Influence of the Pre-shock State on the Prognosis of Medical Patients with Sepsis: A Retrospective Cohort Study.

Objective: To investigate the effects of the pre-shock state on the mortality of patients with sepsis. Methods: We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university hospital. These patients were then classified into three groups: sepsis, pre-shock state, and septic shock. The primary outcome was the 28-day mortality rate. The secondary outcomes were the 90-day, 180-day, and 1-year mortality rates. Results: A total of 303 patients (groups: sepsis 135 [44.6%]), pre-shock state (93 [30.7%]), and septic shock (75 [24.8%]) completed the 1-year follow-up. The mortality rates at 28 days, 90 days, and 180 days and 1 year were significantly higher in the pre-shock state group than those of the sepsis group, but significantly lower than those in the septic shock group, especially among older patients. When compared with the pre-shock state group, the sepsis group had significantly lower mortality risks at 28 days, 90 days, and 180 days and 1 year, whereas the sepsis shock group had higher mortality risks at these time points. Conclusion: The mortality rates of patients in the pre-shock state were notably different from those of patients with sepsis or septic shock. The introduction of a modified sepsis severity classification, which includes sepsis, pre-shock state, and septic shock, could offer valuable additional prognostic information.

Untreated Prior Pulmonary Tuberculosis Adversely Affects Pregnancy Outcomes in Infertile Women Undergoing in vitro Fertilization and Embryo Transfer: A Large Retrospective Cohort Study.

OBJECTIVE: Prior pulmonary tuberculosis (PTB) on chest X-ray (CXR) was commonly found in infertile patients receiving examinations before in vitro fertilization and embryo transfer (IVF-ET). It was unclear whether untreated PTB would affect pregnancy outcomes after IVF-ET. METHOD: We conducted a retrospective cohort study of 14,254 infertile patients who had received IVF-ET at Peking University Third Hospital in 2017. Prior PTB was defined as the presence of signs suggestive of old or inactive PTB on CXR, with or without a clinical TB history. Patients who had prior PTB on CXR but had not received a clinical diagnosis and anti-TB therapy were included for analysis. Live birth, clinical pregnancy, and miscarriage rates were compared between the untreated PTB and non-PTB groups. RESULTS: The untreated PTB group had significantly lower clinical pregnancy (31.7% vs. 38.1%) and live birth (23.8% vs. 30.6%) rates than the non-PTB group (both P < 0.001). Multivariate analysis revealed that untreated PTB was a risk factor for decreased live birth rate [odds ratio ( OR), 0.80; 95% confidence interval ( CI), 0.66-0.98; P = 0.028] in all patients and for increased miscarriage ( OR, 4.19; 95% CI, 1.69-10.39; P = 0.002) and decreased live birth ( OR, 0.45; 95% CI, 0.24-0.83; P = 0.011) rates in patients with unexplained infertility. CONCLUSIONS: Untreated PTB was associated with adverse pregnancy outcomes after IVF-ET, especially in patients with unexplained infertility, highlighting the clinical significance of PTB in this specific patient population.

Metabolomic Profiling Differences among Asthma, COPD, and Healthy Subjects: A LC-MS-based Metabolomic Analysis.

OBJECTIVE: Asthma and chronic obstructive pulmonary disease (COPD) feature different inflammatory and cellular profiles in the airways, indicating that the cellular metabolic pathways regulating these disorders are distinct. METHODS: We aimed to compare the serum metabolomic profiles among mild persistent asthmatic patients, individuals with stable COPD, and healthy subjects and to explore the potential metabolic biomarkers and pathways. The serum metabolomic profiles of 17 subjects with mild persistent asthma, 17 subjects with stable COPD, and 15 healthy subjects were determined by an untargeted metabolomic analysis utilizing liquid chromatography-mass spectrometry. A series of multivariate statistical analyses was subsequently used. RESULTS: Multivariate analysis indicated a distinct separation between the asthmatic patients and healthy controls in electrospray positive and negative ions modes, respectively. A total of 19 differential metabolites were identified. Similarly, a distinct separation between asthma and COPD subjects was detected in the two ions modes. A total of 16 differential metabolites were identified. Among the identified metabolites, the serum levels of hypoxanthine were markedly higher in asthmatic subjects compared with those in COPD or healthy subjects. CONCLUSION: Patients with asthma present a unique serum metabolome, which can distinguish them from individuals with COPD and healthy subjects. Purine metabolism alteration may be distinct and involved in the pathogenesis of asthma.

Metabolomic Analysis of Serum Glycerophospholipid Levels in Eosinophilic and Neutrophilic Asthma.

OBJECTIVE: To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. METHODS: Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ⪖ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ⪖ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis. RESULTS: The serum lysophosphatidylglycerol level was significantly higher in the group with ⪖ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ⪖ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ⪖ 71% and the group with sputum neutrophils < 71%. CONCLUSION: Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.

Pharmacokinetic-pharmacodynamic analysis of ciprofloxacin in elderly Chinese patients with lower respiratory tract infections caused by Gram-negative bacteria.

BACKGROUND: Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad have shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gram-negative bacteria. METHODS: From September 2012 to June 2014, as many as 33 patients were empirically administered beta-lactam and ciprofloxacin combination therapy. Patients were infused with 200 or 400 mg of ciprofloxacin every 12 h, which was determined empirically by the attending physician based on the severity of the LRTI and the patient's renal condition. Ciprofloxacin serum concentrations were determined by high-performance liquid chromatography. Bacterial culture was performed from sputum samples and/or endotracheal aspirates, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. The ratios of the area under the serum concentration-time curve to the MIC (AUC/MIC) and of the maximum serum concentration of the drug to the MIC (Cmax/MIC) were calculated. The baseline data and pharmacokinetic parameters were compared between clinical success group and clinical failure group, bacteriologic success group and bacteriologic failure group. RESULTS: Among the 33 patients enrolled in the study, 17 were infected with Pseudomonas aeruginosa, 14 were infected with Acinetobacter baumannii, and two were infected with Klebsiella pneumoniae. The mean age of the patients was 76.9 ± 6.7 years. Thirty-one patients (93.4%) did not reach the target AUC/MIC value of >125, and 29 patients (87.9%) did not reach the target Cmax/MIC value of >8. The AUC/MIC and Cmax/MIC ratios in the clinical success group were significantly higher than those in the clinical failure group (61.1 [31.7-214.9] vs. 10.4 [3.8-66.1], Z = -4.157; 9.6 [4.2-17.8] vs. 1.3 [0.4-4.7], Z = -4.018; both P < 0.001). The AUC/MIC and Cmax/MIC ratios in the patients for whom the pathogens were eradicated were significantly higher than those in the patients without the pathogens eradicated (75.3 [31.7-214.9] vs. 10.5 [3.8-66.1], Z = -3.938; 11.4 [4.2-17.8] vs. 1.4 [0.4-5.4], Z = -3.793; P < 0.001 for both). Receiver operating characteristic curve analysis showed that the AUC/MIC and Cmax/MIC values were closely associated with clinical and bacteriologic efficacies (P < 0.001 in both). CONCLUSIONS: Ciprofloxacin is inadequately dosed against Gram-negative bacteria, especially for those with relatively high MIC values. Consequently, the target values, AUC/MIC > 125 and Cmax/MIC > 8, cannot be reached.

[Expression and significance of programmed cell death 5 in patients of branchial asthma].

OBJECTIVE: To explore the expression and significance of serum programmed cell death 5 (PDCD5) in patients with bronchial asthma. METHODS: From June to December 2011, a total of 40 adults with bronchial asthma treated in Peking University Third Hospital were enrolled. Among them, the categories were acute phase (n = 12), chronic phase (n = 14) and remission phase (n = 14). Fifteen healthy adults were selected into the control group. The percentages of peripheral blood neutrophils and eosinophils were collected and detected for each patient. Serum PDCD5 was detected with enzyme-linked immunosorbent assay (ELISA) and asthma control test (ACT) questionnaire filled in. The relevant pulmonary functional indicators were analyzed with a pulmonary spirometer. Two-independent sample t-test and Pearson's correlation analysis were used for statistical analysis. RESULTS: No significant difference was found between two groups with regards to the percentages of peripheral blood eosinophils and neutrophils (all P > 0.05). Serum PDCD5 was significantly higher in the patient group ((47.7 ± 29.6) vs (19.3 ± 9.8) µg/L, P < 0.05). Patients of chronic and acute phases showed a significant higher expression in PDCD5 than the remission phase ((55.2 ± 24.5) & (68.5 ± 22.1) vs (16.0 ± 7.9) µg/L, both P < 0.05). Serum PDCD5 of asthmatics showed a negative correlation with FEV(1)%, FEV(1)/FVC ratio and ACT scores (r = -0.539 to -0.798, all P < 0.05). CONCLUSIONS: PDCD5 participates in the inflammatory process of asthmatic airway. Its abnormal expression may be associated with the uncontrolled state of asthmatics. It may serve as an indicator of assessing the levels of asthma control or a target for the treatment of asthma.

[The relationship between sputum eosinophils and responses to treatment of inhaled glucocorticoids in patients with persistent asthma].

OBJECTIVE: To evaluate the treatment responses of asthmatics with and without sputum eosinophilia to inhaled glucocorticoids, and therefore to verify whether low sputum eosinophils predict poor response to treatment with inhaled glucocorticoids. METHODS: Forty-two symptomatic asthmatic patients, who had not received glucocorticoid therapy in the 3 months preceding the study, were examined before and 1 month and 3 months after treatment with inhaled glucocorticoids. At each visit, all patients underwent spirometry, symptom scoring and sputum induction. The level of eosinophil cationic protein (ECP) in the sputum supernatants was measured by radioimmunoassay. The patients were divided into 2 groups according to sputum eosinophil (EOS) percentages, an EOS group (EOS > 3%) and a non-EOS group (EOS < 3%). The response to inhaled glucocorticoid therapy (as measured by symptom scores and FEV(1)% pred) and the changes of sputum measurements were compared between the 2 groups. RESULTS: In the EOS group, the baseline EOS [0.080 (0.063 - 0.178)] and ECP level [(324 +/- 149) microg/L] were significantly higher than those of the non-EOS group [0.017 (0.006 - 0.021) and (152 +/- 68) microg/L, respectively, t = 4.40, 3.33, both, all P < 0.01]. Baseline FEV(1), FEV(1)% pred and symptom scores were not different between the 2 groups [EOS group: (1.98 +/- 0.67) L, (65 +/- 20)%, 7.0 (5.0 - 10.0), non-EOS group: (2.07 +/- 1.05) L, (66 +/- 27)%, 5.0 (2.0 - 9.0), t = -0.62, -0.09, 1.32, respectively, all P > 0.05]. After 1 month and 3 months inhaled glucocorticoid therapy, the sputum EOS, ECP, the symptom score, FEV(1) and FEV(1)% pred were [0.019 (0.010 - 0.060), [0.036 (0.006 - 0.070); (173 +/- 153) microg/L, (173 +/- 122) microg/L; 3.0 (1.0 - 6.0), 3.0 (1.0 - 5.0); (2.42 +/- 0.64) L, (2.43 +/- 0.76) L; (77 +/- 13)%, (77 +/- 18)%; respectively in the EOS group, which were significantly different as compared to baseline values (F = 6.73, 6.71, 5.93, 7.38, 5.78, respectively, all P < 0.05). But in the non-EOS group, the sputum EOS, ECP, the symptom score, FEV(1) and FEV(1)% pred were 0.013 (0.000 - 0.025), 0.012 (0.004 - 0.031), (111 +/- 50) microg/L, (117 +/- 50) microg/L; 3.0 (0.0 - 6.0), 3.0 (1.0 - 7.3), (2.22 +/- 0.86) L, (2.21 +/- 0.24) L, (71 +/- 20)%, (65 +/- 21)%; respectively at 1 and 3 months, which showed that the sputum EOS, FEV(1) and FEV(1)% pred did not change (F = 1.98, 0.80, 1.37, respectively, all P > 0.05), but the ECP level and the symptom score improved (F = 3.78, 3.59, respectively, both P < 0.05). Multiple stepwise regression showed that baseline FEV(1), severity degree and sputum EOS correlated significantly with changes in FEV(1) after treatment. Among the baseline indexes examined, sputum EOS had the highest negative predictive value (89.5%) for the response to treatment. CONCLUSIONS: In asthmatics with low sputum EOS, inhaled glucocorticoid therapy for 3 months failed to improve pulmonary function. The result confirmed that low sputum EOS was the best predictor for poor glucocorticoid effect in asthma.