%) patients, with classical signs and symptoms of appendicitis, underwent appendicectomy without radiological imaging and were subsequently diagnosed with PIMS-TS. During the same period, 18 patients underwent appendicectomy for histologically confirmed appendicitis. Serum CRP and ferritin levels were significantly higher in the PIMS-TS cohort compared with children with appendicitis. CONCLUSIONS: PIMS-TS is a novel paediatric condition that may mimic appendicitis. It should be considered in patients presenting with abdominal pain to avoid unnecessary surgery in children at risk of cardiovascular instability.


Assuntos
COVID-19/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Adolescente , Apendicectomia , Apendicite/diagnóstico , Apendicite/cirurgia , Biomarcadores/sangue , Proteína C-Reativa/análise , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Ferritinas/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Lactente , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos
4.
Int J Mol Sci ; 22(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34445367

RESUMO

Rheumatoid arthritis (RA) is a chronic multisystem disease, therapy of which remains a challenge for basic research. The present work examined the effect of unconjugated bilirubin (UCB) administration in adjuvant-induced arthritis (AIA)-an experimental model, in which oxidative stress (OS), inflammation and inadequate immune response are often similar to RA. Male Lewis rats were randomized into groups: CO-control, AIA-untreated adjuvant-induced arthritis, AIA-BIL-adjuvant-induced arthritis administrated UCB, CO-BIL-control with administrated UCB. UCB was administered intraperitoneally 200 mg/kg of body weight daily from 14th day of the experiment, when clinical signs of the disease are fully manifested, to 28th day, the end of the experiment. AIA was induced by a single intradermal immunization at the base of the tail with suspension of Mycobacterium butyricum in incomplete Freund's adjuvant. Clinical, hematologic, biochemical and histologic examinations were performed. UCB administration to animals with AIA lead to a significant decrease in hind paws volume, plasma levels of C-reactive protein (CRP) and ceruloplasmin, drop of leukocytes, lymphocytes, erythrocytes, hemoglobin and an increase in platelet count. UCB administration caused significantly lowered oxidative damage to DNA in arthritic animals, whereas in healthy controls it induced considerable oxidative damage to DNA. UCB administration also induced atrophy of the spleen and thymus in AIA and CO animals comparing to untreated animals. Histological signs of joint damage assessed by neutrophils infiltration and deposition of fibrin were significantly reduced by UCB administration. The effects of exogenously administered UCB to the animals with adjuvant-induced arthritis might be identified as therapeutic, in contrast to the effects of UCB administration in healthy animals rather classified as toxic.


Assuntos
Anti-Inflamatórios/administração & dosagem , Artrite Experimental/tratamento farmacológico , Bilirrubina/administração & dosagem , Adjuvante de Freund/efeitos adversos , Lipídeos/efeitos adversos , Mycobacterium/imunologia , Animais , Anti-Inflamatórios/farmacologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Bilirrubina/farmacologia , Proteína C-Reativa , Ceruloplasmina/metabolismo , Injeções Intraperitoneais , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/sangue , Distribuição Aleatória , Ratos , Ratos Endogâmicos Lew , Resultado do Tratamento
5.
Front Immunol ; 12: 625732, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194422

RESUMO

The etiological agent of COVID-19 SARS-CoV-2, is primarily a pulmonary-tropic coronavirus. Infection of alveolar pneumocytes by SARS-CoV-2 requires virus binding to the angiotensin I converting enzyme 2 (ACE2) monocarboxypeptidase. ACE2, present on the surface of many cell types, is known to be a regulator of blood pressure homeostasis through its ability to catalyze the proteolysis of Angiotensin II (Ang II) into Angiotensin-(1-7) [Ang-(1-7)]. We therefore hypothesized that SARS-CoV-2 could trigger variations of ACE2 expression and Ang II plasma concentration in SARS-CoV-2-infected patients. We report here, that circulating blood cells from COVID-19 patients express less ACE2 mRNA than cells from healthy volunteers. At the level of circulating cells, this ACE2 gene dysregulation mainly affects the monocytes, which also show a lower expression of membrane ACE2 protein. Moreover, soluble ACE2 (sACE2) plasma concentrations are lower in prolonged viral shedders than in healthy controls, while the concentration of sACE2 returns to normal levels in short viral shedders. In the plasma of prolonged viral shedders, we also found higher concentrations of Ang II and angiotensin I (Ang I). On the other hand, the plasma levels of Ang-(1-7) remains almost stable in prolonged viral shedders but seems insufficient to prevent the adverse effects of Ang II accumulation. Altogether, these data evidence that the SARS-CoV-2 may affect the expression of blood pressure regulators with possible harmful consequences on COVID-19 outcome.


Assuntos
Angiotensina II/sangue , Angiotensina I/sangue , Enzima de Conversão de Angiotensina 2/sangue , COVID-19/sangue , Fragmentos de Peptídeos/sangue , Adulto , Enzima de Conversão de Angiotensina 2/genética , COVID-19/virologia , Feminino , Perfilação da Expressão Gênica , Antígenos HLA-DR , Humanos , Receptores de Lipopolissacarídeos , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Projetos Piloto , Estudos Prospectivos , RNA Mensageiro , Eliminação de Partículas Virais
6.
Biomolecules ; 11(6)2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207346

RESUMO

BACKGROUND: Underage drinking is associated with health risk behaviors. Serum keratin-18 (CK18) levels are increased in liver diseases and may be biomarkers of outcome. The purpose of this study was to determine if the total CK18 (M65) or caspase-cleaved CK18 (M30) levels were different in adolescents admitted to hospital because of alcohol intoxication and controls with excluded liver diseases. METHODS: A prospective study included 57 adolescents after alcohol use and 23 control subjects. The concentrations of M30 and M65 in the serum samples were evaluated using an enzyme-linked immunosorbent assay. RESULTS: The median age was 15 (14-17) years and 49% were male. There were significant differences in M65 levels between the study and control groups (p = 0.03). The concentrations of M30 and M65 were insignificant in adolescents divided into subgroups according to blood alcohol concentrations (BAC). Significant positive correlations were found between BAC and M65 levels (p = 0.038; r = 0.3). In receiver operating characteristic (ROC) analysis M65 (cut-off = 125.966 IU/l, Se = 70.2%, Sp = 43.5%) allowed to differentiate between patients with and without alcohol intoxication (AUC = 0.66, p = 0.03). CONCLUSION: M65 appears to be a promising non-invasive biomarker of hepatocyte injury during alcohol intoxication in adolescents. Moreover, a higher concentration of M65 may indicate early organ injury before the increase in the activity of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Hepatócitos/patologia , Queratina-18/análise , Adolescente , Alanina Transaminase/sangue , Intoxicação Alcoólica/sangue , Intoxicação Alcoólica/fisiopatologia , Apoptose , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatócitos/metabolismo , Humanos , Queratina-18/sangue , Masculino , Fragmentos de Peptídeos/sangue , Polônia , Dados Preliminares , Estudos Prospectivos , Curva ROC , Consumo de Álcool por Menores
7.
Life Sci ; 282: 119792, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34229006

RESUMO

AIMS: Exercise training increases circulating and tissue levels of angiotensin-(1-7) [Ang-(1-7)], which was shown to attenuate inflammation and fibrosis in different diseases. Here, we evaluated whether Ang-(1-7)/Mas receptor is involved in the beneficial effects of aerobic training in a chronic model of asthma. MATERIAL AND METHODS: BALB/c mice were subjected to a protocol of asthma induced by ovalbumin sensitization (OVA; 4 i.p. injections) and OVA challenge (3 times/week for 4 weeks). Simultaneously to the challenge period, part of the animals was continuously treated with Mas receptor antagonist (A779, 1 µg/h; for 28 days) and trained in a treadmill (TRE; 60% of the maximal capacity, 1 h/day, 5 days/week during 4 weeks). PGC1-α mRNA expression (qRT-PCR), plasma IgE and lung cytokines (ELISA), inflammatory cells infiltration (enzymatic activity assay) and airway remodeling (by histology) were evaluated. KEY FINDINGS: Blocking the Mas receptor with A779 increased IgE and IL-13 levels and prevented the reduction in extracellular matrix deposition in airways in OVA-TRE mice. Mas receptor blockade prevented the reduction of myeloperoxidase activity, as well as, prevented exercise-induced IL-10 increase. These data show that activation of Ang-(1-7)/Mas receptor pathway is involved in the anti-inflammatory and anti-fibrotic effects of aerobic training in an experimental model of chronic asthma. SIGNIFICANCE: Our results support exercise training as a non-pharmacological tool to defeat lung remodeling induced by chronic pulmonary inflammation. Further, our result also supports development of new therapy based on Ang-(1-7) or Mas agonists as important tool for asthma treatment in those patients that cannot perform aerobic training.


Assuntos
Angiotensina I/metabolismo , Asma/terapia , Fragmentos de Peptídeos/metabolismo , Pneumonia/terapia , Angiotensina I/sangue , Animais , Asma/sangue , Asma/metabolismo , Modelos Animais de Doenças , Terapia por Exercício , Masculino , Camundongos Endogâmicos BALB C , Fragmentos de Peptídeos/sangue , Pneumonia/sangue , Pneumonia/metabolismo
8.
Am J Cardiol ; 152: 120-124, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34130823

RESUMO

Since the first report of an association between cardiac troponin (cTn) and adverse outcome in hypertrophic cardiomyopathy (HD), there is a paucity in confirmative data. We performed a prospective, prespecified 5-year follow-up cohort study of 135 HC patients who participated in a national multicenter project and underwent clinical evaluation, MRI (cine, LGE and T2-weighted imaging) and biomarker assessment (high-sensitivity cTnT (hs-cTnT), N-terminal pro-B-type natriuretic peptide, soluble tumorgenicity suppressor-2, Galectin-3, Growth differentiation factor-15, C-terminal Propeptide of Type I Collagen (CICP)). An elevated hs-cTnT concentration was defined as ≥14ng/L. Follow-up was systematically performed for the primary endpoint: a composite of sudden cardiac death, heart failure related death, stroke-related death, heart failure hospitalization, hospitalization for stroke, spontaneous sustained ventricular tachycardia (VT) or appropriate ICD discharge, and progression to NYHA class III-IV. Elevated hs-cTnT was present in 33 of 135 (24%) HC patients. During a median follow-up of 5.0 years (IQR: 4.9-5.1) 18 patients reached the primary endpoint. Using Cox regression analysis, elevated hs-cTnT was univariately associated with the primary endpoint (HR: 3.4 (95%CI: 1.4-8.7, p=0.009). Also female sex, previous syncope, previous non-sustained VT, reduced LV ejection fraction (<50%) and CICP were associated with the primary endpoint. In multivariable analysis, elevated hs-cTnT remained independently associated with outcome (aHR: 4.7 (95%CI: 1.8-12.6, p = 0.002). In conclusion, this 5-year follow-up study is the first to prospectively confirm the association of elevated hs-cTnT and adverse outcomes. In addition to established clinical variables, cTn seems the biomarker of interest to further improve risk prediction in HC, which should be evaluated in larger prospective registries.


Assuntos
Cardiomiopatia Hipertrófica/sangue , Morte Súbita Cardíaca/epidemiologia , Insuficiência Cardíaca/mortalidade , Taquicardia Ventricular/epidemiologia , Troponina T/sangue , Idoso , Proteínas Sanguíneas , Estudos de Coortes , Desfibriladores Implantáveis , Cardioversão Elétrica/estatística & dados numéricos , Feminino , Seguimentos , Galectinas/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Hospitalização/estatística & dados numéricos , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Prognóstico , Estudos Prospectivos , Acidente Vascular Cerebral/mortalidade , Taquicardia Ventricular/terapia
10.
Anesth Analg ; 133(3): 570-577, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34153017

RESUMO

BACKGROUND: Acute kidney injury (AKI) is associated with mortality after cardiac surgery. Novel risk factors may improve identification of patients at risk for renal injury. The authors evaluated the association between preoperative biomarkers that reflect cardiac, inflammatory, renal, and metabolic disorders and cardiac surgery-associated AKI (CSA-AKI) in elderly patients. METHODS: This was a secondary analysis of the 2-center prospective cohort study "Anesthesia Geriatric Evaluation." Twelve biomarkers were determined preoperatively in 539 patients. Primary outcome was CSA-AKI. The association between biomarkers and CSA-AKI was investigated with multivariable logistic regression analysis. Secondary outcomes were 1-year mortality and patient-reported disability and were assessed with relative risks (RR) between patients with and without CSA-AKI. RESULTS: CSA-AKI occurred in 88 (16.3%) patients and was associated with increased risk of mortality (RR, 6.70 [95% confidence interval {CI}, 3.38-13.30]) and disability (RR, 2.13 [95% CI, 1.53-2.95]). Preoperative concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitive C-reactive protein (hs-CRP), hemoglobin, and magnesium had the strongest association with CSA-AKI. Identification of patients with CSA-AKI improved when a biomarker panel was used (area under the curve [AUC] 0.75 [95% CI, 0.69-0.80]) compared to when only clinical risk factors were used (European System for Cardiac Operative Risk Evaluation [EuroSCORE II] AUC 0.67 [95% CI, 0.62-0.73]). CONCLUSIONS: Preoperative cardiac, inflammatory, renal, and metabolic biomarkers are associated with CSA-AKI and may improve identification of patients at risk.


Assuntos
Injúria Renal Aguda/etiologia , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Fatores Etários , Idoso , Proteína C-Reativa/análise , Procedimentos Cirúrgicos Cardíacos/mortalidade , Avaliação da Deficiência , Feminino , Estado Funcional , Avaliação Geriátrica , Hemoglobinas/análise , Humanos , Magnésio/sangue , Masculino , Peptídeo Natriurético Encefálico/sangue , Países Baixos , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
11.
Eur J Clin Invest ; 51(9): e13629, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34184268

RESUMO

Background During COVID-19 outbreak, Italy was the first country in Europe to be heavily affected with an intensive care unit mortality of 26%. In order to reduce this percentage, physicians should establish clear and objective criteria to stratify COVID-19 patients at high risk of in-hospital death. Thus, the aim has been to test a large spectrum of variables ranging from clinical evaluation to laboratory biomarkers to identify which parameter would best predict all-cause in-hospital mortality in COVID-19 patients. Design observational study. Results Multivariate Cox regression analysis showed that each 5 years of increase in age corresponded to a hazard ratio (HR) of 1.28 (95% CI 1.00-1.65, P = .050); each increment of 803 ng/L of N-terminal pro-B-type natriuretic peptide (NT-proBNP) corresponded to a HR of 1.24 (95% CI 1.11-1.39, P < .001); each increment of 58 ng/L of interleukin (IL)-6 corresponded to a HR of 1.23 (95% CI 1.09-1.40, P < .001), and each increment of 250 U/L of lactate dehydrogenase (LDH) corresponded to a HR of 1.23 (95% CI 1.10-1.37, P < .001). According to the calculated cut-points for age (≥70 years), NT-proBNP (≥803 ng/L), IL-6 (≥58 ng/L) and LDH (≥371 U/L) when 2 out of these 4 were overcome, the HR was 2.96 (95% CI 1.97-4.45, P < .001). Conclusion In COVID-19 patients, besides age, the evaluation of three biochemical parameters, available in few hours after hospital admission can predict in-hospital mortality regardless of other comorbidities.


Assuntos
COVID-19/mortalidade , Mortalidade Hospitalar , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Fatores Etários , Idoso , Biomarcadores , COVID-19/sangue , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , SARS-CoV-2
12.
Arch Cardiovasc Dis ; 114(5): 394-406, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34154954

RESUMO

BACKGROUND: Although women account for up to half of patients hospitalized for coronavirus disease 2019 (COVID-19), no specific data have been reported in this population. AIMS: To assess the burden and impact of cardiovascular comorbidities in women with COVID-19. METHODS: All consecutive patients hospitalized for COVID-19 across 24 hospitals from 26 February to 20 April 2020 were included. The primary composite outcome was transfer to an intensive care unit or in-hospital death. RESULTS: Among 2878 patients, 1212 (42.1%) were women. Women were older (68.3±18.0 vs. 65.4±16.0 years; P<0.001), but had less prevalent cardiovascular comorbidities than men. Among women, 276 (22.8%) experienced the primary outcome, including 161 (13.3%) transfers to an intensive care unit and 115 (9.5%) deaths without transfer to intensive care unit. The rate of in-hospital death or transfer to an intensive care unit was lower in women versus men (crude hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.53-0.72). Age (adjusted HR: 1.05 per 5-year increase, 95% CI: 1.01-1.10), body mass index (adjusted HR: 1.06 per 2-unit increase, 95% CI: 1.02-1.10), chronic kidney disease (adjusted HR: 1.57, 95% CI: 1.11-2.22) and heart failure (adjusted HR: 1.52, 95% CI: 1.04-2.22) were independently associated with the primary outcome in women. Elevated B-type natriuretic peptide/N-terminal prohormone of B-type natriuretic peptide (adjusted HR: 2.41, 95% CI: 1.70-3.44) and troponin (adjusted HR: 2.00, 95% CI: 1.39-2.88) concentrations at admission were also associated with the primary outcome, even in women free of previous coronary artery disease or heart failure. CONCLUSIONS: Although female sex was associated with a lower risk of transfer to an intensive care unit or in-hospital death, COVID-19 remained associated with considerable morbimortality in women, especially in those with cardiovascular diseases.


Assuntos
COVID-19/epidemiologia , Doenças Cardiovasculares/epidemiologia , Idoso , Asma/epidemiologia , Biomarcadores , Doenças Cardiovasculares/sangue , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , França/epidemiologia , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Distribuição por Sexo , Fumar/epidemiologia , Troponina/sangue
13.
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
14.
J Stroke Cerebrovasc Dis ; 30(8): 105933, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34157668

RESUMO

OBJECTIVES: The study aimed to investigate whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration and/or left atrial volume index (LAVI), as atrial cardiopathy biomarkers, were associated with infarct patterns on diffusion-weighted imaging in patients with embolic strokes of undetermined source (ESUS). MATERIALS AND METHOD: We retrospectively evaluated patient with ESUS from our stroke registry between January 2018 and November 2019. Cut-off values for atrial cardiopathy biomarkers were defined as >250 pg/mL for NT-proBNP and >34 mL/m2 for LAVI. Eligible patients were then assigned to 3 groups and infarct patterns were compared according to their atrial cardiopathy markers: Group 1 (no atrial cardiopathy markers), Group 2 (one marker), and Group 3 (both markers). RESULTS: Among 194 eligible patients with ESUS (76 women; mean age, 69.2 years), simultaneous increases of NT-proBNP concentration and LAVI were identified in 39 (20.1%). Group 3 had a significantly larger infarct volume, relative to Group 1 and Group 2 (P=0.043) Multivariable logistic regression analyses revealed that these patients (Group 3) were significantly more likely to have multi-territorial infarcts (adjusted odds ratio [aOR]: 3.03, 95% confidence interval [CI]: 1.05-8.72; P=0.04), a maximal lesion diameter >15mm (aOR: 4.51, 95% CI: 1.70-11.93; P=0.001), and large cortical infarctions (aOR: 4.17, 95% CI: 1.75-9.96; P=0.001). CONCLUSION: We found that simultaneously increased values for NT-proBNP concentration and LAVI were independently associated with multi-territorial and large cortical infarct patterns in patients with ESUS. These findings suggest that NT-proBNP and LAVI may be useful biomarkers for identifying cardioembolic subtypes and guiding treatment selection in patients with ESUS.


Assuntos
Função do Átrio Esquerdo , Remodelamento Atrial , Infarto Encefálico/diagnóstico por imagem , Cardiomiopatias/complicações , Imagem de Difusão por Ressonância Magnética , Ecocardiografia , AVC Embólico/diagnóstico por imagem , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Infarto Encefálico/etiologia , Cardiomiopatias/sangue , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , AVC Embólico/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sistema de Registros , Estudos Retrospectivos , Fatores de Tempo
15.
Nat Commun ; 12(1): 3555, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117234

RESUMO

Plasma biomarkers of amyloid, tau, and neurodegeneration (ATN) need to be characterized in cognitively unimpaired (CU) elderly individuals. We therefore tested if plasma measurements of amyloid-ß (Aß)42/40, phospho-tau217 (P-tau217), and neurofilament light (NfL) together predict clinical deterioration in 435 CU individuals followed for an average of 4.8 ± 1.7 years in the BioFINDER study. A combination of all three plasma biomarkers and basic demographics best predicted change in cognition (Pre-Alzheimer's Clinical Composite; R2 = 0.14, 95% CI [0.12-0.17]; P < 0.0001) and subsequent AD dementia (AUC = 0.82, 95% CI [0.77-0.91], P < 0.0001). In a simulated clinical trial, a screening algorithm combining all three plasma biomarkers would reduce the required sample size by 70% (95% CI [54-81]; P < 0.001) with cognition as trial endpoint, and by 63% (95% CI [53-70], P < 0.001) with subsequent AD dementia as trial endpoint. Plasma ATN biomarkers show usefulness in cognitively unimpaired populations and could make large clinical trials more feasible and cost-effective.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Biomarcadores/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/sangue , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Fragmentos de Peptídeos/sangue , Proteínas tau/sangue
16.
J Zoo Wildl Med ; 52(2): 499-506, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130392

RESUMO

Cardiac disease is an important cause of mortality in African wild dogs in human care. Vertebral heart scale (VHS) is a well-documented objective measure of cardiac size and is commonly used in domestic dogs. The VHS of 63 clinically healthy African wild dogs housed in zoological institutions was retrospectively calculated. Using the robust method of reference interval (RI) calculation, the RI for VHS in captive African wild dogs was 9.3-10.8. Echocardiographic measurements from 16 clinically healthy and 2 African wild dogs with preclinical dilated cardiomyopathy are reported. The cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) were measured in a subset of African wild dogs. The median plasma NT-proBNP measurement was 845 pM/L (range 366-1,388) and the median serum cTnI measurement was 0.02 ng/ml (0.01-0.04). These data can be used for the assessment and identification of cardiac disease in this endangered species.


Assuntos
Anestesia/veterinária , Canidae , Ecocardiografia/veterinária , Coração/anatomia & histologia , Animais , Animais de Zoológico , Biomarcadores , Feminino , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Troponina/sangue
19.
Am Heart J ; 239: 110-119, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34052212

RESUMO

BACKGROUND: Decongestion is a primary goal during hospitalizations for decompensated heart failure (HF). However, data surrounding the preferred route and strategy of diuretic administration are limited with varying results in prior studies. METHODS: This is a retrospective analysis using patients from ASCEND-HF with a stable diuretic strategy in the first 24 hours following randomization. Patients were divided into three groups: intravenous (IV) continuous, IV bolus and oral strategy. Baseline characteristics, in-hospital outcomes, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality were compared across groups. Inverse propensity weighted modeling was used for adjustment. RESULTS: Among 5,738 patients with a stable diuretic regimen in the first 24 hours (80% of overall ASCEND trial), 3,944 (68.7%) patients received IV intermittent bolus administration of diuretics, 799 (13.9%) patients received IV continuous therapy and 995 (17.3%) patients with oral administration. Patients in the IV continuous group had a higher baseline creatinine (IV continuous 1.4 [1.1-1.7]; intermittent bolus 1.2 [1.0-1.6]; oral 1.2 [1.0-1.4] mg/dL; P <0.001) and high NTproBNP (IV continuous 5,216 [2,599-11,603]; intermittent bolus 4,944 [2,339-9,970]; oral 3,344 [1,570-7,077] pg/mL; P <0.001). There was no difference between IV continuous and intermittent bolus group in weight change, total urine output and change in renal function till 10 days/discharge (adjusted P >0.05 for all). There was no difference in 30 day mortality and HF readmission (adjusted OR 1.08 [95%CI: 0.74, 1.57]; P = 0.701) and 180 days mortality (adjusted OR 1.04 [95%CI: 0.75, 1.43]; P = 0.832). CONCLUSION: In a large cohort of patients with decompensated HF, there were no significant differences in diuretic-related in-hospital, or post-discharge outcomes between IV continuous and intermittent bolus administration. Tailoring appropriate diuretic strategy to different states of acute HF and congestion phenotypes needs to be further investigated.


Assuntos
Furosemida , Insuficiência Cardíaca , Infusões Intravenosas , Injeções Intravenosas , Creatinina/sangue , Diuréticos/administração & dosagem , Diuréticos/efeitos adversos , Monitoramento de Medicamentos/métodos , Feminino , Furosemida/administração & dosagem , Furosemida/efeitos adversos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Infusões Intravenosas/efeitos adversos , Infusões Intravenosas/métodos , Injeções Intravenosas/efeitos adversos , Injeções Intravenosas/métodos , Masculino , Pessoa de Meia-Idade , Mortalidade , Peptídeo Natriurético Encefálico/sangue , Avaliação de Processos e Resultados em Cuidados de Saúde , Readmissão do Paciente/estatística & dados numéricos , Fragmentos de Peptídeos/sangue , Tempo para o Tratamento , Estados Unidos/epidemiologia
20.
Am J Physiol Lung Cell Mol Physiol ; 321(1): L213-L218, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34009036

RESUMO

The renin-angiotensin system (RAS) is fundamental to COVID-19 pathobiology, due to the interaction between the SARS-CoV-2 virus and the angiotensin-converting enzyme 2 (ACE2) coreceptor for cellular entry. The prevailing hypothesis is that SARS-CoV-2-ACE2 interactions lead to an imbalance of the RAS, favoring proinflammatory angiotensin II (ANG II)-related signaling at the expense of the anti-inflammatory ANG-(1-7)-mediated alternative pathway. Indeed, multiple clinical trials targeting this pathway in COVID-19 are underway. Therefore, precise measurement of circulating RAS components is critical to understand the interplay of the RAS on COVID-19 outcomes. Multiple challenges exist in measuring the RAS in COVID-19, including improper patient controls, ex vivo degradation and low concentrations of angiotensins, and unvalidated laboratory assays. Here, we conducted a prospective pilot study to enroll 33 patients with moderate and severe COVID-19 and physiologically matched COVID-19-negative controls to quantify the circulating RAS. Our enrollment strategy led to physiological matching of COVID-19-negative and COVID-19-positive moderate hypoxic respiratory failure cohorts, in contrast to the severe COVID-19 cohort, which had increased severity of illness, prolonged intensive care unit (ICU) stay, and increased mortality. Circulating ANG II and ANG-(1-7) levels were measured in the low picomolar (pM) range. We found no significant differences in circulating RAS peptides or peptidases between these three cohorts. The combined moderate and severe COVID-19-positive cohorts demonstrated a mild reduction in ACE activity compared with COVID-19-negative controls (2.2 ± 0.9 × 105 vs. 2.9 ± 0.8 × 105 RFU/mL, P = 0.03). These methods may be useful in designing larger studies to physiologically match patients and quantify the RAS in COVID-19 RAS augmenting clinical trials.


Assuntos
Angiotensina II/sangue , Angiotensina I/sangue , Enzima de Conversão de Angiotensina 2/sangue , COVID-19/sangue , Fragmentos de Peptídeos/sangue , Sistema Renina-Angiotensina , Insuficiência Respiratória/sangue , SARS-CoV-2/metabolismo , Adulto , Idoso , COVID-19/patologia , COVID-19/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Insuficiência Respiratória/patologia , Insuficiência Respiratória/fisiopatologia
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