Optimal cut-off value of serum procalcitonin in predicting bacterial infection induced acute exacerbation in chronic obstructive pulmonary disease: A prospective observational study.

OBJECTIVE: To explore the optimal cut-off value of serum procalcitonin (PCT) level in predicting bacterial infection in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: 204 hospitalized patients with AECOPD were enrolled in this study. Their diagnoses and treatments followed routine protocols in Fu-Xing Hospital affiliated to Capital Medical University, Beijing, China. Extra blood samples were taken for serum PCT level testing and the results were blinded to the treating physicians. On discharge, clinical data were collected and the treating physicians made comprehensive analyses to determine whether the AECOPD were triggered by respiratory tract bacterial infection or non-bacterial causes according to the "new diagnostic criteria" defined in this study. In the AECOPD patients with bacterial infection, treating physicians decided whether they had bacterial pneumonia based on imaging studies. Receiver operating characteristic curve (ROC) was used to analyze the accuracy of serum PCT level in predicting bacterial infection. RESULTS: In the 173 AECOPD patients who did not have pneumonia, 115 had evidences of bacterial infection while 58 did not. The median PCT levels were 0.1(0.08, 0.18) ng/ml and 0.07 (0.05, 0.08) ng/ml for each group, which were statistically different. The proposed optimal cut-off value of serum PCT level in predicting bacterial infection was 0.08 ng/mL according to this study, with a sensitivity of 81%, specificity of 67% and area under the ROC curve (AUC) of 0.794. There were 31 AECOPD patients diagnosed with pneumonia, their median PCT level was 0.23 ng/mL. CONCLUSIONS: The serum PCT levels slightly increased in the majority of hospitalized patients with AECOPD compared with reference range. When PCT level was ≥0.08 ng/mL, AECOPD was more likely to be caused by bacterial infection. A significantly elevated PCT levels may indicate combination of AECOPD and bacterial pneumonia.

Biomarkers for iron metabolism among patients hospitalized with community-acquired pneumonia caused by infection with SARS-CoV-2, bacteria, and influenza.

Ferritin, the central iron storage protein, has attracted attention as a biomarker of severe COVID-19. Few studies have investigated regulators of iron metabolism in the context of COVID-19. The aim was to evaluate biomarkers for iron metabolism in the acute phase response to community-acquired pneumonia (CAP) caused by SARS-CoV-2 compared with CAP caused by bacteria or influenza virus in hospitalized patients. A cross-sectional study of 164 patients from the Surviving Pneumonia Cohort recruited between January 8, 2019 and May 26, 2020. Blood samples were collected at admission and analyzed for levels of C-reactive protein (CRP), ferritin, soluble transferrin receptor, erythroferrone, and hepcidin. Median (IQR) hepcidin was higher in SARS-CoV-2 with 143.8 (100.7-180.7) ng/mL compared with bacterial and influenza infection with 78.8 (40.1-125.4) and 53.5 (25.2-125.8) ng/mL, respectively. The median ferritin level was more than 2-fold higher in patients with SARS-CoV-2 compared with the other etiologies (p < 0.001). Patients with SARS-CoV-2 had lower levels of erythroferrone and CRP compared with those infected with bacteria. Higher levels of hepcidin and lower levels of erythroferrone despite lower CRP levels among patients with SARS-CoV-2 compared with those infected with bacteria indicate alterations in iron metabolism in patients with SARS-CoV-2 infection.

Soluble form of suppression of tumorigenicity-2 predicts clinical stability of inpatients with community-acquired pneumonia.

The soluble form of the suppression of tumorigenicity-2 (sST2) is a biomarker for risk classification and prognosis of heart failure, and its production and secretion in the alveolar epithelium are significantly correlated with the inflammation-inducing in pulmonary diseases. However, the predictive value of sST2 in pulmonary disease had not been widely studied. This study investigated the potential value in prognosis and risk classification of sST2 in patients with community-acquired pneumonia. Clinical data of ninety-three CAP inpatients were retrieved and their sST2 and other clinical indices were studied. Cox regression models were constructed to probe the sST2's predictive value for patients' restoring clinical stability and its additive effect on pneumonia severity index and CURB-65 scores. Patients who did not reach clinical stability within the defined time (30 days from hospitalization) have had significantly higher levels of sST2 at admission (P < 0.05). In univariate and multivariate Cox regression analysis, a high sST2 level (≥72.8 ng/mL) was an independent reverse predictor of clinical stability (P < 0.05). The Cox regression model combined with sST2 and CURB-65 (AUC: 0.96) provided a more accurate risk classification than CURB-65 (AUC:0.89) alone (NRI: 1.18, IDI: 0.16, P < 0.05). The Cox regression model combined with sST2 and pneumonia severity index (AUC: 0.96) also provided a more accurate risk classification than pneumonia severity index (AUC:0.93) alone (NRI: 0.06; IDI: 0.06, P < 0.05). sST2 at admission can be used as an independent early prognostic indicator for CAP patients. Moreover, it can improve the predictive power of CURB-65 and pneumonia severity index score.

Plasma Ferritin as Marker of Macrophage Activation-Like Syndrome in Critically Ill Patients With Community-Acquired Pneumonia.

OBJECTIVES: Plasma ferritin levels above 4,420 ng/mL have been proposed as a diagnostic marker for macrophage activation-like syndrome in sepsis and used for selection of sepsis patients for anti-inflammatory therapy. We here sought to determine the frequency, presentation, outcome, and host response aberrations of macrophage activation-like syndrome, as defined by admission ferritin levels above 4,420 ng/mL, in critically ill patients with community-acquired pneumonia. DESIGN: A prospective observational cohort study. SETTING: ICUs in two tertiary hospitals in the Netherlands. PATIENTS: One hundred fifty-three patients admitted with community-acquired pneumonia. MEASUREMENTS AND MAIN RESULTS: Patients were stratified in community-acquired pneumonia-macrophage activation-like syndrome (n = 15; 9.8%) and community-acquired pneumonia-control groups (n = 138; 90.2%) based on an admission plasma ferritin level above or below 4,420 ng/mL, respectively. Community-acquired pneumonia-macrophage activation-like syndrome patients presented with a higher disease severity and had a higher ICU mortality (46.7% vs 12.3% in community-acquired pneumonia-controls; p = 0.002). Twenty-three plasma biomarkers indicative of dysregulation of key host response pathways implicated in sepsis pathogenesis (systemic inflammation, cytokine responses, endothelial cell activation, and barrier function, coagulation activation) were more disturbed in community-acquired pneumonia-macrophage activation-like syndrome patients. Hematologic malignancies were overrepresented in community-acquired pneumonia-macrophage activation-like syndrome patients (33.3% vs 5.1% in community-acquired pneumonia-controls; p = 0.001). In a subgroup analysis excluding patients with hematologic malignancies (n = 141), differences in mortality were not present anymore, but the exaggerated host response abnormalities in community-acquired pneumonia-macrophage activation-like syndrome patients remained. CONCLUSIONS: Macrophage activation-like syndrome in critically ill patients with community-acquired pneumonia occurs more often in patients with hematologic malignancies and is associated with deregulation of multiple host response pathways.

Extrathoracic multiple trauma dysregulates neutrophil function and exacerbates pneumonia-induced lung injury.

BACKGROUND: Forty percent of critically ill trauma patients will develop an infectious complication. Pneumonia is the most common cause of death of trauma patients surviving their initial insult. We previously demonstrated that polytrauma (PT), defined as two or more severe injuries in at least two areas of the body, induces emergency hematopoiesis characterized by accelerated myelopoiesis in the bone marrow and increased myeloid cell frequency in the peripheral tissues. We hypothesized that PT alone induces priming of neutrophils, resulting in hyperactivation upon secondary exposure to bacteria and causing acute lung injury and increased susceptibility to secondary exposure to Pseudomonas aeruginosa pneumonia. METHODS: C57BL/6 mice were subjected to PT consisting of a lower extremity pseudofracture, liver crush injury, and 15% blood-volume hemorrhage. Pneumonia was induced by intratracheal injection of 5 × 106 CFU live P. aeruginosa or 1 × 107 of heat-killed P. aeruginosa (HKPA). For reactive oxygen species (ROS), studies polymorphonuclear neutrophils (PMNs) were isolated by immunomagnetic bead negative selection and stimulated ex-vivo with HKPA. Reactive oxygen species production was measured by immunofluorescence. For histology, lung sections were stained by hematoxylin-eosin and analyzed by a blinded grader. RESULTS: Polytrauma induced persistent changes in immune function at baseline and to secondary infection. Pneumonia after injury resulted in increased mortality (60% vs. 5% p < 0.01). Blood neutrophils from PT mice had higher resting (unstimulated) ROS production than in naive animals (p < 0.02) demonstrating priming of the neutrophils following PT. After intratracheal HKPA injection, bronchoalveolar lavage PMNs from injured mice had higher ROS production compared with naive mice (p < 0.01), demonstrating an overexuberant immunopathologic response of neutrophils following PT. CONCLUSION: Polytrauma primes neutrophils and causes immunopathologic PMN ROS production, increased lung injury and susceptibility to secondary bacterial pneumonia. These results suggest that trauma-induced immune dysfunction can cause immunopathologic response to secondary infection and suggests neutrophil-mediated pulmonary damage as a therapeutic target for posttrauma pneumonia.

Blood cultures and blood microbiota analysis as surrogates for bronchoalveolar lavage fluid analysis in dogs with bacterial pneumonia.

BACKGROUND: Diagnosis of canine bacterial pneumonia relies on airway lavage to confirm septic, suppurative inflammation, and a positive bacterial culture. Considering risks of bronchoalveolar lavage fluid (BALF) collection, minimally invasive methods like culture or next generation sequencing of blood would be appealing. In dogs with bacterial pneumonia, our study aims included (1): determining proportion of agreement between cultivable bacteria in BALF and blood (2); characterizing BALF, blood, and oropharyngeal (OP) microbiota and determining if bacteria cultured from BALF were present in these communities; and (3) comparing relatedness of microbial community composition at all three sites. Bacterial cultures were performed on BALF and blood. After DNA extraction of BALF, blood and OP, 16S rRNA amplicon libraries were generated, sequenced, and compared to a bacterial gene sequence database. RESULTS: Disregarding one false positive, blood cultures were positive in 2/9 dogs (5 total isolates), all 5 isolates were present in BALF cultures (16 total isolates). Based on sequencing data, all sites had rich and diverse microbial communities. Comparing cultured BALF bacterial genera with sequenced taxa, all dogs had ≥1 cultured isolate present in their microbiota: cultured BALF isolates were found in microbiota of BALF (12/16), blood (7/16), and OP (6/11; only 7 dogs had OP swabs). Of 394 distinct taxa detected in BALF, these were present in 75% OP and 45% blood samples. BALF community composition was significantly different than OP (p = 0.0059) and blood (p = 0.0009). CONCLUSIONS: Blood cultures are insensitive but specific for cultured BALF bacteria in canine bacterial pneumonia. Cultivable BALF bacteria were present in BALF, blood and OP microbiota to differing degrees.

Chronic infection with Chlamydia pneumoniae in asthma: a type-2 low infection related phenotype.

BACKGROUND: Chlamydia pneumoniae and Mycoplasma pneumoniae have been implicated in the pathogenesis of asthma and are responsible for chronic inflammation when host immune system fails to eradicate the bacteria. METHOD: We performed a prospective study on 410 patients who underwent a visit at the asthma clinic of CHU of Liege between June 2016 and June 2018 with serology testing for C. pneumoniae and M. pneumoniae. RESULTS: 65% of our asthmatic population had serum IgA and/or IgG towards C. pneumoniae, while only 12.6% had IgM and/or IgG against M. pneumoniae. Compared to seronegative asthmatics, asthmatics with IgA+ and IgG+ against C. pneumoniae were more often male and older with a higher proportion of patients with smoking history. They received higher doses of inhaled corticosteroids (ICS) and displayed lower FEV1/FVC ratio, higher RV/TLC ratio and lower conductance. They had higher levels of fibrinogen, though in the normal range and had lower sputum eosinophil counts. Patients with IgA- and IgG+ against C. pneumoniae were older and had higher blood monocyte counts and alpha-1-antitrypsin levels as compared to seronegative patients. Patients with IgM and/or IgG towards M. pneumoniae were more often males than seronegative asthmatics. In a subpopulation of 14 neutrophilic asthmatics with Chlamydia pneumoniae IgA + /IgG + treated with macrolides, we found a significant decrease in blood neutrophils and normalization of sputum neutrophil count but no effect on asthma quality of life and exacerbations. CONCLUSION: Positive Chlamydia serologic test is more common than positive Mycoplasma serology. Asthmatics with IgA and IgG against C. pneumoniae have more severe disease with increased airway obstruction, higher doses of ICS, more signs of air trapping and less type-2 inflammation.

Utilization of serum procalcitonin as a biomarker in the diagnosis and treatment of children with bacterial hospital-acquired pneumonia.

Hospital-acquired pneumonia (HAP) is one of the common infections in hospitalized patients. Early and prompt diagnosis of HAP is important because it aids in the appropriate selection of antibiotics and decreases the mortality and morbidity of patients. The investigation on serum procalcitonin (PCT) levels in pediatric patients is limited. Herein we aimed to evaluate the role of PCT in the early diagnosis of children with bacterial HAP. The study enrolled 264 children (< 14 years old) who were radiographically detected by pulmonary condensation chest X-rays. The HAP patients were stratified by patterns of microbiological detection of pathogens. Baseline white blood cell (WBC) count, neutrophil proportion, PCT, and C-reactive protein (CRP) were measured on admission. The laboratory findings and microbiological findings were analyzed and compared among groups. The median PCT concentration of patients with typical bacterial pathogens (3.95 ± 3.75 ng/mL) was significantly higher than the one of the patients with other pathogen types (median lower than 1.20 ng/mL). Correlation analysis indicated a significant correlation between PCT concentrations and the main inflammation makers including WBC count, neutrophil proportion, and CRP. PCT level was significantly decreased to 0.86 ± 1.46 ng/mL in post-treatment patients (p < 0.001). This cohort study with 264 pediatric HAP patients demonstrated the reliability of PCT level as a biomarker in patients with typical bacterial pathogens. Specifically, PCT cutoffs of 2 ng/mL accurately identified HAP children with typical bacterial pathogens. This finding suggested that PCT may serve as a reliable biomarker for the early diagnosis and treatment indicator of children with HAP.

Procalcitonin Correlates With but Is Not Superior to Other Diagnostic Markers of Bacterial Pneumonia.

OBJECTIVES: Despite extensive research on procalcitonin (PCT)-guided therapy in lower respiratory tract infections, the association between PCT and bacterial pneumonia remains unclear. METHODS: We evaluated retrospectively the performance of PCT in patients presenting with lower respiratory tract infection symptoms and grouped by seven diagnoses. All patients had microbial testing, chest imaging, and CBC counts within 1 day of PCT testing. RESULTS: Median PCT level in patients diagnosed with bacterial pneumonia was significantly higher than in patients diagnosed with other sources of infections or those not diagnosed with infections. Median PCT levels were not different among patients grouped by type or quantity of pathogen detected. They were significantly higher in patients with higher pathogenicity scores for isolated bacteria, those with abnormal WBC count, and those with chest imaging consistent with bacterial pneumonia. A diagnostic workup that included imaging, WBC count, and Gram stain had an area under the receiver operating characteristic curve of 0.748, and the addition of PCT increased it to 0.778. CONCLUSIONS: PCT was higher in patients diagnosed with bacterial pneumonia. Less clear is its diagnostic ability to detect bacterial pneumonia over and above imaging and laboratory data routinely available to clinicians.

Serum Procalcitonin as A Diagnostic and Prognostic Marker for Bacterial Community - Acquired Pneumonia.

For community acquired pneumonia (CAP), the discrimination between typical and atypical bacterial causes could influence antibiotic choice and outcome of patients. Objective of this study was to evaluate the utility of serum procalcitonin (PCT) level as a diagnostic and prognostic marker for CAP. Typical bacteria were isolated and identified by conventional methods. An indirect immunoflourescence assay was used to diagnose atypical bacteria. Serum level of PCT was measured by ELISA and clinical outcome was evaluated. Out of 240 enrolled CAP patients, 95 (39.6%) had bacterial etiology (30.8 % typical bacterial pneumonia and 8.8% atypical pneumonia). Ninety five bacterial CAP patients were divided into 3 groups; group 1 (mortality, 20.1%), group 2 (complications, 52.6 %) and group 3 (discharge, 26.3 %). Group 1 patients had the highest PCT level in serum compared to other groups with a statistically significant difference (P < 0.001). A statistically significant higher serum level of PCT was detected in typical than atypical pneumonia (P < 0.001). In conclusion, serum PCT level may serve as a diagnostic and prognostic marker in CAP.

Targeting coagulation activation in severe COVID-19 pneumonia: lessons from bacterial pneumonia and sepsis.

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.

Procalcitonin and lung ultrasound algorithm to diagnose severe pneumonia in critical paediatric patients (PROLUSP study). A randomised clinical trial.

BACKGROUND: Lung ultrasound (LUS) in combination with a biomarker has not yet been studied. We propose a clinical trial where the primary aims are: 1. To assess whether an algorithm with LUS and procalcitonin (PCT) may be useful for diagnosing bacterial pneumonia; 2. To analyse the sensitivity and specificity of LUS vs chest X-ray (CXR). METHODS/DESIGN: A 3-year clinical trial. INCLUSION CRITERIA: children younger than 18 years old with suspected pneumonia in a Paediatric Intensive Care Unit. Patients will be randomised into two groups: Experimental Group: LUS will be performed as first lung image. CONTROL GROUP: CXR will be performed as first pulmonary image. Patients will be classified according to the image and the PCT: a) PCT < 1 ng/mL and LUS/CXR are not suggestive of bacterial pneumonia (BN), no antibiotic will be prescribed; b) LUS/CXR are suggestive of BN, regardless of the PCT, antibiotic therapy is recommended; c) LUS/CXR is not suggestive of BN and PCT > 1 ng/mL, antibiotic therapy is recommended. CONCLUSION: This algorithm will help us to diagnose bacterial pneumonia and to prescribe the correct antibiotic treatment. A reduction of antibiotics per patient, of the treatment length, and of the exposure to ionizing radiation and in costs is expected. TRIAL REGISTRATION: NCT04217980 .

Lipoprotein concentrations over time in the intensive care unit COVID-19 patients: Results from the ApoCOVID study.

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.

Accuracy of C-reactive protein, procalcitonin, serum amyloid A and neopterin for low-dose CT-scan confirmed pneumonia in elderly patients: A prospective cohort study.

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.

Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis.

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.

Dynamic Change of Neutrophil to Lymphocyte Ratios and Infection in Patients with Acute Ischemic Stroke.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) on admission was reported to be a predictor of pneumonia after stroke. The aim of this study was to investigate the association between the temporal change of NLR and post-stroke infection and whether infection modified the effect of NLR on the outcome. METHODS: We enrolled patients with acute ischemic stroke within 24 h after onset. The blood was collected on admission, day 1, 3, 7 after admission to detect white blood cells (WBC), neutrophils, and lymphocytes. Primary outcomes included pneumonia, urinary tract infection (UTI), other infection, and the secondary outcome was 3-month death. RESULTS: Of 798 stroke patients, 299 (37.66%) developed infection with 240 (30.23%) pneumonia, 78 (9.82%) UTI, and 9 (1.13%) other infection. The median time of infection occurrence was 48 h (interquartile range 27-74 h) after onset. NLR reached to the peak at 36 h. For all outcomes, NLR at 36 h after stroke had the highest predictive value than WBC, neutrophil, lymphocyte. NLR was independently associated with the presence of any infection (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.17), pneumonia (OR 1.12, 95%CI 1.05-1.19), but not UTI (OR 0.95, 95%CI 0.89-1.01). Adding infection or the interaction term did not substantially change the OR of NLR predicting 3-month death (OR 1.09, 95%CI 1.01, 1.17). CONCLUSION: Increased NLR around 36 h after stroke was a predictor of infection in patients with acute ischemic stroke. The increased NLR value was associated with a higher risk of 3-month death, which was independent of poststroke infection.

Calprotectin, a new biomarker for diagnosis of acute respiratory infections.

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.

The role of procalcitonin in differential diagnosis between acute radiation pneumonitis and bacterial pneumonia in lung cancer patients receiving thoracic radiotherapy.

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.