Catheter ablation vs. antiarrhythmic drug therapy in patients with symptomatic atrioventricular nodal re-entrant tachycardia: a randomized, controlled trial.

Aims: To conduct a randomized trial in order to guide the optimum therapy of symptomatic atrioventricular nodal re-entrant tachycardia (AVNRT). Methods and Results: Patients with at least one symptomatic episode of tachycardia per month and an electrophysiologic diagnosis of AVNRT were randomly assigned to catheter ablation or chronic antiarrhythmic drug (AAD) therapy with bisoprolol (5 mg od) and/or diltiazem (120-300 mg od). All patients were properly educated to treat subsequent tachycardia episodes with autonomic manoeuvres or a 'pill in the pocket' approach. The primary endpoint of the study was hospital admission for persistent tachycardia cardioversion, during a follow-up period of 5 years. Sixty-one patients were included in the study. In the ablation group, 1 patient was lost to follow-up, and 29 were free of arrhythmia or conduction disturbances at a 5-year follow-up. In the AAD group, three patients were lost to follow-up. Of the remainder, 10 patients (35.7%) continued with initial therapy, 11 patients (39.2%) remained on diltiazem alone, and 7 patients (25%) interrupted their therapy within the first 3 months following randomization, and subsequently developed an episode requiring cardioversion. During a follow-up of 5 years, 21 patients in the AAD group required hospital admission for cardioversion. Survival free from the study endpoint was significantly higher in the ablation group compared with the AAD group (log-rank test, P < 0.001). Conclusions: Catheter ablation is the therapy of choice for symptomatic AVNRT. Antiarrhythmic drug therapy is ineffective and not well tolerated

The Josephson heat interferometer

The Josephson effect represents perhaps the prototype of macroscopic phase coherence and is at the basis of the most widespread interferometer, i.e., the superconducting quantum interference device (SQUID). Yet, in analogy to electric interference, Maki and Griffin predicted in 1965 that thermal current flowing through a temperature-biased Josephson tunnel junction is a stationary periodic function of the quantum phase difference between the superconductors. The interplay between quasiparticles and Cooper pairs condensate is at the origin of such phase-dependent heat current, and is unique to Josephson junctions. In this scenario, a temperature-biased SQUID would allow heat currents to interfere thus implementing the thermal version of the electric Josephson interferometer. The dissipative character of heat flux makes this coherent phenomenon not less extraordinary than its electric (non-dissipative) counterpart. Albeit weird, this striking effect has never been demonstrated so far. Here we report the first experimental realization of a heat interferometer. We investigate heat exchange between two normal metal electrodes kept at different temperatures and tunnel-coupled to each other through a thermal `modulator' in the form of a DC-SQUID. Heat transport in the system is found to be phase dependent, in agreement with the original prediction. With our design the Josephson heat interferometer yields magnetic-flux-dependent temperature oscillations of amplitude up to ~21 mK, and provides a flux-to-temperature transfer coefficient exceeding ~ 60mK/Phi_0 at 235 mK [Phi_0 2* 10^(-15) Wb is the flux quantum]. Besides offering remarkable insight into thermal transport in Josephson junctions, our results represent a significant step toward phase-coherent mastering of heat in solid-state nanocircuits, and pave the way to the design of novel-concept coherent caloritronic devices.Comment: 4+ pages, 3 color figure

Dentist’s drill allergy?

Subcutaneous emphysema of the face and neck can develop following restorative dentistry, particularly when air turbine drills are used. We present a case in which the dentist mistook the subcutaneous emphysema following such a procedure for an allergic/anaphylactic reaction and sent him to the emergency department in an ambulance. The differential diagnosis and the subsequent management, including the role of oxygen and techniques to prevent such complications, are discussed

Nanoscale phase-engineering of thermal transport with a Josephson heat modulator

Macroscopic quantum phase coherence has one of its pivotal expressions in the Josephson effect [1], which manifests itself both in charge [2] and energy transport [3-5]. The ability to master the amount of heat transferred through two tunnel-coupled superconductors by tuning their phase difference is the core of coherent caloritronics [4-6], and is expected to be a key tool in a number of nanoscience fields, including solid state cooling [7], thermal isolation [8, 9], radiation detection [7], quantum information [10, 11] and thermal logic [12]. Here we show the realization of the first balanced Josephson heat modulator [13] designed to offer full control at the nanoscale over the phase-coherent component of thermal currents. Our device provides magnetic-flux-dependent temperature modulations up to 40 mK in amplitude with a maximum of the flux-to-temperature transfer coefficient reaching 200 mK per flux quantum at a bath temperature of 25 mK. Foremost, it demonstrates the exact correspondence in the phase-engineering of charge and heat currents, breaking ground for advanced caloritronic nanodevices such as thermal splitters [14], heat pumps [15] and time-dependent electronic engines [16-19].Comment: 6+ pages, 4 color figure

Pro-asthmatic cytokines regulate unliganded and ligand-dependent glucocorticoid receptor signaling in airway smooth muscle

To elucidate the regulation of glucocorticoid receptor (GR) signaling under pro-asthmatic conditions, cultured human airway smooth muscle (HASM) cells were treated with proinflammatory cytokines or GR ligands alone and in combination, and then examined for induced changes in ligand-dependent and -independent GR activation and downstream signaling events. Ligand stimulation with either cortisone or dexamethsone (DEX) acutely elicited GR translocation to the nucleus and, comparably, ligand-independent stimulation either with the Th2 cytokine, IL-13, or the pleiotropic cytokine combination, IL-1β/TNFα, also acutely evoked GR translocation. The latter response was potentiated by combined exposure of cells to GR ligand and cytokine. Similarly, treatment with either DEX or IL-13 alone induced GR phosphorylation at its serine-211 residue (GRSer211), denoting its activated state, and combined treatment with DEX+IL-13 elicited heightened and sustained GRSer211phosphorylation. Interestingly, the above ligand-independent GR responses to IL-13 alone were not associated with downstream GR binding to its consensus DNA sequence or GR transactivation, whereas both DEX-induced GR:DNA binding and transcriptional activity were significantly heightened in the presence of IL-13, coupled to increased recruitment of the transcriptional co-factor, MED14. The stimulated GR signaling responses to DEX were prevented in IL-13-exposed cells wherein GRSer211 phosphorylation was suppressed either by transfection with specific serine phosphorylation-deficient mutant GRs or treatment with inhibitors of the MAPKs, ERK1/2 and JNK. Collectively, these novel data highlight a heretofore-unidentified homeostatic mechanism in HASM cells that involves pro-asthmatic cytokine-driven, MAPK-mediated, non-ligand-dependent GR activation that confers heightened glucocorticoid ligand-stimulated GR signaling. These findings raise the consideration that perturbations in this homeostatic cytokine-driven GR signaling mechanism may be responsible, at least in part, for the insensirtivity to glucocorticoid therapy that is commonly seen in individuals with severe asthma

Cost-effectiveness of In-home Automated External Defibrillators for Individuals at Increased Risk of Sudden Cardiac Death

In-home automated external defibrillators (AEDs) are increasingly recommended as a means for improving survival of cardiac arrests that occur at home. The current study was conducted to explore the relationship between individuals' risk of cardiac arrest and cost-effectiveness of in-home AED deployment. Design : Markov decision model employing a societal perspective. Patients : Four hypothetical cohorts of American adults 60 years of age at progressively greater risk for sudden cardiac death (SCD): 1) all adults (annual probability of SCD 0.4%); 2) adults with multiple SCD risk factors (probability 2%); 3) adults with previous myocardial infarction (probability 4%); and 4) adults with ischemic cardiomyopathy unable to receive an implantable defibrillator (probability 6%). Intervention : Strategy 1: individuals suffering an in-home cardiac arrest were treated with emergency medical services equipped with AEDs (EMS-D). Strategy 2: individuals suffering an in-home cardiac arrest received initial treatment with an in-home AED, followed by EMS. Results : Assuming cardiac arrest survival rates of 15% with EMS-D and 30% with AEDs, the cost per quality-adjusted life-year gained (QALY) of providing in-home AEDs to all adults 60 years of age is $216,000. Costs of providing in-home AEDs to adults with multiple risk factors (2$132,000, $104,000, and$88,000, respectively. Conclusions : The cost-effectiveness of in-home AEDs is intimately linked to individuals' risk of SCD. However, providing in-home AEDs to all adults over age 60 appears relatively expensive.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72168/1/j.1525-1497.2005.40247.x.pd

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS