Transvenous lead extraction on uninterrupted anticoagulation: A safe approach?

IntroductionCurrent guidelines advocate reviewing peri-procedural anticoagulation on individual case basis for transvenous lead extraction (TLE). We investigated the safety of TLE on uninterrupted warfarin with therapeutic INR.MethodsRetrospective registry of consecutive patients undergoing TLE on uninterrupted warfarin (Warfarin Group) across two centres. Age and sex matched controls not on anticoagulation (No-Warfarin Group) and undergoing TLE over the same time-period were included. Both groups were compared over one-year.Results121 TLEs over 18-months. 22 patients on uninterrupted anticoagulation were compared to 22 controls. Groups were well matched for baseline demographics other than INR. Warfarin group had mean INR of 2.2 ± 0.6 (range 2–3.5). Primary end point was procedural safety and efficacy. Amongst cases, 43/45 (96%) leads were removed in their entirety compared to 37/40 (93%) in controls (p = 0.66). In the cases, these included 44% defibrillator, 47% pace-sense and 9% CS leads of average duration 7yrs. There was no reported tamponade, haemothorax or procedural mortality in either group. One patient amongst cases required inotropic support while two patients amongst controls had device-site haematomas. No significant difference reported in Hb drop post-procedure or overall complication rate between the groups (p = 0.11,0.32). Cox regression showed a significant association between procedural success and device infection, number of leads extracted, serum creatinine (p = 0.03, 0.04, 0.02). Over a 1-year follow-up, there was lead displacement in one case and one control had infection of the re-implanted device.ConclusionTLE can be carried out safely in anticoagulated patients with therapeutic INRs. Larger multicentre studies are required to confirm these findings.     

Pacemaker lead endocarditis: A rare diagnosis with a varied presentation

We present a patient with a pacemaker lead endocarditis who showed no signs of pocket infection but with high fever and signs of infection in the routine laboratory tests. A diagnosis of pacemaker lead endocarditis must be considered in all patients with fever and infection parameters who have a pacemaker inserted, not only in the first weeks after implantation but also late after implantation, as long as no other cause of infection has been found. Transthoracal echocardiography alone is not sensitive enough to establish the correct diagnosis. Transoesophageal echocardiography (TEE) is mandatory to demonstrate the presence or absence of a vegetation on a pacemaker lead.     

Characteristics of cardiac device infections in the Isala Hospital; a large volume tertiary care cardiology centre

Aims

To determine the frequency, characteristics and risk factors of cardiac device infections in the Isala Hospital.

Methods

We retrospectively studied all patients who underwent cardiac device procedures performed in the cardiac catheterisation lab and the operating room from 2010 to 2012. All patients who developed a cardiac device infection were reviewed for its characteristics.

Results

31/2026 patients developed a cardiac device infection (1.5 %). One (3.2 %) patient died within 30 days of hospitalisation. Device infection rates for procedures in the catheterisation lab and operating room were similar (p = 0.60). Positive cultures were present in 27/31 (87 %) cases. These consisted predominantly of micro-organisms that are part of the skin flora (84 %). The mean time between device procedure and infection was 14 ± 21 months (range 0–79). Cardiac device infection was significantly associated with device revision, (65 % were revisions in patients with device infection vs. 30 % revisions in patients without device infection, p = 0.011) and placement of a left ventricular lead in pacemaker implantations (59 % of patients with vs. 51 % of patients without device infection, p < 0.001).

Conclusion

The frequency of cardiac device infection was 1.5 % with a mortality of 3.2 % within 30 days, which is lower compared with other registries. Cardiac device infections were associated with device revisions and placement of left ventricular leads in pacemaker implantations.     

Regulatory T cells and infection: a dangerous necessity

Surviving a given infection requires the generation of a controlled immune response. Failure to establish or restore homeostatic conditions during or following the onset of an infection can lead to tissue damage. Investigation of the immunoregulatory network that arises in response to the infectious process or that is induced by the pathogen itself should provide insight into therapeutic approaches for the control of infection and any subsequent immunopathology. In this Review, I discuss current hypotheses and points of polemic associated with the origin, mode of action and antigen specificity of the various populations of regulatory T cells that arise during infection.     

A gonorrhea model treating sensitive and resistant strains in a multigroup population

In recent years gonorrhea infection with antibiotic-resistant strains, especially PPNG, has become a significant public health problem. Drawing on the gonorrhea model of Lajmanovich and Yorke, a multigroup model that embraces both resistant and sensitive strains of the organism is introduced. It is shown that, like the Lajmanovich and Yorke (single-strain) model, in the general case the sensitive-resistant model has a unique globally asymptotic equilibrium. As a function of the interplay between contact rates, cure rates, and reversion rates, the equilibrium can lead to endemic infection with sensitive infection only, resistant infection only, or both, or to elimination of sensitive and resistant infection.     

Immune responses to the major capsid protein during parvovirus infection of rats

Rat virus (RV) is a common parvovirus of laboratory rodents which can disrupt rat-based research. Prenatal or perinatal infection can be pathogenic or lead to persistent infection, whereas infection of adult rats is typically self-limiting. Effects on the host immune system have been documented during RV infection, but little is known about immune responses necessary for viral clearance. Our studies were conducted to identify humoral and cellular responses to the predominant capsid protein, VP2, during experimental infection of adult rats. We observed VP2-specific proliferation, gamma interferon production, and an immunoglobulin G2a humoral response that is maintained for at least 35 days following RV infection. These results strongly suggest the induction of virus-specific Th1-mediated immunity.     

Multiple Stable Periodic Oscillations in a Mathematical Model of CTL Response to HTLV-I Infection

Stable periodic oscillations have been shown to exist in mathematical models for the CTL response to HTLV-I infection. These periodic oscillations can be the result of mitosis of infected target CD4⁺ cells, of a general form of response function, or of time delays in the CTL response. In this study, we show through a simple mathematical model that time delays in the CTL response process to HTLV-I infection can lead to the coexistence of multiple stable periodic solutions, which differ in amplitude and period, with their own basins of attraction. Our results imply that the dynamic interactions between the CTL immune response and HTLV-I infection are very complex, and that multi-stability in CTL response dynamics can exist in the form of coexisting stable oscillations instead of stable equilibria. Biologically, our findings imply that different routes or initial dosages of the viral infection may lead to quantitatively and qualitatively different outcomes.     

Inadvertent Lead Placement In The Left Ventricle: A Case Report And Brief Review

Inadvertent lead placement in the left ventricle (LV) is an uncommon and often under-diagnosed complication of cardiac device implantation. Thromboembolic (TE) events are common and usually secondary to fibrosis or thrombus formation on or around the lead. Anticoagulation can prevent TE events. Percutaneous and surgical LV lead extractions have been performed successfully, but the risks of percutaneous lead removal are not well-defined. In this report, we describe a case of inadvertent LV lead placement and briefly review the contemporary literature.     

Restricted expression of herpes simplex virus lytic genes during establishment of latent infection by thymidine kinase-negative mutant viruses.

Infection of cells by herpes simplex virus (HSV) can lead to either lytic, productive infection or nonlytic, latent infection. The factors influencing this infection pathway decision are largely unknown. Thymidine kinase-negative mutant viruses can establish latent infection in neurons of mouse trigeminal ganglia but do not replicate productively in these cells. We show that during the early stages of establishment of latency by these mutants, expression of viral lytic genes is drastically reduced or undetectable as assayed by in situ hybridization. Thus, establishment of latent infection by HSV can occur despite severely restricted levels of lytic gene expression. This suggests that the block to productive replication during establishment of latent infection by HSV occurs before or early during the expression of alpha genes.     

The amphibian microbiome exhibits poor resilience following pathogen-induced disturbance

Infectious pathogens can disrupt the microbiome in addition to directly affecting the host. Impacts of disease may be dependent on the ability of the microbiome to recover from such disturbance, yet remarkably little is known about microbiome recovery after disease, particularly in nonhuman animals. We assessed the resilience of the amphibian skin microbial community after disturbance by the pathogen, Batrachochytrium dendrobatidis (Bd). Skin microbial communities of laboratory-reared mountain yellow-legged frogs were tracked through three experimental phases: prior to Bd infection, after Bd infection (disturbance), and after clearing Bd infection (recovery period). Bd infection disturbed microbiome composition and altered the relative abundances of several dominant bacterial taxa. After Bd infection, frogs were treated with an antifungal drug that cleared Bd infection, but this did not lead to recovery of microbiome composition (measured as Unifrac distance) or relative abundances of dominant bacterial groups. These results indicate that Bd infection can lead to an alternate stable state in the microbiome of sensitive amphibians, or that microbiome recovery is extremely slow—in either case resilience is low. Furthermore, antifungal treatment and clearance of Bd infection had the additional effect of reducing microbial community variability, which we hypothesize results from similarity across frogs in the taxa that colonize community vacancies resulting from the removal of Bd. Our results indicate that the skin microbiota of mountain yellow-legged frogs has low resilience following Bd-induced disturbance and is further altered by the process of clearing Bd infection, which may have implications for the conservation of this endangered amphibian.Subject terms: Microbial ecology, Community ecology     

DRY-ROT DISEASE OF THE POTATO

A study has been made of the incidence of dry rot in seed potatoes in relation to commercial handling methods, and it has been shown that infection following grading by mechanical reciprocating riddles fitted with bare wire screens is more serious than that following normal handling at harvest or during transport. Hand picking, hand riddling and the use of rubber-spool graders or rubber-coated screens reduced infection by varying amounts. The higher incidence of the disease in 'transported' as against 'home-saved' seed is regarded as being due to machine grading of such stocks some months prior to planting.
Contamination of stores or boxes has not been found to play any material part in the spread of infection under commercial conditions unless tubers are roughly handled during storage. As contact infection has been found to be rare, it is considered that the practice of 'picking over' stocks during the winter to remove diseased tubers is unnecessary and may lead to further infection.
In addition to wounds, lesions of both blight and powdery scab, but not common scab, have been found to be a means of infection.     

Exogenous interleukin-12 protects against lethal infection with coxsackievirus B4

Infections with the group B coxsackieviruses either can be asymptomatic or can lead to debilitating chronic diseases. To elucidate the mechanism by which these viruses cause chronic disease, we developed a mouse model of chronic pancreatitis by using a virulent variant of coxsackievirus B4, CVB4-V. Infection with CVB4-V results in an early, severe pancreatitis, which can lead to mortality or progress to chronic pancreatitis. Chronic pancreatitis, in this model, is due to immunopathological mechanisms. We investigated whether interleukin-12 (IL-12) could modulate the outcome of CVB4-V infection. Eighty-five percent of the infected mice treated with 500 ng of IL-12 survived, whereas all untreated mice succumbed. To understand the mechanism underlying the beneficial effect of IL-12, we investigated the role of gamma interferon (IFN-gamma). Three lines of evidence suggest that the protective effect of IL-12 is due to IFN-gamma. First, administration of IL-12 increased the production of endogenous IFN-gamma in CVB4-V-infected mice. Both NK and NKT cells were identified as the source of IFN-gamma. Second, IFN-gamma knockout mice treated with IL-12 succumbed to infection with CVB4-V. Third, wild-type mice treated with IFN-gamma survived infection with CVB4-V. Due to the antiviral effects of IFN-gamma, we examined whether IL-12 treatment affected viral replication. Administration of IL-12 did not decrease viral replication in the pancreas, but it did prevent extensive tissue damage and the subsequent development of chronic pancreatitis. The data suggest that IL-12 treatment during CVB4-V infection is able to suppress the immunopathological mechanisms that lead to chronic disease.     

Role of cervical dendritic cell subsets,co-stimulatory molecules,cytokine secretion profile and beta-estradiol in development of sequalae to Chlamydia trachomatis infection

Background  

Chlamydia trachomatis infection of the female genital tract can lead to serious sequelae resulting in fertility related disorders. Little is known about the mechanism leading to Chlamydia induced pathology and factors responsible for it. As only some of the women develops reproductive disorders while majority of the women clears infection without any severe sequalae, mucosal immune response in women with or without fertility disorders was studied to identify factors which may lead to final clinical outcome of chlamydial infection.     

Repeated passage of wild-type woodchuck hepatitis virus in lymphoid cells does not generate cell type-specific variants or alter virus infectivity

Woodchuck hepatitis virus (WHV), which is closely related to human hepatitis B virus, infects the liver but also invariably establishes persistent infection in the lymphatic system. Although the dose of invading virus appears to be the main factor in determining whether WHV infection is restricted to the lymphatic system or also engages the liver, the nature of WHV lymphotropism remains unclear and a role for a specific lymphotropic variant was not excluded. The availability of woodchuck lymphocyte and hepatocyte cultures susceptible to WHV infection allows investigation of this issue in vitro. We hypothesized that repeated passage of wild-type WHV in lymphoid cells should lead to enrichment of a lymphotropic virus variant, if in fact such a variant exists. For this purpose, wild-type WHV with a homogeneous sequence was used as the inoculum, while lymphoid cells from a single healthy woodchuck donor and a normal woodchuck WCM-260 hepatocyte line served as infection targets. The serial passage of the wild-type virus repeated up to 13 times for both cell types did not lead to the emergence of cell type-specific WHV variants, as revealed by sequence analysis of the virus envelope and the core and X gene sequences. Moreover, the virus passaged in both cell types remained infectious for naive woodchucks, produced infection profiles that depended upon virus dose but not on virus cellular origin, and retained its initial DNA sequence. These results imply that WHV lymphotropism is a natural propensity of the wild-type virus and is not a consequence of infection with a viral variant.     

Bacteriæmia and Oral Sepsis: (Section of Odontology)

Transient streptococcal bacteri?mias are a frequent sequel to dental extractions especially when the mouth is the seat of severe chronic gum infection. Bacteria may also gain admission to the blood-stream in such cases irrespective of operative procedures and probably as the result, in many instances, of minor degrees of gum injury such as is produced by biting on a loose tooth. Acute apical infections do not appear to be especially associated with blood infection of this kind, the focus of infection here apparently being effectively "walled off" by the associated inflammatory reaction.Of the two factors, infection and trauma, involved in the production of these post-operative bacteri?mias, infection appears to be the more important since, when it is marked, very slight degrees of gum injury are sufficient to produce blood-stream invasion. In the complete absence, however, of the type of trauma induced by the "rocking" of a tooth during its removal, extraction may be accomplished without producing a heavy bacterial shower in the blood.Usually these transient bacteri?mias produce no permanent ill-effect, but there is some evidence that, occurring in subjects with abnormal heart valves, they may lead to subacute infective endocarditis. Thirteen cases are reported where the valvular infection appeared to result from a post-operative dental bacteri?mia.Prevention of such bacteri?mias may be achieved by the reduction or elimination of infection and trauma. Complete elimination of the gum infection is difficult although preliminary treatment of the gum margin by some measure such as cauterization may lessen it and lead to a reduction of the post-operative bacterial shower. Similarly, by manipulating an infected tooth as little as possible during its extraction the incidence or degree of blood infection may be decreased.     

Comparative transductions of breast cancer cells by three DNA viruses

Defining the ideal vectors to transduce breast cancer using viruses is currently under intense pre-clinical evaluation. Our study constitutes the first direct comparison of the infection efficiencies of a human serotype 5 (Ad5), a canine serotype 2 (CAV-2) adenovirus, and a human serotype 2 adeno-associated virus (AAV-2) in breast cancer cells. We observed an excellent infection efficiency for Ad5 vector, whereas both CAV-2 and AAV-2 vectors lead to low infection of these cells. Real-time PCR, flow cytometry, and antibody blocking studies suggest that Ad5 and CAV-2 infection ability is not strictly dependent on coxsackie adenovirus receptor (CAR) or alpha(v) integrin levels. In conclusion, our data suggest that human adenoviruses are excellent transducers of breast cancer cells, though it may be difficult to predict the extent of infection solely on CAR or alpha(v) integrin levels.     

Interaction with coxsackievirus and adenovirus receptor, but not with decay-accelerating factor (DAF), induces A-particle formation in a DAF-binding coxsackievirus B3 isolate

Although many coxsackie B viruses interact with decay accelerating factor (DAF), attachment to DAF by itself is not sufficient to initiate infection. We examined the early events in infection that follow virus interaction with DAF, and with the coxsackievirus and adenovirus receptor (CAR). Interaction with soluble CAR in a cell-free system, or with CAR on the surfaces of transfected cells, induced the formation of A particles; interaction with soluble or cell surface DAF did not. The results suggest that CAR, but not DAF, is capable of initiating the conformational changes in the viral capsid that lead to release of viral nucleic acid.     

Maintenance of silastic–teflon shunts for intermittent haemodialysis

The occurrence of infection in the tissues surrounding external arteriovenous shunts was studied and die important relationship of pyogenic infection to clotting was confirmed. The local application of fusidic add tulle and lanolin greatly reduced the occurrence of both infection and clotting and the need for cannula replacement.Urokinase used for declotting shunts when standard procedures had failed, restored blood flow whether dotting was related to infection or to local vascular factors. This treatment is not advised when clotting is associated with a local abscess, as it may make cannula replacement necessary. Severe local vascular factors, such as metastatic calcification, Raynaud''s phenomenon, and venous stenosis, may lead to poor blood flow, so that despite clot lysis elective cannula replacement or the creation of a subcutaneous arteriovenous fistula is required.     

Interaction of mouse hepatitis virus (MHV) spike glycoprotein with receptor glycoprotein MHVR is required for infection with an MHV strain that expresses the hemagglutinin-esterase glycoprotein.

In addition to the spike (S) glycoprotein that binds to carcinoembryonic antigen-related receptors on the host cell membrane, some strains of mouse coronavirus (mouse hepatitis virus [MHV]) express a hemagglutinin esterase (HE) glycoprotein with hemagglutinating and acetylesterase activity. Virions of strains that do not express HE, such as MHV-A59, can infect mouse fibroblasts in vitro, showing that the HE glycoprotein is not required for infection of these cells. The present work was done to study whether interaction of the HE glycoprotein with carbohydrate moieties could lead to virus entry and infection in the absence of interaction of the S glycoprotein with its receptor glycoprotein, MHVR. The DVIM strain of MHV expresses large amounts of HE glycoprotein, as shown by hemadsorption, acetylesterase activity, and immunoreactivity with antibodies directed against the HE glycoprotein of bovine coronavirus. A monoclonal anti-MHVR antibody, MAb-CC1, blocks binding of virus S glycoprotein to MHVR and blocks infection of MHV strains that do not express HE. MAb-CC1 also prevented MHV-DVIM infection of mouse DBT cells and primary mouse glial cell cultures. Although MDCK-I cells express O-acetylated sialic acid residues on their plasma membranes, these canine cells were resistant to infection with MHV-A59 and MHV-DVIM. Transfection of MDCK-I cells with MHVR cDNA made them susceptible to infection with MHV-A59 and MHV-DVIM. Thus, the HE glycoprotein of an MHV strain did not lead to infection of cultured murine neural cells or of nonmurine cells that express the carbohydrate ligand of the HE glycoprotein. Therefore, interaction of the spike glycoprotein of MHV with its carcinoembryonic antigen-related receptor glycoprotein is required for infectivity of MHV strains whether or not they express the HE glycoprotein.     

Complications and lead extraction in cardiac pacing and defibrillation

The only indications for which lead extraction may be really necessary are infected pacing or defibrillation systems. Superfluous non-functional leads can on the whole be more safely abandoned than extracted. Improvements in lead extraction will be more helped by designing and implanting leads that can be more easily removed than current models, than with better extraction tools. Still, as infection and hence lead extraction usually follows surgical interventions of a pacing or defibrillation system, avoiding the latter – or postponing it if possible – is of great importance (Neth Heart J 2008;16 (suppl 1):S28-S31.)