Delayed detection of ventricular tachycardia due to intradevice interactions by implantable atrio-ventricular pacer/cardioverter defibrillator

Current generations of implantable cardioverter defibrillators are capable of providing sophisticated dual chamber atrioventricular and rate-responsive pacing therapies, and even cardiac resynchronization therapy. Appropriate programming of the devices is necessary for them to perform all such sophisticated tasks. In this report, we describe a case where detection of ventricular tachycardia was delayed due to intradevice interactions between the pacemaker and defibrillator components of the device.     

Digital microfluidic assay for protein detection

Global studies of the human proteome have revealed a plethora of putative protein biomarkers. However, their application for early disease detection remains at a standstill without suitable methods to realize their utility in the clinical setting. There thus continues to be tremendous interest in developing new technology for sensitive protein detection that is both low in cost and carries a small footprint to be able to be used at the point of care. The current gold standard method for protein biomarker detection is the ELISA, which measures protein abundance using bulky fluorescent scanners that lack portability. Here, we present a digital microfluidic platform for protein biomarker detection that is low in cost compared with standard optical detection methods, without any compromise in sensitivity. This platform furthermore makes use of simple electronics, enabling its translation into a portable handheld device, and has been developed in a manner that can easily be adapted to assay different types of proteomic biomarkers. We demonstrate its utility in quantifying not only protein abundance, but also activity. Interleukin-6 abundance could be assayed from concentrations as low as 50 pM (an order of magnitude lower than that detectable by a comparable laboratory designed ELISA) using less than 5 μL of sample, and Abelson tyrosine kinase activity was detectable in samples containing 100 pM of kinase.Recent decades of research have shown that the molecular mechanisms underlying human disease are much more complex than originally appreciated, with one or more rare genetic events often playing key roles in the transformation of a normal cell into a diseased cell. Not surprisingly, the diagnosis and treatment of many human diseases continue to struggle from the use of simplified models that are based on a handful of highly expressed biomarkers. Thanks to recent advances in microarray and next-generation sequencing technologies, a steadily increasing number of complete genomes have been sequenced, and considerable progress has been made using genomic biomarkers to better personalize healthcare. However, the ability to provide complete personalized healthcare demands the ability to monitor genetic biomarkers as well as protein biomarkers, and the development of proteomic technologies suitable for analyzing human samples has lagged considerably behind.To be well suited as a clinical diagnostic, a proteomic technology must be sensitive enough to detect endogenous levels of low abundance proteins, require low sample volumes, have a short assay time, and ideally be portable as to allow informed treatment decisions to be made at the point of care. Microfluidics, with its inherent advantages of low sample and reagent volumes, multiplex and automated capabilities, and precise control over the microenvironment, has emerged as a promising operation platform with which to develop sensitive proteomic technologies. Several groups have used microfluidic sandwich immunoassays and enzymatic assays to demonstrate improvements in assay cost (1), amount of reagents and the starting sample needed (2, 3), assay times (4), and, most importantly, sensitivity (5–10). However, to move away from “chips in labs” and to develop true “lab on a chip” technologies that can potentially be portable and even handheld, it is necessary to both miniaturize the fluidics and minimize the footprint of the instrumentation as a whole. Such miniaturization can be accomplished by scaling down the optical readout instrumentation, but also by using electronic detection, which offers the added benefit of being low in cost (11). To date, several attempts at label-free electronic detection, such as detection based on impedance spectroscopy at the surface of microelectrodes (12), capacitive sensing-based approaches (13–15), and field affect transistor-based approaches (16), have been made with varying success. The main challenge with these approaches is the requirement for operation in low salt concentrations. High salt concentrations screen any field emitted from charged macromolecules, such as proteins, making the device unsuitable for analyzing complex biological mixtures like serum, which have salt concentrations in the range of several hundred millimolar. In addition, alternative methods to optical and electrical detection, such as magnetic detection, have also been explored. For example, much promise has been shown in achieving matrix-independent protein detection using nanomagnetic tags together with magnetic-sensing techniques such as giant magnetoresistive (GMR) sensing (17) and Hall sensing (18).Traditional affinity-based protein biosensors, such as those described above, typically work by immobilizing a specific probe molecule onto an active transducing region and are therefore designed such that the capture/reaction and detection steps are coupled to one other. This coupled architecture is limiting in sensitivity as the constraints for designing an optimal capture/reaction chamber inherently contradict with that for an optimal detection chamber. For example, increasing the area of the capture/reaction chamber will increase the sensitivity of the transducer but decrease the rate at which target molecules are captured. Conversely, decreasing the area of the capture/reaction chamber will increase the rate at which target molecules are captured but decrease the sensitivity of the transducer.We set out to develop a digital proteomic technology that has the potential to be more sensitive than existing microfluidic platforms. Our technology builds on a bead-based immunoassay involving bulk electrical impedance measurement of beads (19) but uniquely embodies a decoupled architecture in which the capture/reaction and detection steps are physically separated and thus able to be independently optimized. This decoupled architecture allows us to interrogate a surface several thousand squared micrometers in area and still maintain single bead detection. Here, we demonstrate the feasibility and implementation of this technology as a method to assay both protein abundance using the human cytokine interleukin 6 (IL-6) and enzyme activity using the human tyrosine Abelson (Abl) kinase.     

Improving sensing and detection performance in subcutaneous monitors

Implantable loop recorders (ILRs) are used for continuous assessment of patients at risk for syncope and arrhythmia. Device accuracy depends on appropriate sensing of the patient's electrocardiogram (ECG) signal. However, current methods for sensing cardiac electrical activity rely on simple threshold detectors that are computationally efficient but nonspecific.We test the hypothesis that better ILR implant positions will increase detection accuracy. Ten healthy subjects were studied as they assumed 12 different postures. Body surface potential map (BSM) recordings were used to estimate bipolar R-wave amplitudes for 64 potential implant sites at 360 orientations per site. Optimal sites were identified as the combination of position and orientation that consistently gave the largest signal and the lowest variability during posture changes.Results showed that posture impacts the R-wave amplitude in both BSM and derived bipolar ECGs in healthy subjects. Specific postures are associated with significant drops in R-wave signal amplitude that could cause loss of signal detection in ILRs, especially in positions likely to displace the diaphragm. R-wave changes occurred abruptly as posture was changed. Optimal implant locations cluster near the center of the chest, aligned with the cardiac axis, consistent with the steeper isoelectric gradients known to be associated with these positions.     

Digital fluorographs for early detection and diagnosis of pulmonary tuberculosis

Under the conditions of out health care system it is best to install first small-dose digital fluorographs at urban polyclinics and use as movable plants. The basis of a diagnostic study of pulmonary tuberculosis is to monitor X-ray changes in the process by a series of X-ray images and tomographic scans. At the same time paper imprints obtained by printers (including laser ones) lose as much as 30% of image details so computer images rather than hard paper copies should be used for comparison in practice of the X-ray units of dispensaries. Computers are required for dispensaries: for each X-ray specialist, the head of a unit, deputy head physician in therapeutics so that the use of a digital fluorographic plant should be as much as effective.     

Permutations in pacer wire implantation in patients evaluated for transcatheter tricuspid valve interventions

Pacer wire induced tricuspid regurgitation is not well-understood. The mechanisms behind pacer wired induced tricuspid regurgitation have not been clearly defined. This clinical vignette sets to identify different technical mechanisms behind cardiac lead induced tricuspid regurgitation to help optimize cardiac lead implantation strategies for future device implantation.     

Digital radiography of the chest: detector techniques and performance parameters

Substantial advances in detector technology characterize digital chest radiography. This article compares the various systems from a radiologist's point of view. Computed radiography (CR) is a well-established system that is robust, has good reproducibility, and is relatively inexpensive. Image quality has been continuously improved in recent years while the physical size of the readout units has been reduced and the throughput increased. CR is the only digital system that can be used for bedside chest radiographs. Improved detector properties and dual reading have made it a dose-efficient system. Although now widely available, a 4K image matrix does not appear to offer a general diagnostic improvement for imaging the chest. New developments with respect to detector composition and readout process can be expected in the future. Direct radiography (DR) is the common name for different technologies that are characterized by a direct readout matrix that covers the whole exposure area. Conversion of x-ray intensity into electric signals can either be direct (selenium-based systems) or indirect (scintillator/photodiode systems). Advantages of DR systems are a high image quality and the potential for dose reduction. The role of selenium radiography (Thoravision) has decreased after the advent of DR systems although this dedicated chest unit offers high image quality at 400 speed acquisition dose. Especially in a PACS environment, CR and DR systems will increasingly substitute for conventional radiography with advantages for CR for bedside chest radiographs and for DR for high-end chest stands.     

Head-to-head comparison of arrhythmia discrimination performance of subcutaneous and transvenous ICD arrhythmia detection algorithms: the START study

Arrhythmia Detection with S‐ICD Versus Transvenous ICDs. Background: The development of a totally subcutaneous implantable defibrillator (S‐ICD) system requires a new approach for arrhythmia detection. To evaluate arrhythmia discrimination of one such system, the Subcutaneous versus Transvenous Arrhythmia Recognition Testing (START) study was designed as a prospective, multicenter trial comparing simulated sensing performances of the S‐ICD system with single‐ (SC‐TV) and dual‐chamber transvenous (DC‐TV) implantable cardioverter‐defibrillator (ICD) systems. Methods: At ICD implantation, induced ventricular and atrial arrhythmias were recorded simultaneously in transvenous (right ventricular [RV]→superior vena cava [SVC]+ Coil) and cutaneous electrode configurations. Recorded signals of ventricular (n = 46) and atrial arrhythmias (n = 50) with ventricular rates >170 bpm from 64 patients were used to compare detection performance of the S‐ICD system with TV‐ICD systems from 3 manufacturers. Appropriate detection of ventricular tachyarrhythmias was assessed with devices programmed in single‐zone (rate ≥170 bpm) and dual‐zone configurations (ventricular fibrillation ≥240 bpm; ventricular tachycardia ≥170 bpm). S‐ICD specificity performance for supraventricular arrhythmias was compared to single‐ and dual‐chamber devices in a dual‐zone configuration. Results: Appropriate detection of ventricular tachyarrhythmias for subcutaneous and TV devices in single‐ and dual‐zone configurations was 100% and >99%, respectively. Specificity for supraventricular arrhythmias was significantly better for the S‐ICD system compared to 2 of 3 TV systems, as well as the composite of TV devices (98.0%[S‐ICD] vs 76.7%[SC‐TV range: 64.0–92.0%] vs 68.0%[DC‐TV range: 32.7–89.8%; P < 0.001]). Conclusion: Appropriate ventricular arrhythmia detection is excellent for all ICD systems evaluated; however, specificity of supraventricular arrhythmia discrimination by the S‐ICD system is better than discrimination by 2 of 3 TV systems.     

A proficiency testing study to evaluate laboratory performance for the detection of different genotypes of parvovirus B19

Background and Objectives  In Europe, it is a regulatory requirement that parvovirus B19 (B19V) DNA nucleic acid amplification technique-based testing is performed on plasma pools for certain classes of plasma-derived medicinal products. This proficiency testing study set out to examine the ability of public quality control laboratories and plasma fractionation organizations to detect different genotypes of B19V using nucleic acid amplification technique-based assays.
Materials and Methods  Laboratories were supplied with cloned DNAs representing the main genotypes of B19V. All samples were adjusted to equivalent copy number and were distributed as part of a routine external quality assessment programme investigating the evaluation of B19V containing plasma samples by these laboratories. The plasmid clones were distributed to 25 laboratories, representing 13 quality control laboratories and 12 manufacturers of plasma derivatives. The criteria for acceptable detection of the different genotypes of B19V DNA was based upon the maximum theoretical efficiency for polymerase chain reaction amplification. Proficient laboratories were deemed to be those reporting results within 1 log₁₀ dilution for each of the different virus genotypes.
Results  Data were returned by 23 of the participating laboratories. Some laboratories returned data for more than one type of assay and in total 27 data sets were analysed. Nine of the participating laboratories were able to successfully detect all the virus genotypes according to the applied criteria, all except one used in-house assays.
Conclusions  The results of the study highlight that there are still discrepancies in the detection of a broad spectrum of B19V genotypes, with implications for batch release testing.     

Impact of external quality assessment on antinuclear antibody detection performance

Our objective was to evaluate performance of the clinical laboratories for the detection of antinuclear antibodies (ANA) by using indirect immunofluorescence method (IIF), in France. A national external quality assessment (EQA) on ANA detection was organized by the French health products safety agency once a year since 1998. Between 606 to 687 laboratories together with six university reference laboratories experienced in performing tests in autoimmunity participated in the six-year consecutive survey. Each laboratory had to answer to methodological procedures and give coded responses. Variability in IIF methodological procedure was observed. Use of inappropriate microscope magnifications for reading slides or nonconventional cutoff dilution of serum were pointed out to concerned laboratories. Concerning ANA measurement, the rate of good responses ranged from 92.7% to 99.5% of the laboratories when the samples contained ANA. A wide dispersion of ANA titers obtained on a same sample was repeatly observed every year. Misinterpretation of particular fluorescence pattern was noticed. On ANA negative sample, the rate of good responses was 94.3%. In conclusion, ANA detection in routine practice is far from being standardized. However, EQA may have an impact on ANA detection performance when it is conducted on several consecutive year surveys, by providing advice for participating laboratories to limit inter laboratory variations related to methodological procedures.     

Computed tomographic colonography: assessment of radiologist performance with and without computer-aided detection

BACKGROUND & AIMS: In isolation, computer-aided detection (CAD) for computed tomographic (CT) colonography is as effective as optical colonoscopy for detection of significant adenomas. However, the unavoidable interaction between CAD and the reader has not been addressed. METHODS: Ten readers trained in CT but without special expertise in colonography interpreted CT colonography images of 107 patients (60 with 142 polyps), first without CAD and then with CAD after temporal separation of 2 months. Per-patient and per-polyp detection were determined by comparing responses with known patient status. RESULTS: With CAD, 41 (68%; 95% confidence interval [CI], 55%-80%) of the 60 patients with polyps were identified more frequently by readers. Per-patient sensitivity increased significantly in 70% of readers, while specificity dropped significantly in only one. Polyp detection increased significantly with CAD; on average, 12 more polyps were detected by each reader (9.1%, 95% CI, 5.2%-12.8%). Small- (< or =5 mm) and medium-sized (6-9 mm) polyps were significantly more likely to be detected when prompted correctly by CAD. However, overall performance was relatively poor; even with CAD, on average readers detected only 10 polyps (51.0%) > or =10 mm and 24 (38.2%) > or =6 mm. Interpretation time was shortened significantly with CAD: by 1.9 minutes (95% CI, 1.4-2.4 minutes) for patients with polyps and by 2.9 minutes (95% CI, 2.5-3.3 minutes) for patients without. Overall, 9 readers (90%) benefited significantly from CAD, either by increased sensitivity and/or by reduced interpretation time. CONCLUSIONS: CAD for CT colonography significantly increases per-patient and per-polyp detection and significantly reduces interpretation times but cannot substitute for adequate training.     

毛细管电泳与高效液相色谱法在Hb Q-Thailand检测中的比较研究

目的了解毛细管电泳(CE)与高效液相色谱法(HPLC)在Hb Q-Thailand检测中的差异。方法收集10例CE筛查出的可疑Hb Q-Thailand,经地贫基因分析和DNA测序确诊后,再用HPLC检测比对。结果 10例样本中CE均检出Hb Q-Thailand和Hb Q-Thailand A2(Hb QA2),而HPLC仅检出10例Hb QThailand和5例Hb QA2,而且HPLC错误检出Hb Q-H病1例存在Hb A2。CE和HPLC检出Hb Q-Thailand、Hb A2、Hb QA2的含量分别为(34.41±21.10)%、(1.68±0.57)%、(0.77±0.10)%和(31.72±21.46)%、(2.43±0.22)%、(0.24±0.24)%,两组Hb Q-Thailand差异无统计学意义(P0.05),Hb A2和Hb QA2的差异有统计学意义(P0.01)。结论 CE在检测Hb Q-Thailand中优于HPLC。