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2.
Eur Respir Rev ; 29(157)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33004529

RESUMO

Novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has rapidly spread throughout the world, resulting in a pandemic with high mortality. There are no effective treatments for the management of severe COVID-19 and current therapeutic trials are focused on antiviral therapy and attenuation of hyper-inflammation with anti-cytokine therapy. Severe COVID-19 pneumonia shares some pathological similarities with severe bacterial pneumonia and sepsis. In particular, it disrupts the haemostatic balance, which results in a procoagulant state locally in the lungs and systemically. This culminates in the formation of microthrombi, disseminated intravascular coagulation and multi-organ failure. The deleterious effects of exaggerated inflammatory responses and activation of coagulation have been investigated in bacterial pneumonia and sepsis and there is recognition that although these pathways are important for the host immune response to pathogens, they can lead to bystander tissue injury and are negatively associated with survival. In the past two decades, evidence from preclinical studies has led to the emergence of potential anticoagulant therapeutic strategies for the treatment of patients with pneumonia, sepsis and acute respiratory distress syndrome, and some of these anticoagulant approaches have been trialled in humans. Here, we review the evidence from preclinical studies and clinical trials of anticoagulant treatment strategies in bacterial pneumonia and sepsis, and discuss the importance of these findings in the context of COVID-19.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/sangue , Pneumonia Bacteriana/sangue , Pneumonia Viral/sangue , Sepse/sangue , Biomarcadores/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia
3.
PLoS One ; 15(9): e0239606, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32997689

RESUMO

OBJECTIVE: The diagnosis of pneumonia based on semiology and chest X-rays is frequently inaccurate, particularly in elderly patients. Older (C-reactive protein (CRP); procalcitonin (PCT)) or newer (Serum amyloid A (SAA); neopterin (NP)) biomarkers may increase the accuracy of pneumonia diagnosis, but data are scarce and conflicting. We assessed the accuracy of CRP, PCT, SAA, NP and the ratios CRP/NP and SAA/NP in a prospective observational cohort of elderly patients with suspected pneumonia. METHODS: We included consecutive patients more than 65 years old, with at least one respiratory symptom and one symptom or laboratory finding suggestive of infection, and a working diagnosis of pneumonia. Low-dose CT scan and comprehensive microbiological testing were done in all patients. The index tests, CRP, PCT, SAA and NP, were obtained within 24 hours. The reference diagnosis was assessed a posteriori by a panel of experts considering all available data, including patients' outcome. We used area under the curve (AUROC) and Youden index to assess the accuracy and obtain optimal cut-off of the index tests. RESULTS: 200 patients (median age 84 years) were included; 133 (67%) had pneumonia. AUROCs for the diagnosis of pneumonia was 0.64 (95% CI: 0.56-0.72) for CRP; 0.59 (95% CI: 0.51-0.68) for PCT; 0.60 (95% CI: 0.52-0.69) for SAA; 0.41 (95% CI: 0.32-0.49) for NP; 0.63 (95% CI: 0.55-0.71) for CRP/NP; and 0.61 (95% CI: 0.53-0.70) for SAA/NP. No cut-off resulted in satisfactory sensitivity or specificity. CONCLUSIONS: Accuracy of traditional (CRP, PCT) and newly proposed biomarkers (SAA, NP) and ratios of CRP/NP and SAA/NP was too low to help diagnosing pneumonia in the elderly. CRP had the highest AUROC. CLINICAL TRIAL REGISTRATION: NCT02467092.


Assuntos
Proteína C-Reativa/análise , Neopterina/sangue , Pneumonia Bacteriana/sangue , Pró-Calcitonina/sangue , Proteína Amiloide A Sérica/análise , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/normas , Feminino , Humanos , Masculino , Neopterina/normas , Pneumonia Bacteriana/patologia , Pró-Calcitonina/normas , Sensibilidade e Especificidade , Proteína Amiloide A Sérica/normas
4.
PLoS One ; 15(9): e0239573, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970772

RESUMO

INTRODUCTION: Severe acute respiratory syndrome coronavirus2 has caused a global pandemic of coronavirus disease 2019 (COVID-19). High-density lipoproteins (HDLs), particles chiefly known for their reverse cholesterol transport function, also display pleiotropic properties, including anti-inflammatory or antioxidant functions. HDLs and low-density lipoproteins (LDLs) can neutralize lipopolysaccharides and increase bacterial clearance. HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) decrease during bacterial sepsis, and an association has been reported between low lipoprotein levels and poor patient outcomes. The goal of this study was to characterize the lipoprotein profiles of severe ICU patients hospitalized for COVID-19 pneumonia and to assess their changes during bacterial ventilator-associated pneumonia (VAP) superinfection. METHODS: A prospective study was conducted in a university hospital ICU. All consecutive patients admitted for COVID-19 pneumonia were included. Lipoprotein levels were assessed at admission and daily thereafter. The assessed outcomes were survival at 28 days and the incidence of VAP. RESULTS: A total of 48 patients were included. Upon admission, lipoprotein concentrations were low, typically under the reference values ([HDL-C] = 0.7[0.5-0.9] mmol/L; [LDL-C] = 1.8[1.3-2.3] mmol/L). A statistically significant increase in HDL-C and LDL-C over time during the ICU stay was found. There was no relationship between HDL-C and LDL-C concentrations and mortality on day 28 (log-rank p = 0.554 and p = 0.083, respectively). A comparison of alive and dead patients on day 28 did not reveal any differences in HDL-C and LDL-C concentrations over time. Bacterial VAP was frequent (64%). An association was observed between HDL-C and LDL-C concentrations on the day of the first VAP diagnosis and mortality ([HDL-C] = 0.6[0.5-0.9] mmol/L in survivors vs. [HDL-C] = 0.5[0.3-0.6] mmol/L in nonsurvivors, p = 0.036; [LDL-C] = 2.2[1.9-3.0] mmol/L in survivors vs. [LDL-C] = 1.3[0.9-2.0] mmol/L in nonsurvivors, p = 0.006). CONCLUSION: HDL-C and LDL-C concentrations upon ICU admission are low in severe COVID-19 pneumonia patients but are not associated with poor outcomes. However, low lipoprotein concentrations in the case of bacterial superinfection during ICU hospitalization are associated with mortality, which reinforces the potential role of these particles during bacterial sepsis.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Infecções por Coronavirus/sangue , Pneumonia Bacteriana/sangue , Pneumonia Associada à Ventilação Mecânica/sangue , Pneumonia Viral/sangue , Superinfecção/sangue , Idoso , Betacoronavirus , Infecções por Coronavirus/mortalidade , Feminino , França , Hospitais Universitários , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Bacteriana/mortalidade , Pneumonia Associada à Ventilação Mecânica/mortalidade , Pneumonia Viral/mortalidade , Estudos Prospectivos
5.
J Thromb Thrombolysis ; 50(3): 548-557, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32524516

RESUMO

In the recent outbreak of novel coronavirus infection worldwide, the risk of thrombosis and bleeding should be concerned. We aimed to observe the dynamic changes of D-dimer levels during disease progression to evaluate their value for thrombosis. In this study, we report the clinical and laboratory results of 57 patients with confirmed COVID-19 pneumonia and 46 patients with confirmed community-acquired bacterial pneumonia (CAP). And their concentrations of D-dimer, infection-related biomarkers, and conventional coagulation were retrospectively analyzed. The Padua prediction score is used to identify patients at high risk for venous thromboembolism (VTE). The results found that, on admission, both in COVID-19 patients and CAP patients, D-dimer levels were significantly increased, and compared with CAP patients, D-dimer levels were higher in COVID-19 patients (P < 0.05). Besides, we found that in COVID-19 patients, D-dimer were related with markers of inflammation, especially with hsCRP (R = 0.426, P < 0.05). However, there was low correlation between VTE score and D-dimer levels (Spearman's R = 0.264, P > 0.05) weakened the role of D-dimer in the prediction of thrombosis. After treatments, D-dimer levels decreased which was synchronous with hsCRP levels in patients with good clinical prognosis, but there were still some patients with anomalous increasing D-dimer levels after therapy. In conclusion, elevated baseline D-dimer levels are associated with inflammation but not with VTE score in COVID-19 patients, suggesting that it is unreasonable to judge whether anticoagulation is needed only according to D-dimer levels. However, the abnormal changes of D-dimer and inflammatory factors suggest that anticoagulant therapy might be needed.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Pneumonia Bacteriana/sangue , Pneumonia Viral/sangue , Tromboembolia Venosa/sangue , Idoso , Biomarcadores/sangue , Coagulação Sanguínea , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/microbiologia , Tromboembolia Venosa/virologia
6.
Sci Rep ; 10(1): 4208, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144345

RESUMO

Respiratory tract infections require early diagnosis and adequate treatment. With the antibiotic overuse and increment in antibiotic resistance there is an increased need to accurately distinguish between bacterial and viral infections. We investigated the diagnostic performance of calprotectin in respiratory tract infections and compared it with the performance of heparin binding protein (HBP) and procalcitonin (PCT). Biomarkers were analyzed in patients with viral respiratory infections and patients with bacterial pneumonia, mycoplasma pneumonia and streptococcal tonsillitis (n = 135). Results were compared with values obtained from 144 healthy controls. All biomarkers were elevated in bacterial and viral infections compared to healthy controls. Calprotectin was significantly increased in patients with bacterial infections; bacterial pneumonia, mycoplasma pneumonia and streptococcal tonsillitis compared with viral infections. PCT was significantly elevated in patients with bacterial pneumonia compared to viral infections but not in streptococcal tonsillitis or mycoplasma caused infections. HBP was not able to distinguish between bacterial and viral causes of infections. The overall clinical performance of calprotectin in the distinction between bacterial and viral respiratory infections, including mycoplasma was greater than performance of PCT and HBP. Rapid determination of calprotectin may improve the management of respiratory tract infections and allow more precise diagnosis and selective use of antibiotics.


Assuntos
Biomarcadores/sangue , Complexo Antígeno L1 Leucocitário/sangue , Infecções Respiratórias/sangue , Doença Aguda , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/sangue , Pneumonia por Mycoplasma/sangue , Pró-Calcitonina/sangue , Tonsilite/sangue , Viroses/sangue , Adulto Jovem
7.
Sci Rep ; 10(1): 2941, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076108

RESUMO

Acute Radiation Pneumonitis (ARP) is one of the most common dose-limiting toxicities of thoracic radiotherapy. The accurate diagnosis of ARP remains a challenge because of the lack of a rapid biomarker capable of differentiating ARP from bacterial pneumo (BP). The aim of this study was to investigate the potential usefulness of procalcitonin (PCT) in the differential diagnosis of ARP and BP. Lung cancer patients who had undergone thoracic radiotherapy within 6 months and were admitted to hospital for ARP or BP were retrospectively analyzed. The serum levels of PCT, C-reactive protein (CRP) and white blood cells (WBC) were compared between the two groups. Receiver operating characteristic (ROC) curve was used to assess the diagnostic value of PCT, CRP and WBC in the differential diagnosis of ARP and BP and determine the best cut-off values. One hundred eighteen patients were included. Among them, seventy-seven patients were diagnosed with ARP, and 41 patients were diagnosed with BP. The PCT concentrations for patients diagnosed with ARP group were significantly lower than those in the BP group (P < 0.001). There were no differences in CRP and WBC between the two groups. The areas under the ROC curves (AUC) for PCT, CRP and WBC were 0.745, 0.589 and 0.578, respectively. The best cutoff values of PCT, CRP and WBC were 0.47 µg/L, 54.5 mg/L and 9.9 × 109/L, respectively. Low serum PCT levels are associated with ARP. PCT is a useful biomarker to distinguish ARP from BP.


Assuntos
Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/radioterapia , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/diagnóstico , Pró-Calcitonina/sangue , Pneumonite por Radiação/diagnóstico , Pneumonite por Radiação/etiologia , Doença Aguda , Idoso , Proteína C-Reativa/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Contagem de Leucócitos , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/microbiologia , Valor Preditivo dos Testes , Curva ROC , Pneumonite por Radiação/sangue , Sensibilidade e Especificidade
8.
BMC Infect Dis ; 20(1): 45, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941459

RESUMO

BACKGROUND: Acinetobacter baumannii is a gram-negative aerobic bacillus that is commonly causes of hospital-acquired infections. Community-acquired pneumonia caused by Acinetobacter baumannii (CAP-Ab) is rare but fatal if diagnosis and treatment are delayed. Conventional culture of clinical specimens is the main method for clinical diagnosis of A. baumannii infections which may suffer from limited positive rate and is time consuming. Timely and precise diagnosis of CAP-Ab remains challenging. CASE PRESENTATION: A 66-year-old man with 24 h history of acute fever and dyspnea was admitted to our hospital. He was diagnosed as severe community acquired pneumonia (CAP), septic shock, respiratory failure and acute kidney injury. Next-generation sequencing (NGS) was performed on the patient's sputum and blood, which identified numerous A. baumannii nucleotide sequences in the sample of sputum and led to the rapid diagnosis and treatment of community acquired pneumonia caused by A. baumannii. This result was confirmed by subsequent sputum culture. CONCLUSIONS: This case described that the successful application of the next generation sequencing assisting the speedy diagnosis of A. baumannii infection provides a new idea for the timely diagnosis of CAP-Ab and highlights that NGS is a promising tool in rapid etiological diagnosis of acute and severe infectious diseases.


Assuntos
Infecções por Acinetobacter/diagnóstico , Acinetobacter baumannii/genética , Infecções Comunitárias Adquiridas/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Pneumonia Bacteriana/diagnóstico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Injúria Renal Aguda/complicações , Idoso , Antibacterianos/uso terapêutico , China , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecção Hospitalar , Dispneia/complicações , Febre/complicações , Hospitalização , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/tratamento farmacológico , Insuficiência Respiratória/complicações , Choque Séptico/complicações , Escarro/microbiologia , Resultado do Tratamento
9.
PLoS One ; 15(1): e0227636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31917802

RESUMO

Serum markers that differentiate between tuberculous and non-tuberculous pneumonia would be clinically useful. However, few serum markers have been investigated for their association with either disease. In this study, serum levels of interferon gamma (IFN-γ), matrix metalloproteinases 1 and 9 (MMP-1 and MMP-9, respectively), and periostin were compared between 40 pulmonary tuberculosis (PTB) and 28 non-tuberculous pneumonia (non-PTB) patients. Diagnostic performance was assessed by analysis of receiver-operating characteristic (ROC) curves and classification trees. Serum IFN-γ and MMP-1 levels were significantly higher and serum MMP-9 levels significantly lower in PTB than in non-PTB patients (p < 0.001, p = 0.002, p < 0.001, respectively). No significant difference was observed in serum periostin levels between groups. ROC curve analysis could not determine the appropriate cut-off value with high sensitivity and specificity; therefore, a classification tree method was applied. This method identified patients with limited infiltration into three groups with statistical significance (p = 0.01), and those with MMP-1 levels < 0.01 ng/mL and periostin levels ≥ 118.8 ng/mL included only non-PTB patients (95% confidence interval 0.0-41.0). Patients with extensive infiltration were also divided into three groups with statistical significance (p < 0.001), and those with MMP-9 levels < 3.009 ng/mL included only PTB patients (95% confidence interval 76.8-100.0). In conclusion, the novel classification tree developed using MMP-1, MMP-9, and periostin data distinguished PTB from non-PTB patients. Further studies are needed to validate our cut-off values and the overall clinical usefulness of these markers.


Assuntos
Moléculas de Adesão Celular/sangue , Interferon gama/sangue , Metaloproteinase 1 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Pneumonia Bacteriana/sangue , Tuberculose Pulmonar/sangue , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/diagnóstico , Curva ROC , Sensibilidade e Especificidade , Tuberculose Pulmonar/diagnóstico
10.
Ital J Pediatr ; 46(1): 4, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31918745

RESUMO

BACKGROUND AND OBJECTIVES: The goal of this literature review is to compare current studies regarding the accuracy of different serum markers in differentiating viral from bacterial pneumonia in the pediatric population with what is employed in the medical settings at present. Currently there is still a lack of significant research, that would give us evaluation on biomarkers benefits towards getting a definite diagnosis of pneumonia. Finding out the potential of biomarkers to differentiate between viral and bacterial pneumonia is also important because knowing the exact pathogen would prevent irrational use of antibiotics. At present, irrational, broad-spectrum antibiotic use and increasing antibiotic resistance in microorganisms are still one of the greatest challenges in clinical settings. The use of biomarkers in clinical practice would not only facilitate accurate diagnosis, but would also help to reduce the amount of antibiotics overuse. MATERIALS AND METHODS: Literature search conducted on Medline and Google Scholar using a combination of terms. Articles that were in English and within ten years of the search date were manually sorted according to inclusion and exclusion criteria. RESULTS: Initial search returned n = 13,408. After activating filters, n = 140 were identified of which n = 12 included for literature review. CONCLUSIONS: Rise or drop in the concentration of a single marker is not accurate enough for predicting viral/bacterial community acquired pneumonia. This is because there is overlapping to a varying extent depending on the marker cut-off values, detection methods, analyses, the desired specificity, and sensitivity. Furthermore, the presence of mixed infection makes almost all markers suboptimal to be used universally. New markers such as MxA1 and HMGB1 gave promising results. However, to replicate a similar testing condition in a clinical environment may not be practical. Another approach is to make use of more than one marker and combine with clinical signs and symptoms. This may not be cost-effective in many clinical settings; nevertheless, in many studies, marker combination greatly improved the predictive power.


Assuntos
Biomarcadores/sangue , Pneumonia Bacteriana/sangue , Pneumonia Viral/sangue , Antibacterianos/uso terapêutico , Criança , Diagnóstico Diferencial , Humanos , Prescrição Inadequada/prevenção & controle , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico
11.
Medicine (Baltimore) ; 98(38): e17215, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567977

RESUMO

The aim of the study is to explore whether monocyte-to-lymphocyte ratio (MLR) provides predictive value of the severity in patients with Klebsiella pneumonia infection (KPI).Patients in a tertiary medical center with Klebsiella pneumonia infection from 2014 to 2017 were recruited in this study. Patients with Klebsiella pneumonia infection were stratified into two groups based on the National Early Warning Score (NEWS). MLR was calculated by dividing monocytes count by lymphocytes count obtained from routine blood examination. The area under the curve (AUC) values was determined using the receiver-operating characteristic (ROC) curve. The correlation between the variables was tested with Pearson or Spearman correlation analysis. Ordinal logistic regression analysis was used to assess the relationship between MLR and the severity of Klebsiella pneumonia infection.One hundred fifty-two patients were finally enrolled for analysis. Among those, 43 (28.29%) cases had severe KPI. MLR was found to be an independent risk factor of the serious Klebsiella pneumonia infection (OR: 23.74, 95% CI: 5.41-104.11, P < .001). Besides, MLR was positively correlated with NEWS score (r = 0.57, P < .001). In the receiver-operating characteristic (ROC) curve analysis, MLR, with an optimal cut-off value of 0.665, predicted the severe coronary lesion with a sensitivity of 79.4% and specificity of 84.4%.MLR was an independent predictor of the severe Klebsiella pneumonia infection. Compared with neutrophil-to-lymphocyte ratio (NLR), MLR has a better performance to evaluate the severity of Klebsiella pneumonia infection.


Assuntos
Infecções por Klebsiella/diagnóstico , Klebsiella pneumoniae , Contagem de Leucócitos , Contagem de Linfócitos , Monócitos , Pneumonia Bacteriana/diagnóstico , Idoso , Feminino , Humanos , Infecções por Klebsiella/sangue , Infecções por Klebsiella/microbiologia , Masculino , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/microbiologia , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença
12.
Chest ; 156(6): 1080-1091, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31381883

RESUMO

BACKGROUND: Community-acquired pneumonia (CAP) increases the risk of cardiovascular complications during and following the episode. The goal of this study was to determine the usefulness of cardiovascular and inflammatory biomarkers for assessing the risk of early (within 30 days) or long-term (1-year follow-up) cardiovascular events. METHODS: A total of 730 hospitalized patients with CAP were prospectively followed up during 1 year. Cardiovascular (proadrenomedullin [proADM], pro-B-type natriuretic peptide (proBNP), proendothelin-1, and troponin T) and inflammatory (interleukin 6 [IL-6], C-reactive protein, and procalcitonin) biomarkers were measured on day 1, at day 4/5, and at day 30. RESULTS: Ninety-two patients developed an early event, and 67 developed a long-term event. Significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6 were recorded in patients who developed cardiovascular events. Despite a decrease at day 4/5, levels remained steady until day 30 in those who developed late events. Biomarkers (days 1 and 30) independently predicted cardiovascular events adjusted for age, previous cardiac disease, Pao2/Fio2 < 250 mm Hg, and sepsis: ORs (95% CIs), proendothelin-1, 2.25 (1.34-3.79); proADM, 2.53 (1.53-4.20); proBNP, 2.67 (1.59-4.49); and troponin T, 2.70 (1.62-4.49) for early events. For late events, the ORs (95% CIs) were: proendothelin-1, 3.13 (1.41-7.80); proADM, 2.29 (1.01-5.19); and proBNP, 2.34 (1.01-5.56). Addition of IL-6 levels at day 30 to proendothelin-1 or proADM increased the ORs to 3.53 and 2.80, respectively. CONCLUSIONS: Cardiac biomarkers are useful for identifying patients with CAP at high risk for early and long-term cardiovascular events. They may aid personalized treatment optimization and for designing future interventional studies to reduce cardiovascular risk.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/complicações , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Tempo
13.
Am J Med Sci ; 358(1): 33-44, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31084909

RESUMO

BACKGROUND: The optimal duration of antibiotic treatment has not been established for pneumonia patients. Some investigators reported procalcitonin (PCT)-guided antimicrobial stewardship reduces the duration of antibiotic use without increasing mortality in pneumonia patients. MATERIAL AND METHODS: We prospectively enrolled hospitalized community-acquired pneumonia or healthcare-associated pneumonia patients with PCT levels >0.20 ng/mL on admission, who were admitted between 2014 and 2017. PCT levels were measured on days 5, 8 and 11 and every 3 days thereafter if needed. Physicians were encouraged and strongly encouraged to discontinue antibiotics when PCT levels decreased below 0.20 ng/mL and 0.10 ng/mL, respectively. Those admitted between 2010 and 2014 were included in the study as historical controls. Primary endpoints were duration of antibiotic treatment and recurrence of pneumonia within 30 days after antibiotic discontinuation. RESULTS: The PCT-guided and control groups consisted of 116 patients each. Background factors including pneumonia severity and PCT levels did not differ between the 2 groups. Median duration of antibiotic treatment was 8.0 and 11 days in the PCT-guided and control groups, respectively (P < 0.001). Multivariable regression analysis revealed that PCT-guided antibiotic discontinuation (partial regression coefficient [PRC] -1.9319, P < 0.001), PCT (PRC 0.1501, P = 0.0059) and albumin (PRC -1.4398, P = 0.0096) were significantly related to duration of antibiotic treatment. Pneumonia recurrence within 30 days after antibiotic discontinuation was not statistically different between the 2 groups (4.3% vs. 6.0%, P = 0.5541). CONCLUSIONS: PCT-guided antibiotic discontinuation might be useful for shortening the duration of antibiotic treatment without increasing pneumonia recurrence.


Assuntos
Antibacterianos/administração & dosagem , Duração da Terapia , Pneumonia Bacteriana/tratamento farmacológico , Pró-Calcitonina/sangue , Idoso , Antibacterianos/uso terapêutico , Biomarcadores/sangue , Tomada de Decisão Clínica , Infecções Comunitárias Adquiridas , Infecção Hospitalar , Esquema de Medicação , Feminino , Humanos , Masculino , Pneumonia Bacteriana/sangue , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Recidiva , Resultado do Tratamento
14.
BMC Pulm Med ; 19(1): 71, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940126

RESUMO

BACKGROUND: Differentiating bacterial from viral pneumonia is important for guiding targeted management and judicious use of antibiotics. We assessed if clinical characteristics and blood inflammatory biomarkers could be used to distinguish bacterial from viral pneumonia. METHODS: Western Australian children (≤17 years) hospitalized with radiologically-confirmed community-acquired pneumonia were recruited and clinical symptoms and management data were collected. C-reactive protein (CRP), white cell counts (WCC) and absolute neutrophil counts (ANC) were measured as part of routine care. Clinical characteristics and biomarker levels were compared between cases with definite bacterial pneumonia (clinical empyema and/or bacteria detected in blood or pleural fluid), presumed viral pneumonia (presence of ≥1 virus in nasopharyngeal swab without criteria for definite bacterial pneumonia), and other pneumonia cases (pneumonia in the absence of criteria for either definite bacterial or presumed viral pneumonia). The area-under-curve (AUC) of the receiver operating characteristic (ROC) curve for varying biomarker levels were used to characterise their utility for discriminating definite bacterial from presumed viral pneumonia. For biomarkers with AUC > 0.8 (fair discriminator), Youden index was measured to determine the optimal cut-off threshold, and sensitivity, specificity, predictive values (positive and negative) were calculated. We investigated whether better discrimination could be achieved by combining biomarker values with the presence/absence of symptoms. RESULTS: From May 2015 to October 2017, 230 pneumonia cases were enrolled: 30 with definite bacterial pneumonia, 118 with presumed viral pneumonia and 82 other pneumonia cases. Differences in clinical signs and symptoms across the groups were noted; more definite bacterial pneumonia cases required intravenous fluid and oxygen supplementation than presumed viral or other pneumonia cases. CRP, WCC and ANC were substantially higher in definite bacterial cases. For a CRP threshold of 72 mg/L, the AUC of ROC was 0.82 for discriminating definite bacterial pneumonia from presumed viral pneumonia. Combining the CRP with either the presence of fever (≥38οC) or the absence of rhinorrhea improved the discrimination. CONCLUSIONS: Combining elevated CRP with the presence or absence of clinical signs/ symptoms differentiates definite bacterial from presumed viral pneumonia better than CRP alone. Further studies are required to explore combination of biomarkers and symptoms for use as definitive diagnostic tool.


Assuntos
Biomarcadores/sangue , Pneumonia Bacteriana/diagnóstico , Pneumonia Viral/diagnóstico , Área Sob a Curva , Austrália/epidemiologia , Bactérias/genética , Bactérias/isolamento & purificação , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/diagnóstico , Feminino , Humanos , Lactente , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pneumonia Bacteriana/sangue , Pneumonia Viral/sangue , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade
15.
Clin Lab ; 65(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30969087

RESUMO

BACKGROUND: The differential diagnosis of pulmonary tuberculosis and bacterial community-acquired pneumonia is often a challenging phenomenon. The neutrophil to lymphocyte count ratio, a suitable indicator of inflammation, has been demonstrated to be a useful biomarker for predicting bacteremia. The main aim this study is to evaluate the role of neutrophil to lymphocyte count ratio in the differential diagnosis of pulmonary tuberculosis and bacterial Community-Acquired Pneumonia at Ayder and Mekelle hospitals, Mekelle, Ethiopia. METHODS: A hospital based cross-sectional study was conducted from February to May 2017 on a total of 146 patients at Ayder and Mekelle hospitals. After taking written informed consent, study participants were interviewed for a detailed history and 5 mL of blood was collected for hematological analysis. Pulmonary tuberculosis was diagnosed by using Ziehl-Neelsen and Gene X-pert. Community acquired pneumonia was diagnosed using sputum culture. Student's t-test, Pearson's chi-square test, and receiver operating characteristics curve analysis were used. A p-value < 0.05 was considered statistically significant. RESULTS: The neutrophil to lymphocyte count ratio and eythrocyte sedimentation rate were significantly higher in pulmonary tuberculosis patients than bacterial community-acquired pneumonia patients. Neutrophil to lymphocyte count ratio and eythrocyte sedimentation rate with cutoff values of ≥ 2.72 and ≥ 39, respectively, showed the highest area under the curve (AUC = 0.69; 95% CI: 0.62, 0.77). CONCLUSIONS: Neutrophil to lymphocyte count ratio and eythrocyte sedimentation rate together at a time with their respective cutoff values gave a 69% accuracy in differentiating pulmonary tuberculosis from bacterial community-acquired pneumonia. Therefore, neutrophil to lymphocyte count ratio and erythrocyte sedimentation rate can be used in differentiating pulmonary tuberculosis from PTB patients from bacterial Community-acquired pneumonia, especially in resource-limited settings.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Contagem de Linfócitos , Neutrófilos/citologia , Pneumonia Bacteriana/diagnóstico , Tuberculose Pulmonar/diagnóstico , Adulto , Sedimentação Sanguínea , Infecções Comunitárias Adquiridas/sangue , Estudos Transversais , Diagnóstico Diferencial , Etiópia , Feminino , Hospitalização , Humanos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Pneumonia Bacteriana/sangue , Curva ROC , Tuberculose Pulmonar/sangue , Adulto Jovem
16.
Respir Res ; 20(1): 54, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30866951

RESUMO

BACKGROUND: Recently, lymphoid follicle-confined and circulating CD8+ T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, which was involved in anti-virus immune response. However, the dynamics and role of circulating CXCR5-expressing CD8+ T-cells during bacterial infection is unknown. So, we asked whether CXCR5+ CD8+ T cells were also generated during bacterial infections in lower respiratory tract. METHODS: The clinical data of 65 pneumonia patients were analyzed. The patients were divided into groups as tuberculosis, bronchiectasis and community or hospital acquired pneumonia (CAP, HAP). The sputum/bronchial secretion or bronchoalveolar lavage fluid (BALF) samples were taken for microbiological examination. The procalcitonin (PCT) was used to evaluate disease severity of these groups and compared among patients. We characterized the number and phenotype (PD-1 and CD103) of CXCR5 + CD8+ T cells in the peripheral circulation by flow cytometry in all individuals and analyzed their association with the serum PCT level and disease severity. RESULTS: Patients were mainly infected with Escherichia coli, Acinetobacter baumannii, Klebsiella pneumonia (K.p), Pseudomonas aeruginosa, and Staphylococcus aureus. Of note is the finding that PCT was weakly correlated with severity of respiratory infections. Furthermore, it was revealed an increase of CXCR5-expressing CD8+ T cells in peripheral blood of un-controlled CAP and progressive HAP compared controlled CAP and HAP, respectively (P < 0.05). Strikingly, the circulating CXCR5-expressing CD8+ T-cells in K.p-infected group was higher than that non-K.p-infected group (P < 0.05). Meanwhile, the ratio of CXCR5 + CD8+/CD8 was positively correlated with PCT level (P < 0.05). In clinic, the determination of CXCR5-expressing CD8+ T-cells showed better results compared to PCT and can be useful for the prediction of exacerbation of CAP or HAP. Phenotypically, CXCR5+ CD8 + T cell expressed comparable level of inhibitory molecules PD-1 and lower CD103 compared to their CXCR5- counterparts. CONCLUSION: The circulating CXCR5-expressing CD8+ T-cell has diagnostic value for current pneumonia severity, and could act as a biomarker for identifying a bacteria-associated exacerbation. These cells may provide novel insight for the pathogenesis of pneumonia.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/diagnóstico , Receptores CXCR5/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/genética , Receptores CXCR5/genética , Adulto Jovem
17.
Molecules ; 24(3)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717123

RESUMO

Colistin is administered as its inactive prodrug colistimethate (CMS). Selection of an individualized CMS dose for each patient is difficult due to its narrow therapeutic window, especially in patients with chronic kidney disease (CKD). Our aim was to analyze CMS use in patients with CKD. Secondary objectives were to assess the safety and efficacy of CMS in this special population. In this prospective observational cohort study of CMS-treated CKD patients, CKD was defined as the presence of a glomerular filtration rate (GFR) < 60 mL/min/m² for more than 3 months. The administered doses of CMS were compared with those recently published in the literature. Worsened CKD at the end of treatment (EOT) was evaluated with the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Colistin plasma concentrations (Css) were measured using high-performance liquid chromatography. Fifty-nine patients were included. Thirty-six (61.2%) were male. The median age was 76 (45⁻95) years and baseline GFR was 36.6 ± 13.6. The daily mean CMS dosage used was compared with recently recommended doses (3.36 vs. 6.07; p < 0.001). Mean Css was 0.9 (0.2⁻2.9) mg/L, and Css was <2 mg/L in 50 patients (83.3%). Clinical cure was achieved in 43 (72.9%) patients. Worsened renal function at EOT was present in 20 (33.9%) patients and was reversible in 10 (52.6%). The CMS dosages used in this cohort were almost half those currently recommended. The mean achieved Css were under the recommended target of 2 mg/dL. Despite this, clinical cure rate was high. In this patient cohort, the incidence of nephrotoxicity was similar to those found in other recent studies performed in the general population and was reversible in 52.6%. These results suggest that CMS is safe and effective in patients with CKD and may encourage physicians to adjust dosage regimens to recent recommendations in order to optimize CMS treatments.


Assuntos
Antibacterianos/farmacocinética , Bronquite/tratamento farmacológico , Colistina/análogos & derivados , Pneumonia Bacteriana/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/sangue , Antibacterianos/farmacologia , Bronquite/sangue , Bronquite/complicações , Bronquite/fisiopatologia , Colistina/sangue , Colistina/farmacocinética , Colistina/farmacologia , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/fisiopatologia , Estudos Prospectivos , Infecções por Pseudomonas/sangue , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/fisiopatologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/patogenicidade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Resultado do Tratamento , Infecções Urinárias/sangue , Infecções Urinárias/complicações , Infecções Urinárias/fisiopatologia
18.
J Cardiothorac Surg ; 14(1): 26, 2019 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-30696462

RESUMO

BACKGROUND: Allograft rejection and infection are the major sources of morbidity and mortality after heart transplant. Early differential diagnosis is clinically crucial but difficult. The aim of the study was to examine serum cytokine profiles associated with each entity and whether such profiles could help to differentiate between them. METHODS: Heart allografts from Wistar rats were transplanted to Lewis rats as described by Yokoyama. Cardiac rejection and pulmonary bacterial infection were induced by Cyclosporine cessation and bacteria bronchus injection, and pathologically confirmed. Ninety serological cytokines profiles of the study objects were then simultaneously measured using a biotin label-based cytokine array. The fold change (FC) was used for relative cytokine concentration comparison analysis. RESULTS: Four cytokines in cardiac rejection group were significantly dysregulated as compared to health controls (ß -Catenin, 0.51 FC; E-Selectin, 0.62 FC; IFN-gamma, 1.87 FC; and IL-13, 0.60 FC, respectively). In pulmonary infection animals, 11 cytokines were remarkably dysregulated in comparison with the control group (CINC-3, 0.57 FC; CNTF R alpha, 0.59 FC; E-Selectin, 0.58 FC; FSL1,0.62 FC; Hepassocin, 0.64 FC; IL-2, 0.26 FC; IL-13, 0.49 FC; NGFR, 0.57 FC; RAGE, 0.50 FC; TIMP-1, 0.49 FC; and IFN-gamma, 1.77 FC, respectively). Eleven cytokines were significantly up-regulated in cardiac rejection group comparing to the pulmonary infection animals (FSL1, 2.32FC; Fractalkine, 1.65FC; GFR alpha-1, 1.64FC; IL-2, 2.72FC; IL-5, 1.60FC; MMP-2, 1.71FC; NGFR, 2.25FC; TGF-beta1, 1.58FC; TGF-beta3, 1.58FC; Thrombospondin, 1.64FC, and TIMP-1, 1.52FC, respectively). CONCLUSIONS: The current study illustrated the disease-specific serological cytokine profiles of allograft rejection and pulmonary bacterial infection after cardiac transplant. Such disease associated cytokine portraits might have the potential for early discrimination diagnosis.


Assuntos
Citocinas/sangue , Rejeição de Enxerto/etiologia , Transplante de Coração , Pneumonia Bacteriana/etiologia , Aloenxertos , Animais , Modelos Animais de Doenças , Rejeição de Enxerto/sangue , Masculino , Pneumonia Bacteriana/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Ratos , Ratos Endogâmicos Lew , Ratos Wistar
19.
Drug Chem Toxicol ; 42(3): 309-316, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30257565

RESUMO

Rimulus cinnamon is the dried twig of Cinnamomum cassia Presl. It is widely used in China for the treatment of inflammatory processes, amenorrhea, and other diseases. We aimed to study the protective effects of ethyl acetate extracts of R. cinnamon (EAE) on systemic inflammation and lung injury in endotoxin-poisoned mice. EAE was administered 5 d prior to lipopolysaccharide (LPS) challenge with 15 mg/kg LPS. The administration of EAE increased the levels of interferon-γ (IFN-γ) and decreased the levels of interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) in the serum. Additionally, EAE relieved the pathological changes in the tissues of the lungs and spleen, and significantly reduced the number of neutrophils in the lung tissues. In addition, treatment with EAE decreased the mRNA expression of the NLR family, pyrin domain-containing protein 3 (NLRP3), caspase-1, and interleukin-1ß (IL-1ß) in the lungs, as well as the expression of NLRP3, caspase-1 (p20), and pro-IL-1ß proteins. These results demonstrated the promising anti-inflammatory effects of EAE in endotoxin-poisoned mice. Furthermore, EAE could alleviate the lung injury of endotoxin-poisoned mice by antagonizing the activation of the NLRP3 inflammasome.


Assuntos
Anti-Inflamatórios/uso terapêutico , Cinnamomum aromaticum/química , Medicamentos de Ervas Chinesas/uso terapêutico , Lipopolissacarídeos/toxicidade , Lesão Pulmonar/prevenção & controle , Pneumonia Bacteriana/prevenção & controle , Acetatos/química , Animais , Anti-Inflamatórios/isolamento & purificação , Citocinas/sangue , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Lesão Pulmonar/sangue , Lesão Pulmonar/imunologia , Masculino , Camundongos Endogâmicos , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/imunologia
20.
Cytokine ; 113: 272-276, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30055898

RESUMO

BACKGROUND: The serum cytokine levels among 45 mechanically ventilated, intensive care unit (ICU)-treated severe community-acquired pneumonia (SCAP) patients with known microbial etiology in three different etiology groups were assessed. METHODS: Blood samples for C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-5, IL-6, IL-10, human interferon gamma induced protein (IP)-10, and TNF-α (tumor necrosis factor alpha) were collected at time points 0, 12, 24, 48, 72 and 96 h after study inclusion. RESULTS: There were 21 (43%) pure bacterial infections (bacterial group, BG), 5 (10%) pure viral infections (viral group, VG), and 19 (39%) mixed bacterial-viral infections (mixed group, MG) among 45 mechanically ventilated SCAP patients. CRP and PCT levels were significantly higher in the MG and values decreased with time in all groups. PCT differed also in time and group analysis (P = 0.001), the highest being in the MG. IL-5 levels were significantly higher in the VG compared to others (Ptime = 0.001, Pgroup = 0.051 and Ptimexgroup = 0.016). IL-6 and IP-10 levels decreased over time (Ptime = 0.003 and Ptime = 0.021), but there were no differences between groups. CONCLUSION: SCAP patients with viral etiology have higher IL-5 levels. Patients with mixed viral and bacterial group have higher PCT compared to other etiologies.


Assuntos
Proteína C-Reativa/metabolismo , Quimiocina CXCL10/sangue , Infecções Comunitárias Adquiridas , Interleucina-5/sangue , Interleucina-6/sangue , Pneumonia Bacteriana , Pneumonia Viral , Pró-Calcitonina/sangue , Respiração Artificial , Adulto , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/terapia , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Fatores de Tempo
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