Increased plasma AACT level as an indicator of poor prognosis in patients hospitalised with community-acquired pneumonia: a multicentre prospective cohort study.

BACKGROUND AND OBJECTIVE: Community-acquired pneumonia (CAP) is a common respiratory disease that frequently requires hospitalisation, and is a significant cause of death worldwide. This study aimed to evaluate the usefulness of alpha-1-antichymotrypsin (AACT) as a diagnostic and prognostic biomarker of CAP. METHODS: We conducted a multicentre prospective cohort study in patients hospitalised with CAP. Plasma AACT levels were measured using a quantitative enzyme-linked immunosorbent assay. Receiver-operating characteristic (ROC) curves and Cox proportional hazards regression were used to assess the association between plasma AACT levels and CAP diagnosis and prognosis. RESULTS: A total of 274 patients with CAP were enrolled in the study. AACT levels were elevated in patients with CAP, especially those with severe CAP and non-survivors. The area under the curve (AUC) of AACT and CRP for diagnosing CAP was 0.755 and 0.843. Cox regression showed that CURB-65 and AACT levels were independent predictors of 30-day mortality. ROC curves showed that plasma AACT levels had the highest accuracy for predicting acute respiratory distress syndrome (ARDS), with an AUC of 0.862. Combining AACT with Pneumonia Severity Index and CURB-65 significantly improved their predictive accuracy for predicting 30-day mortality. CONCLUSION: Plasma AACT levels are elevated in patients with CAP, but plasma AACT level is inferior to the C-reactive protein level for diagnosing CAP. The AACT level can reliably predict the occurrence of ARDS and 30-day mortality in patients with CAP.

The predictive value of peripheral blood cell mitochondrial gene expression in identifying the prognosis in pediatric sepsis at preschool age.

Background: Sepsis represents a severe manifestation of infection often accompanied by metabolic disorders and mitochondrial dysfunction. Notably, mitochondrial DNA copy number (mtDNA-CN) and the expression of specific mitochondrial genes have emerged as sensitive indicators of mitochondrial function. To investigate the utility of mitochondrial gene expression in peripheral blood cells for distinguishing severe infections and predicting associated outcomes, we conducted a prospective cohort study. Methods: We established a prospective cohort comprising 74 patients with non-sepsis pneumonia and 67 cases of sepsis induced by respiratory infections, aging from 2 to 6 years old. We documented corresponding clinical data and laboratory information and collected blood samples upon initial hospital admission. Peripheral blood cells were promptly isolated, and both total DNA and RNA were extracted. We utilized absolute quantification PCR to assess mtDNA-CN, as well as the expression levels of mt-CO1, mt-ND1, and mt-ATP6. Subsequently, we extended these comparisons to include survivors and non-survivors among patients with sepsis using univariate and multivariate analyses. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic potential. Results: The mtDNA-CN in peripheral blood cells was significantly lower in the sepsis group. Univariate analysis revealed a significant reduction in the expression of mt-CO1, mt-ND1, and mt-ATP6 in patients with sepsis. However, multivariate analysis did not support the use of mitochondrial function in peripheral blood cells for sepsis diagnosis. In the comparison between pediatric sepsis survivors and non-survivors, univariate analysis indicated a substantial reduction in the expression of mt-CO1, mt-ND1, and mt-ATP6 among non-survivors. Notably, total bilirubin (TB), mt-CO1, mt-ND1, and mt-ATP6 levels were identified as independent risk factors for sepsis-induced mortality. ROC curves were then established for these independent risk factors, revealing areas under the curve (AUCs) of 0.753 for TB (95% CI 0.596-0.910), 0.870 for mt-CO1 (95% CI 0.775-0.965), 0.987 for mt-ND1 (95% CI 0.964-1.000), and 0.877 for mt-ATP6 (95% CI 0.793-0.962). Conclusion: MtDNA-CN and mitochondrial gene expression are closely linked to the severity and clinical outcomes of infectious diseases. Severe infections lead to impaired mitochondrial function in peripheral blood cells. Notably, when compared to other laboratory parameters, the expression levels of mt-CO1, mt-ND1, and mt-ATP6 demonstrate promising potential for assessing the prognosis of pediatric sepsis.

Serum calcium and mortality in pediatric pneumonia patients admitted to the PICU: a retrospective cohort study.

This study investigates serum calcium's prognostic value in pediatric pneumonia, focusing on its correlation with PICU mortality, to enhance understanding and treatment approaches in this field. Data from 414 pediatric pneumonia patients (2010-2019) admitted to the intensive care units at the Children's Hospital, Zhejiang University School of Medicine were analyzed. The study utilized restricted cubic spline analysis, Cox proportional hazard regression, and Kaplan-Meier survival curve analysis to assess the relationship between serum calcium levels at admission and PICU mortality risk. After adjusting for multivariate factors, for each 1 mmol/dL increase in serum calcium, the risk of mortality decreased by 24% (HR: 0.76, 95% CI 0.67-0.87). Among the three levels of serum calcium groups, higher serum calcium levels were linked to a 63% reduction in the mortality rate compared to lower levels (HR: 0.37, 95% CI 0.16-0.84). The cumulative hazard estimates of mortality significantly differed across serum calcium groups (log-rank P = 0.032). This association was consistent across diverse subgroups (P for interaction > 0.05). Higher serum calcium levels are associated with decreased PICU mortality in pediatric pneumonia, highlighting its potential as a prognostic marker.

Lung Ultrasound Efficacy in Monitoring Post-SARS-CoV-2 Pneumonia and Inflammatory Biomarkers in Pediatric Patients.

Background and Objectives: Recognizing the crucial gaps in our understanding of pediatric pneumonia post-SARS-CoV-2 infection, this study aimed to assess the relationship between Pediatric Pneumonia Ultrasound Scores (PedPne) and inflammatory biomarkers. The primary objective of this study is to evaluate the predictive value of PedPne in comparison with inflammatory biomarkers (IL-6 and dNLR) for the development of pneumonia in pediatric patients following SARS-CoV-2 infection. Materials and Methods: This longitudinal observational study collected data from pediatric patients diagnosed with pneumonia after an acute SARS-CoV2 infection. The study focused on analyzing changes in PedPne scores and inflammatory markers such as IL-6 and dNLR from initial admission to follow-up at 7 days. Statistical analysis involved calculating the sensitivity, specificity, and Area Under the Curve (AUC) for each biomarker, alongside regression analysis to determine their hazard ratios for predicting pneumonia development. Results: The analysis identified significant cutoff values for dNLR at 1.88 (sensitivity 77.0%, specificity 85.7%, AUC 0.802, p < 0.001), IL-6 at 6.1 pg/mL (sensitivity 70.3%, specificity 92.9%, AUC 0.869, p < 0.001), and PedPne score at 3.3 (sensitivity 75.7%, specificity 78.6%, AUC 0.794, p < 0.001). Conversely, NLR showed lower diagnostic performance (AUC 0.485, p = 0.327). Regression analysis further highlighted the strong predictive power of these markers, with IL-6 showing a fourfold increase in pneumonia risk (HR = 4.25, CI: 2.07-9.53, p < 0.001), dNLR indicating more than a twofold increase (HR = 2.53, CI: 1.19-6.97, p = 0.006), and PedPne score associated with more than a doubling of the risk (HR = 2.60, CI: 1.33-5.18, p < 0.001). Conclusions: The study conclusively demonstrated that both PedPne ultrasound scores and specific inflammatory biomarkers such as dNLR and IL-6 are significant predictors of pneumonia development in pediatric patients post-COVID-19 infection. These findings advocate for the integration of these biomarkers in routine clinical assessments to enhance the diagnostic accuracy and management of pneumonia in children following SARS-CoV-2 infection.

Stress hyperglycemia ratio and its influence on mortality in elderly patients with severe community-acquired pneumonia: a retrospective study.

BACKGROUND: Community-acquired pneumonia (CAP) is a significant health issue among the elderly, with severe cases (SCAP) having high mortality rates. This study assesses the predictive significance of the stress hyperglycemia ratio (SHR) in elderly SCAP patients and its impact on outcomes in both diabetic and non-diabetic patients. METHODS AND MATERIALS: This retrospective study included 406 SCAP patients aged 65 or older from the Second People's Hospital of Lianyungang (January 2020 to December 2023). Data collected included demographics, medical history, vital signs, and lab results. SHR was calculated from initial blood glucose and estimated average glucose (HbA1c). Statistical analyses, including Cox regression and Kaplan-Meier analysis, evaluated SHR's impact on mortality. Mediation models explored the effects of neutrophil-lymphocyte ratio (NLR) and SHR. RESULTS: The 28-day mortality rate was 21.67%. Deceased patients had higher age, Charlson Comorbidity Index, procalcitonin, NLR, glucose, and SHR levels compared to survivors (P < 0.05). Both SHR and NLR significantly increased mortality risk, particularly in non-diabetic patients. Combining NLR and SHR improved ROC AUC to 0.898, with 89.80% sensitivity and 81.10% specificity. Kaplan-Meier analysis showed higher cumulative survival for SHR < 1.14, regardless of diabetes status (P < 0.05). NLR mediated 13.02% of the SHR-survival relationship, while SHR mediated 14.06% of the NLR-survival relationship. CONCLUSION: Elevated SHR is a significant mortality risk factor in elderly SCAP patients, independent of diabetes status. Stringent glucose control and careful monitoring of SHR may improve outcomes in elderly patients with acute respiratory conditions.

Improving prognostication of pneumonia among elderly patients: usefulness of suPAR.

PURPOSE: Elderly patients with suspected pneumonia represent a significant proportion of hospital admissions, which is a prognostic challenge for physicians. Our research aimed to assess the prognosis of patients with pneumonia using soluble urokinase plasminogen activator receptor (suPAR) combined with clinical data. METHODS: In a prospective observational study including 164 patients > 65 years (mean age 84.2 (+/-7.64) years) who were hospitalized for a suspicion of pneumonia, suPAR was assessed for each patient, as was the prognosis score (PSI, CURB65) and inflammatory biomarkers (C-reactive protein, procalcitonin, white blood cells). The prognostic value of the suPAR for 30-day mortality was assessed using receiver operating characteristic (ROC) curve analyses. Optimal cut-offs with corresponding sensitivity (SE) and specificity (SP) were determined using the Youden index. RESULTS: A suPAR > 5.1 ng/mL was predictive of 30-day mortality with a sensitivity of 100% and a specificity of 40.4%. A combination of the following parameters exhibited an SE of 100% (95% CI, 100-100) for an SP value of 64.9% (95% CI, 57.6-72.2) when at least two of them were above or below the following cut-off threshold values: suPAR > 9.8 ng/mL, BMI < 29.3 kg/m2 and PSI > 106.5. CONCLUSION: The suPAR seems to be a promising biomarker that can be combined with the PSI and BMI to improve the prognosis of pneumonia among elderly patients. Prospective studies with larger populations are needed to confirm whether this new approach can improve patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02467192), 27th may 2015.

The prognosis of pneumonia in geriatric patients remain challenging, can the dosage of suPAR help clinicians determine the prognosis of pneumonia among geriatric patients? The use of individual or clinical parameters should be improved for a better prediction of respiratory complications and mortality. Adding suPAR dosage with PSI and BMI provides the best sensitivity and specificity for 30-day mortality.

Design and validation of novel flow cytometry panels to analyze a comprehensive range of peripheral immune cells in mice.

The use of flow cytometry in mice is constrained by several factors, including the limited availability of mouse-specific antibodies and the need to work with small volumes of peripheral blood. This is particularly challenging for longitudinal studies, as serial blood samples should not exceed 10% of the total blood volume in mice. To address this, we have developed two novel flow cytometry panels designed to extensively analyze immune cell populations in mice during longitudinal studies, using only 50 µL of peripheral blood per panel. Additionally, a third panel has been designed to conduct a more detailed analysis of cytotoxic and inhibitory markers at the end point. These panels have been validated on a lipopolysaccharide (LPS)-induced lung inflammation model. Two experiments were conducted to 1) validate the panels' sensitivity to immune challenges (n=12) and 2) to assess intrinsic variability of measurements (n=5). In both experiments, we collected 50 µL of peripheral blood for each cytometry panel from the maxillary venous sinus. All antibodies were titrated to identify the optimal concentration that maximized the signal from the positive population while minimizing the signal from the negative population. Samples were processed within 1 hour of collection using a MACSQuant Analyzer 16 cytometer. Our results demonstrate that these immunological panels are sensitive enough to detect changes in peripheral blood after LPS induction. Moreover, our findings help determine the sample size needed based on the immune population variability. In conclusion, the panels we have designed enable a comprehensive analysis of the murine immune system with a low blood volume requirement, enabling the measure of both absolute values and relative percentages effectively. This approach provides a robust platform for longitudinal studies in mice and can be used to uncover significant insights into immune responses.

C-Reactive Protein as a Predictor of Severe Respiratory Complications in Measles.

Background and Objectives: Even though measles is easily prevented by vaccination, infection outbreaks are not rare. Infection carries a great risk for pulmonary complications, which are sometimes hard to predict, especially in a group of outpatients. This study aims to evaluate the association between serum CRP changes and the severity of respiratory complications in the group of inpatients treated for measles. Materials and Methods: A total of 207 patients admitted and treated at the Clinic for Infectious Diseases, University Clinical Center, Nis, for measles infection were included in the analysis. The data collected from the patients' medical records included demographic characteristics, disease duration, blood and serum biochemical analysis, general measles-associated symptoms, and disease outcome. Results: Results of the study revealed that there are almost no differences in the clinical presentation of patients with measles and those complicated with pneumonia. The examined CRP changes are found to correlate with the observable degree of pneumonia; however, they do not correspond to the changes visible in chest X-rays. Conclusions: CRP changes in the serum of patients with measles with mild clinical pictures could be a potential predictor for the development of some pulmonary complications.

Association between fibrinogen levels and stroke-associated pneumonia in acute ischemic stroke patients.

PURPOSE: Prior research had indicated a relationship between fibrinogen and stroke-associated pneumonia (SAP), yet the nature of this relationship had not been thoroughly investigated. Therefore, this study was designed to elucidate the prognostic value of fibrinogen levels in forecasting the occurrence of SAP among patients with acute ischemic stroke (AIS). PATIENTS AND METHODS: In this retrospective cross-sectional analysis, we included 1092 patients who had experienced AIS and were admitted to our facility within 72 h of the onset of their symptoms. Based on the SAP diagnostic criteria, patients were classified into two groups: SAP and non-SAP. The correlation between serum fibrinogen concentration and SAP was examined using univariate analysis. Curve fitting and multivariable logistic regression model were utilized for statistical evaluation. RESULTS: Out of the ischemic stroke patients included in the study, SAP was identified in 112 (10.26%) patients. A direct correlation was observed between fibrinogen levels and the incidence of SAP. An increase in fibrinogen levels corresponded with a heightened incidence of SAP. Multivariable logistic regression revealed a significant positive association between fibrinogen levels and SAP incidence (OR = 1.53, 95% confidence interval [CI]: 1.18, 1.99)). CONCLUSION: A linear relationship between serum fibrinogen levels and the incidence of SAP in ischemic stroke patients was shown. The serum fibrinogen levels were positively and linearly correlated to SAP risk.

The clinical value of nutritional and inflammatory indicators in predicting pneumonia among patients with intracerebral hemorrhage.

Immunosuppression and malnutrition play pivotal roles in the complications of intracerebral hemorrhage (ICH) and are intricately linked to the development of stroke-associated pneumonia (SAP). Inflammatory markers, including NLR (neutrophil-to-lymphocyte ratio), SII (systemic immune inflammation index), SIRI (systemic inflammatory response index), and SIS (systemic inflammation score), along with nutritional indexes such as CONUT (controlling nutritional status) and PNI (prognostic nutritional index), are crucial indicators influencing the inflammatory state following ICH. In this study, our objective was to compare the predictive efficacy of inflammatory and nutritional indices for SAP in ICH patients, aiming to determine and explore their clinical utility in early pneumonia detection. Patients with severe ICH requiring ICU admission were screened from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The outcomes included the occurrence of SAP and in-hospital death. Receiver operating characteristic (ROC) analysis, multivariate logistic regression, smooth curve analysis, and stratified analysis were employed to investigate the relationship between the CONUT index and the clinical outcomes of patients with severe ICH. A total of 348 patients were enrolled in the study. The incidence of SAP was 21.3%, and the in-hospital mortality rate was 17.0%. Among these indicators, multiple regression analysis revealed that CONUT, PNI, and SIRI were independently associated with SAP. Further ROC curve analysis demonstrated that CONUT (AUC 0.6743, 95% CI 0.6079-0.7408) exhibited the most robust predictive ability for SAP in patients with ICH. Threshold analysis revealed that when CONUT < 6, an increase of 1 point in CONUT was associated with a 1.39 times higher risk of SAP. Similarly, our findings indicate that CONUT has the potential to predict the prognosis of patients with ICH. Among the inflammatory and nutritional markers, CONUT stands out as the most reliable predictor of SAP in patients with ICH. Additionally, it proves to be a valuable indicator for assessing the prognosis of patients with ICH.

Clinical risk factors and blood protein biomarkers of 10-year pneumonia risk.

BACKGROUND: Chronic inflammation may increase susceptibility to pneumonia. RESEARCH QUESTION: To explore associations between clinical comorbidities, serum protein immunoassays, and long-term pneumonia risk. METHODS: Framingham Heart Study Offspring Cohort participants ≥65 years were linked to their Centers for Medicare Services claims data. Clinical data and 88 serum protein immunoassays were evaluated for associations with 10-year incident pneumonia risk using Fine-Gray models for competing risks of death and least absolute shrinkage and selection operators for covariate selection. RESULTS: We identified 1,370 participants with immunoassays and linkage to Medicare data. During 10 years of follow up, 428 (31%) participants had a pneumonia diagnosis. Chronic pulmonary disease [subdistribution hazard ratio (SHR) 1.87; 95% confidence interval (CI), 1.33-2.61], current smoking (SHR 1.79, CI 1.31-2.45), heart failure (SHR 1.74, CI 1.10-2.74), atrial fibrillation/flutter (SHR 1.43, CI 1.06-1.93), diabetes (SHR 1.36, CI 1.05-1.75), hospitalization within one year (SHR 1.34, CI 1.09-1.65), and age (SHR 1.06 per year, CI 1.04-1.08) were associated with pneumonia. Three baseline serum protein measurements were associated with pneumonia risk independent of measured clinical factors: growth differentiation factor 15 (SHR 1.32; CI 1.02-1.69), C-reactive protein (SHR 1.16, CI 1.06-1.27) and matrix metallopeptidase 8 (SHR 1.14, CI 1.01-1.30). Addition of C-reactive protein to the clinical model improved prediction (Akaike information criterion 4950 from 4960; C-statistic of 0.64 from 0.62). CONCLUSIONS: Clinical comorbidities and serum immunoassays were predictive of pneumonia risk. C-reactive protein, a routinely-available measure of inflammation, modestly improved pneumonia risk prediction over clinical factors. Our findings support the hypothesis that prior inflammation may increase the risk of pneumonia.

Serum C-reactive protein to albumin ratio as a potential risk indicator of pneumonia caused by Chlamydia psittaci: a multicenter retrospective study.

Introduction: The aim of the study was to describe psittacosis pneumonia and to assess the predictive value of the C-reactive protein/albumin ratio in psittacosis pneumonia for severity. Methods: Data on psittacosis pneumonia cases diagnosed using metagenomic sequencing were collected from three hospitals in Shanghai, China from Oct. 2019 to Oct. 2022. Serum levels of C-reactive protein and albumin were measured and the C-reactive protein to albumin ratio (CAR) was calculated. Spearman's correlation analysis, ordered logistic regression analysis, and receiver operating characteristic curve analysis were conducted to examine the correlation and predictive ability of the three indicators on the severity of the disease. Results: A total of 27 patients with psittacosis pneumonia were enrolled, with an average age of 62 years and 70.4% being male. 44.4% of patients had a clear history of contact with poultry or birds. The predominant symptom was fever (100%). Patients treated in the respiratory intensive care unit (RICU) had a higher likelihood of experiencing wheezing (88.9% versus 33.3%, P=0.013) and chest tightness (88.9% vs. 33.3%, P=0.013) than those in the general ward (Non-RICU). The proportion of patients with pleural effusion was significantly higher in the RICU compared to the Non-RICU (88.9% vs. 38.9%, P=0.019). The RICU group had a significantly higher CAR than the Non-RICU group (9.41 vs. 4.05, P=0.017). This result was accompanied by higher intubation and ventilator support (33.3% vs. 0.0%, P=0.029), higher PCT and CRP levels and lower albumin and PaCO2 levels in the RICU than in the Non-RICU. Logistic regression analysis indicated that CAR (OR 1.49; 95% CI 1.07-2.06, P=0.017) was risk factor for prolonged hospitalization (> 14 days). Discussion: Elevated serum CAR levels were found to be associated with a greater risk of severe psittacosis pneumonia. Consequently, it may serve as an uncomplicated and useful diagnostic tool for clinicians to promptly and precisely ascertain the severity of psittacosis pneumonia, ultimately aiding them in devising the most optimal therapeutic plan.

Association between glucose levels at admission and outcomes of pneumonia: a systematic review and meta-analysis.

BACKGROUND: Elevated blood glucose at hospital admission is frequently observed and has been associated with adverse outcomes in various patient populations. This meta-analysis sought to consolidate existing evidence to assess the association between elevated blood glucose at admission and clinical outcomes amongst pneumonia patients. METHODS: We searched PubMed, Medline, Cochrane library, Web of Science (WoS), and Scopus databases for studies, published up to 31 August 2023, and reporting on the clinical outcomes and the blood glucose levels at admission. Data were extracted by two independent reviewers. Random-effects meta-analyses were used to pool odds ratios (ORs) with 95% confidence intervals (CI) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes. RESULTS: A total of 23 studies with 34,000 participants were included. Elevated blood glucose at admission was significantly associated with increased short-term (pooled OR: 2.67; 95%CI: 1.73-4.12) and long-term mortality (pooled OR: 1.70; 95%CI: 1.20-2.42). Patients with raised glucose levels were more likely to require ICU admission (pooled OR: 1.86; 95%CI: 1.31-2.64). Trends also suggested increased risks for hospital readmission and mechanical ventilation, though these were not statistically significant. Elevated blood glucose was linked with approximately 0.72 days longer duration of hospital stay. CONCLUSION: Elevated blood glucose level at the time of hospital admission is associated with several adverse clinical outcomes, especially mortality, in patients with pneumonia. These findings underscore the importance of recognizing hyperglycemia as significant prognostic marker in pneumonia patients. Further research is needed to determine whether targeted interventions to control glucose levels can improve these outcomes.

Analysis of Immune Cell Subsets in Peripheral Blood from Patients with Engineered Stone Silica-Induced Lung Inflammation.

Silicosis caused by engineered stone (ES-silicosis) is an emerging worldwide issue characterized by inflammation and fibrosis in the lungs. To our knowledge, only a few reports have investigated leukocyte/lymphocyte subsets in ES-silicosis patients. The present study was designed to explore the proportions of the main lymphocyte subsets in ES-silicosis patients stratified into two groups, one with simple silicosis (SS) and the other with a more advanced state of the disease, defined as progressive massive fibrosis (PMF). The proportions of B (memory and plasmablasts) cells, T (helper, cytotoxic, regulatory) cells, and natural killer (NK) (regulatory and cytotoxic) cells were investigated by multiparameter flow cytometry in 91 ES-silicosis patients (53 SS patients and 38 PMF patients) and 22 healthy controls (HC). Although the total number of leukocytes did not differ between the groups studied, lymphopenia was observed in patients compared to healthy controls. Compared with those in healthy controls, the proportions of memory B cells, naïve helper T cells, and the CD4+/CD8+ T cells' ratio in the peripheral blood of patients with silicosis were significantly decreased, while the percentages of plasma cells, memory helper T cells, and regulatory T cells were significantly increased. For the NK cell subsets, no significant differences were found between the groups studied. These results revealed altered cellular immune processes in the peripheral blood of patients with ES-silicosis and provided further insight into silicosis pathogenesis.

Inflammatory and endothelial host responses in community-acquired pneumonia: exploring the relationships with HbA1c, admission plasma glucose, and glycaemic gap-a cross-sectional study.

Introduction: Diabetes is associated with dysregulated immune function and impaired cytokine release, while transient acute hyperglycaemia has been shown to enhance inflammatory cytokine release in preclinical studies. Although diabetes and acute hyperglycaemia are common among patients with community-acquired pneumonia (CAP), the impact of chronic, acute, and acute-on-chronic hyperglycaemia on the host response within this population remains poorly understood. This study investigated whether chronic, acute, and acute-on- chronic hyperglycaemia are associated with distinct mediators of inflammatory, endothelial, and angiogenic host response pathways in patients with CAP. Methods: In a cross-sectional study of 555 patients with CAP, HbA1c, admission plasma (p)-glucose, and the glycaemic gap (admission p-glucose minus HbA1c- derived average p-glucose) were employed as measures of chronic, acute, and acute-on-chronic hyperglycaemia, respectively. Linear regression was used to model the associations between the hyperglycaemia measures and 47 proteins involved in inflammation, endothelial activation, and angiogenesis measured at admission. The models were adjusted for age, sex, CAP severity, pathogen, immunosuppression, comorbidity, and body mass index. Adjustments for multiple testing were performed with a false discovery rate threshold of less than 0.05. Results: The analyses showed that HbA1c levels were positively associated with IL-8, IL-15, IL-17A/F, IL-1RA, sFlt-1, and VEGF-C. Admission plasma glucose was also positively associated with these proteins and GM-CSF. The glycaemic gap was positively associated with IL-8, IL-15, IL-17A/F, IL-2, and VEGF-C. Conclusion: In conclusion, chronic, acute, and acute-on-chronic hyperglycaemia were positively associated with similar host response mediators. Furthermore, acute and acute-on-chronic hyperglycaemia had unique associations with the inflammatory pathways involving GM-CSF and IL-2, respectively.

U-shaped association between low-density lipoprotein cholesterol levels and risk of futile reperfusion mediated by stroke-associated pneumonia in acute ischemic stroke after endovascular thrombectomy.

OBJECTIVE: Futile reperfusion (FR) is becoming a major challenge in the treatment of patients with acute ischaemic stroke (AIS) undergoing endovascular thrombectomy. This study aims to determine the dose-response relationship between low-density lipoprotein cholesterol (LDL-C) levels and the risk of FR in patients with AIS undergoing endovascular thrombectomy and to investigate potential mediators. METHODS: A total of 614 patients with AIS undergoing endovascular thrombectomy were enrolled and divided into five groups according to quintiles of LDL-C levels: Q1(≤2.27 mmol/l), Q2 (2.27-2.5 mmol/l), Q3 (2.5-2.59 mmol/l), Q4 (2.59-2.97 mmol/l) and Q5 (≥2.97 mmol/l). Associations between LDL-C levels and the risk of FR and stroke-associated pneumonia (SAP) were estimated using multivariate logistic regression models. Restricted cubic spline curves were used to describe the dose-response relationship between LDL-C levels and the risk of FR and SAP. Mediation effect analysis was performed in R software with 100 bootstrap samples. RESULTS: After adjustment for confounders, both low and high LDL-C levels were significantly associated with a higher risk of FR compared with the reference group (Q3). We observed a U-shaped association between LDL-C levels and the risk of FR (P for nonlinear =0.012). Mediation analysis showed that the association between LDL-C levels and the risk of FR was 29.7 % (95 % CI: 2.96 %-75.0 %, P=0.02) mediated by SAP. CONCLUSIONS: We found a U-shaped association between LDL-C levels and the risk of FR that was mediated by SAP. Clinicians should note that in AIS patients undergoing endovascular thrombectomy, lower LDL-C levels are not always better.

Effect of Xe/O2 Inhalation on Hemostasis in Experimental Thromboplastin Pneumonitis.

We studied the effectiveness of Xe/O2 mixture inhalation (30% Xe and 70% O2, 20 min for 5 days) in a model of experimental thromboplastin pneumonitis. Inhalation of the studied mixture decreased the intensity of the inflammatory process in the lung tissue assessed by the temperature response of animals, changed lung weight and lung weight coefficient. At acute stage of pneumonitis, an increase in xenon consumption was recorded due to its retention in the gas exchange zone and a natural decrease in oxygen consumption due to partial alveolar/capillary block. The formation of pneumonitis was accompanied by a pronounced procoagulant shift in the regulation system of the aggregate state of blood. The Xe/O2 inhalations ensured physiologically optimal levels of prothrombin and activated partial thromboplastin time against the background of a moderate decrease in fibrinogen level throughout the experiment. At the same time, the activity of the natural anticoagulant antithrombin III increased from day 5 to day 14.

Serum SOD1 level predicts the severity and prognosis of community-acquired pneumonia patients.

BACKGROUND: Superoxide dismutase 1 (SOD1) is one of the most important participants of antioxidant enzyme system in biological system. Previous studies have found that SOD1 is associated with many inflammatory diseases. The goal of this study was to assess the associations of serum SOD1 with the severity and prognosis in community-acquired pneumonia (CAP) patients by a prospective cohort study. METHODS: CAP patients were enrolled from the Second Affiliated Hospital of Anhui Medical University. Peripheral blood samples were gathered. The level of serum SOD1 was detected through enzyme linked immunosorbent assay (ELISA). Clinical characteristics and demographic information were analyzed. RESULTS: The level of serum SOD1 was gradually upregulated with elevated CAP severity scores. Spearman correlation coefficient or Pearson rank correlation analyses indicated that serum SOD1 was strongly connected with many clinical parameters among CAP patients. Further linear and logistic regression analyses found that the level of serum SOD1 was positively associated with CRB-65, CURB-65, SMART-COP, and CURXO scores among CAP patients. Moreover, serum higher SOD1 at admission substantially increased the risks of ICU admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stays during hospitalization. Serum SOD1 level combination with CAP severity scores elevated the predictive abilities for severity and death compared with alone serum SOD1 and CAP severity scores in CAP patients during hospitalization. CONCLUSION: The level of serum SOD1 is positively associated with the severity and poor prognosis in CAP patients, suggesting that SOD1 is implicated in the initiation and progression of CAP. Serum SOD1 may be regarded as a biomarker to appraise the severity and prognosis for CAP patients.