Toll-Like Receptor 4 Deficiency Ameliorates Propofol-Induced Impairments of Cognitive Function and Synaptic Plasticity in Young Mice.

Propofol is one of the most used intravenous anesthetic agents, which is widely used in clinical anesthesia induction and maintenance of pediatric patients. Exposure of the developing brain to propofol has been reported to lead to adverse brain changes, which in turn can induce persistent behavioral abnormalities in adulthood. However, the mechanisms by which propofol exposure in the developing brain induces cognitive impairment remain unclear. Here we report that repeated propofol exposure during the second postnatal week impairs spatial learning and memory in young mice. The reduced excitatory synaptic function and synaptogenesis in hippocampal CA1 neurons underlie this cognitive impairment. Propofol exposure specifically activates Toll-like receptor 4 (TLR4)-myeloid differentiation primary response protein 88 (MyD88)-NF-κB signaling pathway. TLR4 deficiency recues propofol exposure-induced synaptic function and cognitive deficits in young mice. Thus, we provide evidence that the activation of the TLR4-mediated pathway by propofol exposure may serve as a crucial trigger for the cognitive impairment in young adulthood caused by repeated exposure to propofol in the developing brain.

Factors associated with outcomes of septic shock patients receiving high dose noradrenaline according to three primary infection sites.

OBJECTIVE: To identify factors associated with outcome of septic shock patients receiving high dose noradrenaline according to three primary infection sites. METHODS: This retrospective study was based on data from a publicly available ICU database (Medical Information Mart for Intensive Care [MIMIC] III. Septic shock patients receiving high dose (≥1 µg/kg per min) noradrenaline and ≥18 years were identified and their characteristics and outcomes were compared according to three primary infection sites (abdominal, respiratory and urinary tract). RESULTS: 154 septic shock patients who received high doses of noradrenaline were identified; (89 [58%] had a respiratory infection, 41 [27%] an abdominal infection and 24 [16%] a urinary infection). There were no differences among the three infection groups in duration/maximum dosage of noradrenaline, length of stay in the ICU/hospital, do not resuscitate (DNR) rates, hypertension and adequate antimicrobial therapy. Patients with urinary infections had a lower risk of death at 28-days compared with those with abdominal or respiratory infections. CONCLUSIONS: The prognosis for septic shock patients receiving high dose noradrenaline is poor. Patients with abdominal or respiratory infections are at higher risk of death compared with those with urinary infections.

High 28-day mortality in critically ill patients with sepsis and concomitant active cancer.

OBJECTIVE: This study was performed to explore the characteristics and outcomes of patients with sepsis accompanied by active cancer who were admitted to the intensive care unit (ICU). METHODS: The baseline characteristics, infection profiles, and outcomes of patients with sepsis were retrospectively analyzed according to the presence of concomitant active cancer. The association between concomitant active cancer and 28-day mortality was explored. RESULTS: Of 23,956 patients with sepsis, 1574 (6.6%) had concomitant active cancer. The most common type was digestive (30.7%). The 28-day mortality ranged from 41.9% to 81.5%. Patients with active cancer had a significantly higher Simplified Acute Physiology Score II and significantly shorter length of ICU stay. Respiratory (32.9%), genitourinary (31.0%), and bloodstream (17.0%) infections were most common. Escherichia coli was the most frequent gram-negative pathogenic bacteria. The 28-day mortality rate was significantly higher in patients with than without active cancer. Concomitant active cancer was associated with increased 28-day mortality in patients with sepsis. Hematological malignancy was associated with a significantly higher risk of death than solid tumors. CONCLUSIONS: Concomitant active cancer was associated with higher 28-day mortality in patients with sepsis requiring ICU admission. Hematological malignancy was associated with a higher risk of death than solid tumors.

Assessment of the effect of continuous sedation with mechanical ventilation on adrenal insufficiency in patients with traumatic brain injury.

The aim of this study was to assess the effect of continuous propofol sedation plus prolonged mechanical ventilation on adrenal insufficiency (AI) in patients with traumatic brain injury (TBI). Eighty-five adult patients diagnosed with moderate TBI (Glasgow Coma Scale (GCS) score 9-13) from October 2011 to October 2012 were included in this prospective study. The patients comprised three groups: no mechanical ventilation and sedation (n=27), mechanical ventilation alone (n=24) and mechanical ventilation plus sedation (n=34). The low-dose short Synacthen test was performed at 8:00 on the first, third, and fifth days after TBI. Logistic regression analysis was performed to identify factors affecting the use of mechanical ventilation and sedation, and the incidence of AI. On the fifth day after injury, the mean baseline cortisol and simulated cortisol levels were significantly lower in the mechanical ventilation plus sedation group compared with the other two groups. Multivariate regression analysis showed that the Acute Physiology and Chronic Health Evaluation (APACHE) score was independently associated with treatment with mechanical ventilation and sedation compared to mechanical ventilation alone. Furthermore, hypoxemia on admission and shock were associated with the development of AI. The findings showed that sedation is associated with an increased incidence of AI. Patients with TBI who are treated with continuous sedation should be monitored for AI carefully.

Antihypertensive therapy with nicardipine for patients with aortic disease is associated with more esmolol usage than urapidil.

BACKGROUND: Acute aortic disease is a common but challenging entity in clinical practice. Titration the blood pressure and heart rate to a target level is of paramount importance in the acute phase regardless of whether the patient will undergo a surgery or not eventually. In addition to the initially intravenous ß-blockers, parenteral infusion of nicardipine and urapidil are the most common used antihypertensive therapy currently in mainland China. However, few empirical data was available with respect to the different effect on patients' outcome of the two antihypertensive strategies. Specifically given the deleterious reflex tachycardia of vasodilators which may increase force of ventricular contraction and potentially worsen aortic disease. Therefore, this study was aimed to evaluate the difference of the abovementioned two antihypertensive strategies on the outcome of patients with aortic disease. METHODS: All patients with new diagnosed aortic diseases presented to our hospitals from January 1, 2013 to June 30, 2014 were retrospectively reviewed. The antihypertensive strategies and their association with patients' outcomes were evaluated with logistics regression. RESULTS: A total of 120 patients with new diagnosed aortic disease were included in the study. Of them, 47 patients received urapidil while 73 patients received nicardipine antihypertensive therapy. Patients with nicardipine were more quickly to reach the target blood pressure level than those treated with urapidil (median, 18 vs. 35 min, P=0.024). After adjustment for patient demographics, co-morbidity, involved extend of aorta, interventional strategies, antihypertensive therapy with nicardipine (with urapidil as reference) for patients with aortic disease was significantly associated with high esmolol cost [odds ratio (OR): 6.2, 95% confidence interval (CI), 1.8-21.6, P=0.004] and longer ICU length of stay (LOS) (OR: 3.9, 95% CI, 1.5-10.3, P=0.006). However, there was no significant correlation between nicardipine use and ICU mortality (OR: 0.3; 95% CI, 0.1-1.4, P=0.123). CONCLUSIONS: Although nicardipine achieved the target blood pressure level more quickly than urapidil for patients with aortic disease, it was associated with more esmolol use and longer ICU LOS.

[Association of the MspI polymorphism of cytochrome P4501A1 gene and smoking to the susceptibility to coronary artery disease].

OBJECTIVE: To investigate the association of MspI polymorphism of Cytochrome P4501A1 (CYP1A1) gene and smoking to the susceptibility to coronary artery disease (CAD). METHODS: The genotypes of CYP1A1 MspI site were detected using the methods of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 349 cases with CAD and 404 non-CAD as controls. CAD diagnosis was confirmed by coronary angiograms. Genetic risk of CYP1A1 genotypes was analyzed by smoking index (SI). RESULTS: The frequency of the predominant homozygotes TT, heterozygotes TC and the rare homozygotes CC in CAD group were not different with that of the controls (chi(2) = 3.224, P = 0.200). But in the smokers, the frequency of CC in CAD group was higher than that of non-CAD group (P = 0.002), while its odds ratio was 3.142 [95% confidence interval (CI) 1.481 - 6.668]. The odds ratio of genotype CC and heterozygote TC was 2.215 (95% CI 1.087 - 4.510) in the low dose cigarette smoking group, and was 1.407 (95% CI 0.709 - 2.791) in the high dose cigarette smoking group. CONCLUSION: Both MspI polymorphism of CYP1A1 gene and smoking exposure promote the development of CAD.