Prognostic Value of High-Sensitivity Troponin T After On-Pump Coronary Artery Bypass Graft Surgery.

INTRODUCTION: High-sensitivity troponin T (hs-TnT), as a single or serial measurement to predict postoperative mortality and morbidity, appears to be attractive due to its direct relationship in assessing myocardial damage and the widespread availability of hs-TnT testing. Therefore, this study aimed to identify any prognostic value of hs-TnT in predicting in-hospital outcomes after coronary artery bypass graft (CABG) surgery. METHOD: We identified all consecutive patients who underwent on-pump CABG between July 2011 and December 2018. To evaluate the prognostic value of hs-TnT after CABG, we assessed the probability and odds ratio (OR) of adverse events concerning the maximum value of postoperative hs-TnT (measured within 24 hrs). TnT was routinely collected at 0, 6, 12 and 72 hours postoperatively. Values were categorised into intervals of 200 for analysis. A fully Bayesian logistic regression of the adverse event with the troponin T interval (0-200) as the reference level was used. A subgroup analysis was performed in patients with normal and elevated preoperative hs-TnT (< or ≥30 ng/L). The pre-specified primary outcome was a major adverse cardiac or cerebrovascular event (MACCE), defined as a composite of death within 30 days of operation for any cause, myocardial infection (MI), or stroke. RESULTS: 1,318 people underwent on-pump CABG during this period. One hundred and twenty-three (123) (9.3%) experienced MACCE, 14 (1.1%) experienced death within 30 days, 105 (8.0%) experienced MI and 14 (1.1%) experienced stroke. Compared to the reference category (hs-TnT ≤200 ng/L) we found there was an increase in OR with increasing level of hs-TnT for MACCE (p<0.001), 30-day mortality (p=0.003), MI (p<0.001) and ICU stay >48 hours (p<0.001). However, there was no statistically significant association present between hs-TnT and stroke, readmission to the intensive care unit (ICU), return to theatre for bleeding, or new-onset renal dysfunction. CONCLUSION: Peak hs-TnT level, greater than 400 ng/L, measured within 24 hours after CABG surgery is associated with MACCE, 30-day mortality, MI and ICU stay >48 hours. Prospectively designed trials, with clear prognostic and outcome variables, may provide further insight into the prognostic value of hs-TnT post-CABG.

Preventive chemotherapy reverses covert, lymphatic-associated tissue change in young people with lymphatic filariasis in Myanmar.

OBJECTIVES: This longitudinal comparative study investigated the effect of preventive chemotherapy (PC) on covert tissue changes associated with lymphatic filariasis (LF) among young people living in an LF-endemic area in Myanmar. METHODS: Tissue compressibility and extracellular free fluid in the lower limbs of people aged 10-21 years were measured using indurometry and bioimpedance spectroscopy (BIS). Baseline measures were taken in October 2014, annual mass drug administration (MDA) of PC was delivered in December, and in March 2015 further PC was offered to LF-positive cases who had missed MDA. Follow-up measures were taken in February and June 2015. RESULTS: A total of 50 antigen-positive cases and 46 antigen-negative controls were included. Self-reported PC consumption was 60.1% during 2014 MDA and 66.2% overall. At second follow-up, 24 of 34 cases and 27 of 43 controls had consumed PC. Significant and clinically relevant between-group differences at baseline were not found post-PC. Bayesian linear mixed models showed a significant change in indurometer scores at both calves for antigen-positive cases who consumed any PC (dominant calf: -0.30 [95% CI -0.52, -0.07], P < 0.05 and non-dominant calf: -0.35 [95% CI -0.58, -0.12], P < 0.01). Changes in antigen-negative participants or those not consuming PC were not significant. CONCLUSION: This study is the first attempt to use simple field-friendly tools to track fluid and tissue changes after treatment of asymptomatic people infected with LF. Results suggested that PC alone is sufficient to reverse covert lymphatic disturbance. Longer follow-up of larger cohorts is required to confirm these improvements and whether they persist over time. These findings should prompt increased efforts to overcome low PC coverage, which misses many infected young people, particularly males, who are unaware of their infection status, unmotivated to take PC and at risk of developing lymphoedema. Indurometry and BIS should be considered in assessment of lymphatic filariasis-related lymphedema.

OBJECTIFS: Cette étude comparative longitudinale a investigué l'effet de la chimiothérapie préventive (CP) sur les modifications tissulaires cachées associées à la filariose lymphatique (FL) chez les jeunes vivant dans une zone d'endémie pour la FL au Myanmar. MÉTHODES: La compressibilité des tissus et le liquide libre extracellulaire dans les membres inférieurs des personnes âgées de 10 à 21 ans ont été mesurés par indurométrie et spectroscopie de bioimpédance (BIS). Les mesures de base ont été prises en octobre 2014, la distribution en masse de médicament (DMM) annuelle a été administrée en décembre et en mars 2015, et une CP additionnelle a été offerte aux cas positifs pour la FL qui avaient manqué la DMM. Des mesures de suivi ont été prises en février et juin 2015. RÉSULTATS: 50 cas positifs pour l'antigène et 46 témoins négatifs ont été inclus. L'administration de CP auto-déclarée était de 60,1% durant la DMM de 2014 et de 66,2% au total. Au deuxième suivi, 24 des 34 cas et 27 des 43 témoins avaient pris la CP. Des différences significatives et cliniquement pertinentes entre les groupes au départ n'ont pas été trouvées après la CP. Les modèles mixtes linéaires bayésiens ont montré un changement significatif des scores d'indurometrie aux deux mollets pour les cas positifs pour l'antigène qui prenaient une CP (mollet dominant: -0,30 [IC95%: -0,52, -0,07], p <0,05, mollet non dominant: - 0,35 [IC95%: -0,58, -0,12], p <0,01). Les changements chez les participants négatifs pour l'antigène ou ceux qui ne prenaient pas de CP n'étaient pas significatifs. CONCLUSION: Cette étude est la première tentative d'utilisation d'outils simples, conviviaux sur le terrain, pour suivre les modifications du tissu conjonctif après le traitement de personnes asymptomatiques infectées par la FL. Les résultats suggèrent que la CP seule est suffisante pour inverser les modifications lymphatiques cachées. Un suivi plus long de plus grandes cohortes est nécessaire pour confirmer ces améliorations et déterminer si elles persistent ou non. Ces résultats devraient inciter à redoubler d'efforts pour surmonter la faible couverture en CP, qui rate beaucoup de jeunes infectés, en particulier les hommes, qui ne sont pas au courant de leur statut d'infection, qui ne sont pas motivés pour prendre une CP et risquent de développer un lymphœdème. L'indurométrie et la BIS devraient être considérées dans l'évaluation du lymphoedème associé à la filariose lymphatique.

Temporal stability and specificity of high bipolar electrogram entropy regions in sustained atrial fibrillation: Implications for mapping.

BACKGROUND: The potential utility of entropy (En) for atrial fibrillation (AF) mapping has been demonstrated in previous studies by multiple groups, where an association between high bipolar electrogram (EGM) entropy and the pivot of rotors has been shown. Though En is potentially attractive new approach to ablation, no studies have examined its temporal stability and specificity, which are critical to the application of entropy to clinical ablation. In the current study, we sought to objectively measure the temporal stability and specificity of bipolar EGM entropy in medium to long term recordings using three studies: i) a human basket catheter AF study, ii) a tachypaced sheep AF study and iii) a computer simulation study. OBJECTIVE: To characterize the temporal dynamics and specificity of Approximate, Sample and Shannon entropy (ApEn/SampEn/ShEn) in human (H), sheep (S), and computer simulated AF. METHODS: 64-electrode basket bi-atria sustained AF recordings (H:15 min; S:40 min) were separated into 5 s segments. ShEn/ApEn/SampEn were computed, and co-registered with NavX 3D maps. Temporal stability was determined in terms of: (i) global pattern stability of En and (ii) the relative stability the top 10% of En regions. To provide mechanistic insights into underlying mechanisms, stability characteristics were compared to models depicting various propagation patterns. To verify these results, cross-validation was performed across multiple En algorithms, across species, and compared with dominant frequency (DF) temporal characteristics. The specificity of En was also determined by looking at the association of En to rotors and areas of wave cross propagation. RESULTS: Episodes of AF were analysed (H:26 epochs, 6040 s; S:15 epochs, 14,160 s). The global pattern of En was temporally unstable (CV- H:13.42% ±â€¯4.58%; S:14.13% ±â€¯8.13%; Friedman- H: p > 0.001; S: p > 0.001). However, within this dynamic flux, the top 10% of ApEn/SampEn/ShEn regions were relatively temporally stable (Kappa >0.6) whilst the top 10% of DF regions were unstable (Kappa <0.06). In simulated AF scenarios, the experimental data were optimally reproduced in the context of an AF pattern with stable rotating waves surrounded by wavelet breakup (Kappa: 0.610; p < 0.0001). CONCLUSION: En shows global temporal instability, however within this dynamic flux, the top 10% regions exhibited relative temporal stability. This suggests that high En regions may be an appealing ablation target. Despite this, high En was associated with not just the pivot of rotors but also with areas of cross propagation, which suggests the need for future work before clinical application is possible.

IgV peptide mapping of native Ro60 autoantibody proteomes in primary Sjögren's syndrome reveals molecular markers of Ro/La diversification.

We have used high-resolution mass spectrometry to sequence precipitating anti-Ro60 proteomes from sera of patients with primary Sjögren's syndrome and compare immunoglobulin variable-region (IgV) peptide signatures in Ro/La autoantibody subsets. Anti-Ro60 were purified by elution from native Ro60-coated ELISA plates and subjected to combined de novo amino acid sequencing and database matching. Monospecific anti-Ro60 Igs comprised dominant public and minor private sets of IgG1 kappa and lambda restricted heavy and light chains. Specific IgV amino acid substitutions stratified anti-Ro60 from anti-Ro60/La responses, providing a molecular fingerprint of Ro60/La determinant spreading and suggesting that different forms of Ro60 antigen drive these responses. Sequencing of linked anti-Ro52 proteomes from individual patients and comparison with their anti-Ro60 partners revealed sharing of a dominant IGHV3-23/IGKV3-20 paired clonotype but with divergent IgV mutational signatures. In summary, anti-Ro60 IgV peptide mapping provides insights into Ro/La autoantibody diversification and reveals serum-based molecular markers of humoral Ro60 autoimmunity.

Protocol describing a systematic review and mixed methods consensus process to define the deteriorated ward patient.

INTRODUCTION: Most patients admitted to hospital recover with treatments that can be administered on the general ward. A small but important group deteriorate however and require augmented organ support in areas with increased nursing to patient ratios. In observational studies evaluating this cohort, proxy outcomes such as unplanned intensive care unit admission, cardiac arrest and death are used. These outcome measures introduce subjectivity and variability, which in turn hinders the development and accuracy of the increasing numbers of electronic medical record (EMR) linked digital tools designed to predict clinical deterioration. Here, we describe a protocol for developing a new outcome measure using mixed methods to address these limitations. METHODS AND ANALYSIS: We will undertake firstly, a systematic literature review to identify existing generic, syndrome-specific and organ-specific definitions for clinically deteriorated, hospitalised adult patients. Secondly, an international modified Delphi study to generate a short list of candidate definitions. Thirdly, a nominal group technique (NGT) (using a trained facilitator) will take a diverse group of stakeholders through a structured process to generate a consensus definition. The NGT process will be informed by the data generated from the first two stages. The definition(s) for the deteriorated ward patient will be readily extractable from the EMR. ETHICS AND DISSEMINATION: This study has ethics approval (reference 16399) from the Central Adelaide Local Health Network Human Research Ethics Committee. Results generated from this study will be disseminated through publication and presentation at national and international scientific meetings.

Renewal Theory as a Universal Quantitative Framework to Characterize Phase Singularity Regeneration in Mammalian Cardiac Fibrillation.

BACKGROUND: Despite a century of research, no clear quantitative framework exists to model the fundamental processes responsible for the continuous formation and destruction of phase singularities (PS) in cardiac fibrillation. We hypothesized PS formation/destruction in fibrillation could be modeled as self-regenerating Poisson renewal processes, producing exponential distributions of interevent times governed by constant rate parameters defined by the prevailing properties of each system. METHODS: PS formation/destruction were studied in 5 systems: (1) human persistent atrial fibrillation (n=20), (2) tachypaced sheep atrial fibrillation (n=5), (3) rat atrial fibrillation (n=4), (5) rat ventricular fibrillation (n=11), and (5) computer-simulated fibrillation. PS time-to-event data were fitted by exponential probability distribution functions computed using maximum entropy theory, and rates of PS formation and destruction (λf/λd) determined. A systematic review was conducted to cross-validate with source data from literature. RESULTS: In all systems, PS lifetime and interformation times were consistent with underlying Poisson renewal processes (human: λf, 4.2%/ms±1.1 [95% CI, 4.0-5.0], λd, 4.6%/ms±1.5 [95% CI, 4.3-4.9]; sheep: λf, 4.4%/ms [95% CI, 4.1-4.7], λd, 4.6%/ms±1.4 [95% CI, 4.3-4.8]; rat atrial fibrillation: λf, 33%/ms±8.8 [95% CI, 11-55], λd, 38%/ms [95% CI, 22-55]; rat ventricular fibrillation: λf, 38%/ms±24 [95% CI, 22-55], λf, 46%/ms±21 [95% CI, 31-60]; simulated fibrillation λd, 6.6-8.97%/ms [95% CI, 4.1-6.7]; R2≥0.90 in all cases). All PS distributions identified through systematic review were also consistent with an underlying Poisson renewal process. CONCLUSIONS: Poisson renewal theory provides an evolutionarily preserved universal framework to quantify formation and destruction of rotational events in cardiac fibrillation.

Information Theory and Atrial Fibrillation (AF): A Review.

Atrial Fibrillation (AF) is the most common cardiac rhythm disorder seen in hospitals and in general practice, accounting for up to a third of arrhythmia related hospitalizations. Unfortunately, AF treatment is in practice complicated by the lack of understanding of the fundamental mechanisms underlying the arrhythmia, which makes detection of effective ablation targets particularly difficult. Various approaches to AF mapping have been explored in the hopes of better pinpointing these effective targets, such as Dominant Frequency (DF) analysis, complex fractionated electrograms (CFAE) and unipolar reconstruction (FIRM), but many of these methods have produced conflicting results or require further investigation. Exploration of AF using information theoretic-based approaches may have the potential to provide new insights into the complex system dynamics of AF, whilst also providing the benefit of being less reliant on empirically derived definitions in comparison to alternate mapping approaches. This work provides an overview of information theory and reviews its applications in AF analysis, with particular focus on AF mapping. The works discussed in this review demonstrate how understanding AF from a signal property perspective can provide new insights into the arrhythmic phenomena, which may have valuable clinical implications for AF mapping and ablation in the future.