Unexplained cardiac arrest may be because of an inherited arrhythmia syndrome. The role of genetic testing in cardiac arrest survivors without a definite clinical phenotype is unclear.
The CASPER ...(Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) is a large registry of cardiac arrest survivors where initial assessment reveals normal coronary arteries, left ventricular function, and resting ECG. Of 375 cardiac arrest survivors in CASPER from 2006 to 2015, 174 underwent genetic testing. Patients were classified as phenotype-positive (n=72) or phenotype-negative (n=102). Genetic testing was performed at treating physicians' discretion in line with contemporary guidelines and availability. All genetic variants identified from original laboratory reports were reassessed by the investigators in line with modern criteria. Pathogenic variants were identified in 29 (17%) patients (60% channelopathy-associated and 40% cardiomyopathy-associated genes) and 70 variants of unknown significance were identified in 32 (18%) patients. Prior syncope (odds ratio, 4.0; 95% confidence interval, 1.6-9.7) and a family history of sudden death (odds ratio, 3.2; 95% confidence interval, 1.1-9.4) were independently associated with the presence of a pathogenic variant. In phenotype-negative patients, broad multiphenotype genetic testing led to higher yields (21% versus 8%;
=0.04) but was associated with more variants of unknown significance (55% versus 5%;
<0.01).
Genetic testing identifies a pathogenic variant in a significant proportion of unexplained cardiac arrest survivors. Prior syncope and family history of sudden death are predictors of a positive genetic test. Both arrhythmia and cardiomyopathy genes are implicated. Broad, multiphenotype testing revealed the highest frequency of pathogenic variants in phenotype-negative patients.
https://www.clinicaltrials.gov. Unique Identifier: NCT00292032.
Objective Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse birth and developmental outcomes in children. We aimed to describe prenatal PAH exposures in a large, ...multisite U.S. consortium. Methods We measured 12 mono-hydroxylated metabolites (OH-PAHs) of 7 PAHs (naphthalene, fluorene, phenanthrene, pyrene, benzo(c)phenanthrene, chrysene, benz(a)anthracene) in mid-pregnancy urine of 1,892 pregnant individuals from the ECHO PATHWAYS consortium cohorts: CANDLE (n = 988; Memphis), TIDES (n = 664; Minneapolis, Rochester, San Francisco, Seattle) and GAPPS (n = 240; Seattle and Yakima, WA). We described concentrations of 8 OH-PAHs of non-smoking participants (n = 1,695) by site, socioeconomic characteristics, and pregnancy stage (we report intraclass correlation coefficients (ICC) for n = 677 TIDES participants). Results Exposure to the selected PAHs was ubiquitous at all sites. 2-hydroxynaphthalene had the highest average concentrations at all sites. CANDLE had the highest average concentrations of most metabolites. Among non-smoking participants, we observed some patterns by income, education, and race but these were not consistent and varied by site and metabolite. ICCs of repeated OH-PAH measures from TIDES participants were ≤ 0.51. Conclusion In this geographically-diverse descriptive analysis of U.S. pregnancies, we observed ubiquitous exposure to low molecular weight PAHs, highlighting the importance of better understanding PAH sources and their pediatric health outcomes attributed to early life PAH exposure.
Aim
Megafire events generate immediate concern for wildlife and human well‐being, but their broader ecological impacts likely extend beyond individual species and single fire events. In the first ...mechanistic study of fire effects focussed on ecosystems, we aimed to assess the sensitivity and exposure of ecosystems to multiple fire‐related threats, placing impacts in the context of changing fire regimes and their interactions with other threats.
Location
Southern and eastern Australia.
Time period
2019–2020.
Major species studied
Australian ecosystems.
Methods
We defined 15 fire‐related threats to ecosystems based on mechanisms associated with: (a) direct effects of fire regime components; (b) interactions between fire and physical environmental processes; (c) effects of fire on biological interactions; and (d) interactions between fire and human activity. We estimated the sensitivity and exposure of a sample of 92 ecosystem types to each threat type based on published relationships and spatial analysis of the 2019–2020 fires.
Results
Twenty‐nine ecosystem types assessed had more than half of their distribution exposed to one or more threat types, and only three of those were listed as nationally threatened. Three fire‐related threat types posed the most severe threats to large numbers of ecosystem types: high frequency fire; pre‐fire drought; and post‐fire invasive predator activity. The ecosystem types most affected ranged from rain forests to peatlands, and included some, such as sclerophyllous eucalypt forests and heathlands, that are traditionally regarded as fire‐prone and fire‐adapted.
Main conclusions
Most impacts of the 2019–2020 fires on ecosystems became apparent only when they were placed in the context of the whole fire regime and its interactions with other threatening processes, and were not direct consequences of the megafire event itself. Our mechanistic approach enables ecosystem‐specific management responses for the most threatened ecosystem types to be targeted at underlying causes of degradation and decline.
Sex differences in the use and outcomes of implantable cardioverter-defibrillators (ICDs) have not been fully studied.
To examine potential sex differences in ICD implantation and device outcomes.
...Health payer-mandated, prospective study of patients referred for ICD implantation, with comprehensive, longitudinal follow-up for complications, deaths, and device outcomes.
18 ICD implantation and follow-up centers in Ontario, Canada.
6021 patients (4733 men) referred for ICD implantation from February 2007 to July 2010.
Multivariate-adjusted ICD implantation rate, complications up to day 45, multivariate-adjusted complications, device outcomes (including appropriate shocks and therapies), and deaths occurring during 1-year follow-up.
Rates of ICD implantation were similar in men and women (relative risk, 0.99 95% CI, 0.97 to 1.02; P = 0.60). However, women were significantly more likely to experience major complications by 45 days (odds ratio, 1.78 CI, 1.24 to 2.58; P = 0.002) and 1 year (hazard ratio HR, 1.91 CI, 1.48 to 2.47; P < 0.001) after implantation. Occurrence of any major or minor complication was also increased in women at both 45-day follow-up (odds ratio, 1.50 CI, 1.12 to 2.00; P = 0.006) and 1-year follow-up (HR, 1.55 CI, 1.25 to 1.93; P < 0.001). After implantation, women were less likely than men to receive appropriate ICD shock (HR, 0.69 CI, 0.51 to 0.93; P = 0.015) or appropriate therapy via shock or antitachycardia pacing (HR, 0.73 CI, 0.59 to 0.90; P = 0.003). Total mortality among defibrillator recipients did not differ between men and women (HR, 1.00 CI, 0.64 to 1.55; P = 0.99).
The differential effects of sex on prereferral events were not examined.
Although ICD implantation rates were similar after referral to an electrophysiologist, women who underwent ICD implantation had greater risks for complications and were less likely to experience appropriate ICD-delivered therapies than men.
Canadian Institutes of Health Research and Ontario Ministry of Health and Long-Term Care.
Implantable cardioverter-defibrillators (ICDs) reduce the risk of sudden cardiac death in patients with left ventricular dysfunction. While short-term mortality benefit of ICD insertion has been ...established in landmark randomized controlled trials, little is known about the long-term outcomes of patients with ICDs in clinical practice. In this paper, we describe the long-term survival of patients following de novo ICD implantation for primary prevention in clinical practice and determine the factors which help predict survival after ICD implant.
Retrospective population-based study of all patients receiving a de novo ICD for primary prevention in Ontario, Canada from 2007 to 2011 using the Ontario ICD Database housed within ICES. Simple random selection was used to split the population into a derivation and internal validation cohort in a ratio of 2:1. Cox proportional hazards regression was used to determine predictors of interest and predict 10-year survival, model performance was assessed using calibration and validation.
In the derivation cohort (n = 3399), mean age was 65.3 years (standard deviation SD = 11.0), 664 patients were female (19.5 %) and 2344 patients (69.0 %) had ischemic cardiomyopathy. Ten year survival was 45.7 % (95 % confidence interval CI 44.0 %–47.4 %). The final prediction model included age, sex, disease factors (ischemic vs nonischemic cardiomyopathy, left ventricular ejection fraction) and patient factors (symptoms, comorbidities), and biomarkers at the time of ICD assessment. This model had good discrimination and calibration in derivation (0.79, 95 % CI 0.77, 0.81) and validation samples (0.78, 95 % CI 0.76, 0.79).
A combination of demographic and clinical factors determined at baseline can be used to predict 10-year survival in patients with implantable cardioverter-defibrillators with good accuracy. Our findings help to identify individuals at risk of long-term mortality and may be useful in targeting future prevention strategies to enhance longevity in this high-risk population.
Porous collagen-glycosaminoglycan (collagen-GAG) scaffolds have shown promising clinical results for wound healing; however, these scaffolds do not replace the dermal and epidermal layer ...simultaneously and rely on local endogenous signaling to direct healing. Functionalizing collagen-GAG scaffolds with signaling factors, and/or additional matrix molecules, could help overcome these challenges. An ideal candidate for this is platelet-rich plasma (PRP) as it is a natural reservoir of growth factors, can be activated to form a fibrin gel, and is available intraoperatively. We tested the factors released from PRP (PRPr) and found that at specific concentrations, PRPr enhanced cell proliferation and migration and induced angiogenesis to a greater extent than fetal bovine serum (FBS) controls. This motivated us to develop a strategy to successfully incorporate PRP homogeneously within the pores of the collagen-GAG scaffolds. The composite scaffold released key growth factors for wound healing (FGF, TGFβ) and vascularization (VEGF, PDGF) for up to 14 days. In addition, the composite scaffold had enhanced mechanical properties (when compared to PRP gel alone), while providing a continuous upper surface of extracellular matrix (ECM) for keratinocyte seeding. The levels of the factors released from the composite scaffold were sufficient to sustain proliferation of key cells involved in wound healing, including human endothelial cells, mesenchymal stromal cells, fibroblasts, and keratinocytes; even in the absence of FBS supplementation. In functional
and
vascularization assays, our composite scaffold demonstrated increased angiogenic and vascularization potential, which is known to lead to enhanced wound healing. Upon pro-inflammatory induction, macrophages released lower levels of the pro-inflammatory marker MIP-1α when treated with PRPr; and released higher levels of the anti-inflammatory marker IL1-ra upon both pro- and anti-inflammatory induction when treated with the composite scaffold. Finally, our composite scaffold supported a co-culture system of human fibroblasts and keratinocytes that resulted in an epidermal-like layer, with keratinocytes constrained to the surface of the scaffold; by contrast, keratinocytes were observed infiltrating the PRP-free scaffold. This novel composite scaffold has the potential for rapid translation to the clinic by isolating PRP from a patient intraoperatively and combining it with regulatory approved scaffolds to enhance wound repair.
An electrically large ultrawideband ultrahigh frequency (UHF) monopole antenna array has been designed to sound up to 3 km of ice and meet the logistical requirements of transportation to arctic ...regions. The monopole array is comprised of 16 planar subarray modules, which in combination form a 16 m by 17 m Mills cross array configuration to maximize sensitivity and spatial selectivity in both cross-track and along-track directions. Each planar subarray module is 1 m by 2 m in size with a 6.35 cm thick rigid insulation foam panel separating the individual monopole elements from metal foil ground plane on the top such that the maximum radiation is directed to nadir. Each subarray panel consists of 4 by 8 circular monopole antenna elements with a spacing of 0.25 m. Each monopole element is printed on a 130 mm by 80 mm 62 mil FR4 board. The total weight of each subarray panel is 9 kg, making for very lightweight and low-profile antenna construction. The antenna array together with the radar system was deployed to the East Greenland Ice-coring Project site in August 2018 for demonstrating surface-based ice sounding at the UHF band.
We evaluated the prevalence and characteristics of early repolarization in patients in CASPER (Cardiac Arrest Survivors With Preserved Ejection Fraction Registry).
Early repolarization has been ...implicated in a syndrome of polymorphic ventricular tachycardia and fibrillation in patients without organic heart disease.
One hundred patients with apparently unexplained cardiac arrest and preserved ejection fraction underwent extensive clinical and genetic testing to unmask subclinical electrical or structural disease. A blinded independent analysis of the 12-lead electrocardiogram (ECG) was performed. Early repolarization was defined as ≥0.1 mV QRS-ST junction (J-point) elevation with terminal QRS slurring or notching in at least 2 contiguous inferior and/or lateral leads.
One hundred cardiac arrest patients were enrolled (40 females, age 43 ± 14 years). Forty-four were diagnosed with an established cause for cardiac arrest. Significant early repolarization was found in 19 patients, including 6 with a primary diagnosis that explained their cardiac arrest (14%), compared with 23% of the 56 patients with idiopathic ventricular fibrillation (IVF) (p = 0.23). J-point elevation in IVF patients had higher amplitude (0.25 ± 0.11 mV vs. 0.13 ± 0.05 mV, p = 0.02) and wider distribution (4.3 ± 1.3 leads vs. 2.8 ± 0.8 leads; p = 0.01) than those with an established cause of cardiac arrest. J-wave amplitude was fluctuant on serial ECGs; at least 1 ECG failed to demonstrate early repolarization in 58% of patients.
Early repolarization is present in a significant proportion of causally diagnosed and idiopathic VF. It is often intermittent and more pronounced in IVF patients. (Registry of Unexplained Cardiac Arrest; NCT00292032).
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