Monitoring anesthesia depth with patient state index during pediatric surgery.

BACKGROUND: Monitoring anesthesia depth in children is challenging. Pediatric anesthesiologists estimate general anesthesia depth using indirect methods such as pharmacokinetic models and neurovegetative reflexes. The application of processed electroencephalography may help to identify the correct anesthesia depth (i.e., patient state index between 25 and 50). AIMS: To determine the median values of patient state index and spectral edge frequency 95% in children undergoing general anesthesia conducted according to indirect evaluation of depth. The relationships between patient state index and spectral edge frequency 95% and indirect monitoring of anesthesia depth, type of anesthesia, age subgroups, and postoperative delirium were also assessed. METHODS: A prospective observational study on children (aged 1-18 years) undergoing surgery longer than 60 min. The SedLine monitor and the novel SedLine pediatric sensors (Masimo Inc., Irvine California) were applied. Patient state index levels were recorded for the duration of the anesthesia until the discharge to the ward at predefined time points. RESULTS: In the 111 enrolled children, median patient state index level at the end of anesthesia induction was 25 (22-32) and ranged from 26 (23-34) to 28 (25-36) in the maintenance phase. Patient state index at extubation was 48 (35-60) and 69 (62-75) at discharge from the operatory room. Median right/left spectral edge frequency 95% values at the end of induction were 10 (6-14)/9 (5-14) Hz and median right/left spectral edge frequency 95% values in the maintenance phase ranged from 10 (6-14) to 12 (11-15) Hz in both hemispheres. At extubation, right/left spectral edge frequency 95% levels were 18 (15-21)/17 (15-21) Hz. We observed 39 episodes of burst suppression in 20 patients (19%). Median patient state index levels were not different between patients undergoing inhalational and intravenous anesthesia and between those undergoing general anesthesia and general anesthesia added to locoregional anesthesia. Children <2 years displayed significantly higher patient state index levels than older patients (p = .0004). The presence of a burst suppression episode was not associated with PAED levels (OR 1.58, 95% CI 0.14-16.74, p` = .18). CONCLUSIONS: NonpEEG-guided anesthesia in children led to median patient state index levels at the low range of recommended unconsciousness values with frequent episodes of burst suppression. Patient state index levels were generally higher in children below 2 years.

Soluble CD40 ligand and outcome in patients with coronary artery disease undergoing percutaneous coronary intervention.

OBJECTIVES: CD40 ligand (CD40L), a transmembrane glycoprotein belonging to the tumor necrosis factor family and expressed by a variety of cells, is involved in the basic mechanisms of inflammation, atherosclerosis and thrombosis. Some studies suggest that the soluble form of CD40L (sCD40L) is a predictor of major cardiovascular events and mortality in a variety of clinical settings, but data from literature are conflicting. METHODS: We studied consecutive patients with acute (ACS) or chronic (CCS) coronary syndrome who underwent percutaneous coronary artery intervention (PCI). Blood samples for sCD40L dosage were taken at baseline immediately before PCI. We tested the relation between sCD40L and pre-specified outcome measures consisting of new ACS, clinical restenosis and all-cause mortality. We recruited 3,841 patients (mean age 64 ± 11 years, 79% men) with ACS (n=2,383) or CCS (n=1,458). RESULTS: During a mean follow-up of two years (±0.6 years), 642 patients developed ACS, 409 developed restenosis (≥70% of at least one of the previously treated coronary segments) and 175 died. For each 1-standard deviation increase in sCD40L (0.80 ng/mL), the hazard ratios (HRs) for ACS, restenosis, and mortality were 1.11 (95% confidence interval [CI]: 1.05 to 1.18, p<0.0001), 1.10 (95% CI: 1.02 to 1.19, p=0.010), and 1.00 (95% CI: 0.86 to 1.16, p=0.983), respectively. In multivariable Cox regression models with adjustment for several potential confounders including age, acute or chronic coronary syndrome, multi-vessel disease, stent placement, diabetes, previous coronary events and dyslipidemia, sCD40L remained an independent predictor of ACS and coronary restenosis. There were no interactions between sCD40L and acute or chronic coronary syndrome or stent placement. CONCLUSIONS: Among patients with ACS or CCS who undergo PCI, higher levels of sCD40L predict an increased risk of acute coronary events and coronary restenosis, but not of mortality.

The myocardial bridge: incidence, diagnosis, and prognosis of a pathology of uncertain clinical significance.

The myocardial bridge (MB) is a common anomaly of the coronary tree, very often clinically silent. The artery typically involved is the left anterior descending in its proximal and/or middle portion. MB can cause ischaemia with various mechanisms, directly proportional to the degree of compression of the intra-myocardial tract, which impairs the coronary flow. It is a dynamic phenomenon that is affected by the adrenergic tone and is therefore often brought by physical exercise. MB, when symptomatic, often begins with angina from exertion; some patients have more severe conditions such as unstable angina or myocardial infarction. Coronary vasospasm related to MB-induced endothelial dysfunction can explain a number of cases that come to observation even with catastrophic pictures such as ventricular fibrillation caused by ischaemia. The diagnostic workup includes the non-invasive study using computed tomography angiography and the invasive study of the haemodynamic impact using pressure and Doppler guides. In symptomatic cases, drug therapy with a beta-blocker is enough to manage angina. When it fails, there is the option of coronary angioplasty or surgical treatment techniques.

Ceftazidime/avibactam resistance is associated with different mechanisms in KPC-producing Klebsiella pneumoniae strains.

This study focused on Klebsiella pneumoniae isolates that were resistant or had low susceptibility to a combination of ceftazidime/avibactam. We aimed to investigate the mechanisms underlying this resistance. A total of 24 multi-drug resistant isolates of K. pneumoniae were included in the study. The phenotypic determination of carbapenemase presence was based on the CARBA NP test. NG-Test CARBA 5 was also performed, and it showed KPC production in 22 out 24 strains. The molecular characterisation of blaKPC carbapenemase gene, ESBL genes (blaCTX-M, blaTEM, and blaSHV) and porin genes ompK35/36 was performed using the PCR. Finally, ILLUMINA sequencing was performed to determine the presence of genetic mutations.Various types of mutations in the KPC sequence, leading to ceftazidime/avibactam resistance, were detected in the analysed resistant strains. We observed that KPC-31 harboured the D179Y mutation, the deletion of the amino acids 167-168, and the mutation of T243M associated with ceftazidime/avibactam resistance. The isolates that did not present carbapenemase alterations were found to have other mechanisms such as mutations in the porins. The mutations both on the KPC-3 enzyme and in the porins confirmed, that diverse mechanisms confer resistance to ceftazidime/avibactam in K. pneumoniae.

The over-expression of miR-34a fails to block DoHH2 lymphoma cell proliferation by reducing p53 via c-MYC down-regulation.

MicroRNAs (miRNAs) might behave as tumor suppressors and for that they are under consideration as novel therapeutic drugs. We tested the tumor suppressor activity of miRNA-34a (miR-34a) by measuring cell proliferation of the follicular lymphoma cell line DoHH2 transfected with this miRNA. We report that miR-34a did not inhibit cell proliferation notwithstanding a marked down-regulation of c-MYC. Interestingly, DoHH2 transfected cells showed a significant p53 down-regulation, suggesting that c-MYC positively controls p53 and the failed inhibition of cell proliferation is probably due to the down-regulation of the c-MYC/p53 axis. In keeping with this, c-MYC silencing also down-regulated p53 and had no effect on cell proliferation. In accordance with this hypothesis, etoposide or nutlin-3 treatment or a small interfering RNA (siRNA) against BCL6 (B-cell lymphoma 6) inhibited the proliferation of DoHH2 cells by up-regulating p53 without affecting either miR-34a or c-MYC levels. These results indicate that the proliferation is controlled by the regulatory axis c-MYC/p53 and suggest that paradoxically miR-34a behaves as a pro-proliferative rather than an anti-proliferative miRNA in DoHH2 cells.