Differentiating wide complex tachycardias: A historical perspective

One of the most critical and challenging skills is the distinction of wide complex tachycardias into ventricular tachycardia or supraventricular wide complex tachycardia. Prompt and accurate differentiation of wide complex tachycardias naturally influences short- and long-term management decisions and may directly affect patient outcomes. Currently, there are many useful electrocardiographic criteria and algorithms designed to distinguish ventricular tachycardia and supraventricular wide complex tachycardia accurately; however, no single approach guarantees diagnostic certainty. In this review, we offer an in-depth analysis of available methods to differentiate wide complex tachycardias by retrospectively examining its rich literature base - one that spans several decades

Wide complex tachycardia differentiation: A reappraisal of the state-of-the-art

The primary goal of the initial ECG evaluation of every wide complex tachycardia is to determine whether the tachyarrhythmia has a ventricular or supraventricular origin. The answer to this question drives immediate patient care decisions, ensuing clinical workup, and long-term management strategies. Thus, the importance of arriving at the correct diagnosis cannot be understated and has naturally spurred rigorous research, which has brought forth an ever-expanding abundance of manually applied and automated methods to differentiate wide complex tachycardias. In this review, we provide an in-depth analysis of traditional and more contemporary methods to differentiate ventricular tachycardia and supraventricular wide complex tachycardia. In doing so, we: (1) review hallmark wide complex tachycardia differentiation criteria, (2) examine the conceptual and structural design of standard wide complex tachycardia differentiation methods, (3) discuss practical limitations of manually applied ECG interpretation approaches, and (4) highlight recently formulated methods designed to differentiate ventricular tachycardia and supraventricular wide complex tachycardia automatically

Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for >10 years. Better understanding the molecular characteristics of the pancreatic adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for personalized medicine and improve current pancreatic cancer treatment. To extend our previous investigation, we examined the proteomes of individual pancreas tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival <14 months). With a given analytical sensitivity, the protein profile of each pancreatic tumor tissue was compared to reveal the proteome alterations that may be associated with pancreatic cancer survival. Pathway analysis of the differential proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated proteins, and VEGFA, APOE and TGFβ-1 were the top three upstream regulators for the VLTS-associated proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition, galectin-1, a previously identified protein with its abundance aversely associated with pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of galectin-1 in pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP, LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and LGALS1 could be potential therapeutic targets to improve pancreatic cancer survival if further validated

Automatic wide complex tachycardia differentiation using mathematically synthesized vectorcardiogram signals

BACKGROUND: Automated wide complex tachycardia (WCT) differentiation into ventricular tachycardia (VT) and supraventricular wide complex tachycardia (SWCT) may be accomplished using novel calculations that quantify the extent of mean electrical vector changes between the WCT and baseline electrocardiogram (ECG). At present, it is unknown whether quantifying mean electrical vector changes within three orthogonal vectorcardiogram (VCG) leads (X, Y, and Z leads) can improve automated VT and SWCT classification. METHODS: A derivation cohort of paired WCT and baseline ECGs was used to derive five logistic regression models: (i) one novel WCT differentiation model (i.e., VCG Model), (ii) three previously developed WCT differentiation models (i.e., WCT Formula, VT Prediction Model, and WCT Formula II), and (iii) one all-inclusive model (i.e., Hybrid Model). A separate validation cohort of paired WCT and baseline ECGs was used to trial and compare each model\u27s performance. RESULTS: The VCG Model, composed of WCT QRS duration, baseline QRS duration, absolute change in QRS duration, X-lead QRS amplitude change, Y-lead QRS amplitude change, and Z-lead QRS amplitude change, demonstrated effective WCT differentiation (area under the curve [AUC] 0.94) for the derivation cohort. For the validation cohort, the diagnostic performance of the VCG Model (AUC 0.94) was similar to that achieved by the WCT Formula (AUC 0.95), VT Prediction Model (AUC 0.91), WCT Formula II (AUC 0.94), and Hybrid Model (AUC 0.95). CONCLUSION: Custom calculations derived from mathematically synthesized VCG signals may be used to formulate an effective means to differentiate WCTs automatically

Resistance to Adenovirally Induced Hyperleptinemia in Rats

Leptin regulates appetite and body weight via hypothalamic targets, but it can act directly on cultured pancreatic islets to regulate their fat metabolism. To obtain in vivo evidence that leptin may act peripherally as well as centrally, we compared the effect of adenovirally induced hyperleptinemia on food intake, body weight, and islet fat content in ventromedial hypothalamic-lesioned (VMHL) rats, shamlesioned (SL) controls, and Zucker Diabetic Fatty (ZDF) rats in which the leptin receptor is mutated. Infusion with recombinant adenovirus containing the rat leptin cDNA increased plasma leptin by z 20 ng/ml in VMHL and ZDF rats but had no effect on their food intake, body weight, or fat tissue weight. Caloric matching of hyperphagic VMHL rats to SL controls did not reduce their resistance to hyperleptinemia. Whereas prediabetic ZDF rats had a fourfold elevation in islet fat, in VMHL rats islet fat was normal and none of them became diabetic. Isolated islets from ZDF rats were completely resistant to the lipopenic action of leptin, while VMHL islets exhibited 50% of the normal response; caloric matching of VMHL rats to SL controls increased leptin responsiveness of their islets to 92% of controls. We conclude that leptin regulation of adipocyte fat requires an intact VMH but that islet fat content is regulated independently of the VMH. ( J. Clin. Invest. 1998. 102:728–733.

Resistance to Adenovirally Induced Hyperleptinemia in Rats

Leptin regulates appetite and body weight via hypothalamic targets, but it can act directly on cultured pancreatic islets to regulate their fat metabolism. To obtain in vivo evidence that leptin may act peripherally as well as centrally, we compared the effect of adenovirally induced hyperleptinemia on food intake, body weight, and islet fat content in ventromedial hypothalamic-lesioned (VMHL) rats, shamlesioned (SL) controls, and Zucker Diabetic Fatty (ZDF) rats in which the leptin receptor is mutated. Infusion with recombinant adenovirus containing the rat leptin cDNA increased plasma leptin by z 20 ng/ml in VMHL and ZDF rats but had no effect on their food intake, body weight, or fat tissue weight. Caloric matching of hyperphagic VMHL rats to SL controls did not reduce their resistance to hyperleptinemia. Whereas prediabetic ZDF rats had a fourfold elevation in islet fat, in VMHL rats islet fat was normal and none of them became diabetic. Isolated islets from ZDF rats were completely resistant to the lipopenic action of leptin, while VMHL islets exhibited 50% of the normal response; caloric matching of VMHL rats to SL controls increased leptin responsiveness of their islets to 92% of controls. We conclude that leptin regulation of adipocyte fat requires an intact VMH but that islet fat content is regulated independently of the VMH. ( J. Clin. Invest. 1998. 102:728–733.

Process evaluation for complex interventions in primary care: understanding trials using the normalization process model

Background: the Normalization Process Model is a conceptual tool intended to assist in understanding the factors that affect implementation processes in clinical trials and other evaluations of complex interventions. It focuses on the ways that the implementation of complex interventions is shaped by problems of workability and integration.Method: in this paper the model is applied to two different complex trials: (i) the delivery of problem solving therapies for psychosocial distress, and (ii) the delivery of nurse-led clinics for heart failure treatment in primary care.Results: application of the model shows how process evaluations need to focus on more than the immediate contexts in which trial outcomes are generated. Problems relating to intervention workability and integration also need to be understood. The model may be used effectively to explain the implementation process in trials of complex interventions.Conclusion: the model invites evaluators to attend equally to considering how a complex intervention interacts with existing patterns of service organization, professional practice, and professional-patient interaction. The justification for this may be found in the abundance of reports of clinical effectiveness for interventions that have little hope of being implemented in real healthcare setting

Investigation of biochemical biorefinery sizing and environmental sustainability impacts for conventional bale system and advanced uniform biomass logistics designs

The 2011 US Billion-Ton Update1 estimates that there are enough agricultural and forest resources to sustainably provide enough biomass to displace approximately 30% of the country’s current petroleum consumption. A portion of these resources are inaccessible at current cost targets with conventional feedstock supply systems because of their remoteness or low yields. Reliable analyses and projections of US biofuels production depend on assumptions about the supply system and biorefinery capacity, which, in turn, depend on economics, feedstock logistics, and sustainability. A cross-functional team has examined optimal combinations of advances in feedstock supply systems and biorefinery capacities with rigorous design information, improved crop yield and agronomic practices, and improved estimates of sustainable biomass availability. Biochemical-conversion-to-ethanol is analyzed for conventional bale-based system and advanced uniform-format feedstock supply system designs. The latter involves ‘pre-processing’ biomass into a higher-density, aerobically stable, easily transportable format that can supply large-scale biorefineries. Feedstock supply costs, logistics and processing costs are analyzed and compared, taking into account environmental sustainability metrics