Potential biomarkers for the diagnosis and differential diagnosis of immune-mediated demyelinating diseases screened by tandem mass spectrometry technology / 中华检验医学杂志

Objective:To screen the potential biomarkers for the diagnosis and differential diagnosis of immune-mediated demyelinating diseases by tandem mass tags (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology.Methods:Twenty patients with demyelinating diseases (demyelinating group) and 10 patients with noninflammatory neurological diseases (NND group) from Beijing Tiantan Hospital affiliated to Capital Medical University from January 2020 to January 2021 were enrolled in this study. The demyelinating group included 10 patients with Guillain-Barre syndrome (GBS subgroup) and 10 patients with multiple sclerosis (MS subgroup). TMT proteomics was used to screen out the different protein expression patterns between the demyelinating group and the NND group and between the GBS subgroup and the MS subgroup (difference>2 or<0.5 and with statistical significance), and String database was used to perform gene ontology (GO) analysis and Kyoto encyclopedia of gene and genomes (KEGG) analysis on the pathways involved in the differently expressed proteins between the groups. In addition, 80 demyelinating patients (demyelinating diseases validation group) and 40 healthy subjects (healthy control group) were selected for retrospective analysis of general lipid indexes. The demyelinating diseases validation group included 40 GBS patients (GBS validation group) and 40 MS patients (MS validation group). Receiver operating characteristic (ROC) curve was obtained to evaluate the value of general lipid indexes for the diagnosis of demyelinating diseases and the differential diagnosis between GBS and MS groups.Results:A total of 362 proteins were detected by TMT proteomics. There were 101 differentially expressed proteins between the demyelinating group and the NND group, and 45 differentially expressed proteins between the GBS group and the MS group. Compared with the NND group, GO enrichment analysis showed that the top five enrichment pathways in the demyelinating group were macrophage colony stimulating factor and receptor complex, negative regulation of cholesterol input, negative regulation of very low density lipoprotein particle clearance, triglyceride-rich lipoprotein particle remodeling, and cholesterol reverse transport. Compared with MS group, the top five enriched pathways in GBS group were high-density lipoprotein particle receptor binding, negative regulation of very low density lipoprotein particle remodeling, negative regulation of cholesterol input, negative regulation of very low density lipoprotein particle clearance, and medium density lipoprotein particle. KEGG enrichment analysis results showed that differentially expressed proteins in the demyelinating group and the NND group were enriched in 8 pathways, including phosphatidylinositide 3-kinases-protein kinase B signaling pathway, complement and coagulation cascade reaction, extracellular matrix and its receptor interaction, Staphylococcus aureus infection, cholesterol metabolism, RAS signaling pathway, phagosome, and mitogen-activated protein kinase signaling pathway. Differentially expressed proteins in GBS group and MS group were enriched in 9 pathways: cholesterol metabolism, complement and coagulation cascade, platelet activation, peroxisome proliferators-activated receptors signaling pathway, vitamin digestion and absorption, novel coronavirus infection, fat digestion and absorption, axon guidance, and neutrophil extracellular trap formation pathway. The levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) were significantly higher, while high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels were significantly lower in the demyelinating disease validation group than in the healthy control group (all P<0.05 or 0.01). Area under the curve (AUC) of TG, TC, HDL-C, LDL-C, apoA1 and apoB alone or in combination for the diagnosis of immune-mediated demyelinating diseases was 0.746, 0.643, 0.798, 0.703, 0.806, 0.708 and 0.868, respectively. The AUC of HDL-C, apoA1, LDL-C and apoB for differential diagnosis between GBS and MS was 0.692, 0.653, 0.632, 0.695 and 0.718, respectively. Conclusions:There are differences in cerebrospinal fluid proteomics between patients with immune-mediated demyelinating disease and patients with NND, GBS and MS, and the differentially expressed protein patterns mainly exist in the pathways related to lipid metabolism. Lipid related indicators may be used as biomarkers for the diagnosis and differential diagnosis of immune-mediated demyelinating disease.

Relationship between carbon dioxide combining power and the short-term prognosis in acute ischemic stroke patients after thrombolysis / 中华危重病急救医学

Objective:To investigate the effect of venous blood carbon dioxide binding capacity (CO 2-CP) on the short-term prognosis of patients with acute ischemic stroke (AIS) after thrombolytic therapy. Methods:A total of 86 AIS inpatients who received thrombolytic therapy in the emergency department of Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University from April 2019 to May 2021 were analyzed retrospectively. According to the venous blood CO 2-CP levels at admission, the patients were divided into two groups: low CO 2-CP group (CO 2-CP < 23 mmol/L, n = 52) and high CO 2-CP group (CO 2-CP ≥ 23 mmol/L, n = 34). The CO 2-CP levels and changes between the two groups before and after thrombolytic therapy were compared. The National Institutes of Health Stroke scale (NIHSS) score was used to evaluate the improvement rate of patients after thrombolytic therapy [NIHSS score at admission-NIHSS score at discharge)/NIHSS score at admission ×100%] and in-hospital death was also recorded. The correlation between CO 2-CP levels and prognosis of patients with AIS during emergency visit was analyzed, the receiver operator characteristic curve (ROC curve) was drawn and the area under the ROC curve (AUC) was calculated to evaluate the predictive value of CO 2-CP in the prognosis of AIS patients. Results:The CO 2-CP levels of low CO 2-CP group and high CO 2-CP group after thrombolytic therapy were significantly higher than those before treatment (mmol/L: 23.08±2.34 vs. 20.46±1.51, 25.24±2.16 vs. 23.94±1.07, both P < 0.05). The differences of CO 2-CP before and after treatment in low CO 2-CP group were significantly higher than those in high CO 2-CP group (mmol/L: 2.62±0.83 vs. 1.30±1.09, P < 0.05). The improvement rate of CO 2-CP levels in the high CO 2-CP group (NIHSS improvement rate > 45%) was significantly higher than that in the low CO 2-CP group [85.29% (29/34) vs. 23.08% (12/52)], while the mortality in the low CO 2-CP group was significantly higher than that in the high CO 2-CP group [11.54% (6/52) vs. 0% (0/34), P < 0.05]. The AUC of CO 2-CP for the prognosis of patients with AIS thrombolysis was 0.820, the 95% confidence interval (95% CI) was 0.727-0.924, P = 0.000 1. Conclusion:AIS patients with CO 2-CP levels less than 23 mmol/L have a poor short-term prognosis, which has certain predictive and clinical reference value for choosing thrombolytic time in emergency stroke patients.

Serum ceramide concentrations are associated with depression in patients after ischemic stroke-A two-center case-controlled study.

BACKGROUND AND AIMS: The present study aims to correlate the severity of post-stroke depression (PSD) and serum ceramide concentration. MATERIALS AND METHODS: In this two-center case-control study, we prospectively collected clinical and demographical information from age and gender-matched 51 PSD patients, 56 non-post-stroke depression (Non-PSD) patients, and 39 patients with major depression (MD) to perform the suitable biochemical analysis to bring a correlation in causing depression in patients soon after the stroke. The ROC curve method was used to evaluate ceramide's diagnostic efficacy in all three groups of patients. A follow-up analysis was also conducted based on PSD severity to associate serum ceramide levels and neuropsychiatric symptoms. The severity of the patient's depressive symptoms was assessed by using the self-rating depression scale (SDS). RESULTS: In comparison between PSD and MD patients, three serum ceramide species were found to be significantly different. Compared with Non-PSD patients, PSD patients had significantly higher levels of all the four serum ceramides, and increasing levels ofC16:0, C18:0(VS MD) and C16: 0(VS Non-PSD) serve as a diagnostic tool and an independent risk factor in all three categories of patients. Moreover, the follow-up analysis results showed that, as the treatment progressed, the differences in the 3 serum ceramide species were statistically significant. CONCLUSION: There was a stage-specific association between serum ceramides and PSD, and the potential pathophysiological mechanism has to be investigated in future research.

Epidemiology and risk factors of neurosurgical bacterial meningitis/encephalitis induced by carbapenem resistant Enterobacteriaceae.

OBJECTIVES: This is a retrospective observational study conducted in one of the largest clinical center of neurosurgery in China. Our aim was to determine the epidemiological characteristics of carbapenem-resistant Enterobacteriaceae (CRE) related meningitis/encephalitis and to elucidate the risk factors for CRE neurosurgical infections. PATIENTS AND METHODS: We performed a retrospective study between January 2012 and December 2017 of patients who underwent neurosurgery. The medical records of each patient were reviewed, and 20 clinical variables on risk factors were extracted and evaluated by Multivariate logistic analysis for CRE-meningitis/encephalitis. RESULTS: In 2012-2017, the positive rate of neurosurgical meningitis/encephalitis was 7.9% (2947/29605), Enterobacteriaceae accounted for 6.3% (185/2947) of all bacterial infections. Totally, 133 Enterobacteriaceae include 26 CRE isolates were available in this study. Of them, Univariate analysis showed that the risk factors of CRE meningitis were ventilator, bacteremia, Intensive Care Unit (ICU) admission, hospital acquired pneumonia and mortality attribute to infection. Multivariate logistic analysis showed that hospital acquired pneumonia and mortality attribute to infection were independent risk factors for CRE meningitis. CONCLUSION: CRE is one of the most serious drug-resistant bacteria published by World Health Organization (WHO) in 2016, and meningitis/encephalitis caused by CRE is an important sign of the failure of the neurosurgery, which demands the physician's immediate attention.

Application of a microfluidic chip platform in rapid diagnosis of post-neurosurgical bacterial infection / 临床检验杂志

Objective@#To establish and evaluate a microfluidic chip platform for the rapid diagnosis of post-neurosurgical bacterial infection. @*Methods@#The pathogens isolated from patients with post-neurosurgical bacterial infection in Beijing Tiantan Hospital Affiliated to Capital Medical University during 2007 and 2016 and the epidemiological data from China drug resistance monitoring network CHINET were analyzed retrospectively. Based on the retrospective data and the molecular epidemiological information of drug-resistant bacteria reported in the literature, target pathogens and drug resistance gene parameters were selected. The microbial identification parameters from 10 different bacteria, including Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus epidermidis, Enterobacter cloacae, Staphylococcus aureus, Escherichia coli, Enterococcus faecium, Enterococcus faecalis, Stenotrophomonas maltophilia and Pseudomonas aeruginosa, and the parameters of 15 drug resistance genes, including mecA, vanA, vanB, aacC1, aadA1, bla CTX-M-1 , bla CTX-M-9 , bla GES-1 , bla OXA-23 , bla OXA-24 , bla OXA-58 , bla OXA-66 , bla KPC-2 , bla IMP-4 and bla VIM-2 , were selected for designing a microfluidic chip platform. Using MAIDI-TOF MS for bacterial identification, multiplex PCR for the detection of drug resistance genes, micro-broth dilution method for the detection of drug resistance phenotypes and ESBLs screening test as reference methods, 13 known bacteria were used to evaluate the preliminary performance of the established microfluidic chip platform, and 108 cerebrospinal fluid bacterial culture positive specimens were used to evaluate the clinical application value of the microfluidic chip platform. @*Results@#The identification rates of 13 known strains and the coincidence rate of drug resistance genes were 100%. The coincidence rate of identification results for 108 cerebrospinal fluid bacterial culture positive specimens between the microfluidic chip platform and the MALDI-TOF MS method was as high as 94.44%. The coincidence rates of drug resistance phenotype of carbapenems, oxacillin, vancomycin, ESBLs and genotype between the microfluidic chip platform and the micro-broth dilution method or ESBLs screening test were above 90%. @*Conclusion@#The established microfluidic chip platform is fast and accurate, and has application value in microbial identification and the prediction of drug resistance, which may be used as an important supplementary method in the diagnosis of post-neurosurgical bacterial infection.

Epidemiological and lethal risk factors of Klebsiella pneumoniae infection in neurosurgical patients / 中国综合临床

Objective We performed a retrospective study to determine the epidemiological characteristics of Klebsiella pneumoniae infection after neurosurgery and to elucidate the risk.Methods Patients who underwent neurosurgery between January 2012 and December 2016 were included.Demographic,clinical,laboratory,and microbiological data were systemically recorded.17 clinical trials and 7 clinical laboratory indicators were evaluated as risk factors for meningitis.Results Forty-five cases of neurosurgery patients led to K.pneumoniae infection were analyzed,K.pneumoniae ESBLs production ratio is 37.8％ (17/45),the sensitivity rate of carbapenem antibiotics was more than 80.0％ (36/45).The patients were mainly in the north of China with an average age of 36.3±18.3 years old and a male ratio of 53.3％ (24/45).The highest proportion of patients are pituitary adenoma and glioblastoma and the mortality rate was 22.2％ (10/45).The mean length of hospital stay was 29.2± 13.7 days,and the most likely to develop K.pneumoniae were 7.8±6.9 days after neurosurgery.The ICU occupancy rate was 51.1％ (23/45).Chi-square test showed that older age (＞50 years old) and sepsis were risk factors for death from K.pneumoniae infection after neurosurgery.Multivariate logistic analysis showed that the risk of infection was associated with the incidence of sepsis (OR 16.199,P =0.010).There were no statistically significant differences between the survival and death patients by seven laboratory tests (P＞0.05).Conclusion The infection of neurosurgery caused by K.pneumoniae has a high mortality rate.Among them,concurrent sepsis is the lethal risk factor of infection.Clinically,identification of the risk factors as soon as possible will help physicians to improve patient care and improve the surgical success.

Diagnostic value of procalcitonin and lactate in cerebrospinal fluid combined with conventional biomarkers for post-neurosurgical bacterial meningitis / 中华临床感染病杂志

Objective To investigate the diagnostic value of procalcitonin ( PCT) and lactate in cerebrospinal fluid (CSF) combined with conventional biomarkers for post-neurosurgical bacterial meningitis (PBM).Methods Clinical data of 213 patients with post-neurosurgical meningitis admitted in Beijing Tiantan Hospital, Capital Medical University from March 2017 to December 2017 were retrospectively analyzed, including 85 cases of PBM and 128 cases of post-neurosurgical aseptic meningitis ( PAM).The diagnostic value of CSF procalcitonin , lactate and other 12 conventional biomarkers for PBM was analyzed by multivariate logistic regression.A prediction algorithm was generated and its diagnostic value for PBM was assessed with receiver operating characteristic curve (ROC).Results The univariate analysis showed that CSF cell count, CSF leukocyte count , CSF protein concentration , CSF glucose concentration, CSF glucose／blood glucose ratio, CSF PCT and CSF lactate were significantly associated with PBM.Multivariate logistic regression analysis showed that CSF PCT , CSF lactate, CSF protein concentration and CSF glucose ／blood glucose ratio were independent predictive factors for PBM.The predictive algorithm score ＝4.315 ×CSF PCT+0.822×CSF Lactate+0.009×CSF protein concentration -5.480×CSF glucose／blood glucose ratio-3.074.The predictive algorithm has the largest area under the ROC curve ( AUC ＝0.947), and the sensitivity and specificity of the predictive algorithm score were 90.60% and 85.10%, respectively.The positive predictive value , negative predictive value and the accurate rate of the algorithm in diagnosis of PBM were 84.06%, 94.44% and 90.40%, respectively.Conclusion The predictive algorithm based on the combination of CSF PCT and CSF lactate with CSF protein concentration and CSF glucose ／blood glucose ratio has a good diagnostic value for PBM.It can shorten the diagnosis time of PBM and improve the clinical outcomes.

Analysis of drug resistance of pathogenic bacteria from different origins in neurosurgery ward / 国际检验医学杂志

Objective To explore the differences in antibiotic resistance among pathogenic bacteria isolated from respiratory tract and cerebrospinal fluid specimens in neurosurgery wards .Methods Antibiotic resist-ance tests were performed to analyze the antibiotic sensitivities of pathogenic bacteria isolated from respiratory tract and cerebrospinal fluid specimens in the neurosurgery wards at Beijing tiantan hospital affiliated to cap-ital medical university ,from January 2012 to December 2016 .Statistical analysis was performed using the t test or M-W test to determine the differences between the two independent samples were statistically significant . Results From January 2012 to December 2016 ,6 091 strains isolated from respiratory tract and 1 597 strains isolated from CSF specimens were obtained from patients in the neurosurgery wards of a hospital .Based on the results of the t test ,differences in the antibiotic sensitivities of pathogenic bacteria isolated from these two specimens were statistically significant .Three Gram-negative bacteria ,Pseudomonas aeruginosa ,Klebsiella pneumoniae and Acinetobacter baumannii ,showed statistically significant differences in antibiotic sensitivities between respiratory tract and cerebrospinal fluid specimens (P＜0 .05) ,but this difference was not statistically significant in Staphylococcus aureus (P＞0 .05) .Pathogenic bacteria isolated from two specimens showed sta-tistically significant differences in sensitivity to β-lactam antibiotics ,polymyxin B ,vancomycin and linezolid (P＜0 .05) .Conclusion The sensitivity differences between bacteria isolated from respiratory tract and cere-brospinal fluid specimens are statistically significant .Several reasons ,such as antibiotic-induced antibiotic re-sistance ,horizontal gene transfer are responsible for this result .

A comparative research between traditional positioning device and a new type percutaneous kyphoplasty positioning device / 中国医学装备

Objective:To compare the accuracy and safety between percutaneous kyphoplasty (PKP) positioning device and traditional positioning device which posit entry point of pedicle of vertebral arch by using the C-arm X-ray.Methods: 117 patients with spinal centrum compression fractures were divided into positioning device group (57 cases) and Kirschner wire group (60 cases) depended on the entry point marked by the preoperative C arm X-ray irradiation. To compare the excellence rate, operation time and exposure times between PKP positioning device and traditional device.Results: The positioning times of the PKP positioning device group and Kirschner wire group were (2.3±0.9)min and (6.8±1.3)min, respectively. The exposure times of the two group were 1.6 times and 4.7 times, respectively. And both of the two differences were statistical significant (t=21.062,t=18.521;P0.05).Conclusion: There are series of advantages in developed PKP positioning device, such as portable, easy and simple control, higher accuracy and safety, less positioning time and exposure times of C arm X-ray.

Distribution and antimicrobial resistance of coagulase-negative staphylococci isolated from cerebrospinal fluids in neurosurgical patients / 中华临床感染病杂志

Objective To investigate the distribution and antimicrobial resistance of Coagulase-negative staphylococci ( CoNS) isolated from cerebrospinal fluids in neurosurgical patients.Methods CoNS strains isolated from cerebrospinal fluids of neurosurgical patients were collected from Beijing Tiantan Hospital of Capital Medical University during January 2013 and December 2015.CoNS infection was diagnosed according to the standards of US Centers for Disease Control and Prevention, and the distribution and antimicrobial resistance of pathogenic CoNS strains were analyzed. Results A total of 19 756 cerebrospinal fluid specimens were collected and 1 386 bacterial strains were isolated, in which 650 (46.9%) were CoNS.Among 650 CoNS strains, 130 were diagnosed as the pathogen, and the top 4 CoNS species were Staphylococcus epidermidis (77/130, 59.2%), Staphylococcus hominis (18/130, 13.8%), Staphylococcus haemolyticus (11/130, 8.5%) and Staphylococcus capitis (9/130, 6.9%).The rest 520 CoNS strains were contaminating strains.According to antimicrobial susceptibility test, there were 103 strains of methicillin-resistant CoNS (MR-CoNS) accounting for 79.1% (103/130).And among 77 Staphylococcus epidermidis isolates, 67 were MR-CoNS strains (87.0%) .More than 90.0%Staphylococcus epidermidis isolates were sensitive to vancomycin and linezolid, and the rest CoNS strains were also highly sensitive to these two antibacterial agents.Conclusions CoNS plays an important role in post-surgery infection in neurosurgical patients, and Staphylococcus epidermidis is the dominant CoNS species.Most CoNS strains are methicillin-resistant, but are highly sensitive to vancomycin and linezolid.