[Infections in interventional electrophysiology]. / Infections en rythmologie interventionnelle.

The implantation of pacemakers and defibrillators carries the highest risk of infection in interventional electrophysiology. The use of implantable cardiac devices is continually increasing with almost 2 million devices implanted worldwide each year. The recipients' profile may also be associated with an increased risk of infection. Several measures can be implemented to reduce the risk of device-related infection. Systematic antibiotic prophylaxis has proven to be beneficial provided that prescription modalities are respected, especially with respect to the selection of the appropriate molecule and timing of administration prior to the procedure. Despite all the precautions taken during surgery (asepsis, prophylactic antibiotic therapy….) the estimated rate of peri-procedural infection is around 2%. Device related infections are associated with a high rate of morbidity and mortality as well as substantial healthcare costs. Staphylococcus aureus (SA) and epidermidis (SE) are the pathogenic agents involved in most cases. Prevention is crucial given the difficulties in treating such infections because of the near-systematic need to remove the device and antibiotic resistance. Leadless pacemakers and subcutaneous defibrillators are potential alternatives to implantable endocardial devices, albeit with certain limitations. A group of experts has recently issued consensus paper on the prevention, diagnosis and treatment of infections associated with endocardial implantable cardiac devices.

Psoriatic epidermis is associated with upregulation of CDK2 and inhibition of CDK4 activity.

BACKGROUND: The cyclin-dependent kinases (CDKs) CDK2 and CDK4 are involved in regulation of cell-cycle progression, and psoriasis is characterized by hyperproliferation of basal epidermal cells. CDK inhibitory proteins (CKIs) such as p16INK 4A (p16) bind CDK4/6 kinases and prevent their interaction with D-type cyclins. CKIs such as p21Cip1 (p21) and p27Kip1 (p27) associate with CDK-cyclin complexes and prevent their activation. OBJECTIVES: To gain insight into the molecular implication of CDK2 and CDK4 kinases in psoriasis, we sought to characterize expression of these kinases and associated cyclins, as well as of CKIs, and addressed the status of CDK2 and CDK4 activity in human psoriatic epidermis. METHODS: A cohort of 24 patients with psoriasis participated in the study. Biopsies were removed from a chronic plaque and from nonlesional skin. CDK2, CDK4, cyclin D1, cyclin E and CKI protein expression was assessed by immunoblotting, immunohistochemistry and immunofluorescence. CDK4 and CDK2 mRNA expression was determined by real-time polymerase chain reaction. Specific kinase activities of CDK2 and CDK4 were evaluated using fluorescent peptide biosensors. RESULTS: CDK2-cyclin E expression and activity were significantly increased in psoriatic epidermis compared with uninvolved adjacent skin. In contrast, CDK4-cyclin D1 activity was inhibited, although its expression was increased in psoriatic epidermis and its transcription slightly inhibited. p27 expression was reduced, while p16 and p21 expression was induced in psoriatic epidermis. CONCLUSIONS: Epidermal CDK2 activity is increased in psoriatic epidermis while CDK4 activity is completely inhibited. These alterations are not associated with changes in CDK transcription and instead involve post-translational control mediated by decreased expression of p27 and p16 overexpression, respectively. What's already known about this topic? Cyclin-dependent kinases (CDKs) are involved in cell-cycle progression. The levels of cyclin partners and CDK inhibitors regulate their activity. Psoriasis is a chronic T-cell-driven inflammatory skin disease characterized by hyperproliferation of basal epidermal cells. What does this study add? Thanks to fluorescent peptide biosensors, this study demonstrates that epidermal CDK2 activity is increased in psoriatic epidermis while CDK4 activity is completely inhibited. These alterations involve post-translational control mediated by decreased expression of p27, and p16 overexpression, respectively. What is the translational message? CDK2 and CDK4 are involved in regulation of cell-cycle progression, and psoriasis is characterized by hyperproliferation of basal epidermal cells. Epidermal CDK2 activity is increased in psoriatic epidermis while CDK4 activity is completely inhibited. These alterations are not associated with changes in CDK transcription and instead involve post-translational control mediated by decreased expression of p27 and p16 overexpression, respectively. Pharmacological modulation of CDK2 and CDK4 may constitute a promising therapeutic strategy.

[Transcatheter aortic valve implantation and conduction disturbances]. / Implantation percutanée de valve aortique et troubles conductifs.

Transcatheter aortic valve implantation (TAVI) is currently becoming the treatment of choice for patients with calcific aortic stenosis. Despite several technical improvements, the incidence of conduction disturbances has not diminished and remains TAVI's major complication. These disturbances include the occurrence of left bundle branch block and/or high-grade atrioventricular block often requiring pacemaker implantation. The proximity of the aortic valve to the conduction system (conduction pathways) accounts for the occurrence of these complications. Several factors have been identified as carrying a high risk of conduction disturbances like the presence of pre-existing right bundle branch block, the type of valve implanted, the volume of aortic and mitral calcifications, the size of the annulus and the depth of valve implantation. Left bundle branch block is the most frequent post TAVI conduction disturbance. Whereas the therapeutic strategy for persistent complete atrioventricular block is simple, it becomes complex in the presence of fluctuating changes in PR interval and left bundle branch block duration. The QRS width threshold value (150-160 ms) indicative of the need for pacemaker implantation is still being debated. Although there are currently no recommendations regarding the management of these conduction disturbances, the extension of TAVI indications to patient at low surgical risk calls for a standardization of our practice. However, a decision algorithm was recently proposed by a group of experts composed of interventional cardiologists, electrophysiologists and cardiac surgeons. There are still uncertainties about the appropriate timing of pacemaker implantation and the management of new onset left bundle branch block.

Transvenous cryo-ablation of the slow pathway for the treatment of atrioventricular nodal re-entrant tachycardia: a single-centre initial experience study.

AIMS: Within the last several years, transvenous cryo-ablation has become an alternative method to perform ablation of the slow-pathway. This study evaluated the acute and long-term safety and effectiveness of atrio-ventricular nodal re-entrant tachycardia (AVNRT) cryo-ablation. METHODS AND RESULTS: The first 69 consecutive patients with AVNRT (60 slow-fast, 4 fast-slow, and 5 slow-slow) who underwent slow-pathway cryo-ablation were included. Mean age was 37 +/- 15, body weight 68 +/- 14 kg, symptom duration 125 +/- 104 months, and number of ineffective antiarrhythmic (AA) drugs 1.8 +/- 1.4. A 7 Fr cryo-catheter (Cryocath(A)) was used, with initially 4-mm-tip and later with 6-mm-tip electrode. Cryo-mapping (n = 7.9 +/- 8.4 per pt) was performed at the temperature of -30 degrees C to test the effect on the target ablation site. Successful cryo-mapping was defined as abolition of nodal conduction jump or AV nodal refractory period prolongation. Cryo-ablation (n = 5.1 +/- 4.9 per pt) was then applied by freezing to -75 degrees C for 4 min in duration if no AV-block occurred. Acute procedural success (defined as AVNRT non-inducibility) after the first cryo-ablation attempt was achieved in 60/69 patients (87%). During cryo-ablation, inadvertent transient AV-block was encountered in 14 patients (five I AV-block and nine II-III AV-block). A mid-septal target site was the only variable correlated with inadvertent AV-block occurrence during cryo-ablation (P < 0.02). Long-term clinical success after cryo-ablation was globally achieved in 56/66 (85%) with a mean follow-up of 18 +/- 9 months (3 pts dropped-out). After the first procedure, 41/66 (62%) had no relapse, eight had a dramatic reduction in AVNRT duration-frequency and considered themselves cured, and five needed previously ineffective AA (with no relapse in three, drastic reduction in AVNRT duration-frequency in two). The five last patients needed one or more procedures, after which one had no recurrence and one had reduction in duration-frequency. Absence of recurrence after the first procedure was positively correlated with 6-mm-tip cryo-catheter use (<0.001) and negatively with acute procedural success (<0.001). At multivariate analysis, both were independently significant (<0.04 and <0.008, respectively). Long-term clinical success was correlated only with 6-mm-tip cryo-catheter use (<0.001). CONCLUSIONS: Slow pathway cryo-ablation is associated with an acute success but a higher recurrence rate. A 6-mm-tip cryo-catheter seems to assure during cryo-ablation a large acute and long-term success. AV-block seems non-guaranteed by a negative cryo-mapping, stressing on need of a careful surveillance. Nevertheless, the theoretical advantage of avoiding the risk of permanent AV-block when compared with radiofrequency needs larger series to be demonstrated.

[Glucocorticoid-induced hypertrophic cardiomyopathy in premature infants: apropos of 4 cases]. / Myocardiopathie hypertrophique induite par les glucocorticoïdes chez le prématuré: à propos de quatre cas.

BACKGROUND: The steroidal treatment used to prevent bronchopulmonary dysplasia (BD) in the preterm babies may be the cause of several complications, one of them being hypertrophic cardiomyopathy. CASE REPORT: Four infants developed hypertrophic cardiomyopathy during glucocorticoid (dexamethasone and/or betamethasone) treatment for bronchopulmonary dysplasia. In one of them, septal hypertrophy led to left ventricular outflow tract obstruction and congestive heart failure. All four were premature infants born after 2 weeks of gestation and weighing 780 to 1,080 g. The first echocardiographic changes appeared between the 4th and 15th day of the glucocorticoid course when the cumulated dose was respectively 1.82-1.87-3.51 and 3.86 mg/kg. Hypertrophic cardiomyopathy resolved completely between 2 and 4 weeks after cessation of the treatment. CONCLUSION: The glucocorticoid dosage to prevent BD should be reduced to 0.3 mg/kg/j and the myocardial function should be monitored by repeated echocardiograms during the first 15 days of treatment.

[Macular edema caused by contraction of the posterior hyaloid in diabetic retinopathy. Surgical treatment of a series of 22 cases]. / Oedèmes maculaires induits par la contraction de la hyaloïde postérieure dans la rétinopathie diabétique. Traitement chirurgical sur une série de 22 cas.

We have observed some patients with diabetic macular edema who did not respond to grid laser treatment and who improved with spontaneous posterior vitreous detachment or vitrectomy. These cases have a taut and glistening vitreo-macular interface. Three such cases are presented in detail. Pars plana vitrectomy with separation of the posterior hyaloid was performed in 22 cases. All of them had proliferative diabetic retinopathy, previously treated by panretinal photocoagulation. Fourteen cases had an ineffective macular grid laser treatment. Postoperative visual acuity was improved in 19 eyes and was unchanged in three eyes. The macular edema disappeared in 12 eyes and decreased in 10. Complications included a vitreous hemorrhage in 6 eyes, a paramacular tear in 1 eye, a reghmatogenous retinal detachment in 1 eye and cataract formation in 2 eyes. Vitreous surgery can improve the visual prognosis in cases of diabetic macular edema associated with a pathological vitreo-macular interface.

Determination of zolpidem and zopiclone in serum by capillary column gas chromatography.

A gas chromatographic method using a short, high-resolution capillary column connected to a specific thermoionic detector and requiring a simple and short extraction step without evaporation was developed for the rapid and precise determination of two new hypnotics, zolpidem and zopiclone, in serum at concentrations greater than 5 ng/mL. The assay was linear between 5 and 200 ng/mL, with coefficients of intra- and interassay variation less than 5% for both. The method was validated and then used to analyze zolpidem serum concentrations in nine rabbits after oral administration of 0.5 mg/kg and zopiclone serum concentrations in six patients treated orally with a 7.5-g dose.