Serum Krebs von den Lungen-6 is associated with in-Hospital mortality of patients with severe Community-Acquired Pneumonia: A retrospective cohort study.

BACKGROUND: Currently, no ideal biomarker can accurately stratify the risk of patients with severe community-acquired pneumonia (SCAP). This study aimed to evaluate the role of serum Krebs von den Lungen-6 (sKL-6) in predicting in-hospital mortality in adults with SCAP. METHODS: In this retrospective cohort study, 249 severe pneumonia adult patients were recruited between 6 May 2021 to 30 April 2023 in Xiangya Hospital of Central South University. The sKL-6 level within 48 h of admission was measured, and the primary outcome assessed was in-hospital mortality. Multivariable logistic regression analysis was performed to calculate adjusted odds ratios (OR) with 95% confidence intervals (CI). Survival curves were plotted and subgroup analyses were conducted, stratified by relevant covariates. RESULTS: A total of 249 patients were included in the study,with 124 patients having normal sKL-6 levels, and 125 patients having abnormal sKL-6 levels. The overall in-hospital mortality rate was 28.9% (72 out of 249 patients). Univariate and multivariate logistic regression analysis revealed that the patients with abnormal sKL-6 levels had a higher risk of in-hospital mortality compared to those with normal sKL-6 levels, both in the total SCAP patient population (OR: 5.38, 95%CI: 2.41-12.01, P < 0.001) and the non-COVID-19 SCAP patients subgroup (OR: 8.12, 95%CI: 3.16-20.84, P < 0.001). Subgroup and interaction analyses confirmed the stability of the relationship between sKL-6 levels and in-hospital mortality(P for interaction > 0.05). Kaplan-Meier survival curves showed that patients with abnormal sKL-6 levels had a higher in-hospital mortality rate than those with normal sKL-6 levels (P < 0.05). However, the results of restricted cubic spline plots(RCS) analysis demonstrated a nonlinear association between sKL-6 levels (as a continuous variable) and in-hospital mortality in patients with SCAP. Similar results were observed in non-COVID-19 SCAP patients. Furthermore, the receiver operating characteristic curve (ROC) analysis revealed that sKL-6 had superior predictive performance compared to existing biomarkers (e.g., APACHE-II, SOFA, BUN/Cr, PCT, and D-dimer) for in-hospital mortality in non-COVID-19 SCAP patients. CONCLUSION: sKL-6 is a practical and useful biomarker for predicting in-hospital mortality in patients with SCAP.

Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia.

OBJECTIVE: Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. METHODS: Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. RESULTS: The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. CONCLUSION: The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.

Knocking down TNFAIP1 alleviates inflammation and oxidative stress in pediatric pneumonia through PI3K/Akt/Nrf2 pathway

Background: Pneumonia is an acute respiratory infection with increasing global incidences. Children are more susceptible to pneumonia than adults, and its incidences grow extremely high during peak seasons. Thus, it is necessary to investigate the pathogenesis and molecular mechanism of childhood pneumonia. Methods: This study examined the role of tumor necrosis factor alpha-inducible protein 1 (TNFAIP1) in lipopolysaccharide (LPS)-induced pneumonia mice. After LPS exposure, lung function, TNFAIP1 activation, infarction volume, oxidative stress, lung tissue apoptosis ratio, and inflammatory response were assessed by immunohistochemistry staining, hematoxylin and eosin staning, Western blot analysis, terminal deoxynucleotidyl transferase dUTP nick end labelling assay, and enzyme-linked-immunosorbent serologic assay, respectively. The mechanism of TNFAIP1 regulating phosphoinositide 3-kinases (PI3K)–protein kinase B (Akt)–nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was analyzed by Western blot analysis. Results: TNFAIP1 expression was enhanced in the LPS-induced pneumonia mice but was negatively correlated with the LPS-induced lung injury. Silencing TNFAIP1 alleviated inflammatory response, production of reactive oxygen species (ROS), and cellular apoptosis in LPS-induced pneumonia. Moreover, PI3K/Akt/Nrf2 signaling pathways were predominantly involved in the TNFAIP1-mediated lung injury, which also played a role in the process of LPS-induced pneumonia. Conclusion: This study suggested that TNFAIP1 acted as a negative regulator of acute pneumonia by attenuating inflammatory response, production of ROS, and cellular apoptosis via PI3K/Akt/Nrf2 pathway. The findings suggested that TNFAIP1 is a potential candidate for pneumonia therap (AU)

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor-related pneumonitis.

Background: Checkpoint inhibitor-related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined. Methods: We conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase's characteristics. Results: There were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P<0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005). Conclusions: The general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised.

Evaluation of the significance of interleukin-6 in the diagnosis of postoperative pneumonia: a prospective study.

BACKGROUND: Postoperative pneumonia (PP) is one of the most common complications after cardiac surgery. This study was designed to access the diagnostic value of interleukin-6 (IL-6) for pneumonia within the first 5 days after cardiac surgery in adults. METHOD: This prospective observational study enrolled 694 patients who admitted to our center from 10 October 2020 to 30 June 2021. Blood samples were collected after admission and on five consecutive days after surgery to measure IL-6, procalcitonin (PCT), C-reactive protein (CRP) and white blood cells (WBC) respectively. Combined with clinical data, we assessed the diagnostic performance of different biomarkers using univariate and multifactorial analyses as well as receiver operating characteristic curves (ROC) and the area under the curve (AUC). RESULT: Finally, 68 patients were diagnosed with PP (PP Group). In addition, 626 cases were assigned to the control group (Non-PP Group). From postoperative day 1 (POD1) to day 5, IL-6 and PCT levels showed higher diagnostic value (P < 0.001, P < 0.05, respectively); meanwhile, there was no difference in white blood cell counts between the two groups; CRP showed some value from POD2 onwards (P < 0.001). Among these biomarkers, IL-6 on POD1 [AUC: 0.78, 95% confidence interval (CI): 0.71-0.83], IL-6 on POD2 (AUC: 0.77, 95% CI: 0.71-0.82) and CRP levels on POD3 (AUC: 0.77, 95% CI: 0.70-0.84) had the highest diagnostic value. Multivariate analysis found that smoking status [odds ratio(OR): 7.79, 95% CI: 3.05, 19.88, p < 0.001], drinking status (OR: 22.68, 95% CI: 9.29, 55.37, p < 0.001) and hypertension (OR: 2.85, 95% CI: 1.28, 6.35, p = 0.011), IL-6 on POD2 (OR: 1.01, 95% CI: 1.00, 1.01, p = 0.018), mechanical ventilation time (OR: 1.03, 95% CI: 1.00, 1.05, p = 0.040) and intensive care unit stay time (OR: 1.01, 95% CI: 1.00, 1.02, p < 0.001) were independent risk factors for postoperative pneumonia. CONCLUSION: Smoking, drinking, hypertension, prolonged duration of mechanical ventilation and intensive care unit stay, and IL-6 on POD2 were independent risk factors for pneumonia after cardiovascular surgery. IL-6 level on POD2 may serve as a promising indicator, better than WBC, PCT and CRP.

Behavior of clinical and humoral variables on admission as predictors of death in patients with community-acquired pneumonia. Comparative study between adults and older adults. / Comportamiento de variables clínicas y humorales al ingreso, como predictores de fallecimiento en pacientes con neumonía adquirida en la comunidad. Estudio comparativo entre adultos y adultos mayores

Community-acquired pneumonia is recognized as one of the main infectious health problems worldwide. The objective was to determine the condition of predictors of death for a group of selected clinical conditions, and for laboratory variables frequently used in practice. Study with descriptive design, which included 967 patients with pneumonia hospitalized between 2016 and 2019, and whose information was obtained from clinical records. Statistical treatment included bivariate and multivariate analysis (logistic regression); it was used the ratio of crossed products (odds ratio) and its 95% confidence interval. Several manifestations were significantly more frequent in older adults: dyspnea (OR 1.5[1.07,2.1]), absence of productive cough (OR 1.7 [1.3, 2.4]), neuropsychological manifestations (OR 2 [1.4,2.8]), tachypnea (OR 1.5 [1.1,2.1]), arterial hypotension (OR 2.1 [1.2,3.6]), anemia (OR 1.6[1.2,2.2]), elevated creatinine (OR 1.6[1.2,2.3]) and hypoproteinemia (OR 3.3[1.9,5.7]); showed a significant association with death: absence of productive cough, neuropsychological manifestations, temperature below 36 degrees Celsius, blood pressure below 110/70 mmHg, respiratory rate above 20 per minute, hemoglobin below 100 g/L, erythrosedimentation greater than 20 mm/L, leukopenia less than 5 x 109/L and serum creatinine above 130 micromol/L. As conclusions certain clinical and laboratory conditions present in the patient at the time of hospital admission, of routine exploration in the comprehensive assessment of the patient, were predictors of death. Additionally, the existence of evident differences in the number of conditions with a predictive nature of death between the population with pneumonia under 60 years of age and the elderly, as well as in the frequency of these conditions in both subgroups, is verified.

La neumonía adquirida en la comunidad está reconocida como uno de los principales problemas de salud de tipo infeccioso al nivel mundial. La investigación tuvo como objetivo determinar el carácter de predictores de fallecimiento de un grupo de condiciones clínicas seleccionadas, y de variables de laboratorio de uso frecuente en la práctica. Se realizó un estudio con diseño descriptivo, que incluyó a 967 pacientes con neumonía hospitalizados entre 2016 y 2019, y cuya información se obtuvo de los expedientes clínicos. El tratamiento estadístico incluyó análisis bivariante y multivariado (regresión logística); como estadígrafo se utilizó la razón de productos cruzados (odds ratio) y su intervalo de confianza de 95%. Entre los resultados se destacan los siguientes: varias manifestaciones fueron significativamente más frecuentes en los adultos mayores: disnea (OR 1,5[1,07;2,1]), ausencia de tos productiva (OR 1,7[1,3;2,4]), manifestaciones neuropsicológicas (OR 2[1,4;2,8]), taquipnea (OR 1,5[1,1;2,1]), hipotensión arterial (OR 2,1[1,2;3,6]), anemia (OR 1,6[1,2;2,2]), creatinina elevada (OR 1,6[1,2;2,3]) e hipoproteinemia (OR 3,3[1,9;5,7]); mostraron asociación significativa con el fallecimiento: ausencia de tos productiva, manifestaciones neuropsicológicas, temperatura por debajo de 36 grados Celsius, tensión arterial inferior a 110/70 mmHg, frecuencia respiratoria por encima de 20 por minuto, hemoglobina inferior a 100 g/L, velocidad de sedimentación eritrocitaria superior a 20 mm/L, leucopenia inferior a 5 x 109/L y creatinina sérica por encima de 130 micromol/L. Se concluye que ciertas condiciones clínicas y de laboratorio presentes en el paciente al momento del ingreso hospitalario, de exploración habitual en la valoración integral del enfermo, constituyeron predictores de fallecimiento. Adicionalmente, se comprueba la existencia de evidentes diferencias en el número de condiciones con carácter predictor de muerte entre la población con neumonía menor de 60 años y los adultos mayores, así como en la frecuencia de estas condiciones en ambos subgrupos.

Blood urea nitrogen to albumin ratio as a predictive factor for pneumonia: A meta-analysis.

Background Pneumonia remains a substantial cause of mortality worldwide. The need for markers that better categorize patients is growing. We have performed a meta-analysis of Blood Urea Nitrogen to Albumin (BUN/ALB) ratio as a predictive factor regarding patients with pneumonia. Methods Three researchers systematically searched MEDLINE (1966-2021), Clinicaltrials.gov (2008-2021), Cochrane Central Register of Controlled Trials (CENTRAL) (1999-2021), Google Scholar (2004-2021) databases using a structured algorithm. Included studies contained patients with various types of pneumonia. The articles were assessed using the Quality Assessment of Diagnostic Accuracy tool. Results For more than 1900 patients with various types of pneumonia the pooled sensitivity, specificity and AUC were: 0.551, 0.892, 0.717. The optimal cutoff point was calculated at 13.290. Specificity of BUN/ALB ratio is higher than 0.85 in all subgroups and outcomes, making this ratio a great marker for ruling in patients with high risk of poor prognosis. Poor prognosis outcomes included ICU admission or death. Conclusions Regarding CAP patients we calculated an optimal cutoff of BUN/ALB ratio at 15.946 with a sensitivity of 0.587 and a specificity of 0.926 and an AUC equal to 0.732. Future studies are needed in order to assess its value in more patients without community acquired pneumonia.

Prognostic Value of Histidine-Rich Glycoprotein for Community-Acquired Pneumonia.

PURPOSE: Histidine-rich glycoprotein (HRG) is abundant in serum and has been implicated in several processes including blood coagulation and immune response. This prospective study is aimed at exploring HRG as a biomarker in patients hospitalized for community-acquired pneumonia (CAP). METHODS: A total of 160 patients (73 severe CAP, 57 nonsevere CAP), and 30 healthy controls were enrolled in 2019. Demographic and clinical data were recorded for all patients. Serum HRG concentration was measured upon admission using ELISA. RESULTS: HRG levels were significantly lower in severe CAP patients compared with other groups, regardless of etiology, and were negatively correlated with serum interleukin-6 and disease severity index scores. Combination of CURB-65, PSI, and APACHE II scores with HRG values significantly improved the accuracy of predicting 30-day mortality in these patients. Cox regression analysis showed that HRG could serve as an independent risk factor for 30-day mortality. Notably, patients with HRG ≤ 16.92 µg/mL had significantly lower cumulative survival than those with HRG > 16.92 µg/mL. CONCLUSION: Serum HRG levels are lower in patients with severe CAP and are negatively correlated with disease severity scores. Measurement of HRG upon admission can provide valuable prognostic information for patients with CAP.

Value of D-dimer in predicting various clinical outcomes following community-acquired pneumonia: A network meta-analysis.

BACKGROUND: Whether high D-dimer level before treatment has any impact on poor outcomes in patients with community-associated pneumonia (CAP) remains unclear. Therefore, we conducted the first meta-analysis focusing specifically on prognostic value of high D-dimer level before treatment in CAP patients. METHODS: Pubmed, Embase, the Cochrane Central Register of Controlled Trials and World Health Organization clinical trials registry center were searched up to the end of March 2021. Randomized clinical trials (RCT) and observational studies were included to demonstrate the association between the level of D-dimer and clinical outcomes. Data were extracted using an adaptation of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS-PF). When feasible, meta-analysis using random-effects models was performed. Risk of bias and level of evidence were assessed with the Quality in Prognosis Studies tool and an adaptation of Grading of Recommendations Assessment, Development, and Evaluation. Data were analyzed using STATA 14.0 to complete meta and network analysis. MAIN OUTCOMES AND MEASURES: Besides d-dimer levels in CAP patients with poor outcomes, we also analyzed proportion of patients with or without poor outcomes correctly classified by the d-dimer levels as being at high or low risk. The poor outcome includes severe CAP, death, pulmonary embolism (PE) and invasive mechanical ventilators. RESULTS: 32 studies with a total of 9,593 patients were eventually included. Pooled effect size (ES) suggested that d-dimer level was significantly higher in severe CAP patients than non-severe CAP patients with great heterogeneity (SMD = 1.21 95%CI 0.87-1.56, I2 = 86.8% p = 0.000). D-dimer level was significantly elevated in non-survivors compared to survivors with CAP (SMD = 1.22 95%CI 0.67-1.77, I2 = 85.1% p = 0.000). Prognostic value of d-dimer for pulmonary embolism (PE) was proved by hierarchical summary receiver operating characteristic curve (HSROC) with good summary sensitivity (0.74, 95%CI, 0.50-0.89) and summary specificity (0.82, 95%CI, 0.41-0.97). Network meta-analysis suggested that there was a significant elevation of d-dimer levels in CAP patients with poor outcome than general CAP patients but d-dimer levels weren't significantly different among poor outcomes. CONCLUSION: The prognostic ability of d-dimer among patients with CAP appeared to be good at correctly identifying high-risk populations of poor outcomes, suggesting potential for clinical utility in patients with CAP.

Effect of COVID 19 pneumonia on hyperglycemia: Is it different from non COVID pneumonia?

BACKGROUND AND AIMS: Glycemic control in critical illness has been linked to outcomes. We sought to investigate if COVID pneumonia was causing disrupted glycemic control compared to historically similar diseases. METHODS: At Intermountain Healthcare, a 23-hospital healthcare system in the intermountain west, we performed a multicenter, retrospective cohort observational study. We compared 13,268 hospitalized patients with COVID pneumonia to 6673 patients with non -COVID-pneumonia. RESULTS: Patients with COVID-19 were younger had fewer comorbidities, had lower mortality and greater length of hospital stay. Our regression models demonstrated that daily insulin dose, indexed for weight, was associated with COVID-19, age, diabetic status, HgbA1c, admission SOFA, ICU length of stay and receipt of corticosteroids. There was significant interaction between a diagnosis of diabetes and having COVID-19. Time in range for our IV insulin protocol was not correlated with having COVID after adjustment. It was correlated with ICU length of stay, diabetic control (HgbA1C) and prior history of diabetes. Among patients with subcutaneous (SQ) insulin only percent of glucose checks in range was correlated with diabetic status, having Covid-19, HgbA1c, total steroids given and Elixhauser comorbidity score even when controlled for other factors. CONCLUSIONS: Hospitalized patients with COVID-19 pneumonia who receive insulin for glycemic control require both more SQ and IV insulin than the non-COVID-19 pneumonia counterparts. Patients with COVID-19 who received SQ insulin only had a lower percent of glucose checks in range.

Serum 8-Hydroxydeoxyguanosine Is a Potential Indicator for the Severity and Prognosis in Patients with Community-Acquired Pneumonia: A Prospective Cohort Study.

Previous studies have demonstrated that 8-hydroxydeoxyguanosine (8-OHdG) exerted key roles in various pulmonary diseases, but the evidence for its role in community-acquired pneumonia (CAP) was lacking. The goal of this research was to evaluate the correlations of serum 8-OHdG with the severity and prognosis among patients with CAP through a prospective cohort study. A total of 239 patients with CAP and 239 healthy participants were enrolled. Fasting blood samples were collected. 8-OHdG and inflammatory cytokines were measured by ELISA. On admission, serum 8-OHdG was significantly increased in patients with CAP compared with control subjects. Besides, serum 8-OHdG was incrementally increased in line with CAP severity scores. Pearson correlative analysis found that serum 8-OHdG was correlated with clinical characteristics and inflammatory cytokines in patients with CAP. Linear and logistic regression analysis showed that serum 8-OHdG was positively associated with CAP severity scores. Furthermore, the prognostic outcomes were tracked. Higher serum 8-OHdG on admission increased the risks for intensive care unit admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stay among patients with CAP. Serum 8-OHdG combination with confusion, respiratory rate, blood pressure, and age ≥65 y or pneumonia severity index had stronger predictive powers for death than single 8-OHdG, CAP severity scores, or several inflammatory cytokines in patients with CAP. These results indicated that serum 8-OHdG is positively associated with the severity and poor prognosis in patients with CAP, demonstrating that 8-OHdG may be involved in the pathophysiology process of CAP.

Temporal course of peripheral inflammation markers and indexes following acute ischemic stroke: prediction of mortality, functional outcome, and stroke-associated pneumonia.

BACKGROUND: Complete blood count derived indexes such as lymphocyte-to-neutrophil ratio (NLR) may help in predicting pneumonia and prognosis in acute stroke. However, the optimal time point for using these biomarkers is not known. METHODS: In 205 consecutive severe (NIHSS>10) acute ischemic stroke patients, daily leukocyte, lymphocyte, neutrophil, monocyte, platelet, albumin, fibrinogen, hematocrit, NLR, PLR (Platelet-to-lymphocyte-ratio), LMR (Lymphocyte-to-monocyte-ratio), and SII (systemic-immune-inflammation-index) were determined. General linear models for repeated measures (GLMR) and receiver operating characteristics [ROC] analyses were conducted to define their daily discriminative ability. RESULTS: GLMR-prognosis modeling documented that the main determinants of significant daily variations of 12 parameters studied were age and 24th-hour-NIHSS. In addition, daily changes of NLR, neutrophil, leukocyte (all increased on day-2 and remained higher) and platelet count (decreased after day-6 and stayed lower) were related significantly to survival status (mortality in 19.5%). Albumin levels (lower after day-2) were marginally associated by functional prognosis (modified-Rankin-Score≤3 in 28%). There was a borderline relationship (p = 0.05) between NLR (between day-1 and day-8) and pneumonia development (in 36%). Useful discrimination capability (95% confidence interval lower limit of area-under-curve of ROC≥0.7) was noted for NLR measured on day-6 for mortality, NLR (for 6 days, from day-3-to-day-7, and day-11) and albumin (for every day except day-11 after day-4) for reasonable prognosis and none for pneumonia development. CONCLUSIONS: Inflammatory parameters from peripheral routine blood tests showed significant variations during the first two weeks following stroke, but discriminative capacity of these changes is limited due to confounders such as age and post-treatment clinical stroke severity.

Deregulated Expression of miR-483-3p Serves as a Diagnostic Biomarker in Severe Pneumonia Children with Respiratory Failure and Its Predictive Value for the Clinical Outcome of Patients.

Severe pneumonia in children is a group of inflammatory diseases of respiratory tract caused by pathogenic microorganisms. Increasing evidence suggested the crucial effects of microRNA on inflammatory diseases. This study aimed to reveal the expression and role of miR-483-3p in the serum of children with severe pneumonia, and to explore the effect of miR-483-3p on the biological function of lipopolysaccharide (LPS)-induced MRC-5 cells. MRC-5 cells were disposed with LPS to construct an in vitro pneumonia cell model. The relative expression level of miR-483-3p was measured by qRT-PCR. ROC curve was used to evaluate the diagnostic value of miR-483-3p in severe pneumonia. The Kaplan-Meier curve was performed to test the characteristics of survival distribution of different miRNA classifications. Cell viability and apoptosis were performed by CCK-8 assay and flow cytometry. IL-1ß, TNF-α, and IL-6 were detected by ELISA. Luciferase reporter gene assay and western blot analysis were performed to detect the interaction between miR-483-3p and IGF-1. The expression of serum miR-483-3p in severe pneumonia patients was higher than in controls. The AUC value of the ROC curve was 0.919, indicating that miR-483-3p had diagnostic value for severe pneumonia. The survival curve showed that patients with high expression of miR-483-3p had higher mortality. Cell viability and apoptosis assay showed that overexpression of miR-483-3p suppressed cell proliferation and promoted apoptosis. And upregulation of miR-483-3p promoted generation of inflammatory cytokines. Luciferase report gene assay and western blot assay both illustrated that IGF-1 might be the target gene of miR-483-3p. Serum miR-483-3p can be used as a biomarker for the diagnosis of severe pneumonia. High expression of miR-483-3p promoted the development of severe pneumonia.

Development and validation of a new scoring system for prognostic prediction of community-acquired pneumonia in older adults.

The discriminative power of CURB-65 for mortality in community-acquired pneumonia (CAP) is suspected to decrease with age. However, a useful prognostic prediction model for older patients with CAP has not been established. This study aimed to develop and validate a new scoring system for predicting mortality in older patients with CAP. We recruited two prospective cohorts including patients aged ≥ 65 years and hospitalized with CAP. In the derivation (n = 872) and validation cohorts (n = 1,158), the average age was 82.0 and 80.6 years and the 30-day mortality rate was 7.6% (n = 66) and 7.4% (n = 86), respectively. A new scoring system was developed based on factors associated with 30-day mortality, identified by multivariate analysis in the derivation cohort. This scoring system named CHUBA comprised five variables: confusion, hypoxemia (SpO2 ≤ 90% or PaO2 ≤ 60 mmHg), blood urea nitrogen ≥ 30 mg/dL, bedridden state, and serum albumin level ≤ 3.0 g/dL. With regard to 30-day mortality, the area under the receiver operating characteristic curve for CURB-65 and CHUBA was 0.672 (95% confidence interval, 0.607-0.732) and 0.809 (95% confidence interval, 0.751-0.856; P < 0.001), respectively. The effectiveness of CHUBA was statistically confirmed in the external validation cohort. In conclusion, a simpler novel scoring system, CHUBA, was established for predicting mortality in older patients with CAP.

Evaluation of serum zinc level and IL-18 mRNA expression in children with pneumonia.

Pneumonia is currently one of the leading causes of death in children. Increased susceptibility to pneumonia may be due to their decreased immunity. One of the reasons for the decrease in immunity is zinc deficiency. In children with pneumonia, on the other hand, some cytokines are secreted, resulting in inflammation that spreads, persists, and makes treatment difficult for specialists. In this study, we investigated the serum zinc level in children with pneumonia and healthy children. Also, we tried to find its relationship with IL-18 mRNA expression as an inflammatory cytokine. For this purpose, serum zinc levels and IL-18 mRNA expression were evaluated in 120 children aged 3-60 months with pneumonia and 120 healthy children. After taking 2ml of blood from children and measuring serum zinc level, the level of the IL-18 mRNA was measured by real-time PCR. Total RNA was extracted by bioZOL™-G RNA Isolation Reagent kit. The primary cDNA was amplified by the extracted RNA, and in the next step, 2µl of cDNA were amplified by specific primers to measure IL-18 mRNA. The Beta-actin gene was also used as internal control and housekeeping gene. Results showed that the level of zinc in the patient group was 412.625±28.87?M and in the control group was 514.40±49.67?M. This difference was statistically significant (P=0.0053). Also, the expression of the IL-18 gene was increased in children with pneumonia, significantly (P=0.0015). Therefore, from the results, it can be deduced that children with zinc deficiency were at higher risk for a lung infection. Inflammatory cytokines such as IL-18 also were increased in these children. Hence, it can be concluded that zinc levels can reduce the expression of IL-18 mRNA and play an important role in the prevention and treatment of children with pneumonia.

Serum interleukin-17 predicts severity and prognosis in patients with community acquired pneumonia: a prospective cohort study.

BACKGROUND: Some studies previously demonstrated that interleukin-17 (IL-17) involves in pulmonary diseases progression. Nevertheless, the role of IL-17 in community-acquired pneumonia (CAP) remains unknown. This study aims to examine the correlations between serum IL-17 with the severity and prognosis in CAP patients through a prospective cohort study. METHODS: All 239 CAP patients were recruited. Serum IL-17 was detected by enzyme-linked immunosorbent assay (ELISA). The CAP severity was evaluated through CAP severity scores, including CURB-65, CRB-65, PSI, SMART-COP, CURXO and APACHE II. RESULTS: Serum IL-17 was gradually increased consistent with the severity of CAP. Correlative analysis suggested that serum IL-17 was associated with clinical physiologic indicators among CAP patients. Logistic regression indicated that serum IL-17 was positively related to CAP severity scores. Additionally, the prognostic outcomes were tracked among CAP patients. The levels of IL-17 on admission were significantly increased in CAP patients with ICU admission, mechanical ventilation, vasoactive agent, death and longer hospitalization days. Logistic regression analyses revealed serum higher IL-17 on admission elevated the risks of vasoactive agent usage and longer hospital stays in CAP patients. The cut-off concentrations of serum IL-17 for death, ICU admission, mechanical ventilation and ≥ 14 hospital stays were 86.80 ng/mL, 84.92 ng/mL, 84.92 ng/mL and 60.29 ng/mL respectively. CONCLUSIONS: Serum IL-17 on admission is positively associated with the severity and poor prognosis among CAP patients, revealing that IL-17 may implicate in the pathological process of CAP. Therefore, serum IL-17 may become an effective biomarker for diagnosis, prognosis and therapy for CAP patients.

Functional Ex Vivo Testing of Alveolar Monocytes in Patients with Pneumonia-Related ARDS.

Biomarkers of disease severity might help with individualizing the management of patients with acute respiratory distress syndrome (ARDS). During sepsis, a sustained decreased expression of the antigen-presenting molecule human leucocyte antigen-DR (HLA-DR) on circulating monocytes is used as a surrogate marker of immune failure. This study aimed at assessing whether HLA-DR expression on alveolar monocytes in the setting of a severe lung infection is associated with their functional alterations. BAL fluid and blood from immunocompetent patients with pneumonia-related ARDS admitted between 2016 and 2018 were isolated in a prospective monocentric study. Alveolar and blood monocytes were immunophenotyped using flow cytometry. Functional tests were performed on alveolar and blood monocytes after in vitro lipopolysaccharide (LPS) stimulation. Phagocytosis activity and intracellular tumor necrosis factor (TNF) production were quantified using fluorochrome-conjugated-specific antibodies. Ten ARDS and seven non-ARDS control patients were included. Patients with pneumonia-related ARDS exhibited significantly lower HLA-DR expression both on circulating (p < 0.0001) and alveolar (p = 0.0002) monocytes. There was no statistically significant difference observed between patient groups (ARDS vs. non-ARDS) regarding both alveolar and blood monocytes phagocytosis activity. After LPS stimulation, alveolar (p = 0.027) and blood (p = 0.005) monocytes from pneumonia-related ARDS patients had a significantly lower intracellular TNF expression than non-ARDS patients. Monocytes from pneumonia-related ARDS patients have a deactivated status and an impaired TNF production capacity but display potent phagocytic activity. HLA-DR level expression should not be used as a surrogate marker of the phagocytic activity or the TNF production capacity of alveolar monocytes.

Associations of Serum S100A12 With Severity and Prognosis in Patients With Community-Acquired Pneumonia: A Prospective Cohort Study.

Background: Previous studies indicated the calcium-binding protein S100A12 to be involved in the pathophysiology of pulmonary inflammatory diseases. However, the role of S100A12 has remained elusive in patients with community-acquired pneumonia (CAP). Therefore, the purpose of this prospective cohort study was to evaluate the association between serum S100A12 with severity and prognosis in CAP patients. Methods: Two groups with either 239 CAP patients or 239 healthy controls were enrolled in our study. Fasting blood and clinical characteristics were collected. On admission, serum S100A12 was measured using enzyme-linked immunosorbent assay (ELISA). Results: Serum S100A12 was increased in CAP patients compared to control subjects. Furthermore, serum S100A12 was elevated according to the severity of CAP. Correlative analysis suggested that the level of serum S100A12 was associated with blood routine indices, renal function markers, inflammatory cytokines and other clinical parameters among CAP patients. Additionally, linear and logistical regression analyses indicated that serum S100A12 was positively associated with CAP severity scores in CAP patients. In addition, the association of high serum S100A12 and prognosis was accessed using a follow-up research. Elevated serum S100A12 on admission increased the risk of death and hospital stay in CAP patients during hospitalization. Conclusions: Elevated serum S100A12 on admission is positively associated with the severity and adverse prognosis in CAP patients, suggesting that S100A12 may involve in the pathophysiological process of CAP. The titre of serum S100A12 may be used as a biomarker for diagnosis and prognosis among CAP patients.

Atypical lymphocytes in the peripheral blood of COVID-19 patients: A prognostic factor for the clinical course of COVID-19.

BACKGROUND: Clinical observations have shown that there is a relationship between coronavirus disease 2019 (COVID-19) and atypical lymphocytes in the peripheral blood; however, knowledge about the time course of the changes in atypical lymphocytes and the association with the clinical course of COVID-19 is limited. OBJECTIVE: Our purposes were to investigate the dynamics of atypical lymphocytes in COVID-19 patients and to estimate their clinical significance for diagnosis and monitoring disease course. MATERIALS AND METHODS: We retrospectively identified 98 inpatients in a general ward at Kashiwa Municipal Hospital from May 1st, 2020, to October 31st, 2020. We extracted data on patient demographics, symptoms, comorbidities, blood test results, radiographic findings, treatment after admission and clinical course. We compared clinical findings between patients with and without atypical lymphocytes, investigated the behavior of atypical lymphocytes throughout the clinical course of COVID-19, and determined the relationships among the development of pneumonia, the use of supplemental oxygen and the presence of atypical lymphocytes. RESULTS: Patients with atypical lymphocytes had a significantly higher prevalence of pneumonia (80.4% vs. 42.6%, p < 0.0001) and the use of supplemental oxygen (25.5% vs. 4.3%, p = 0.0042). The median time to the appearance of atypical lymphocytes after disease onset was eight days, and atypical lymphocytes were observed in 16/98 (16.3%) patients at the first visit. Atypical lymphocytes appeared after the confirmation of lung infiltrates in 31/41 (75.6%) patients. Of the 13 oxygen-treated patients with atypical lymphocytes, approximately two-thirds had a stable or improved clinical course after the appearance of atypical lymphocytes. CONCLUSION: Atypical lymphocytes frequently appeared in the peripheral blood of COVID-19 patients one week after disease onset. Patients with atypical lymphocytes were more likely to have pneumonia and to need supplemental oxygen; however, two-thirds of them showed clinical improvement after the appearance of atypical lymphocytes.