Noninvasive electrocardiographic imaging of dynamic atrioventricular delay programming in a patient with left bundle branch block

Introduction The response to cardiac resynchronization therapy (CRT) is determined by various factors, including left ventricular (LV) lead location, atrioventricular (AV) delay, and inter-/intraventricular delays. Advances in quadripolar lead technology and device algorithms have improved patient response, yet selection of optimal settings remains challenging. Studies have shown acute improvement in electrical synchrony with manual AV optimization by fusion optimized intervals1,2; automated device algorithms, for example AdaptivCRT (Medtronic, Minneapolis, MN),3 SmartDelay (Boston Scientific, Marlborough, MA),4 and SyncAVTM (Abbott, Sylmar, CA)5; and pacing from multiple LV lead electrodes with MultiPoint Pacing (MPP).6,7 The aim of this clinical case report was to evaluate the acute benefits of SyncAV Plus in the new-generation, Bluetooth-enabled GallantTM CRT device (Abbott, Sylmar, CA). SyncAV Plus continually programs the paced AV delay shorter than the intrinsic PR interval by a programmable offset (% of PR duration) to synchronize intrinsic and ventricular paced activation wavefronts. Twelve-lead electrocardiogram (ECG) and noninvasive electrocardiographic imaging (ECGi) epicardial mapping analyses were performed to characterize the impact of SyncAV Plus on electrical synchrony during a range of CRT programming strategies, including biventricular (BiV) pacing, MPP, LV-only pacing, and LV-only pacing with MPP

Chronic subclinical inflammation after phakic intraocular lenses implantation: Comparison between Artisan and Artiflex models

Purpose To compare chronic subclinical inflammation induced after implantation of Artisan vs. Artiflex phakic intraocular lenses (pIOLs). Methods This prospective, comparative, non-randomized study included consecutive patients with moderate to high myopia who underwent Artisan or Artiflex pIOL implantation with standard surgery and postoperative care. Anterior chamber flare was assessed quantitatively using laser flare photometry (LFP) at baseline, 1 week, 1 month, 3 months, 6 months, and 2 years after surgery. Results PIOLs were implanted in 72 eyes (40 patients); Artisan pIOLs in 16 eyes (Artisan group) and Artiflex pIOLs in 56 eyes (Artiflex group). The mean preoperative anterior chamber flare was 6.5 ± 2.3 (range, 4.2�9.5) photons per millisecond (ph/ms) and 4.2 ± 0.9 (range, 2.5�11.7) ph/ms in Artisan and Artiflex groups, respectively (P = 0.400). In spite of early postoperative rise, the flare value returned to preoperative levels 6 months after pIOL implantation and remained stable up to 2 years. The amount of flare was not statistically different between Artisan and Artiflex groups in any postoperative follow-up (all P > 0.05). The trend in flare changes was not different between the studied groups (ANCOVA, P = 0.815). Conclusion The inflammatory response induced by implantation of either type of Artisan and Artiflex pIOLs is short-lived without statistically significant difference between the two models. © 2017 Iranian Society of Ophthalmolog

Tracking preleukemic cells in vivo to reveal the sequence of molecular events in radiation leukemogenesis

Epidemiological studies have demonstrated an increased leukemia incidence following ionizing radiation exposure, but to date, the target cells and underlying mechanisms of radiation leukemogenesis remain largely unidentified. We engineered a mouse model carrying a different fluorescent marker on each chromosome 2, located inside the minimum deleted region occurring after radiation exposure and recognized as the first leukemogenic event. Using this tailored model, we report that following radiation exposure, more than half of asymptomatic CBA Sfpi1GFP/mCh mice presented with expanding clones of preleukemic hematopoietic cells harboring a hemizygous interstitial deletion of chromosome 2. Moreover, following isolation of preleukemic hematopoietic stem and progenitor cells irradiated in their native microenvironment, we identified the presence of Sfpi1 point mutations within a subpopulation of these preleukemic cells expanding rapidly (increasing from 6% to 55% in 21 days in peripheral blood in one case), hence identifying for the first time the presence of such cells within a living animal. Importantly, we also report a previously undescribed gender difference in the phenotype of the preleukemic cells and leukemia, suggesting a gender imbalance in the radiation-induced leukemic target cell. In conclusion, we provide novel insights into the sequence of molecular events occurring during the (radiation-induced) leukemic clonal evolution

Comparison of established and emerging biodosimetry assays

Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools

Long term conservation of electrical synchrony by multipoint pacing with dynamic atrioventricular delays

Introduction Automatic adjustment of atrioventricular delay (AVD) with SyncAV has been shown to improve electrical synchronization. However, the long term effects of SyncAV optimization on electrical synchrony are unknown. Purpose Evaluate the effect of SyncAV programming on 6-month (6mo) QRS duration during biventricular (BiV) and left ventricle only MultiPoint Pacing (MPP). Methods Patients with LBBB and QRS duration (QRSd) ≥ 150 ms scheduled for CRT-P/D device implantation with quadripolar LV lead were enrolled in this prospective study. QRSd was measured post-implant from 12-lead surface ECG by blinded experts during the following pacing modes: intrinsic conduction, MPP (MPP=RV+LV1+LV2) and LV-only MPP (LVMPP=LV1+LV2). For each mode, SyncAV was enabled (e.g. MPP+SyncAV) with the patient-tailored SyncAV offset that minimized QRSd. Patients were then randomized 1:1 to receive MPP+SyncAV or LVMPP+SyncAV with the optimal offset identified at implant, and QRSd was re-evaluated at the 6mo follow-up. Results Fifty-nine patients (72% male, 41% ischemic, 26% ejection fraction, 166 ms intrinsic QRSd) completed device implant and QRSd assessment. Relative to intrinsic conduction at implant, the MPP+SyncAV group (n=30) had a QRSd reduction of 26% at implant (162 to 122 ms, p<0.001), and 20% at 6mo (162 to 130 ms, p<0.001). The LVMPP+SyncAV group (n=29) had a QRSd reduction of 24% at implant (165 to 128 ms, p<0.001), and 15% at 6mo (165 to 140 ms, p<0.001). In the MPP+SyncAV group, 28/30 (93%) of patients had more than 10% reduction in QRSd with respect to intrinsic at implant, with 27/30 (90%) maintaining this trend at 6 mo follow up. With LVMPP+SyncAV pacing, only 25/29 (86%) of patients had more than 10% reduction in QRSd with respect to intrinsic at implant, and this reduced to 18/29 (62%) maintaining this trend at 6 mo follow up. Conclusion MPP combined with SyncAV significantly improved acute electrical synchrony at implant in CRT patients with LBBB, as assessed by QRSd reduction. Significant QRSd reduction was maintained at 6 months post-implant by both biventricular and LV-only MPP configurations

Study of the impacts of droplets deposited from the gas core onto a gas-sheared liquid film

The results of an experimental study on droplet impactions in the flow of a gas-sheared liquid film are presented. In contrast to most similar studies, the impacting droplets were entrained from film surface by the gas stream. The measurements provide film thickness data, resolved in both longitudinal and transverse coordinates and in time together with the images of droplets above the interface and images of gas bubbles entrapped by liquid film. The parameters of impacting droplets were measured together with the local liquid film thickness. Two main scenarios of droplet-film interaction, based on type of film perturbation, are identified; the parameter identifying which scenario occurs is identified as the angle of impingement. At large angles an asymmetric crater appears on film surface; at shallow angles a long, narrow furrow appears. The most significant difference between the two scenarios is related to possible impact outcome: craters may lead to creation secondary droplets, whereas furrows are accompanied by entrapment of gas bubbles into the liquid film. In addition, occurrence of partial survival of impacting droplet is reported

Hypothesis: are neoplastic macrophages/microglia present in glioblastoma multiforme?

Most malignant brain tumours contain various numbers of cells with characteristics of activated or dysmorphic macrophages/microglia. These cells are generally considered part of the tumour stroma and are often described as TAM (tumour-associated macrophages). These types of cells are thought to either enhance or inhibit brain tumour progression. Recent evidence indicates that neoplastic cells with macrophage characteristics are found in numerous metastatic cancers of non-CNS (central nervous system) origin. Evidence is presented here suggesting that subpopulations of cells within human gliomas, specifically GBM (glioblastoma multiforme), are neoplastic macrophages/microglia. These cells are thought to arise following mitochondrial damage in fusion hybrids between neoplastic stem cells and macrophages/microglia

Dicentric Dose Estimates for Patients Undergoing Radiotherapy in the RTGene Study to Assess Blood Dosimetric Models and the New Bayesian Method for Gradient Exposure.

The RTGene study was focused on the development and validation of new transcriptional biomarkers for prediction of individual radiotherapy patient responses to ionizing radiation. In parallel, for validation purposes, this study incorporated conventional biomarkers of radiation exposure, including the dicentric assay. Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumors. For the dicentric assay, two samples were taken from each patient: prior to radiotherapy and before the final fraction. Blood samples were set up using standard methods for the dicentric assay. All the baseline samples had dicentric frequencies consistent with the expected background for the normal population. For blood taken before the final fraction, all the samples displayed distributions of aberrations, which are indicative of partial-body exposures. Whole-body and partial-body cytogenetic doses were calculated with reference to a 250-kVp X-ray calibration curve and then compared to the dose to blood derived using two newly developed blood dosimetric models. Initial comparisons indicated that the relationship between these measures of dose appear very promising, with a correlation of 0.88 (P = 0.001). A new Bayesian zero-inflated Poisson finite mixture method was applied to the dicentric data, and partial-body dose estimates showed no significant difference (P > 0.999) from those calculated by the contaminated Poisson technique. The next step will be further development and validation in a larger patient group