BACKGROUND: Meningeal metastasis (MM) is a form of malignant metastasis where tumor cells spread from the primary site to the pia mater, dura mater, arachnoid, subarachnoid space, and other cerebrospinal fluid compartments. Lung cancer is one of the most common malignant tumor types with MM. MM not only signifies that the lung cancer has progressed to an advanced stage but also leads to a range of severe clinical symptoms due to meningeal involvement. Currently, the risk factors associated with the development of MM are not fully elucidated. The aim of this study was to investigate the risk factors for MM in patients with lung adenocarcinoma (LUAD) who underwent non-surgical interventions, in order to identify LUAD patients at high risk for MM. METHODS: This retrospective study analyzed the clinical data of patients diagnosed with LUAD at the First Affiliated Hospital of Zhengzhou University from January 2020 to July 2024. Missing data were imputed using multiple imputation methods, and risk factors were identified through LASSO, univariate, and multivariate Logistic regression analyses. RESULTS: A total of 170 patients with LUAD were included in this study and divided into two groups: 87 patients with MM and 83 patients without MM. Univariate and multivariate Logistic regression analyses revealed that younger age at diagnosis (P=0.004), presence of the epidermal growth factor receptor (EGFR) L858R gene mutation (P=0.008), and concurrent liver metastasis at baseline (P=0.004) were independent risk factors for developing MM in LUAD patients who did not undergo surgical intervention. Conversely, higher baseline globulin levels (P=0.039) and the presence of the anaplastic lymphoma kinase (ALK) gene mutation (P=0.040) were associated with a reduced risk of MM development. CONCLUSIONS Age at diagnosis, EGFR L858R mutation status, ALK gene mutation status, concurrent liver metastasis, globulin levels at baseline were significantly associated with the risk of developing MM in patients with LUAD patients who did not undergo surgical intervention. For patients diagnosed at a younger age, carrying the EGFR L858R mutation, or presenting with baseline liver metastasis, early implementation of tertiary prevention strategies for MM is crucial. Regular monitoring of MM status should be conducted in these high-risk groups.
Humans ; Male ; Adenocarcinoma of Lung/therapy* ; Female ; Middle Aged ; Risk Factors ; Lung Neoplasms/therapy* ; Retrospective Studies ; Aged ; Meningeal Neoplasms/genetics* ; Adult

Objective:To explore the prognostic value of assessing plasma thrombin-antithrombin complex (TAT) and D-dimer (D-D) in patients with acute ischemic stroke (AIS).Methods:This prospective cohort study enrolled 538 AIS patients admitted to the General Hospital of Tianjin Medical University from July 2021 to May 2024, including 306 males and 232 females, with an average age of (69.5±11.5) years. Among them, there were 147 cases of lacunar infarction, 166 cases of large artery atherosclerosis type, 122 cases of cardioembolic type, and 103 cases of cancer-related type. Follow-up observations were conducted on enrolled patients, data within 30 days after the initiation of acute phase treatment for one week were collected, thrombus-related cerebral ischemic events recurrence served as the endpoint event, starting from August 5, 2021, to June 19, 2024. During the follow-up period, 68 patients experienced endpoint events, including 14 cases of large artery atherosclerosis type, 23 cases of cardioembolic type, and 31 cases of cancer-related type. The plasma levels of TAT and D-D were determined by chemiluminescence method and enzyme-linked immunofluorescence assay respectively. The receiver operating characteristic (ROC) curve was used to analyze the prediction performance of TAT and D-dimer for recurrent ischemic events in AIS patients during the 30-day follow-up period, and the Kaplan-Meier curve was used for survival analysis.Results:Statistically differences were observed in the plasma TAT and D-D levels among patients with different types of AIS ( P<0.05), with cancer-related type had higher levels than cardioembolic type ( P<0.05), and cardioembolic type had higher levels than large artery atherosclerosis type ( P<0.05). In the non-recurrent ischemic event group, the plasma TAT and D-D levels of patients with large artery atherosclerosis type, cardioembolic type and cancer-related type were lower in post-treatment than pre-treatment ( P<0.05). In the recurrent ischemic event group, the plasma D-D levels were higher in post-treatment than pre-treatment in the patients with large artery atherosclerosis type ( P<0.05); there was no statistically difference between the post-treatment and pre-treatment in plasma TAT and D-D levels in patients with cardioembolic type ( P>0.05); in patients with cancer-related type, the TAT and D-D levels were lower in post-treatment than pre-treatment ( P<0.05), but higher than those in the non-recurrence group ( P<0.05). The ROC curve showed that the area under the curve for predicting the risk of ischemic event recurrence within 30 days in AIS patients by plasma TAT combined with D-D on day 7 after treatment was all >0.9 (0.950 for large artery atherosclerosis type, 0.965 for cardioembolic type, and 0.907 for cancer-related types). Survival analysis indicated that various patients with both indicators above the critical value had an increased cumulative risk probability of adverse events (log-rank χ 2=93.667, 109.266, and 58.433, respectively, with all P<0.001). Conclusion:The changes of plasma TAT and D-D levels in AIS patients are associated with stroke type and coagulation activation, and dynamic monitoring of these two indicators could help evaluate the treatment effect and predict the risk of recurrent ischemic events.

In the progression process of liver diseases, pathological changes occur in the vascular endothelium, platelets, coagulation, anticoagulation, fibrinolysis systems of patients, and "rebalancd haemostasis" is formed. The coexistence of hypocoagulation and hypercoagulation tendency in the peripheral blood of patients made the laboratory testing data complex and difficult to interpret, especially prothrombin time and activated partial thromboplastin time could not truly reflect the net effect of haemostasis disorder in patients with liver diseases, which often led to misjudgment and overtreatment by doctors and led to adverse clinical consequences. In recent years, thromboelastography, rotational thromboelastometry and thrombin generation assay had been used to assess bleeding risk in patients with liver diseases and had made progress in transfusion management. On the other hand, von Willebrand factor and thrombospondin type 1 motif member 13 has been shown to be closely related to the progression of liver diseases and could warn the adverse clinical outcomes effectively.

Objective:To explore the prognostic value of assessing plasma thrombin-antithrombin complex (TAT) and D-dimer (D-D) in patients with acute ischemic stroke (AIS).Methods:This prospective cohort study enrolled 538 AIS patients admitted to the General Hospital of Tianjin Medical University from July 2021 to May 2024, including 306 males and 232 females, with an average age of (69.5±11.5) years. Among them, there were 147 cases of lacunar infarction, 166 cases of large artery atherosclerosis type, 122 cases of cardioembolic type, and 103 cases of cancer-related type. Follow-up observations were conducted on enrolled patients, data within 30 days after the initiation of acute phase treatment for one week were collected, thrombus-related cerebral ischemic events recurrence served as the endpoint event, starting from August 5, 2021, to June 19, 2024. During the follow-up period, 68 patients experienced endpoint events, including 14 cases of large artery atherosclerosis type, 23 cases of cardioembolic type, and 31 cases of cancer-related type. The plasma levels of TAT and D-D were determined by chemiluminescence method and enzyme-linked immunofluorescence assay respectively. The receiver operating characteristic (ROC) curve was used to analyze the prediction performance of TAT and D-dimer for recurrent ischemic events in AIS patients during the 30-day follow-up period, and the Kaplan-Meier curve was used for survival analysis.Results:Statistically differences were observed in the plasma TAT and D-D levels among patients with different types of AIS ( P<0.05), with cancer-related type had higher levels than cardioembolic type ( P<0.05), and cardioembolic type had higher levels than large artery atherosclerosis type ( P<0.05). In the non-recurrent ischemic event group, the plasma TAT and D-D levels of patients with large artery atherosclerosis type, cardioembolic type and cancer-related type were lower in post-treatment than pre-treatment ( P<0.05). In the recurrent ischemic event group, the plasma D-D levels were higher in post-treatment than pre-treatment in the patients with large artery atherosclerosis type ( P<0.05); there was no statistically difference between the post-treatment and pre-treatment in plasma TAT and D-D levels in patients with cardioembolic type ( P>0.05); in patients with cancer-related type, the TAT and D-D levels were lower in post-treatment than pre-treatment ( P<0.05), but higher than those in the non-recurrence group ( P<0.05). The ROC curve showed that the area under the curve for predicting the risk of ischemic event recurrence within 30 days in AIS patients by plasma TAT combined with D-D on day 7 after treatment was all >0.9 (0.950 for large artery atherosclerosis type, 0.965 for cardioembolic type, and 0.907 for cancer-related types). Survival analysis indicated that various patients with both indicators above the critical value had an increased cumulative risk probability of adverse events (log-rank χ 2=93.667, 109.266, and 58.433, respectively, with all P<0.001). Conclusion:The changes of plasma TAT and D-D levels in AIS patients are associated with stroke type and coagulation activation, and dynamic monitoring of these two indicators could help evaluate the treatment effect and predict the risk of recurrent ischemic events.

In the progression process of liver diseases, pathological changes occur in the vascular endothelium, platelets, coagulation, anticoagulation, fibrinolysis systems of patients, and "rebalancd haemostasis" is formed. The coexistence of hypocoagulation and hypercoagulation tendency in the peripheral blood of patients made the laboratory testing data complex and difficult to interpret, especially prothrombin time and activated partial thromboplastin time could not truly reflect the net effect of haemostasis disorder in patients with liver diseases, which often led to misjudgment and overtreatment by doctors and led to adverse clinical consequences. In recent years, thromboelastography, rotational thromboelastometry and thrombin generation assay had been used to assess bleeding risk in patients with liver diseases and had made progress in transfusion management. On the other hand, von Willebrand factor and thrombospondin type 1 motif member 13 has been shown to be closely related to the progression of liver diseases and could warn the adverse clinical outcomes effectively.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective:To study the changing characteristics of the levels of plasma thrombin-antithrombin complex (TAT) in atherosclerosis obliterans (ASO) patients with different conditions and the clinical value of predicting luminal restenosis after revascularization.Methods:A total of 386 ASO patients were collected, including 209 males and 177 females, aged 70 (44-97) years old, including 196 patients with intermittent claudication and 190 patients with critical limb ischemia. There were 172 patients with intermittent claudication and 185 patients with critical limb ischemia who received revascularization therapy. During the 30-day follow-up period, 23 patients with intermittent claudication and 49 patients with critical limb ischemia developed restenosis after surgery. Venous blood samples were collected before surgery, on the 3rd day after surgery, and on the 7th day after surgery. Plasma TAT levels were determined by Shine i2900-automatic chemiluminescence immunoassay analyzer; Kruskal-Wallis H test was used for comparison among multiple groups; Mann-Whitney U test was used for data comparison between the two groups; continuous comparison of patient data in the same group was done by using Friedman rank test; multivariate correlation analysis by Logistic regression was conducted to obtain odds ratio( OR). The diagnostic performance of TAT was evaluated by ROC analysis. Kaplan-Meier curve was used to analyze the survival curve, and the hazard ratio (HR) was obtained by Cox proportional hazard regression model. Results:Compared with the healthy control group, the level of plasma TAT in patients with intermittent claudication was significantly higher ( P<0.001); the level of plasma TAT in patients with critical limb ischemia was significantly higher than that in patients with intermittent claudication ( P<0.001). The plasma TAT of patients with Rutherford grade 3 >grade2, grade4 >grade3, and grade6 >grade5 ( P values were 0.038, <0.001, and 0.013, respectively).In the intermittent claudication group, the plasma TAT levels of the patients with restenosis on the 3rd and the 7th day after revascularization were both higher than that of the patients with unobstructed blood flow ( P values were 0.004 and <0.001, respectively); The plasma TAT level of patients with unobstructed blood flow on the 7th day after surgery was lower than that on the 3rd day after surgery and before surgery (both P values <0.001); the plasma TAT level of patients with restenosis on the 7th day after surgery was lower than that on the 3rd day after surgery and higher than before surgery (both P values < 0.001). In the critical limb ischemia group, before surgery, on the 3rd and the 7th day after surgery,the plasma TAT levels of the patients with restenosis were higher than that of the patients with unobstructed blood flow ( P values were 0.001, 0.013, and <0.001, respectively); The plasma TAT level of patients with unobstructed blood flow on the 7th day after surgery was lower than that on the 3rd day after surgery and before surgery (both P values <0.001); the plasma TAT level of patients with restenosis on the 7th day after surgery was lower than that on the 3rd day after surgery ( P<0.001), but was not significantly difference from that before surgery. The ROC analysis showed that the areas under the curve (AUC) of plasma TAT on the 7th day after surgery to predict postoperative restenosis in all the patients, patients with intermittent claudication and those with critical limb ischemia were 0.839, 0.783 and 0.853, respectively. Survival analysis indicated that in the critical limb ischemia group, patients with plasma TAT levels higher than the critical value (≥7.66 ng/ml) on the 7th day after surgery showed significantly higher cumulative risk of restenosis events within 30 days after surgery (Log-rank χ 2=93.674, P<0.001). Cox regression analysis showed that the plasma TAT level on the 7th day after the surgery could be used as an independent indicator to predict the occurrence of restenosis within 30 days after surgery in the critical limb ischemia group ( HR=2.259, P<0.001). Conclusion:Plasma TAT can reflect the hypercoagulable state of ASO patients in different conditions, which is helpful for stratification of disease severity. In addition, TAT is highly sensitive for luminal restenosis after revascularization and can be used as an independent marker for evaluating postoperative restenosis events in patients with critical limb ischemia.

Objective:Study on the feature of thrombin-antithrombin complex (TAT) during traumatic brain injury and the predicting performance with adverse clinical outcomes.Methods:From January 2018 to December 2019, 147 patients with traumatic brain injury(TBI) were enrolled, including 112 males and 35 females, aged 36 (26-48) years old. The plasma levels of TAT were detected on the 0th, 1st, 3rd and 7th day after TBI attack. Kruskal-Wallis H test was used for comparison among multiple groups; Mann-Whitney U test was used for data comparison between the two groups; continuous comparison of patient data in the same group using Friedman rank test; the diagnostic performance of TAT with adverse event risk predicting was evaluated by ROC analysis; Kaplan-Meier curve was used to analyze the survival curve; the risk ratio (HR) was obtained by Cox proportional hazard regression model.Results:Among the patients groups with mild, moderate and severe phenotype, the TAT levels were gradually decreased on the 0th, 1st, 3rd and 7th day after TBI attack(χ 2 values were 95.612, 133.555, and 132.453, respectively, all P values<0.001). The TAT levels on the 0th, 1st, 3rd and 7th day in the adverse event group were higher than in the group of patients with stable condition ( U values were 959.0, 321.0, 36.0 and 1.0 respectively, all P values<0.001). In the stable condition group, the TAT levels on the 0th and 1st day in the severe group were higher than in the mild group ( U values were 0 and 1.0 respectively, both P values<0.001), while there was no statistically significant difference of TAT levels between the 3rd and 7th day in the severe group ( U values were 342.5 and 272.5, P values were 0.486 and 0.065 respectively). The TAT levels of the moderate group on 0th and 1st day were higher than those of the mild group ( U values were 0 and 280.0, respectively, both P<0.001), while there was no significant difference between the TAT levels on the 3rd and 7th day ( U values were 628.0 and 647.0, P values were 0.826 and 0.996, respectively). ROC curves analysis showed that when the TAT diagnostic thresholds were 68.75 ng/ml, 29.05 ng/ml, 17.25 ng/ml and 13.85 ng/ml on the 0th, 1st, 3rd and 7th day, the diagnostic sensitivities of predicting adverse events were 86.8%, 94.3%, 100% and 100%; while the diagnostic specificities were 71.3%, 78.7%, 91.5% and 96.8%, respectively. Survival analysis showed that the cumulative probability of adverse outcomes was significantly higher in patients above the critical value. Cox analysis showed that the HR on the 0th, 1st, 3rd and 7th day to predict adverse clinical outcomes by TAT levels were 1.818, 2.257, 3.526 and 4.813, respectively ( P value<0.001). Conclusion:There was strong relationship between the plasma TAT level and the severity of the patient′s condition, and persistent increasing with TAT level could reflect the risk of adverse events, which could be used as an effective index to comprehensively predicting the development tendency of the TBI patient′s condition.