No abstract

Temporary postoperative cardiac pacing requires devices with percutaneous leads and external wired power and control systems. This hardware introduces risks for infection, limitations on patient mobility, and requirements for surgical extraction procedures. Bioresorbable pacemakers mitigate some of these disadvantages, but they demand pairing with external, wired systems and secondary mechanisms for control. We present a transient closed-loop system that combines a time-synchronized, wireless network of skin-integrated devices with an advanced bioresorbable pacemaker to control cardiac rhythms, track cardiopulmonary status, provide multihaptic feedback, and enable transient operation with minimal patient burden. The result provides a range of autonomous, rate-adaptive cardiac pacing capabilities, as demonstrated in rat, canine, and human heart studies. This work establishes an engineering framework for closed-loop temporary electrotherapy using wirelessly linked, body-integrated bioelectronic devices.

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'Does tranexamic acid stop haemoptysis'? Altogether 49 papers were found using the reported search strategy, of which 13 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. This consisted of one systematic review including a meta-analysis of two double-blind randomized controlled trials (RCTs), the two RCTs, one cohort study, two case-series and seven case reports. Main outcomes included bleeding time, bleeding volume and occurrence of thromboembolic complications after start of treatment. Based on results from the meta-analysis, no difference in remission of bleeding within 1 week was found between tranexamic acid (TA) and placebo groups (odds ratio 1.56, 95% CI: 0.44-5.46). However, overall bleeding time was significantly shorter for the TA group (weighted mean difference -19.47, 95% CI: -26.90, -12.03 h). In one RCT, TA reduced both the duration and the volume of bleeding compared with patients receiving placebo (both P < 0.0005). However, the other RCT failed to find a difference in bleeding time (P = 0.2). In these studies, no patient suffered from thromboembolic complications. Two case reports, however, describe development of pulmonary embolism during TA treatment. Several case reports on the use of TA for treatment of haemoptysis secondary to cystic fibrosis were found. In general, they suggest that TA may be a useful and well-tolerated medication for the treatment of intractable haemoptysis in this patient group. We conclude that limited research on the use of TA for treatment of haemoptysis exists. As aetiology of haemoptysis as well as length of treatment, dosage and form of TA administration varied between the studies, strong recommendations are difficult to give. Current best evidence, however, indicates that TA may reduce both the duration and volume of bleeding, with low risk of short-term thromboembolic complications, in patients with haemoptysis.

No abstract

Background: Atrial fibrillation (AF) is the most common heart rhythm disorder in adults and a major cause of stroke. Unfortunately, current treatments of AF are suboptimal because they are not targeted to the molecular mechanisms underlying AF. Using a highly novel gene therapy approach in a canine, rapid atrial pacing model of AF, we demonstrate that NADPH oxidase 2 (NOX2) generated oxidative injury causes upregulation of a constitutively active form of acetylcholine-dependent K + current ( I KACh ), called I KH ; this is an important mechanism underlying not only the genesis, but also the perpetuation of electric remodeling in the intact, fibrillating atrium. Methods: To understand the mechanism by which oxidative injury promotes the genesis and maintenance of AF, we performed targeted injection of NOX2 short hairpin RNA (followed by electroporation to facilitate gene delivery) in atria of healthy dogs followed by rapid atrial pacing. We used in vivo high-density electric mapping, isolation of atrial myocytes, whole-cell patch clamping, in vitro tachypacing of atrial myocytes, lucigenin chemiluminescence assay, immunoblotting, real-time polymerase chain reaction, immunohistochemistry, and Masson trichrome staining. Results: First, we demonstrate that generation of oxidative injury in atrial myocytes is a frequency-dependent process, with rapid pacing in canine atrial myocytes inducing oxidative injury through the induction of NOX2 and the generation of mitochondrial reactive oxygen species. We show that oxidative injury likely contributes to electric remodeling in AF by upregulating I KACh by a mechanism involving frequency-dependent activation of PKC ε (protein kinase C epsilon). The time to onset of nonsustained AF increased by >5-fold in NOX2 short hairpin RNA–treated dogs. Furthermore, animals treated with NOX2 short hairpin RNA did not develop sustained AF for up to 12 weeks. The electrophysiological mechanism underlying AF prevention was prolongation of atrial effective refractory periods, at least in part attributable to the attenuation of I KACh . Attenuated membrane translocation of PKC ε appeared to be a likely molecular mechanism underlying this beneficial electrophysiological remodeling. Conclusions: NOX2 oxidative injury (1) underlies the onset, and the maintenance of electric remodeling in AF, as well, and (2) can be successfully prevented with a novel, gene-based approach. Future optimization of this approach may lead to a novel, mechanism-guided therapy for AF.