ADAPT-2: A Randomized Clinical Trial to Reduce Intraoperative EEG Suppression in Older Surgical Patients Undergoing Major Noncardiac Surgery.

BACKGROUND: Recent limited evidence suggests that the use of a processed electroencephalographic (EEG) monitor to guide anesthetic management may influence postoperative cognitive outcomes; however, the mechanism is unclear. METHODS: This exploratory, single-center, randomized clinical trial included patients who were ≥65 years of age undergoing elective noncardiac surgery. The study aimed to determine whether monitoring the brain using a processed EEG monitor reduced EEG suppression and subsequent postoperative delirium. The interventional group received processed EEG-guided anesthetic management to keep the Patient State Index (PSI) above 35 computed by the SEDline Brain Function Monitor (Masimo, Inc, Irvine, CA), while the standard care group was also monitored, but the EEG data were blinded from the clinicians. The primary outcome was intraoperative EEG suppression. A secondary outcome was incident postoperative delirium during the first 3 days after surgery. RESULTS: All outcomes were analyzed using the intention-to-treat paradigm. Two hundred and four patients with a mean age of 72 ± 5 years were studied. Minutes of EEG suppression adjusted by the length of surgery was found to be less for the interventional group than the standard care group (median [interquartile range], 1.4% [5.0%] and 2.5% [10.4%]; Hodges-Lehmann estimated median difference [95% confidence interval {CI}] of -0.8% [-2.1 to -0.000009]). The effect of the intervention on EEG suppression differed for those with and without preoperative cognitive impairment (interaction P = .01), with the estimated incidence rate ratio (95% CI) of 0.39 (0.33-0.44) for those with preoperative cognitive impairment and 0.48 (0.44-0.51) for those without preoperative cognitive impairment. The incidence of delirium was not found to be different between the interventional (17%) and the standard care groups (20%), risk ratio = 0.85 (95% CI, 0.47-1.5). CONCLUSIONS: The use of processed EEG to maintain the PSI >35 was associated with less time spent in intraoperative EEG suppression. Preoperative cognitive impairment was associated with a greater percent of surgical time spent in EEG suppression. A larger prospective cohort study to include more cognitively vulnerable patients is necessary to show whether an intervention to reduce EEG suppression is efficacious in reducing postoperative delirium.

Modeling bivariate geyser eruption system with covariate-adjusted recurrent event process.

Geyser eruption is one of the most popular signature attractions at the Yellowstone National Park. The interdependence of geyser eruptions and impacts of covariates are of interest to researchers in geyser studies. In this paper, we propose a parametric covariate-adjusted recurrent event model for estimating the eruption gap time. We describe a general bivariate recurrent event process, where a bivariate lognormal distribution and a Gumbel copula with different marginal distributions are used to model an interdependent dual-type event system. The maximum likelihood approach is used to estimate model parameters. The proposed method is applied to analyzing the Yellowstone geyser eruption data for a bivariate geyser system and offers a deeper understanding of the event occurrence mechanism of individual events as well as the system as a whole. A comprehensive simulation study is conducted to evaluate the performance of the proposed method.

Development of a SPECT Tracer to Image c-Met Expression in a Xenograft Model of Non-Small Cell Lung Cancer.

Elevated expression of the c-Met receptor plays a crucial role in cancers. In non-small cell lung cancer (NSCLC), aberrant activation of the c-Met signaling pathway contributes to tumorigenesis and cancer progression and may mediate acquired resistance to epidermal growth factor receptor-targeted therapy. c-Met is therefore emerging as a promising therapeutic target for NSCLC, and methods for noninvasive in vivo assessment of c-Met expression would improve NSCLC treatment and diagnosis. Methods: We developed a new c-Met-binding peptide (cMBP) radiotracer, 99mTc-hydrazine nicotinamide (HYNIC)-cMBP, for SPECT imaging. Cell uptake assays were performed on 2 NSCLC cell lines with different c-Met expressions: H1993 (high expression) and H1299 (no expression). In vivo tumor specificity was assessed by SPECT imaging in tumor-bearing mice at 0.5, 1, 2, and 4 h after injection of the probe. Blocking assays, biodistribution, and autoradiography were also conducted to determine probe specificity. Results:99mTc-HYNIC-cMBP was prepared with high efficiency and showed higher uptake in H1993 cells than in H1299 cells. Biodistribution and autoradiography also showed significantly higher percentages of the injected dose for 99mTc-HYNIC-cMBP in H1993 tumors than in H1299 tumors at 0.5 h (4.74 ± 1.43%/g and 1.00 ± 0.37%/g, respectively; P < 0.05). H1993 tumors were clearly visualized at 0.5 h in SPECT images, whereas H1299 tumors were not observed at any time. The specificity of 99mTc-HYNIC-cMBP for c-Met was demonstrated by a competitive block with an excess of nonradiolabeled peptide. Conclusion: For c-Met-targeted SPECT imaging of NSCLC, we developed 99mTc-HYNIC-cMBP, a tracer that specifically binds to c-Met with favorable pharmacokinetics in vitro and in vivo.

Revisit 18F-fluorodeoxyglucose oncology positron emission tomography: "systems molecular imaging" of glucose metabolism.

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography has become an important tool for detection, staging and management of many types of cancer. Oncology application of 18F-FDG bases on the knowledge that increase in glucose demand and utilization is a fundamental features of cancer. Pasteur effect, Warburg effect and reverse Warburg effect have been used to explain glucose metabolism in cancer. 18F-FDG accumulation in cancer is reportedly microenvironment-dependent, 18F-FDG avidly accumulates in poorly proliferating and hypoxic cancer cells, but low in well perfused (and proliferating) cancer cells. Cancer is a heterogeneous and complex "organ" containing multiple components, therefore, cancer needs to be investigated from systems biology point of view, we proposed the concept of "systems molecular imaging" for much better understanding systems biology of cancer.This article revisits 18F-FDG uptake mechanisms, its oncology applications and the role of 18F-FDG PET for "systems molecular imaging".

Evaluation of (99) (m)TcN-MPO as a new myocardial perfusion imaging agent in normal dogs and in an acute myocardial infarction canine model: comparison with (99) (m)Tc-sestamibi.

PURPOSE: (99) (m)TcN-MPO ([(99) (m)TcN(mpo)(PNP5)](+): mpo = 2-mercaptopyridine oxide and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a cationic (99) (m)Tc-nitrido complex, which has favorable biodistribution and myocardial uptake with rapid liver clearance in Sprague Dawley rats. The objective of this study was to compare the biodistribution and pharmacokinetics of (99) (m)TcN-MPO and (99) (m)Tc-Sestamibi in normal dogs, and to evaluate the potential of (99) (m)TcN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction. METHODS: Five normal mongrel dogs were injected intravenously with (99) (m)TcN-MPO. Venous blood samples were collected via a femoral vein catheter at 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 60, and 90 min post-injection (p.i.). Anterior-posterior planar images were acquired by γ-camera at 10, 20, 30, 60, 90, and 120 min p.i. Regions of interest (ROIs) were drawn around the heart, liver, and lungs. The heart/liver and heart/lung ratios were calculated by dividing the mean counts in heart ROI by the mean counts in the liver and lung ROI, respectively. For comparison, (99) (m)Tc-sestamibi was also evaluated in the same five dogs. The interval period between the two examinations was 1 week to eliminate possible interference between these two radiotracers. In addition, single positron emission computed tomography (SPECT) images in the canine infarct model were collected 24 h after myocardial infarction at 30 and 60 min after the administration of (99) (m)TcN-MPO (n = 4) or (99) (m)Tc-Sestamibi (n = 4). RESULTS: It was found that (99) (m)TcN-MPO and (99) (m)Tc-Sestamibi displayed very similar blood clearance characteristics during the first 90 min p.i. Both (99) (m)TcN-MPO and (99) (m)Tc-Sestamibi had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min and less than 5% at 30 min p.i. (99) (m)TcN-MPO and (99) (m)Tc-Sestamibi both showed good heart/lung contrast. The heart/liver ratio of (99) (m)TcN-MPO increased with time (0.53 ± 0.06 at 10 min, 0.90 ± 0.062 at 30 min, and 1.22 ± 0.06 at 60 min p.i.), whereas the heart/liver ratio of (99) (m)Tc-Sestamibi remained low at all time points (0.50 ± 0.03 at 10 min, 0.64 ± 0.03 at 30 min, and 0.60 ± 0.02 at 60 min p.i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of (99) (m)TcN-MPO but not after (99) (m)Tc-Sestamibi. CONCLUSION: The combination of reasonable heart uptake with rapid hepatobiliary excretion makes (99) (m)TcN-MPO a promising new radiotracer for myocardial perfusion imaging.