[Prognostic value of left ventricular ejection fraction on admission in patients with septic cardiomyopathy].

OBJECTIVE: To investigate the prognostic value of cardiac ultrasound left ventricular ejection fraction (LVEF) on admission in patients with septic cardiomyopathy. METHODS: A retrospective cohort study was conducted. The patients with septic cardiomyopathy hospitalized in the intensive care unit of Zhoupu Hospital Affiliated to Shanghai Health College from January 2019 to March 2023 were enrolled. The general information including gender and age, LVEF on admission, severity of illness scores within 24 hours after admission [acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score], procalcitonin (PCT), cardiac biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), and MB isoenzyme of creatine kinase (CK-MB)], mitochondria related indicators [aspartate aminotransferase (AST), AST/alanine aminotransferase (ALT) ratio], blood lactate (Lac), the usage of vasoactive drugs and mechanical ventilation, and the prognosis during hospitalization were collected. The differences in above clinical data between the two groups were compared. The variables with statistically significant differences in univariate analysis were incorporated into multivariate Logistic regression analysis to analyze the independent risk factors for death during hospitalization in patients with septic cardiomyopathy. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the prognostic value of LVEF by echocardiography on admission in patients with septic cardiomyopathy during hospitalization. RESULTS: A total of 62 patients were enrolled, including 36 males and 26 females. Thirty-nine cases died and 23 cases survived during hospitalization, and the mortality was 62.90%. Compared with the survival group, the LVEF of patients on admission was lower in the death group [0.51 (0.40, 0.57) vs. 0.56 (0.51, 0.63), P < 0.01], APACHE II score, SOFA score, Lac, NT-proBNP, CK-MB within 24 hours after admission were higher [APACHE II score: 22.18±8.38 vs. 17.39±8.22, SOFA score: 9.90±3.87 vs. 7.09±3.27, Lac (mmol/L): 5.10 (2.63, 11.50) vs. 2.00 (1.40, 5.00), NT-proBNP (µg/L): 5.24 (2.84, 11.29) vs. 2.53 (0.35, 6.63), CK-MB (U/L): 1.88 (0.21, 5.33) vs. 0.17 (0.02, 1.62), all P < 0.05], and the proportion of vasoactive drug application was higher (82.05% vs. 47.83%, P < 0.01). Multivariate Logistic regression analysis showed that LVEF on admission was an independent risk factor for predicting the prognosis of patients with septic cardiomyopathy during hospitalization [odds ratio (OR) = 0.920, 95% confidence interval (95%CI) was 0.855-0.990, P = 0.025]. ROC curve analysis showed that the area under the ROC curve (AUC) of LVEF on admission for predicting the death of patients with septic cardiomyopathy was 0.715 (95%CI was 0.585-0.845, P = 0.005). When LVEF ≤ 0.52, the sensitivity was 73.9%, and the specificity was 61.5%. CONCLUSIONS: The lower cardiac ultrasound LVEF on admission, the worse the prognosis of patients with septic cardiomyopathy. The cardiac ultrasound LVEF on admission can be used as a clinical index to evaluate the severity of the condition and predict the prognosis of patients with septic cardiomyopathy.

The molecular mechanism of cardiac injury in SARS-CoV-2 infection: Focus on mitochondrial dysfunction.

BACKGROUND: Coronavirus disease 2019(COVID-19) caused a large number of infections worldwide. Although some patients recovered from the disease, some of the other problems that accompanied it, such as cardiac injury, could affect the patient's subsequent quality of life and prognosis. OBJECTIVES: To clarify the molecular mechanism of cardiac injury in SARS-CoV-2 Infection. METHODS: The RNA-Seq dataset (GSE184715) comparing expression profiling of Mock human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and SARS-CoV-2-infected hiPSC-CMs was downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes(DEGs) were performed by the R software. Degs were analyzed by enrichment analysis to clarify the affected pathways. Hub genes were screened out by a PPI network constructed from Degs. Finally, Connectivity Map was used to screen for the treatment of COVID-19 induced cardiac injury. RESULTS: 2705 differentially expressed genes were identified. Enrichment analysis confirmed that mitochondrial dysfunction was caused by SARS-CoV-2, meanwhile, cardiac muscle contraction was suppressed and NF-κB was activated. Based on the PPI network, 15 hub genes were identified. These 15 down-regulated hub genes were mainly involved in the reduced activity of complexes in the mitochondrial respiratory chain associated with mitochondrial dysfunction. Moreover, 5 candidate drugs were identified to treat cardiac injury. CONCLUSION: In conclusion, SARS-CoV-2 infection of cardiomyocytes causes mitochondrial dysfunction, including reduced mitochondrial respiratory chain complex activity and decreased ATP synthesis, leading to cardiomyocyte apoptosis, while the activated NF-κB also induced cytokine storms, ultimately resulting in cardiac injury.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study.

Background: Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods: We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings: 264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation: Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding: National Natural Science Foundation of China (grant number: 82172152, 81873944).

Combination of hepcidin with neutrophil gelatinase-associated lipocalin for prediction of the development of sepsis-induced acute kidney injury.

BACKGROUND AND AIMS: The early prediction of the development of acute kidney injury (AKI) in critically ill patients with sepsis would facilitate early effective intervention. Recently, interest has focused on the biomarkers for AKI-linked iron metabolism. This study aimed to assess the early predictive values of hepcidin, neutrophil gelatinase-associated lipocalin (NGAL), and their combination for secondary AKI in patients with sepsis. MATERIALS AND METHODS: A prospective cohort study was performed in septic patients. Serum and urine hepcidin, and urine NGAL were analyzed at admission. The primary outcome measure was occurrence of sepsis-induced AKI based on 2011 Kidney Disease: Improving Global Outcomes (KDIGO) criteria during the first week of ICU stay. RESULTS: Of the 90 patients analyzed finally in the study, 44 (48.9%) patients developed AKI. Patients with AKI occurrence were more likely than those without AKI to have higher serum hepcidin and urine NGAL levels at admission (P < 0.01). Higher concentrations of these biomarkers were each independent predictor of the development of AKI in critically septic patients within the first week of their ICU stay. Serum hepcidin and urine NGAL (AUROC 0.787, 95% CI 0.688 to 0.8660 and AUROC 0.729, 95% CI 0.625 to 0.818, respectively) were comparable predictive indicators of AKI occurrence (P = 0.43 for DeLong's test). Combining both biomarkers increased the AUROC to 0.828(95% CI 0.733 to 0.899), and this performance was statistically significantly better than urine NGAL alone (P = 0.03 for DeLong's test). CONCLUSION: Serum hepcidin measured at admission predicts the development of AKI similarly to urine NGAL. However, serum hepcidin adds significant accuracy to this prediction in combination with urine NGAL alone and has a good predictive value in patients with sepsis. Larger studies are needed to validate and explain these findings.

Kinetic changes in serum procalcitonin predict persistent acute kidney injury in critical patients.

PURPOSE: Persistent acute kidney injury (AKI) has been shown to be closely associated with poor prognosis in critical patients. Recent studies have shown that procalcitonin (PCT) is valuable for the early prediction of AKI in critically patients. Our aim was to determine whether PCT and its kinetic changes could predict the occurrence of persistent AKI in critical patients. METHODS: This is a prospective observational study. The definition of AKI was based on the Kidney Disease: Improving Global Outcomes criteria. Persistent AKI was defined as renal function that does not return to baseline serum creatinine levels within 48 h. Blood samples were obtained at the onset of AKI and two subsequent days of hospital stay. 24-h PCT change (ΔPCT-24 h) was defined as 24 h PCT minus baseline PCT (day 0). RESULTS: A total of 91 critical patients with AKI were included in this study. The persistent AKI group had a stepwise increase in PCT concentration. ΔPCT-24 h was higher in the persistent AKI group (p < .01). Logistic regression analysis showed that ΔPCT-24 h (p = .04) was independent predictors of persistent AKI. The receiver operating characteristic curves showed that area under the curve of ΔPCT-24 h was 0.84 (p < .01), and the cut-off value for PCT to predict persistent AKI was 0.56 ng/ml. CONCLUSION: Our study showed that the observation of kinetic changes in PCT is more significant for the early prediction of persistent AKI than the index of PCT at a single time point. ΔPCT-24 h is a good predictor of persistent AKI in critical patients.

Mesenchymal stem cell exosomes reverse acute lung injury through Nrf-2/ARE and NF-κB signaling pathways.

Acute lung injury (ALI) is associated with histopathological diffuse alveolar damage. The potential role of mesenchymal stem cells (MSCs) in the treatment of various clinical disorders have been widely documented, such as those for ALI. Recent evidence has demonstrated that exosomes from endothelial progenitor cells can improve outcomes of the lipopolysaccharide (LPS)-induced ALI. However, there has been no research on the potential role of MSC-exosomes in the treatment of sepsis-induced ALI, which is worth further exploration. Thus, the objective of our study was to identify whether the MSC-exosomes could reverse ALI. The ALI model induced by LPS was established in this study. MTT assay was performed to test cell proliferation. Expression of inflammatory factors (TNF-α, IL-6, and IL-10) in the LPS-treated type II alveolar epithelial cells (AECs) (MLE-12) was detected by ELISA. After co-culture of MSC-exosomes with LPS-treated MLE-12 cells, we found that the cell proliferation of MLE-12 cells gradually increased. Furthermore, we selected five of the Nrf-2/ARE- and NF-κB signaling pathway-related genes to explore if MSC-exosomes could reverse LPS-induced ALI through Nrf-2/ARE and NF-κB signaling pathways. QRT-PCR and western blot experiment results showed that the expression of these five genes were significantly regulated after stimulation with high-concentration LPS and exosome intervention. Taken together, these findings highlighted the fact that MSC-exosomes could reverse ALI through the Nrf-2/ARE and NF-κB signaling pathways. The MSC-exosome may be the potential future therapeutic strategy for the treatment of ALI.

[Value of Hepcidin as a diagnostic biomarker of sepsis in critically ill adults].

OBJECTIVE: To investigate the diagnostic value of Hepcidin as a sepsis biomarker in critically ill adults. METHODS: An observational study was conducted. The patients with suspected or proven infection admitted to intensive care unit (ICU) of Zhoupu Hospital Affiliated to Shanghai University of Medicine and Health Sciences from March 2016 to November 2017 were enrolled. According to the third international consensus definitions for sepsis and septic shock (Sepsis-3), the patients were divided into non-sepsis group and sepsis group, and the septic patients were subdivided into general sepsis subgroup and septic shock subgroup according to the severity of disease. The differences in serum Hepcidin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), C-reactive protein (CRP), white blood cell (WBC), neutrophil granulocytes (NEUT) and lactic acid (Lac) within 1 hour after ICU admission between non-sepsis and sepsis groups and among the sepsis subgroups were compared. The acute physiology and chronic health evaluation II (APACHE II) within 24 hours after ICU admission and sequential organ failure score (SOFA) were recorded, and the mortality rate was followed up for 28 days. Receiver operation characteristic curve (ROC) was used to evaluate and compare the diagnostic value of Hepcidin and PCT, CRP, WBC for sepsis. Logistic regression model was used to estimate the association between Hepcidin and sepsis. Spearman correlation analysis was used to analyze the correlation between Hepcidin and other parameters of sepsis patients. RESULTS: A total of 183 patients were enrolled, 93 in the non-sepsis group and 90 in the sepsis group (48 with general sepsis and 42 with septic shock). (1) The levels of Hepcidin, IL-6, TNF-α, PCT, Lac in serum, and APACHE II and SOFA scores in the sepsis group were significantly higher than those in the non-sepsis group. ROC analysis showed that the area under the ROC curve (AUC) of Hepcidin and PCT for sepsis diagnosis were 0.865 [95% confidence interval (95%CI) = 0.807-0.911] and 0.848 (95%CI = 0.788-0.897), respectively, without statistical significance (Z = 0.443, P = 0.657). Furthermore, the AUC of Hepcidin for sepsis diagnosis was significantly higher than that of the conventional biomarkers CRP and WBC [AUC was 0.530 (95%CI = 0.455-0.604) and 0.527 (95%CI = 0.452-0.601), respectively] with statistical significance (both P < 0.01). When Hepcidin > 54.00 µg/L, its sensitivity for sepsis diagnosis was 95.56%, specificity was 66.67%, positive and negative predictive value was 73.51% and 93.94%, respectively. Parallel test was conducted for combination of Hepcidin and PCT, which showed that the AUC was 0.885, and the sensitivity and negative predictive value was significantly improved to 98.96% and 98.36%, respectively. Logistic regression analysis demonstrated that after adjusted for PCT, Hepcidin > 54.00 µg/L was also associated with sepsis independently, with odds ratio (OR) of 1.011 (95%CI = 1.008-1.015, P < 0.001), indicating that Hepcidin and PCT were not completely overlapped in the diagnosis of sepsis. (2) With the increase in infection severity, serum Hepcidin, PCT, IL-6, TNF-α, Lac, APACHE II, SOFA score and 28-day mortality all showed an increasing trend in patients. There was a significantly positive correlation between Hepcidin and IL-6, TNF-α, PCT, APACHE II, and SOFA in the sepsis patients (r value was 0.526, 0.449, 0.591, 0.359, and 0.374, respectively, all P < 0.01), but no correlation was found between Hepcidin and Lac (r = 1.104, P > 0.05). CONCLUSIONS: Serum Hepcidin is a useful biomarker for the diagnosis of sepsis, and it is correlated to the severity of the sepsis. The combination of Hepcidin and PCT can improve the accuracy of diagnosis of sepsis. CLINICAL TRIAL REGISTRATION: China Clinical Trial Registration Center, ChiCTR-DDD-16008522.

Gender Differences in the Symptoms, Signs, Disease History, Lesion Position and Pathophysiology in Patients with Pulmonary Embolism.

Advances in research relating to pulmonary embolisms (PE) can assist physicians in selecting the best management strategies for PE patients. However, the symptoms, signs, disease history, lesion position and pathophysiology linked to different genders in patients with PE have rarely been evaluated. One hundred and forty-nine PE patients (73 males and 76 females) were sequentially recruited to this study over the last five years whilst attending our Emergency Department. Data relating to the symptoms, signs, disease history, biochemical testing, cardiac electrophysiology, imaging detection, treatment and outcome were collected and the gender differences were analyzed. We found that embolisms occurred significantly more frequently in the right lung (89.7%) than in the left lung (42.6%). The presence of dyspnea, the number of patients presenting with tumors, the number of patients with chronic pulmonary disease, those with emboli in the right pulmonary artery and emboli in the right lung, as well as the average systolic and diastolic blood pressure were: 78.1%, 15.1%, 31.5%, 32.9%, 94.5%, 129.9+20.0 and 75.0+11.2 in the male patients and 59.2%, 1.3%, 14.5%, 17.1%, 69.7%, 125.1+14.6 and 69.3+11.0 in the female patients. These indicators were found to be significantly higher in male patients. In contrast, the rate of V1-V4 T-wave inversion and level of D-dimer in the blood were significantly lower in males than in females. No significant difference was observed in the remaining observational indicators. Gender differences regarding the symptoms, signs, disease history, lesion position and pathophysiology exist in patients with PE and should be considered in clinical practice.

Platelet-Derived Growth Factor and Transforming Growth Factor ß1 Regulate ARDS-Associated Lung Fibrosis Through Distinct Signaling Pathways.

BACKGROUND/AIMS: Severe acute lung injury (ALI) often develops into acute respiratory distress syndrome (ARDS). Previous studies have shown that platelet-derived growth factor (PDGF) and transforming growth factor ß1 (TGFß1) participate in the pathogenesis of ARDS by stimulation of fibroblast proliferation, leading to the development of pulmonary fibrosis. However, the exact pathways downstream of PDGF and TGFß receptor signaling have not been completely elucidated. METHOD: We treated human lung fibroblasts (HLF) with PDGF, or TGFß1, or combined, and examined the activation of p38 MAPK, p42/p44 MAPK and SMAD3. We used a specific inhibitor PD98059 to antagonize phosphorylation of p42/p44 MAPK, or used a specific inhibitor SN203580 to antagonize phosphorylation of p38 MAPK, or used a specific inhibitor SIS3 to antagonize phosphorylation of SMAD3. We then examined the effects of these inhibitors on the activation of collagen I and α-smooth muscle actin (α-SMA) induced by PDGF or TGFß1 stimulation. RESULTS: PDGF activated p38 MAPK and p42/p44 MAPK, but not SMAD3 in HLF cells. TGFß1 activated p38 MAPK and SMAD3, but not p42/p44 MAPK in HLF cells. Activation of p38 MAPK by either PDGF or TGFß1 induced α-SMA but not collagen I in HLF cells, while activation of p42/p44 MAPK by PDGF induced collagen I but not α-SMA in HLF cells. Activation of SMAD3 by TGFß1 did not affect either collagen I or α-SMA in HLF cells. CONCLUSION: PDGF and TGFß1 regulate ARDS-associated lung fibrosis through distinct signaling pathway-mediated activation of fibrosis-related proteins. Treatments with both PDGF and TGFß1 antagonists may result in a better anti-fibrotic outcome for ALI-induced lung fibrosis.

Angiotensin-converting enzyme I/D polymorphism and acute respiratory distress syndrome.

BACKGROUND: Some studies have assessed the association between angiotensin-converting enzyme (ACE) I/D polymorphism and acute respiratory distress syndrome (ARDS) risk. However, the results have been inconclusive and contradictory. Therefore, we performed a meta-analysis to investigate the association between ACE I/D polymorphism and ARDS risk. METHODS: All relevant studies were searched using PubMed and EMBASE. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using random-effects models or fixed-effects models. RESULTS: A total of 14 studies with 5218 subjects were included in this meta-analysis. We found that ACE I/D polymorphism significantly associated with an increased ARDS risk (OR=1.57; 95% CI 1.30-1.89; P<0.00001). In the subgroup analysis by race, Caucasians with ACE I/D polymorphism showed increased ARDS risk (OR=1.63; 95% CI 1.32-2.02; P<0.00001). However, Asians with this polymorphism did not show significantly increased ARDS risk (OR=1.31; 95% CI 0.90-1.90; P=0.95). In the subgroup analysis by age group, adults showed increased ARDS risk (OR=1.60; 95% CI 1.32-1.93; P<0.00001), while pediatric patients did not have increased ARDS risk (OR=1.15; 95% CI 0.57-2.30; P=0.70). CONCLUSIONS: This meta-analysis suggested that ACE I/D polymorphism might contribute to the susceptibility for ARDS.

The CC genotype of the delta-sarcoglycan gene polymorphism rs13170573 is associated with obstructive sleep apnea in the Chinese population.

Obstructive sleep apnea (OSA) is a highly heterogeneous sleep disorder, and increasing evidence suggests that genetic factors play a role in the etiology of OSA. Airway muscle dysfunction might promote pharyngeal collapsibility, mutations or single nucleotide polymorphisms (SNPs) in the delta-sarcoglycan (SCGD) gene associated with muscle dysfunction. To evaluate if SCGD gene SNPs are associated with OSA, 101 individuals without OSA and 97 OSA patients were recruited randomly. The genotype distributions of SNPs (rs157350, rs7715464, rs32076, rs13170573 and rs1835919) in case and control populations were evaluated. The GG, GC and CC genotypes of rs13170573 in control and OSA groups were 51.5% and 37.1%, 36.6% and 35.1%, and 11.9% and 27.8%, respectively. Significantly fewer OSA patients possessed the GG genotype and significantly more possessed the CC genotype compared with controls. Further multivariate logistic regression analysis showed that the CC genotype was an independent risk factor for OSA, with an odds ratio (OR) of 2.17 (95% confidence interval [CI]: 1.19-6.01). Other factors, such as age ≥ 50 years, male gender, body mass index (BMI) ≥ 25 kg/m(2), low-density lipoprotein cholesterol (LDL-C) level ≥ 3.33 mg/dL, smoking and hypertension, were also independent risk factors for OSA in our multivariate logistic regression model.

Age-group-specific associations between the severity of obstructive sleep apnea and relevant risk factors in male and female patients.

AIM: To seek accurate and credible correlation manner between gender, age, and obesity; and the severity of obstructive sleep apnea (OSA) in large-scale population. METHODS: Totals of 1,975 male and 378 female OSA patients were sequentially recruited. Centralized covariant tendencies between age, body mass index (BMI), and waist hip ratio (WHR); and OSA severity, were explored in a gender-specific manner via multiple statistical analyses. The accuracies of observed correlations were further evaluated by adaptive multiple linear regression. RESULTS: All of age, BMI, WHR, smoking, drinking, and OSA severity differed between males and females. BMI and WHR were positively and (approximately) linearly associated with OSA severity in both males and females. Restricted cubic spline analysis was more effective than was the Pearson correlation approach in correlating age with AHI, and provided age crossover points allowing further piecewise linear modeling for both males and females. Multiple linear regression showed that increasing age was associated with OSA exacerbation in males aged ≤ 40 years and in females aged 45-53 years. BMI, WHR, and diabetes were independently associated with OSA severity in males with age-group-specific pattern. In females, only BMI was associated with OSA severity at all ages. CONCLUSIONS: In male patients, BMI and WHR are prominent risk factors for OSA exacerbation. Age and diabetes are associated with OSA severity in males of particular ages. In females, BMI is also a prominent risk factor for severe OSA, and OSA severity increased with age in the range 45-53 years.

Budesonide inhibits interleukin-32 expression in a rat model of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lung, and is the fifth leading cause of morbidity worldwide. A novel proinflammatory factor, interleukine-32 (IL-32), is suggested as a risk factor of COPD. Budesonide is widely used for COPD treatment as anti-inflammatory drug. However, the inflammatory inhibition mechanism of budesonide is not fully understood. In this study, we used a rat model with COPD to investigate the effect of budesonide on IL-32 expression in lung tissue. We found that cigarette smoking (CS) strongly induced IL-32 expression in lung tissue, seriously weakened lung function, and damaged pulmonary tissue. Budesonide inhibited the expression of IL-32 in lung tissue. In budesonide-treated rats, we observed no repair of damaged lung tissue but the pulmonary function was partly recovered. To our knowledge, this is the first report that budesonide inhibits the expression of IL-32 in lung tissues, which is strongly induced by CS.

Procalcitonin guidance for reduction of antibiotic use in low-risk outpatients with community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: Use of antibiotics in outpatients with community-acquired pneumonia (CAP) is empirical, which may lead to overuse and selection pressure for resistance. Procalcitonin (PCT) levels may predict the severity of CAP and may be used to guide antibiotic use in hospitalized patients. This study evaluated the value of PCT measurements for guiding antibiotic use in low-risk outpatients with CAP. METHODS: This was a randomized intervention trial conducted between February 2005 and December 2008 that included 172 consecutive patients with suspected CAP, of whom 156 completed the study. The control group received antibiotics according to current guidelines. In the PCT group, antibiotic treatment was based on PCT levels as follows: <0.1 µg/L, strongly discouraged; ≤0.25 µg/L, discouraged; >0.25 µg/L, encouraged. The primary end-points were total antibiotic use and duration of antibiotic treatment; laboratory and clinical outcomes were measured. RESULTS: Prescription of antibiotics on admission (84.4% vs 97.5%; P = 0.004), total antibiotic exposure (relative risk 0.55, 95% CI: 0.51-0.60; P = 0.003) and duration of antibiotic treatment (median 5 days vs 7 days; P < 0.001) were reduced in the PCT guidance group, compared with patients treated according to current guidelines. At 4-week follow up, all patients had survived and laboratory and clinical outcomes were similar in the two groups. CONCLUSIONS: Under PCT guidance, antibiotic use was reduced and duration of antibiotic treatment was shortened in low-risk outpatients with CAP, without apparent harm.

Visfatin levels in patients with severe pneumonia.

BACKGROUND: As a cytokine highly expressed in internal organs, visfatin could be used as a biomarker of systemic inflammation response for chronic obstructive pulmonary diseases, but few studies have reported the use of visfatin in severe pneumonia. The present study was undertaken to determine the plasma levels of visfatin in patients with severe pneumonia. METHODS: A total of 70 patients, including 40 patients with severe pneumonia (group A) and 30 patients with non severe pneumonia (group B) who had been admitted to the ICU from June 2009 to June 2010, were enrolled in this prospective study. And another 30 healthy physical examinees served as healthy controls (group C). Patients were excluded if they suffered from severe diseases of the heart, brain and kidney, cancers, autoimmune diseases, or received special treatment in the latest month. The plasma levels of visfatin, IL-6, IL-8 and TNF-α were measured by ELISA, while the level of CRP was determined by immuneturbidimetry, and the routine blood test was performed. Blood gas analysis and Acute Physiology and Chronic Health Evaluation II (APACHE II) were performed in patients with pneumonia. Comparisons between the groups were conducted by Student's t test, ANOVA or nonparametric test. Correlation analysis was carried out by Pearson's correlation test or Spearman's rank-order correlation test. RESULTS: The plasma level of visfatin in group A was significantly higher than that in groups B and C (P<0.001), and the level of visfatin in group B was significantly higher than that in group C (P<0.001). The plasma level of visfatin was positively correlated with CRP, TNF-α, APACHE II and PMN% in patients with severe pneumonia (rho =0.653, r=0.554, r=0.558, r=0.484, respectively, P<0.05 for all), while it was negatively correlated with PaO2 and PaO2/FiO2 (rho =-0.422, r=-0.543, respectively, P<0.05 for all). CONCLUSION: Visfatin may be involved in the systematic inflammation response in patients with severe pneumonia as a pro-inflammatory cytokine, and it is valuable in assessing the severity of pneumonia..

A new inflammation marker of chronic obstructive pulmonary disease-adiponectin.

BACKGROUND: This study was undertaken to measure the concentration of adiponectin (APN) in serum and induced sputum in patients with chronic obstructive pulmonary disease (COPD during acute exacerbation (AECOPD) and at stable stage and to determine the role of APN as a marker of inflammation in the pathogenesis of COPD. METHODS: All the patients in this prospective study were enrolled from October 2008 to October 2009, including 30 male AECOPD patients from the emergency department, 30 male stable COPD patients from the department of respiratory diseases, and 30 healthy non-smoking male controls from the department of medical examination. The serum and induced sputum were collected from each patient. All of the patients had normal weight (BMI range 18.5-24.9 kg/m(2)). Patients with severe bronchial asthma, bronchiectasis or autoimmune disease were excluded. Cell count and classification was performed for the induced sputum. The concentrations of APN, IL-8, IL-6 and TNF-α were measured by ELISA. Pulmonary function was tested among the three groups. Comparisons between the groups were conducted by Student's t test, ANOVA analysis or nonparametric test. Correlation analysis was carried out by Pearson's product-moment correlation coefficient test or Spearman's rank-order correlation coefficient test. RESULTS: The concentrations of APN in the serum or induced sputum in AECOPD patients were significantly higher than those in stable COPD patients or healthy non-smoking controls (P<0.01). The concentration of APN in stable COPD patients was significantly higher than that in healthy non-smoking controls (P<0.01). For the AECOPD patients, APN was positively correlated with IL-8 and TNF-α in the serum and induced sputum (r=0.739, 0.734, 0.852, 0.857 respectively, P<0.05). For the stable COPD patients, APN was also positively correlated with IL-8 and TNF-α in the serum and induced sputum (r=0.751, 0.659, 0.707, 0.867 respectively, P<0.05). In addition, for the AECOPD patients, APN was positively correlated with the percentage of neutrophils in the induced sputum (r=0.439, P<0.05). CONCLUSIONS: APN is involved in the process of systematic and airway inflammation of COPD. This process is related to neutrophils in the airway, IL-8 and TNF-α. APN could be used as a new marker for inflammation of COPD.

[The value of serum procalcitonin in treatment of community acquired pneumonia in outpatient].

OBJECTIVE: To evaluate the value of serum procalcitonin (PCT) on antibiotic use in treatment of community acquired pneumonia (CAP) in outpatient. METHODS: From November 2006 to February 2008, a total of 127 patients with CAP in outpatient were randomly assigned into two groups: PCT group (n = 63) and control group (n = 64). PCT levels of all patients were measured after study admission. On the base of similarly normal treatment, the control group received antibiotics according to the attending physicians and the PCT group were treated with antibiotics according to serum PCT levels: antibiotic treatment was applied with PCT level > or = 0.25 microg/L and was discouraged with PCT level < 0.25 microg/L. Clinical efficacy, rate of antibiotics use, duration courses and costs of antibiotics were observed. RESULTS: Clinical efficacy of the PCT group was similar with the control group (92.1% vs 87.5%, P > 0.05); rate and costs of antibiotics use was lower, antibiotic duration of the PCT group was shorter than that of the control group (P < 0.05, P < 0.001, P < 0.001). CONCLUSION: PCT could be used in treatment of CAP for antibiotic use in outpatient, which may reduce antibiotic use, shorten antibiotic duration and lower costs of antibiotic.