Analysis based on Monte Carlo simulation: How effective is tigecycline in routine antimicrobial therapy?

OBJECTIVE: This paper aims to assess the efficacy of tigecycline in the treatment of several different infections from a pharmacokinetic/pharmacodynamic (PK/PD) perspective. MATERIALS AND METHODS: The minimum inhibitory concentration (MIC) test strip test was used to determine the MICs of clinical isolates of tigecycline. A 5,000-subjects simulation was performed by Crystal Ball software to calculate the probability of achieving the required PK/PD exposure. RESULTS: The use of standard tigecycline dosing is predicted to have a good clinical outcome for patients suffering from complicated skin and skin structure infection (cSSSI) with MICs ≤ 0.25 mg×L-1, patients suffering from complicated intra-abdominal infection (cIAI) with MICs ≤ 1 mg×L-1, and patients suffering from hospital-acquired pneumonia (HAP) with MICs ≤ 0.5 mg×L-1. Generally, Gram-positive bacteria are highly sensitive to tigecycline, while Gram-negative bacteria are less sensitive: for patients with HAP and cIAI, the tolerable outcome was achieved using the standard regimen for most Gram-negative pathogens; the desired outcomes could be obtained for the increased-dose treatment; with increasing dose (100 mg every 12 hours), the average cumulative fractions of response (CFRs) markedly increased from 38.18 to 56.21% for cSSSI patients. When tigecycline, a standard regimen, was used to treat carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Enterobacter spp. (CRE) infections, the cumulative response scores were 4.96 - 66.39% and 13.14 - 95.18%, respectively, and the CFRs of the increased dose also increased correspondingly. CONCLUSION: Currently, the standard dose of tigecycline is feasible in the treatment of common bacterial infections, and PK/PD indexes are needed to optimize the regimens for refractory carbapenem-resistant bacterial infections.

FM Combined With NIHSS Score Contributes to Early AIS Diagnosis and Differential Diagnosis of Cardiogenic and Non-Cardiogenic AIS.

A growing researchers have suggested that fibrin monomer (FM) plays an important role in early diagnosis of thrombotic diseases. We explored the application of FM in the diagnosis and classification of acute ischemic stroke (AIS). The differences in FM, D-dimer, and NIHSS scores between different TOAST (Trial of ORG 10172 in Acute Stroke Treatment) types were analyzed with one-way ANOVA; the correlation between FM, D-dimer and NIHSS score in patients with different TOAST classification was analyzed by Pearson linear correlation. The ROC curve was utilized to analyze the diagnostic performance. 1. FM was more effective in diagnosing patients with AIS than D-dimer. 2. The FM level in cardiogenic AIS was significantly different from that in non-cardiogenic patients (P < 0.05); the NIHSS score in cardiogenic stroke was significantly higher than in atherosclerotic and unexplained stroke group. Whereas, no statistical difference was observed in the D-dimer level between these groups (P > 0.05). 3. The correlation between FM and NIHSS scores in the cardiogenic (r = 0.3832) and atherosclerotic (r = 0.3144) groups was statistically significant. 4. FM exhibited the highest diagnostic efficacy for cardiogenic AIS; furthermore, FM combined with the NIHSS score was more conducive to the differential diagnosis of cardiogenic and non-cardiogenic AIS. FM detection contributes to the early diagnosis of AIS, and is important for the differential diagnosis of different TOAST types of AIS. Moreover, FM combined with the NIHSS score is valuable in the differential diagnosis of cardiogenic and non-cardiogenic AIS.

Quantitatively monitoring acute ischemic stroke patients post recombinant tissue plasminogen activator treatment.

BACKGROUND AND AIMS: Thrombolytic therapy is widely used to treat acute ischemic stroke (AIS) patients. As intracerebral hemorrhage is a life-threatening complication of this therapy, monitoring the fibrinolytic and coagulation systems is imperative. However, existing studies on plasmin inhibitor complex (PIC) and thrombin-antithrombin III complex (TAT) mostly apply the enzyme-linked immunosorbent assay (ELISA) method. The aim of this study is to establish the baseline of thrombolytic treatment for AIS patients; to monitor the fibrinolytic and coagulation system following alteplase administration; to ascertain the proper time point to predict intracerebral hemorrhage. METHODS: The method used to assess a patient's intravascular situation, namely chemiluminescence, was used to quantitatively assess the PIC, TAT, and thrombomodulin (TM). Immuno-turbidimetric was used to assess the concentration of D-dimer, fibrin/fibrinogen degradation products (FDP), and the Von Willebrand factor (vWF). The Clauss clotting method was used to assay the activated partial thromboplastin time (APTT), prothrombin time (PT) and FIB. RESULTS: PIC increased to its peak concentration at 3 hours post intravenous (IV) alteplase infusion and decreased by nearly 50% every 3 hours thereafter. After 24 hours, PIC returned to its normal range, while D-dimer and FDP decreased 3 hours later compared to PIC. PT and APTT exhibited no obvious change during the 24-hour period. TM also exhibited no changes during the treatment. CONCLUSION: PIC decreased 3 hours earlier than D-dimer and FDP. The combined test of PIC, D-dimer, and fibrinogen can be used to monitor the fibrinolytic system after the IV alteplase infusion. The use of IV alteplase had no impact on the endothelium. Creating a patient's individual data curve could assist in the prediction of hemorrhagic transformation (HT) and a stroke occurring.

Pharmacokinetic Characterizations of Ginsenoside Ocotillol, RT5 and F11, the Promising Agents for Alzheimer's Disease from American Ginseng, in Rats and Beagle Dogs.

BACKGROUND: Ocotillol, RT5 and F11, the main active components of ocotillol type ginsenosides, have attracted a lot of attention due to their beneficial effects on neurodegenerative disease models of Alzheimer's disease. Pharmacokinetic (PK) is a bridge linking the herbal medicines and their pharmacological responses. However, few data are available regarding PK behaviors of ocotillol type ginsenosides. METHODS: The liquid chromatography-tandem mass spectrometry methods were developed and validated to calculate the concentrations of 3 ginsenosides in different biological matrices. Rat and beagle dog plasma samples were deproteinized with methanol and separated on Shim-pack GIST C18 column. All of the analytes were detected in positive ion mode using multiple reaction monitoring. RESULTS: The methods showed good linearity (r > 0.996) in the established concentration range. All validated data, such as specificity, intra- and inter-day precision, accuracy, extraction recovery, matrix effect, and stability were within required limits. The values of Cmax and AUC(0-t) indicated ocotillol type ginsenosides had low systemic exposure and poor absorption into blood. T1/2 and MRT(0-t) demonstrated the elimination process of ocotillol type ginsenosides might be slow. Double peaks were observed in the mean plasma concentration versus time profiles of ocotillol, RT5, and F11 after oral intake. CONCLUSIONS: This was the first PK investigation of the ocotillol type ginsenosides in rats and beagle dogs. The results we found here were helpful to our understanding of the absorption mechanism of ocotillol type ginsenosides and provided the scientific basis for further pre-clinical research.

CTAPIII/CXCL7: a novel biomarker for early diagnosis of lung cancer.

It is desirable to have a biomarker which can facilitate low-dose CT in diagnosis of early stage lung cancer. CTAPIII/CXCL7 is reported to be a potential biomarker for diagnosis of early lung cancer. In this study, we investigated the serum level of CTAPIII/CXCL7 in patients at different stage of lung cancer and the diagnostic efficacy of CTAPIII/CXCL7 in NSCLC. The plasma level of CTAPIII/CXCL7 was assayed by ELISA. CEA, SCCAg, and Cyfra211 were measured using a commercial chemiluminescent microparticle immunoassay. A total of 419 subjects were recruited, including 265 NSCLC patients and 154 healthy individuals. The subjects were randomly assigned to a training set and a test set. Receiver operating characteristic (ROC) and binary logistic regression analyses were conducted to evaluate the diagnostic efficacy and establish diagnostic mathematical model. Plasma CTAPIII/CXCL7 levels were significantly higher in NSCLC patients than in controls, which was independent of the stage of NSCLC. The diagnostic efficiency of CTAPIII/CXCL7 in NSCLC (training set: area under ROC curve (AUC) 0.806, 95% CI: 0.748-0.863; test set: AUC 0.773, 95% CI: 0.711-0.835) was greater than that of SCCAg, Cyfra21-1, or CEA. The model combining CTAPIII/CXCL7 with CEA, SCCAg, and Cyfra21-1 was more effective for NSCLC diagnosis than CTAPIII/CXCL7 alone. In addition, plasma level of CTAPIII/CXCL7 may contribute to the early diagnosis of NSCLC. CTAPIII/CXCL7 can be used as a plasma biomarker for the diagnosis of NSCLCs, particularly early stage lung cancer, with relatively high sensitivity and specificity.

[Clinical diagnostic value of potential polypeptides associated with rheumatoid arthritis].

OBJECTIVE: To obtain the mimotope recognized by anti-keratin antibody (AKA) by screening a phage random peptide library and evaluate its diagnostic value. METHODS: IgG was purified from AKA positive pooled serum of rheumatoid arthritis (RA) patients by 33.3% (NH4)2SO4 (AKA measured with indirect immunofluorescence). Then the antibody was used as the ligand for biopanning of a 12-mer phage random peptide library. The serum of patients with RA, SLE and normal people were detected with the positive clone by indirect ELISA. RESULTS: After 4 rounds of screening, the peptide of mimotope associated with RA was acquired. The diagnostic specificity, positive predictive value and Youden's index were 95.6%, 90% and 155.6% respectively. Its amino acid sequence was QSESAGPTTSRR. This sequence was similar to 137-148 amino acid sequence of human filaggrin. CONCLUSION: The RA-associated peptide is acquired by screening a phage random peptide library using polyclonal AKA of RA patients. It may be a specific diagnostic tool of RA.

[Embolization of high flow arteriovenous malformations with HepaSphere microspheres].

OBJECTIVE: To determine the effect, safety, and feasibility of embolization of high flow arteriovenous malformations (AVMs) with HepaSphere microspheres. METHODS: HepaSphere particles swell by absorbing fluids and become soft and deformable with a precisely calibrated diameter. 13 patients with AVMs were treated by transarterial embolization with HepaSphere particles. 3 cases underwent a following AVMs resection surgery. The follow-up period was 3 months to 3 years. Symptoms improvement and image examination were studied. RESULTS: 28 transarterial embolizations were performed in 13 cases. The resection operation was performed in 3 cases after transarterial embolizations. The symptoms in diffused AVMs improved after several transarterial embolizations. Histologically, HepaSphere particles penetrated into the intralesional vessels and conformed to the vessel lumen, resulting in vessel occlusion. Minimal perivascular reaction was observed. CONCLUSIONS: Embolization of high flow AVMs with HepaSphere microspheres is safe and effective. Combined treatment is necessary for diffuse AVMs.