Comparison of complications and shocks in paediatric and young transvenous and subcutaneous implantable cardioverter-defibrillator patients

Background

Young implantable cardioverter-defibrillator (ICD) patients are prone to complications and inappropriate shocks (IAS). The subcutaneous ICD (S-ICD) may avoid lead-related complications. This study aims to describe the incidence and nature of device-related complications in young transvenous ICD (TV-ICD) and S?ICD patients.

Methods

Single-chamber TV-ICD and S?ICD patients up to and including the age of 25 years implanted between 2002 and 2015 were retrospectively analysed. Complications were defined as device-related complications requiring surgical intervention. IAS were defined as shocks for anything other than ventricular tachycardia or ventricular fibrillation. Follow-up data were collected 5 years post-implantation. Kaplan-Meier estimates for complications at 5?year follow-up were calculated with a corresponding 95% confidence interval.

Results

Eighty-one patients (46 TV-ICD, 35 S-ICD) were included (median age 19.0 (IQR 16.0–23.0) and 16.5 (IQR 13.0–20.2) years respectively). Median follow-up was 60 and 40 months respectively. All-cause complication rate was 34% in the TV-ICD group and 25% in the S?ICD group (p?=?0.64). TV-ICD patients had more lead complications: 23% (10–36%) versus 0% (p?=?0.02). The rate of infections did not differ between TV-ICD and S?ICD: 2% (0–6%) versus 10% (0–21%) (p?=?0.15). No systemic infections occurred in the S?ICD patients. The rates of IAS were similar, TV-ICD 22% (9–35%) versus S?ICD 14% (0–30%) (p?=?0.40), as were those for appropriate shocks: 25% (11–39%) versus 27% (6–48%) (p?=?0.92).

Conclusion

The rates of all-cause complications in this cohort were equal, though the nature of the complications differed. S?ICD patients did not suffer lead failures or systemic infections. An era effect is present between the two groups.

     

Contact allergy to a subcutaneous implantable cardiac defibrillator – A rare problem with a golden solution

Contact allergy to implantable cardiac defibrillators (ICD) is an uncommon and underdiagnosed complication. We report a case of a 20-years-old man patient that was resuscitated from sudden cardiac death. Workup imaging study was unremarkable, but genetic testing identified a mutation in the KCNH2 gene of uncertain significance. The patient underwent a subcutaneous implantable cardiac defibrillator (S-ICD) implantation, with no complications. The patient suffered two hospital re-admissions due to a device-related inflammatory reaction, leading to two device re-implantations. At the first time, it was considered a bacterial infection and the S-ICD was replaced by an endovascular device. At the second time, a tissue-device interaction, with hypersensitivity reaction and device rejection was suspected. The skin patch-tests were inconclusive, but it was decided to implant a custom-made gold-coated endovascular ICD. Indeed, the tendency is an initial misdiagnosis as an infection and a high clinical suspicion is essential to an early diagnosis.     

S-ICD oversensing detected by remote monitoring using a new atrial fibrillation diagnostic algorithm

A 64-year-old male with a high body mass index, and subcutaneous implantable cardioverter defibrillator, (S-ICD) presented with a remote transmission of inappropriately diagnosed AF episodes, due to oversensing of P and T waves. The AF monitor can be an early warning for inappropriate sensing. Oversensing, due to small amplitude signals, can be caused by the lead position not being adequately opposed to the sternum.     

A Case of Inappropriate Therapies for Atrial Flutter From a Subcutaneous ICD

Hypertrophic cardiomyopathy’s (HCM) association with sudden cardiac death is well recognised. The risk of sudden cardiac death is known to increase when there is a history of unexplained syncope, abnormal blood pressure response during exercise, severe left ventricular hypertrophy or a family history of unexplained death.Implantable Cardioverter Defibrillator (ICD) implantation has been widely used for primary and secondary prevention of sudden cardiac death (SCD) in people with HCM. Subcutaneous ICD (S-ICD) therapy has been developed to overcome some of the problems associated with the transvenous leads used in conventional ICDs.In this article, we report the use of S-ICD in a patient with HCM and multiple risk factors for sudden cardiac death, this device had to be extracted due to recurrent inappropriate shocks caused by over sensing of atrial flutter and failure to treat a VT episode. We are not aware of any reports of inappropriate shocks caused by atrial flutter in people with a S-ICD.     

“973”项目“农林危险生物入侵机理与控制基础研究”简介

2002年12月,国家重点基础研究发展计划("973"项目)"农林危险生物入侵机理与控制基础研究"经科技部批准正式立项,2003年启动。文章主要介绍该项目的立项背景、主要研究内容、研究方案和技术路线、总体研究目标及研究进展。     

Advances in In Situ Air Sparging/Biosparging

In situ air sparging (IAS) is a technology commonly used for treatment of submerged source zones and dissolved groundwater plumes. The acceptance of IAS by regulatory agencies, environmental consultants, and industry is remarkable considering the degree of skepticism initially surrounding the technology in the early 1990s. Much has been learned and reported in the literature since that time, but it appears that practice has changed little. In particular, conventional pilot testing, design, and operation practices reflect a lack of appreciation of the complex phenomena governing IAS performance and the unforgiving nature of this technology. Many systems are poorly monitored and likely to be inefficient or ineffective. Key lessons-learned since the early 1990s are reviewed and their implications for practice are discussed here. Of particular importance are issues related to: (a) the understanding of air flow distributions and the effects of geology and injection flowrate, (b) the need to characterize air flow distributions at the pilot- and field-scale, (c) how changes in operating conditions (e.g., pulsing) can affect performance improvements and reduce equipment costs, and (d) how conventional monitoring approaches are incapable of assessing if systems are performing as designed.     

Development of a mathematical model that predicts the outcome of hormone therapy for prostate cancer

We propose a mathematical model that quantitatively reproduces the dynamics of the serum prostate-specific antigen (PSA) level under intermittent androgen suppression (IAS) for prostate cancer. Taking into account the biological knowledge that there are reversible and irreversible changes in a malignant cell, we constructed a piecewise-linear dynamical model where the testosterone dynamics are modelled with rapid shifts between two levels, namely the normal and castrate concentrations of the male hormone. The validity of the model was supported by patient data obtained from a clinical trial of IAS. It accurately reproduced the kinetics of the therapeutic reduction of PSA and predicted the future nadir level correctly. The coexistence of reversible and irreversible changes within the malignant cell provided the best explanation of early progression to androgen independence. Finally, since the model identified patients for whom IAS was effective, it potentially offers a novel approach to individualized therapy requiring the input of time sequence values of PSA only.     

Shoulder Joint Dislocation as an Unusual Complication of Defibrillation Threshold Testing Following Subcutaneous Implantable Cardioverter-Defibrillator Implantation

A 53-year-old man underwent implantation of a totally subcutaneous ICD (S-ICD; Boston Scientific). He was positioned supine, with the left arm abducted, externally rotated (i.e. palm up) and strapped to the arm extender. The generator was placed in the left mid-axillary line along the 5th-6th intercostal spaces and the defibrillation coil was tunneled anterior to the sternum. Defibrillation threshold (DFT) testing with 65 Jcaused a forceful pectoralis twitch. The patient woke up with a painful anteriorly dislocated left shoulder. Glenohumeral dislocation due to DFT testing has not been previously reported. It is likely that this complication is specific to the S-ICD implantation, and is related to positioning with the arm abducted, externally rotated, and immobilized, and use of greater defibrillation energy with current pathway through the bulk of the pectoralis muscle.Precautions may include extending the arm palm down, strapping the arm loosely, and adduction of the arm for DFT testing.     

A Practical Approach for the Selection, Pilot Testing, Design, and Monitoring of In Situ Air Sparging/Biosparging Systems

The use of in situ air sparging (IAS) has increased rapidly since the early 1990s, and it is now likely to be the most practiced engineered in situ remediation option when targeting the treatment of hydrocarbon-impacted aquifers. To date, IAS system design has remained largely empirical, with significant variability in approaches and results. Here, the valuable knowledge gained from IAS studies and applications over the past decade has been integrated into a new paradigm for feasibility assessment, pilot testing, design, and operation. The basis for this Design Paradigm, the initial feasibility assessment, monitoring, and the overall design approach are discussed in detail here; other referenced documents contain the details of specific recommended activities. The proposed design approach is unique in that it contains two design routes; the first is a non-site-specific approach requiring minimal site characterization and testing (Standard Design Approach), while the second is a more site-specific approach (Site-Specific Design Approach).     

American petroleum institute in situ air sparging database

An evaluation of data detailing in situ air sparging (IAS) systems at 59 sites has been assembled into an American Petroleum Institute in situ Air Sparging Database (API‐IAS Database). The database was developed to provide site managers insights concerning the state‐of‐the‐art of IAS system design, operation, and evaluation. The IAS radius of influence (ROI) is often evaluated based on changes in a number of physical, chemical, or biological monitoring parameters. Measurements of groundwater dissolved oxygen levels was the technique used most often to determine the ROI. Other parameters such as pressure changes in the vadose and saturated zones, groundwater mounding, air bubbling in wells and tracer gases were also used to aid in the determination of the IAS ROI. A review of 37 pilot studies revealed that the IAS ROI is generally between 10 to 26 ft. IAS technology is generally being applied in sandy soils. The application of IAS technology was deemed infeasible at seven sites where soils contained high levels of silts or clay. Analysis of design and operation data at 40 IAS sites revealed that a typical IAS well is 2 in. in diameter, with a 2‐ft screen, positioned 5 to 10 ft beneath the water table. The wells typically were operated at an overpressure (i.e., pressure in excess of that required to overcome the hydrostatic head) of less than 5 psi with a flow rate of less than 5 cfm. At several sites when IAS system pressures and flows were doubled, only slight increases in ROI resulted. Significant reductions of dissolved volatile organic hydrocarbon (VOCs) were observed at 12 sites as a result of IAS. However, long‐term water quality data following an IAS system shutdown was very limited.     

Optimization and validation of a cost‐effective protocol for biosurveillance of invasive alien species

Environmental DNA (eDNA) metabarcoding has revolutionized biodiversity monitoring and invasive pest biosurveillance programs. The introduction of insect pests considered invasive alien species (IAS) into a non‐native range poses a threat to native plant health. The early detection of IAS can allow for prompt actions by regulating authorities, thereby mitigating their impacts. In the present study, we optimized and validated a fast and cost‐effective eDNA metabarcoding protocol for biosurveillance of IAS and characterization of insect and microorganism diversity. Forty‐eight traps were placed, following the CFIA''s annual forest insect trapping survey, at four locations in southern Ontario that are high risk for forest IAS. We collected insects and eDNA samples using Lindgren funnel traps that contained a saturated salt (NaCl) solution in the collection jar. Using cytochrome c oxidase I (COI) as a molecular marker, a modified Illumina protocol effectively identified 2,535 Barcode Index Numbers (BINs). BINs were distributed among 57 Orders and 304 Families, with the vast majority being arthropods. Two IAS (Agrilus planipennis and Lymantria dispar) are regulated by the Canadian Food Inspection Agency (CFIA) as plant health pests, are known to occur in the study area, and were identified through eDNA in collected traps. Similarly, using 16S ribosomal RNA and nuclear ribosomal internal transcribed spacer (ITS), five bacterial and three fungal genera, which contain species of regulatory concern across several Canadian jurisdictions, were recovered from all sampling locations. Our study results reaffirm the effectiveness and importance of integrating eDNA metabarcoding as part of identification protocols in biosurveillance programs.     

Different arguments,same conclusions: how is action against invasive alien species justified in the context of European policy?

The prevention and management of invasive alien species (IAS) has become a high priority in European environmental policy. At the same time, ways of evaluating IAS continue to be a topic of lively debate. In particular, it is far from clear how directly policy makers’ value judgements are linked to the European (EU) policy against IAS. We examine the arguments used to support value judgements of both alien species and invasive alien species as well as the relation between these value judgements and the policy against IAS being developed at European level. Our study is based on 17 semi-structured interviews with experts from EU policy making and from the EU member states Austria, Belgium, Germany and Hungary. We found that our interviewees conceived of IAS in very different ways, expressed a variety of visions of biodiversity and ecosystem services, and adhered to widely different values expressed in their perceptions of IAS and the impacts of IAS. However, only some of these conceptualizations and value judgements are actually addressed in the rationale given in the preamble to the European IAS Regulation. Although value judgements about IAS differed, there was considerable agreement regarding the kind of action to be taken against them.     

Cellular regulation of basal tone in internal anal sphincter smooth muscle by RhoA/ROCK

Sustained contractions of smooth muscle cells (SMC) maintain basal tone in the internal anal sphincter (IAS). To examine the molecular bases for the myogenic tone in the IAS, the present studies focused on the role of RhoA/ROCK in the SMC isolated from the IAS vs. the adjoining phasic tissues of the rectal smooth muscle (RSM) and anococcygeus smooth muscle (ASM) of rat. We also compared cellular distribution of RhoA/ROCK, levels of RhoA-GTP, RhoA-Rho guanine nucleotide dissociation inhibitor (GDI) complex formation, levels of p(Thr696)-MYPT1, and SMC relaxation caused by RhoA inhibition. Levels of RhoA/ROCK were higher at the cell membrane in the IAS SMC compared with those from the RSM and ASM. C3 exoenzyme (RhoA inhibitor) and Y 27632 (ROCK inhibitor) caused a concentration-dependent relaxation of the IAS SMC. In addition, active ROCK-II (primary isoform of ROCK in SMC) caused further shortening in the IAS SMC. C3 exoenzyme increased RhoA-RhoGDI binding and reduced the levels of RhoA-GTP and p(Thr696)-MYPT1. ROCK inhibitor attenuated PKC-induced contractions in IAS SMC. Conversely, a PKC inhibitor (G? 6850, which causes partial relaxation of the SMC) had no significant effect on ROCK-II-induced contractions. Further experiments showed the highest levels of RhoA, active form of RhoA (RhoA-GTP), ROCK-II, 20-kDa myosin regulatory light chain (MLC(20)), phospho-MYPT1, and phospho-MLC(20) in the IAS vs. RSM and ASM SMC. However, the trend was the reverse with the levels of inactive RhoA (GDP-RhoA-RhoGDI complex) and MYPT1. We conclude that RhoA/ROCK play a critical role in maintenance of spontaneous tone in the IAS SMC via inhibition of myosin light chain phosphatase.     

Development of a three-dimensional physiological model of the internal anal sphincter bioengineered in vitro from isolated smooth muscle cells

Fecal incontinence affects people of all ages and social backgrounds and can have devastating psychological and economic consequences. This disorder is largely attributed to decreased mechanical efficiency of the internal anal sphincter (IAS), yet little is known about the pathophysiological mechanisms responsible for the malfunction of sphincteric smooth muscle at the cellular level. The object of this study was to develop a three-dimensional (3-D) physiological model of the IAS bioengineered in vitro from isolated smooth muscle cells. Smooth muscle cells isolated from the IAS of rabbits were seeded in culture on top of a loose fibrin gel, where they migrated and self-assembled in circumferential alignment. As the cells proliferated, the fibrin gel contracted around a 5-mm-diameter SYLGARD mold, resulting in a 3-D cylindrical ring of sphincteric tissue. We found that 1) the bioengineered IAS rings generated a spontaneous basal tone, 2) stimulation with 8-bromo-cAMP (8-Br-cAMP) caused a sustained decrease in the basal tone (relaxation) that was calcium-independent, 3) upon stimulation with ACh, bioengineered IAS rings showed a calcium- and concentration-dependent peak contraction at 30 s that was sustained for 4 min, 4) addition of 8-Br-cAMP induced rapid relaxation of ACh-induced contraction and force generation of IAS rings, and 5) bioengineered sphincter rings show striking functional differences when compared with bioengineered rings made from isolated colonic smooth muscle cells. This is the first report of a 3-D in vitro model of a gastrointestinal smooth muscle IAS. Bioengineered IAS rings demonstrate physiological functionality and may be used in the elucidation of the mechanisms causing sphincter malfunction.     

Mechanism of internal anal sphincter relaxation by CORM-1, authentic CO, and NANC nerve stimulation

The present studies compared the effects of CO-releasing molecule (CORM-1), authentic CO, and nonadrenergic noncholinergic (NANC) nerve stimulation in the internal anal sphincter (IAS). Functional in vitro experiments and Western blot studies were conducted in rat IAS smooth muscle. We examined the effects of CORM-1 (50-600 microM) and authentic CO (5-100 microM) and NANC nerve stimulation by electrical field stimulation (EFS; 0.5-20 Hz, 0.5-ms pulse, 12 V, 4-s train). The experiments were repeated after preincubation of the tissues with the neurotoxin TTX, the guanylate cyclase inhibitor 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ), the selective heme oxygenase (HO) inhibitor tin protoporphyrin IX (SnPP-IX), the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA), and SnPP-IX + L-NNA. We also investigated the effects of the HO substrate hematin (100 microM). CORM-1, as well as CO, produced concentration-dependent IAS relaxation, whereas hematin had no effect. TTX abolished and L-NNA significantly blocked IAS relaxation by EFS without any effect on CORM-1 and CO. ODQ blocked IAS relaxation by CORM-1, authentic CO, and EFS. SnPP-IX had no significant effect on IAS relaxation by CORM-1, CO, or EFS. The presence of neuronal nitric oxide synthase, HO-1, and HO-2 in IAS smooth muscle was confirmed by Western blot studies. CORM-1 and CO, as well as NANC nerve stimulation, produced IAS relaxation via guanylate cyclase/cGMP-dependent protein kinase activation. The advent of CORM-1 with potent effects in the IAS has significant implications in anorectal motility disorders with regard to pathophysiology and therapeutic potentials.     

Functional constraints of CAM leaf anatomy: tight cell packing is associated with increased CAM function across a gradient of CAM expression

Increased cell size, increased leaf succulence, reduced intercellular air space (IAS), and reduced surface of mesophyll exposed to IAS (L(mes)/area) are traits associated with the Crassulacean acid metabolism (CAM) photosynthetic pathway. An examination was carried out to determine whether these anatomical and structural traits are related to the degree of CAM function in eight CAM species, as measured by CO(2) assimilation during the CAM and C(3) phases. Increased cell size and leaf succulence were not closely related to the degree of CAM function, indicating that succulence beyond a certain threshold does not enhance CAM function. Reduced IAS and L(mes)/area were positively related to CAM function, and negatively related to C(3) function. These results indicate that reduced IAS and L(mes)/area are beneficial for CAM function through the reduction of CO(2) efflux and the improvement of carbon economy. However, reduced IAS and L(mes)/area limit C(3) photosynthesis, potentially mediating a bimodal distribution of weak and strong CAM species with high and low IAS and L(mes)/area values, respectively.     

Public support for invasive alien species eradication programs: insights from the Netherlands

Over the last few decades, the number of invasive alien species (IAS) has increased worldwide. IAS can have negative impacts on biodiversity, human health, and the economy. For a number of reasons, IAS policies and management schemes that have been implemented have not been sufficient to tackle the problem. In this article, we focus on IAS eradication and a main obstacle to eradication, namely a lack of public support. By analyzing three specific cases of IAS eradication in the Netherlands (Indian house crow; Pallas's squirrel; and American bullfrog), we show how factors initially affecting public support for eradication interact with each other and influence the effectiveness of the measures that IAS eradication managers implement in order to achieve support for their eradication programs. Our analysis provides a better understanding of the manipulability of factors affecting public support. Finally, it reveals concrete measures that IAS managers can implement in order to gain public support. A lesson for IAS eradication managers is that they can effectively aim for support for eradication, even if low public support for eradication is to be expected in first instance. In addition, this article provides insight into practical measures that IAS eradication managers can implement.     

Autocrine regulation of internal anal sphincter tone by renin-angiotensin system: comparison with phasic smooth muscle

The myogenic control mechanisms that govern the basal tone in the internal anal sphincter (IAS) are not known. The present studies determined the autocrine regulation of ANG II in the IAS. The studies were performed in the freshly isolated smooth muscle cells (SMC) of the IAS. We determined the presence of ANG II precursor angiotensinogen (Angen), and the enzymes that convert it into ANG II, using functional, molecular biology, and immunocytochemical studies in rats. ANG II levels in the SMC were determined using ELISA. The IAS SMC generate ANG II at a rate severalfold higher than those from the adjoining smooth muscle of rectum (RSM). RT-PCR data show that IAS exclusively expresses significant higher levels of renin, Angen, and angiotensin-converting enzyme (ACE). These data were confirmed using Western blot analyses and immunocytochemistry. In the IAS SMC, H-77 (10 microM; renin inhibitor) and captopril (1 microM; ACE inhibitor) decreased the basal as well as Angen-increased levels of ANG II. The following functional data corroborate the role of renin-angiotensin system (RAS) in the IAS tone. Angen produced concentration-dependent shortening of the IAS SMC that was inhibited by H-77 and captopril. In addition, H-77 or captopril caused a concentration-dependent fall in the IAS tone vs. nontonic tissues. Basal tone in IAS is partially under the autocrine control of cellular RAS evident by the expression of mRNA coding Angen, renin, and ACE and translation to the respective proteins in the SMC.     

Bioengineered human IAS reconstructs with functional and molecular properties similar to intact IAS

Because of its critical importance in rectoanal incontinence, we determined the feasibility to reconstruct internal anal sphincter (IAS) from human IAS smooth muscle cells (SMCs) with functional and molecular attributes similar to the intact sphincter. The reconstructs were developed using SMCs from the circular smooth muscle layer of the human IAS, grown in smooth muscle differentiation media under sterile conditions in Sylgard-coated tissue culture plates with central Sylgard posts. The basal tone in the reconstructs and its changes were recorded following 0 Ca(2+), KCl, bethanechol, isoproterenol, protein kinase C (PKC) activator phorbol 12,13-dibutyrate, and Rho kinase (ROCK) and PKC inhibitors Y-27632 and G?-6850, respectively. Western blot (WB), immunofluorescence (IF), and immunocytochemical (IC) analyses were also performed. The reconstructs developed spontaneous tone (0.68 ± 0.26 mN). Bethanechol (a muscarinic agonist) and K(+) depolarization produced contraction, whereas isoproterenol (β-adrenoceptor agonist) and Y-27632 produced a concentration-dependent decrease in the tone. Maximal decrease in basal tone with Y-27632 and G?-6850 (each 10(-5) M) was 80.45 ± 3.29 and 17.76 ± 3.50%, respectively. WB data with the IAS constructs' SMCs revealed higher levels of RhoA/ROCK, protein kinase C-potentiated inhibitor or inhibitory phosphoprotein for myosin phosphatase (CPI-17), phospho-CPI-17, MYPT1, and 20-kDa myosin light chain vs. rectal smooth muscle. WB, IF, and IC studies of original SMCs and redispersed from the reconstructs for the relative distribution of different signal transduction proteins confirmed the feasibility of reconstruction of IAS with functional properties similar to intact IAS and demonstrated the development of myogenic tone with critical dependence on RhoA/ROCK. We conclude that it is feasible to bioengineer IAS constructs using human IAS SMCs that behave like intact IAS.