Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

Adult ; Aged ; China/epidemiology* ; Cohort Studies ; Female ; Humans ; Male ; Metabolic Syndrome/etiology* ; Middle Aged ; Parks, Recreational/supply & distribution* ; Prevalence ; Residence Characteristics/statistics & numerical data* ; Rural Population/statistics & numerical data* ; Young Adult

OBJECTIVE: To investigate the predictive significance of prognostic nutritional index(PNI)for intraabdominal infections(IAIs)in gerontal liver cancer patients who received hepatectomy.METHODS: The clinical data of270 gerontal(age≥60 y)patients with primary liver cancer(PLC)who received hepatectomy in the First Affiliated Hospital of Xi' an Jiaotong University were retrospectively analyzed.Receiver operating characteristic curve(ROC),multivariate analysis and survival curve were used to conduct the predictive significance of preoperative PNI for IAIs.RESULTS: The incidence of IAIs was 12.59%(34/270)in this cohort.The cut-off value of preoperative PNI for the prediction of postoperative IAIs was 47.58(P<0.05).Patients with diabetes mellitus,anemia and PNI<47.58 were demonstrated as the independent risk factors for postoperative IAIs(P<0.05,respectively).Patients with PNI<47.58 suffered lower but not significantly short-term over-all and disease-free survival rate(P>0.05).CONCLUSION: Preoperative PNI determination has predictive value for postoperative IAIs in gerontal liver cancer patients who received hepatectomy.

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with organ dysfunction secondary to intra-abdominal infections(IAIs).METHODS: 606 patients with organ dysfunction secondary to IAIs who admitted to the First Affiliated Hospital of Xi' an Jiaotong University from January 2014 to December 2017 were recruited for retrospective analysis.Demographic,treatment and outcome data of all patients were collected.Incidence,mortality,treatment and risk factors were adopted for reveal the prevalence of organ dysfunction secondary to IAIs.RESULTS: The morbidity and mortality of patients with organ dysfunction secondary to IAIs were 40.6% and 14.7%,respectively.The mortality rate increased with the number of dysfunctional organs.The univariate analysis results indicated that the number of dysfunctional organs,location of primary infection,continuous renal replacement therapy(CRRT) treatment,artificial liver support,presence of comorbidities,acute physiology and chronic health status(APACHEII)score,sequential organ failure(SOFA)score were associated with the prognosis.The multivariate analysis results showed that the number of dysfunctional organs,artificial liver support,APACHE Ⅱ score and SOFA score were risk factors for the prognosis of patients with organ dysfunction secondary to IAIs.CONCLUSION: The morbidity and mortality of organ dysfunction in IAIs were high.The number of dysfunctional organs,artificial liver support,APACHE Ⅱscore and SOFA score were risk factors for the prognosis of patients with organ dysfunction secondary to IAIs.

BACKGROUNDPlatelet function tests are widely used in clinical practice to guide personalized antiplatelet therapy. In China, the thromboelastography (TEG) test has been well accepted in clinics, whereas VerifyNow, mainly used for scientific research, has not been used in routine clinical practice. The aim of the current study was to compare these two point-of-care platelet function tests and to analyze the consistency between the two tests for evaluating on-clopidogrel platelet reactivity in Chinese acute myocardial infarction patients undergoing percutaneous coronary intervention (PCI).

METHODSA total of 184 patients admitted to Fuwai Hospital between August 2014 and May 2015 were enrolled in the study. On-clopidogrel platelet reactivity was assessed 3 days after PCI by TEG and VerifyNow using adenosine diphosphate as an agonist. Based on the previous reports, an inhibition of platelet aggregation (IPA) <30% for TEG or a P2Y12 reaction unit (PRU) >230 for VerifyNow was defined as high on-clopidogrel platelet reactivity (HPR). An IPA >70% or a PRU <178 was defined as low on-clopidogrel platelet reactivity (LPR). Correlation and agreement between the two methods were analyzed using the Spearman correlation coefficient (r) and kappa value (κ), respectively.

RESULTSOur results showed that VerifyNow and TEG had a moderate but significant correlation in evaluating platelet reactivity (r = -0.511). A significant although poor agreement (κ = 0.225) in identifying HPR and a significantly moderate agreement in identifying LPR (κ = 0.412) were observed between TEG and VerifyNow. By using TEG as the reference for comparison, the cutoff values of VerifyNow for the Chinese patients in this study were identified as PRU >205 for HPR and PRU <169 for LPR.

CONCLUSIONSBy comparing VerifyNow to TEG which has been widely used in clinics, VerifyNow could be an attractive alternative to TEG for monitoring on-clopidogrel platelet reactivity in Chinese patients.

Adenosine Diphosphate ; therapeutic use ; Aged ; Aspirin ; therapeutic use ; Blood Platelets ; drug effects ; China ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; surgery ; Percutaneous Coronary Intervention ; methods ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; therapeutic use ; Point-of-Care Systems ; Receptors, Purinergic P2Y12 ; metabolism ; Thrombelastography ; Ticlopidine ; analogs & derivatives ; therapeutic use

BACKGROUNDTo compare the clinicopathological features and prognosis between younger and aged patients with hepatocellular carcinoma (HCC).

METHODSWe analyzed the outcome of 451 HCC patients underwent liver resection, transcatheter arterial chemoembolization and radiofrequency ablation, respectively. Then risk factors for aged and younger patients' survival were evaluated by multivariate analysis, respectively.

RESULTSThe patients who were older than 55 years old were defined as the older group. The overall survival for aged patients was significantly worse than those younger patients. The younger patients had similar liver functional reserve but more aggressive tumor factors than aged patients. Cox regression analysis showed that the elevated levels of aspartate aminotransferase (AST) (Wald χ2 = 3.963, P = 0.047, hazard ratio [HR] =1.453, 95% confidence interval [CI]: 1.006-2.098), lower albumin (Wald χ2 = 12.213, P < 0.001, HR = 1.982, 95% CI: 1.351-2.910), tumor size (Wald χ2 = 8.179, P = 0.004, HR = 1.841, 95% CI: 1.212-2.797), and higher alpha-fetoprotein level (Wald χ2 = 4.044, P = 0.044, HR = 1.465, 95% CI: 1.010-2.126) were independent prognostic factors for aged patients, while only elevated levels of AST (Wald χ2 = 14.491, P < 0.001, HR = 2.285, 95% CI: 1.493-3.496) and tumor size (Wald χ2 = 21.662, P < 0.001, HR = 2.928, 95% CI: 1.863-4.604) were independent prognostic factors for younger patients.

CONCLUSIONSAge is a risk factor to determine the prognosis of patients with HCC. Aged patients who have good liver functional reserve are still encouraged to receive curative therapy.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; mortality ; Female ; Humans ; Liver Neoplasms ; mortality ; Male ; Middle Aged ; Retrospective Studies ; Survival Analysis ; Young Adult

OBJECTIVETo investigated the curative effect of autologous hematopoietic stem cell transplantation (ASCT) for malignant lymphoma.

METHODSThe clinical data of 81 patients with malignant lymphoma received ASCT from April 1999 to October 2013 were retrospectively analyzed. Of 81 patients, 70 were non-Hodgkin's lymphoma (NHL) and 11 Hodgkin's lymphoma (HL). High dose of etoposide combined with G-CSF was used to mobilize peripheral hematopoietic stem cell. Preconditioning regimen was BEAM (carmustine + cytarabine + etoposide + melphalan).

RESULTSEnough peripheral blood stem cells were collected from all patients. All of the patients after transplantation achieved hematopoietic reconstitution, the median time of the absolute neutrophil count (ANC) recovery to >0.5×10⁹/L time was 10(7-16) d, and the median time of platelet count recovery to >20×10⁹/L was 10(6-17) d. With the follow-up of 23(2-139) months, progression free survival (PFS) was 72.7%, and overall survival (OS) was 88.6%. The median PFS and OS were not reached. Complete remission (CR) before ASCT was an independent prognostic factor of PFS. No transplant related death happened.

CONCLUSIONASCT was a safe and effective method for treatment of malignant lymphoma.

Adolescent ; Adult ; Aged ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Transplantation, Autologous

OBJECTIVETo study the effect of intracellular reactive oxygen species (ROS) levels on T cell activation and apoptosis of synovial cells in collagen induced arthritis (CIA) rats, and to explore the mechanism of Fengshining Capsule (FSN) in the treatment of rheumatoid arthritis (RA).

METHODSSixty rats were randomly divided into the normal control group, the CIA model group, the Tripterygium Poly-glycoside Tablet (TPT) group, the low dose FSN group (at the daily dose of 0.33 g/kg), the middle dose FSN group (at the daily dose of 0.66 g/kg), and the high dose FSN group (at the daily dose of 1.32 g/kg), 10 in each group. T lymphocyte subsets were detected by flow cytometry. The content of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in plasma of rats were detected by ELISA. Its expression of hydroxyl radicals was detected by ultraviolet spectrophotometry. Caspase-3 and Caspase-9 protein expressions were measured by Western blot.

RESULTSCompared with the CIA model group, the levels of ROS were elevated in each dose FSN group (P < 0.01). The level of CD4+ / CD8 was significantly reduced in the middle dose FSN group (P < 0.01). The content of IFN-gamma was obviously lowered in each dose FSN group (P < 0.01), while that of IL-4 was obviously elevated in the high dose FSN group (P < 0.01). Meanwhile, the expression of Caspase-9 and Caspase-3 significantly increased in each dose FSN group (P < 0.05). Besides, the average gray scale of Caspase-9 was significantly higher in the low and middle FSN groups than in the TPT group (P < 0.05, P < 0.01).

CONCLUSIONThe mechanism of FSN for regulating the immune hyperfunction and inhibiting the proliferation of synovial cells in CIA rats might be associated with up-regulating in vivo ROS levels.

Animals ; Apoptosis ; drug effects ; Arthritis, Rheumatoid ; metabolism ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Lymphocyte Activation ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Synovial Membrane ; cytology ; pathology ; T-Lymphocytes ; drug effects ; metabolism

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; diagnosis ; therapy ; Peripheral Blood Stem Cell Transplantation ; Prognosis ; Retrospective Studies ; Transplantation, Autologous ; Treatment Outcome

OBJECTIVETo evaluate plasma arginine vasopressin (AVP) level in patients with traumatic brain injury and investigate the role of AVP in the process of brain edema.

METHODSA total of 30 patients with traumatic brain injury were involved in our study. They were divided into two groups by Glasgow Coma Scale: severe traumatic brain injury group (STBI, GCS less than or equal to 8) and moderate traumatic brain injury group (MTBI, GCS larger than 8). Samples of venous blood were collected in the morning at rest from 15 healthy volunteers (control group)and within 24 h after traumatic brain injury from these patients for AVP determinations by radioimmunoassay. The severity and duration of the brain edema were estimated by head CT scan.

RESULTSPlasma AVP levels (ng/L) were (mean+/-SD): control, 3.06+/-1.49; MTBI, 38.12+/-7.25; and STBI, 66.61+/-17.10. The plasma level of AVP was significantly increased within 24 h after traumatic brain injury and followed by the reduction of GCS, suggesting the deterioration of cerebral injury (P less than 0.01). And the AVP level was correlated with the severity (STBI r equal to 0.919, P less than 0.01; MTBI r equal to 0.724, P less than 0.01) and the duration of brain edema (STBI r equal to 0.790, P less than 0.01; MTBI r equal to 0.712, P less than 0.01).

CONCLUSIONSThe plasma AVP level is closely associated with the severity of traumatic brain injury. AVP may play an important role in pathogenesis of brain edema after traumatic brain injury.

Adult ; Arginine Vasopressin ; blood ; Brain Edema ; blood ; etiology ; physiopathology ; Brain Injuries ; blood ; complications ; physiopathology ; Female ; Humans ; Male ; Middle Aged