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Funding Acknowledgements Type of funding sources: None. Background/Introduction Smartwatch electrocardiograms (SW ECG) have been identified as a promising noninvasive solution to assess heart rhythm abnormalities, especially atrial arrhythmias (AA) which includes atrial fibrillation, atrial flutter and supraventricular tachycardia. This study evaluates the performance of the detection of AA with a smartwatch and compares the accuracy of two algorithms, the latest version of the original companion application (Apple ECG 2.0 App) and a novel deep neural network (DNN), in a population typical of an electrophysiology department. Purpose Determine if a novel DNN can improve the detection of AA on SW ECG in a tertiary care hospital. Methods 101 patients from the electrophysiology department of one tertiary center were included in this ongoing study. Three simultaneous ECGs were collected for each patient: one 12-lead ECG (Mindray BeneHeart R12) and two SW ECGs (Apple Watch) taken from the left wrist (SWw ECG) and the lower left abdomen (SWa ECG). 12-lead ECGs were adjudicated by a blinded expert electrophysiologist as 52 AA and 49 not AA and considered as gold standard. The SW ECGs were processed by the ECG 2.0 App and the DNN in parallel. The proportions of inconclusive diagnoses returned and the performances were assessed and compared. Results Overall, the ECG 2.0 App yielded inconclusive diagnoses for 19% (19/101) of all SWw ECGs while the DNN reduced that number to 0% (0/101). A similar result holds for SWa ECGs (Figure 1). Regarding the detection of AA from SWw ECGs, the ECG 2.0 App had a sensitivity of 81% (95% CI, 67%-90%), a specificity of 97% (95% CI, 87%-100%) and an accuracy of 89% (95% CI, 80%-94%) while the DNN had a sensitivity of 92% (95% CI, 82%-97%), a specificity of 90% (95% CI, 78%-96%) and an accuracy of 91% (95% CI, 84%-95%). For SWa ECGs (Figure 2), the sensitivity of the DNN was found significantly higher compared to the ECG 2.0 App: 96% (95% CI, 89%-98%) vs 76% (95% CI, 61%-87%). Conclusion(s): A novel DNN algorithm decreased the number of inconclusive diagnostics in the detection of AA from SW ECG from around 20% to 0%, which could help limit the overreading time spent by the physicians. Excluding inconclusive diagnostics, we observed no significant difference in performance between the two algorithms except for the sensitivity for SW ECG taken from the abdomen where the DNN outperforms the ECG 2.0 App. Routine application of this SW ECG analysis in tertiary care hospitals offers significant promise in arrhythmia diagnosis.

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Abbott Laboratories Background Pulmonary vein isolation (PVI) is an established treatment option for persistent atrial fibrillation (PersAF). Corresponding long-term success rates remain modest however, advancements in high-density (HD) mapping may better identify substrates. The HD grid-style mapping catheter (HD Grid) allows for simultaneous analysis of adjacent orthogonal bipolar signals that may assist in ablation strategy decisions to achieve favorable outcomes in treating PersAF. Objective This was a prospective, multi-center, observational study to quantify and characterize the use of a market-released HD mapping catheter in PersAF subjects. Methods HD Grid was used in PersAF subjects undergoing radiofrequency (RF) ablation across 25 sites to gather data regarding safety, mapping efficiency and quality, ablation strategies, and procedural outcomes. Results 334 PersAF subjects (average age: 64.2 years; 76% male) were enrolled in this study. Types of maps generated included peak-to-peak voltage (78%; 322/413), local activation time (LAT) (11.4%; 47/413), and complex fractionated electrogram (CFE) mean (7.7%; 32/413). Median total mapping points collected and used were 8428.0 (IQR 4845.0-13366.0) and 2099.0 (IQR 1219.0-2947.0), respectively, in a median of 11.0 (IQR 7.3-16.0) minutes per map. Low voltage, scar/fibrosis, and CFE were searched for in 90.4% (302/334), 53.6% (179/334), and 15.9% (53/334) of subjects, respectively. A PVI approach was used in 93.1% of all ablation procedures and 34.1% (114/334) of subjects received PVI plus additional lesions. HD Grid identified signals of interest not identified by the ablation catheter in 80.4% (205/255) of subjects. The total procedure time was 134.3 ± 51.3 minutes with a fluoroscopy time of 14.5 ± 11.3 minutes and RF ablation time of 32.4 ± 29.6 minutes. Of the subjects in atrial fibrillation (AF) (59.6%; 199/334), AF was terminated in 80.4% (160/199). 87.4% (173/198) of subjects were free from recurrent atrial arrhythmias as detected by 48-hour Holter monitoring at 12 months. 13.8% (46/334) of subjects experienced any adverse event through 12 months including 1 death unrelated to the procedure and 1 event deemed related to HD Grid by the investigator. Conclusion This study demonstrated the use of the HD Grid mapping catheter to create detailed maps and to guide ablation strategies to treat PersAF while maintaining an adequate safety profile.

Funding Acknowledgements Type of funding sources: None. BACKGROUND Several studies have shown the excellent prognostic value of stress cardiovascular magnetic resonance (CMR). However, its prognostic value in patients with pacemaker (PM) remains unknown because most studies excluded PM patients. PURPOSE This study aimed to assess the prognostic value of vasodilator stress perfusion CMR in patients with PM. METHODS Consecutive patients with MR-conditional pacemakers referred for stress perfusion CMR at 1.5 T were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or nonfatal myocardial infarction. Cox regressions analyses were performed to determine the prognostic value of CMR-parameters. The quality of CMR was rated by two observers blinded to clinical details. Data on pacemaker and leads were collected pre- and post-CMR. RESULTS Of 224 patients who completed the stress CMR protocol, 2 patients had inconclusive stress CMR due to artefact and 203 patients (72.9% male, mean age 71.4 ± 8.7 years) completed the follow-up (median [interquartile range], 7.0 [5.2-7.3] years). Among those, 23 experienced a MACE (11.3%). Stress CMR was well tolerated with no major adverse events. All scans were completed successfully with no significant change in lead thresholds or pacing parameters. Overall, the image quality was rated good or excellent in 84.1% of segments. Using Kaplan-Meier analysis, inducible ischemia and late gadolinium enhancement (LGE) were significantly associated with the occurrence of MACE (hazard ratio, HR: 11.80 [95% CI, 4.63-30.30]; and HR: 6.74 [95% CI, 2.47-18.40], both p CONCLUSION Stress CMR is safe, feasible and has a good discriminative prognostic value in consecutive patients with PM.

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Abbott Background 3D mapping systems are pivotal to identify low voltage areas and to define ablation strategies. In this context, high-density multipolar mapping catheters with varying electrode configurations are used for accurate myocardial substrate definition. High density mapping using a grid shaped catheter allows for use of simultaneous analysis of adjacent orthogonal bipolar signals that may assist in more accurate substrate characterization and ablation strategy decisions. Purpose This was a prospective, multicenter observational study to characterize the utility of electroanatomical mapping with a high density grid-style mapping catheter (HD Grid) in subjects undergoing catheter ablation for persistent atrial fibrillation (PersAF) or ventricular tachycardia (VT) in real-world clinical settings. Methods Mapping was performed with the HD Grid catheter to generate high-density maps of cardiac chambers in order to assess the potential influence of the simultaneous orthogonal bipole configuration on PersAF and VT ablation strategies. Differences in substrate identification between simultaneous orthogonal bipole configuration and standard along-the-spline electrode configuration, and potential effects on ablation strategies were investigated. Results During the study period (January 2019 through April 2020), 367 subjects underwent catheter ablation for PersAF (N = 333, average age 64.1yr, 75% male) or VT (N = 34, average age = 64.3yr, 85.3% male). In total, 494 maps were generated to treat patients undergoing PersAF ablation and 57 to treat patients undergoing VT ablation. Compared to standard along-the-spline configuration, mapping with the simultaneous orthogonal bipole configuration showed differences in 57.8% (178/308) of maps generated, with the greatest difference noticed in surface area of low voltage (62.9%) and location of low voltage (55.6%). In comparisons performed live during the procedure (n = 50), simultaneous orthogonal bipole configuration assisted in identification of ablation targets in 70.0% of cases, changing the ablation strategy compared to that identified with along-the-spline configuration in 34.3%. In comparisons performed retrospectively after the procedure (n = 258), the ablation strategy identified with simultaneous orthogonal bipole configuration differed from along-the-spline configuration in 21.7% of maps. Even compared to a higher-density electrode configuration using all-bipoles rather than along-the-spline bipoles, simultaneous orthogonal bipole configuration identified differences in 57.1% of maps. Conclusion The HD grid catheter combined with simultaneous orthogonal bipole configuration can define myocardial substrate more accurately compared to standard along-the-spline configuration. The difference in substrate identification has potential impact on ablation strategy. Further clinical trials are needed to elucidate the role of orthogonal bipole configuration mapping and improved ablation success rates.

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.

Background: Conflicting data exist regarding the benefit of urgent coronary angiogram and percutaneous coronary intervention (PCI) after sudden cardiac arrest, particularly in the absence of ST-segment elevation. We hypothesized that the type of lesions treated (stable versus unstable) influences the benefit derived from PCI. Methods: Data were taken between May 2011 and 2014 from a prospective registry enrolling all sudden cardiac arrest in Paris and suburbs (6.7 million inhabitants). Patients undergoing emergent coronary angiogram were included. Decision to perform PCI was left to the discretion of local teams. We assessed the impact of emergent PCI on survival at discharge according to whether the treated lesion was angiographically unstable or stable, and we investigated the predictive factors for unstable coronary lesions. Results: Among 9265 sudden cardiac arrests occurring during the study period, 1078 underwent emergent coronary angiogram (median age: 59.6 years, 78.3% males): 463 (42.9%) had an unstable lesion, 253 (23.5%) only stable lesions, and 362 (33.6%) no significant lesions. Emergent PCI was performed in 478 patients (91.4% of unstable and 21.7% of stable lesions). At discharge, PCI of unstable lesions was associated with twice-higher survival rate compared with untreated unstable lesions (47.9% versus 25.6%, P =0.013), while stable lesions PCI did not improve survival (25.5% versus 26.3%, P =1.00). After adjustment, PCI of unstable coronary lesions was independently associated with improved survival (odds ratio, 2.09 [95% CI, 1.42–3.09], P P =0.824). Angina, initial shockable rhythm, ST-segment elevation, and absence of known coronary artery disease were independent predictors of unstable lesions. Conclusions: Emergent PCI of unstable lesions is associated with improved survival after sudden cardiac arrest, contrary to PCI of stable lesions. Accordingly, early PCI should only be performed in patients with unstable lesions. Four factors (chest pain, ST-elevation, absence of coronary artery disease history, and shockable initial rhythm) could help identify patients with unstable lesions who would, therefore, benefit from emergent coronary angiogram.

BACKGROUND Analysis of Holter recordings can be challenging and time-consuming, therefore requiring significant clinical resources in order to achieve a high-quality diagnosis. Such resources depend largely on the qualifications of the person conducting the analysis and the duration of the recordings. A novel Holter analysis platform has been developed, based on deep neural networks trained with a dataset of one million ECGs, to allow fast and reliable Holter recording analysis. PURPOSE This study sought to compare the performance of an artificial intelligence (AI)-based Holter analysis platform using deep learning tools with a classical one used on a daily basis in hospitals (the reference). The main endpoints evaluated were duration to complete the analysis by the physician operating it as well as diagnostic accuracy of each strategy, when platforms are used by electrophysiologists (EPs). METHODS For this prospective evaluation, a total of 159 Holter recordings (24-hour) were selected from a large Holter dataset from 1 hospital, with a relatively high prevalence of electrical rhythm and conduction disorders. Recordings were analysed by four EPs using independently both the AI-based and classical analysis platforms. All four EPs had no previous experience with the AI-based platform, except for an introductory 6-hour training session. Three EPs had multiple years of experience with the traditional platform, while one EP had limited experience. For each recording, in addition to the analysis duration, diagnostic accuracy was evaluated through the analysis of the presence or absence of predefined cardiac arrhythmias and conduction disorders (prevalence): pauses (25.2%), ventricular tachycardia (VT, 30.2%), atrial fibrillation (AF, 26.4%), high grade atrioventricular block (AVB, 10.1%) and burden of premature ventricular complex larger than 10% (PVC, 23.9%). Definite diagnostics were established by an expert EP after a careful examination of all available analysis reports. RESULTS Time required for the AI-based analysis was on average 42% shorter compared to the traditional platform (6.65 min vs 11.5 min, p < 0.0001). Regarding accuracy to detect electrical disorders, there was no statistically significant differences between AI-based and classical platforms (AF: 98.7% vs 96.9%, Pause: 99.4% vs 100%, PVC: 98.7% vs 98.7%, VT: 92.5% vs 96.2%, AVB: 98.7% vs 94.3%). CONCLUSION: These preliminary findings suggest that an AI-based strategy to analyse Holter recordings may be highly accurate in detecting cardiac electrical abnormalities, with significant time savings compared to a classical strategy, even for users with no previous experience with the novel AI-based platform. An AI-based Holter analysis platform may contribute to a broader and more resource-efficient adoption of Holter monitoring. Abstract Figure. analysis duration using each strategy

International audience; 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 (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.

The objective of the present study was to develop an accurate and reproducible method for liver sinusoidal endothelial cell (LSEC) isolation in mice. Non parenchymal cells were isolated using a modified two step collagenase digestion combined with Optiprep density gradient centrifugation. LSEC were further purified using two prevalent methods short term selective adherence and CD146+ magnetic activated cell sorting (MACS) and compared in terms of cell yield viability and purity to our purification technique using CD11b cell depletion combined with long term selective adherence. LSEC purification using our technique allowed to obtain 7.07±3.80 million LSEC per liver while CD146+ MACS and short term selective adherence yielded 2.94±1.28 and 0.99±0.66 million LSEC respectively. Purity of the final cell preparation reached 95.10±2.58 when using our method. In contrast CD146+ MACS and short term selective adherence gave purities of 86.75±3.26 and 47.95±9.82 respectively. Similarly contamination by non LSEC was the lowest when purification was performed using our technique with a proportion of contaminating macrophages of only 1.87±0.77. Further isolated cells analysed by scanning electron microscopy presented typical LSEC fenestrations organized in sieve plates demonstrating that the technique allowed to isolate bona fide LSEC. In conclusion we described a reliable and reproducible technique for the isolation of high yields of pure LSEC in mice. This protocol provides an efficient method to prepare LSEC for studying their biological functions.

Introduction Les manifestations cutanees de la tuberculose sont polymorphes : infectieuses ou reactionnelles, elles peuvent se reveler a l’instauration de la quadritherapie antituberculeuse. Observations Une femme de 33 ans, d’origine nigerienne, sans autre antecedent qu’une tuberculose ganglionnaire cervico-axillaire, traitee depuis 4 semaines (quadritherapie 2 semaines puis tritherapie/arret de l’ethambutol car Bacille de Koch [BK] multisensible), presentait une recidive rapide, depuis 1 semaine, de multiples nouures inflammatoires, parfois ulcerees ou surmontees d’une desquamation, des quatre membres. S’y associaient arthromyalgies diffuses, nausees, et sensation febrile. Le premier episode, moindre, 1 an auparavant (epoque d’apparition des adenopathies), s’etait resolu spontanement. Le bilan initial (BK crachats, scanner TAP, IRM mammaire, serologie VIH) etait normal. La biopsie d’une nouure montrait un infiltrat dermo-hypodermique granulomateux focalement necrosant, evoquant une localisation cutanee de tuberculose, malgre l’absence de BK au direct (Ziehl) et en culture mycobacteriologique, avec PCR lepre negative. On ecartait l’hypothese d’erytheme noueux devant les ulcerations et la presence de granulome. On retenait le diagnostic de tuberculose cutanee revelee par le phenomene de reaction paradoxale. L’antibiotherapie etant inchangee, l’evolution etait progressivement favorable (cicatrices et pigmentation post-inflammatoire) ( Fig. 1 et 2 ). Discussion Les reactions paradoxales (RP) suite a l’introduction des antituberculeux sont frequentes (6–30 % des cas) et definies par une exacerbation ou revelation clinique ou radiologique de lesions tuberculeuses preexistantes ou infracliniques. Ces RPs concernent principalement les patients immunodeprimes : VIH ou sujets sous anti-TNFα. Une forte charge bacillaire et l’atteinte ganglionnaire de la tuberculose sont aussi associees a un sur-risque de RP. Les RPs surviennent dans les jours a semaines suivant l’initiation du traitement (moyenne de 8,8 semaines). Seulement 8 cas de RP cutanee sont decrits, sous forme de papules, de lesions purpuriques, abces sous-cutanes des extremites, en petit nombre (moins de 5), survenant dans des delais de 2 semaines a 2 ans, avec des cultures BK positives. Ces RP correspondent au syndrome de restauration immunitaire contre le BK, aidee par les antituberculeux, comparable aux reactions de reversion de la lepre, d’autant que notre cas presentait des signes systemiques (arthromyalgies, etc.). Un traitement par corticotherapie generale peut se justifier selon les cas. Ces reactions ne sont pas associees a un pronostic pejoratif. Conclusion Nous rapportons un cas de RP revelant une tuberculose cutanee, apparue a 3 semaines de l’introduction d’une quadritherapie antituberculeuse pour une tuberculose ganglionnaire chez une jeune femme immunocompetente.

RésuméLa très grande majorité des arythmies de l’enfance sont des tachycardies régulières à QRS fins soit, par définition, des tachycardies supraventriculaires. Ces arythmies peuvent être dues à des phénomènes de réentrée à l’étage atrial (flutter atrial) ou au niveau de la jonction auriculo-ventriculaire (rythme réciproque et réentrée intranodale). Elles peuvent également être secondaires à un foyer ectopique atrial (tachycardie atriale anciennement appelée « tachysystolie ») ou hissien (tachycardie hissienne). La présentation clinique est variable selon l’âge de l’enfant. Chez l’enfant de moins de 1 an, les premiers signes sont souvent des difficultés alimentaires. Mais les signes d’insuffisance cardiaque peuvent être plus alarmants en cas de cardiomyopathie rythmique. L’histoire naturelle des tachycardies supraventriculaires à l’âge pédiatrique est variable selon le mécanisme de la tachycardie mais aussi selon l’âge au diagnostic. Ainsi, les arythmies diagnostiquées avant la première voire les deux premières années de vie ont un fort potentiel de résolution spontanée. La prise en charge de ces formes précoces repose principalement sur le traitement médical préventif des récidives. Ce traitement est maintenu jusqu’à la guérison ou la rémission spontanée des accès de tachycardies. Pour les enfants plus grands, les options thérapeutiques sont plus vastes et dépendent du substrat de l’arythmie, de l’efficacité du traitement médical et du retentissement hémodynamique des accès de tachycardies. L’acceptabilité du traitement médical et le souhait de l’enfant et de ses parents sont à prendre en compte lorsque se pose la question d’un traitement définitif par ablation endocavitaire.SummaryRegular narrow QRS tachycardia - so-called supraventricular tachycardia - is the most common arrhythmia in the paediatric population. Different mechanisms can be involved: macrore entrant circuit within the atrium (intra-atrial reentrant tachycardiaatrial flutter); re entrant circuit between the atrium and the ventricle (atrioventricular reentrant tachycardia or atrioventricular node reentrant tachycardia); and abnormal automaticity of the atrium (atrial ectopic tachycardia) or the His bundle (junctional ectopic tachycardia). Among infants, the major clinical presentation is failure to thrive. However, a rare patient may present with potentially life-threatening congestive heart failure in case of tachycardia-mediated cardiomyopathy. The natural history of supraventricular tachycardia in children differs according to mechanism and age at presentation. Spontaneous resolution of supraventricular tachycardia beyond age 1–2 years is not rare. In this population, chronic antiarrhythmic medication is the firstline treatment to prevent recurrence. This treatment is maintained until resolution or remission of the arrhythmia. For older children, several different treatment options can be considered, depending on diagnosis, haemodynamic tolerance of the tachycardia and efficacy of the medical treatment. When antiarrhythmic therapy is ineffective or not desired, an ablation procedure offers the possibility of a definitive cure.

Resume Souvent rencontres aux urgences, les troubles du rythme cardiaque font l'objet de prises en charge specifiques selon leur tolerance clinique, le risque potentiel de complications qu'ils comportent, et l'eventualite d'une pathologie cardiaque ou extracardiaque sous-jacente. Les troubles du rythme atriaux posent essentiellement le probleme du traitement symptomatique (antiarythmique, ralentisseur) et de la gestion du traitement anticoagulant au long cours qui est le plus souvent indique. La reduction immediate des tachycardies jonctionnelles est bien codifiee aux urgences ; l'orientation therapeutique ulterieure englobe l'abstention therapeutique, le traitement antiarythmique au long cours, et l'ablation par radiofrequence. Les troubles du rythme ventriculaire sont a considerer systematiquement comme une urgence vitale, malgre un pronostic variable selon les etiologies. Leur prise en charge doit avoir pour objectifs de certifier le diagnostic rythmologique, d'identifier une etiologie et de stratifier le risque de mort subite, afin d'adapter le choix therapeutique (antiarythmique ou defibrillateur implantable dont les indications vont en s'elargissant).

Resume La corticotherapie proposee dans la prevention de la dysplasie bronchopulmonaire peut etre a l'origine d'un certain nombre de complications dont une hypertrophie myocardique. Observations. - Quatre observations d'hypertrophie myocardique induite par les glucocorticoides dont l'une s'est manifestee par une defaillance cardiaque sont rapportees. Il s'agissait de prematures d'âge gestationnel de 26 semaines et de poids de naissance compris entre 780 g et 1 080 g, traites par dexamethasone et/ou betamethasone pour une dysplasie bronchopulmonaire debutante. Les signes echographiques d'hypertrophie myocardique sont apparus 4 a 15 jours apres le debut du traitement alors que les enfants avaient recu une dose cumulee de glucocorticoides de, respectivement, 1,82 - 1,87 - 3,51 et 3,86 mg/kg. Cette myocardiopathie a toujours regresse a l'arret du traitement dans un delai de 2 a 4 semaines. Conclusion. - Pour prevenir cette complication, il est propose d'utiliser une posologie initiale de corticoides relativement faible (0,3 mg/kg/j) et de realiser une surveillance echographique systematique de ces enfants dans les 15 premiers jours de traitement.

Les protheses servant a traiter les pathologies de la conduction cardiaque (stimulateurs cardiaques ou pacemakers), ou encore a prevenir la mort subite rythmique dans les populations a risque (defibrillateurs implantables) representent une problematique quotidienne et croissante pour l’imagerie magnetique. Chaque annee sont implantes en France environ 50 000 stimulateurs et 10 000 defibrillateurs. Le vieillissement de la population et l’elargissement des indications ont nettement fait progresser ces chiffres ces dix dernieres annees.

Ten patients with orthotopic liver transplants were investigated during routine therapeutic monitoring to study the relationship between the concentrations of cyclosporin and its metabolites in blood, bile and urine, and whether this information can provide early signs of severe hepatic disorders post-transplantation. Cyclosporin (Sandimmun®) was administered by continuous infusion at a constant rate of 5 mg/kg/day, modified to keep the blood cyclosporin concentration within the target range (400 to 500 μg/L). The concentrations of cyclosporin and combined cyclosporin-metabolites in blood, bile and urine were assayed daily during the 3 post-transplantation weeks that the patients spent in intensive care.All patients developed cholestatis and cytolysis during the first week. The severity of these liver transplant disorders increased in 5 patients and decreased in the other 5 in the second week. The pharmacokinetics of cyclosporin differed in the 2 groups: in patients without severe hepatic disorders, the blood metabolites/cyclosporin ratio (M/C) stabilised at 1.2 ± 0.4 in week 2 and at 0.8 ± 0.2 in week 3, bile cyclosporin/blood cyclosporin (bile C/blood C) fluctuated around 13.5 (13.5 ± 9.5 in week 2 and 13.5 ± 9.0 in week 3) and the bile metabolite/blood metabolite (bile M/blood M) ratio was very high and variable (131 ± 86 in week 2 and 159 ± 116 in week 3). Metabolites significantly accumulated in the blood of patients with severe hepatic disorders (M/C = 2.8 ± 0.6 in week 2 and 3.5 ± 1.0 in week 3); bile C/blood C (2.6 ± 2.1 in week 2 and 3.4 ± 1.1 in week 3) and bile M/blood M (11.9 ± 7.8 in week 2 and 12.5 ± 7.9 in week 3) significantly decreased and showed less interindividual variability.Blood cyclosporin is usually monitored to help optimise the dosage. However, if this was extended to include the monitoring of metabolites in the blood, and cyclosporin and metabolites in the bile, it could provide an early indication of severe hepatic disorders in patients with transplanted livers.

The biotransformation of Arabian Light oil asphaltene has been studied with an n-alkane mixture as a co-substrate. The experiments were conducted in synthetic sea water with a hydrocarbonoclastic mixed population of 10 bacterial strains. After a one-month exposure, the mass loss of asphaltenes in the test flasks was partly due to an abiotic process (18 %) and to a biotic process by co-metabolism (5 %). Hydrocarbons previously trapped in the asphaltenic matrix were also released in the evaporation control flasks. Aromatic and polar fractions appeared in both test and control flasks were analysed by GC/FID, GC/MS and FTIR showing qualitative and quantitative differences, involving the identification of aromatic degradation products.

The improved in vitro bioremediation of Arabian Light crude oil in synthetic sea water by a mixed culture of bacteria is reported. Effects of fish meal, meat meal 80 % proteins and sophorolipids on the biodegradation were evaluated during a three-week incubation using GC/FID and GC/MS analysis of the remaining oil. Fish meal and more particularly meat meal 80 % proteins used at 0,5 mg.ml−1 involve no nitrogen and phosphorous limits when used as sole source of nutrients. Biodegradation processes in the first four days of the incubation supplemented with sophrolipids are accelerated two fold over controls.

Introduction Le syndrome d’activation macrophagique (SAM) est rare et de pronostic pejoratif (jusqu’a 50 % de mortalite). Il peut etre primitif ou secondaire (infections, cancers, maladies de systeme). L’ipilimumab est une immunotherapie utilisee dans le traitement du melanome metastatique et dont les principaux effets secondaires sont immunologiques. Nous presentons le cas d’un patient atteint d’un melanome metastatique ayant developpe des anomalies clinico-biologiques permettant de diagnostiquer un SAM au decours d’une perfusion d’ipilimumab. Observation Un patient de 42 ans, atteint d’un melanome metastatique (poumon, ganglions profonds) depuis 2013, etait initialement traite par nivolumab. Devant une progression tumorale lente, il recevait une premiere perfusion d’ipilimumab. A j5, il presentait brutalement une alteration de l’etat general (AEG), une hyperthermie a 40 °C, des douleurs pre-hepatiques et des cephalees. Le bilan biologique montrait des transaminases a 7 N, des γGT a 33N, une thrombopenie a 118 000/mm 3 , une leucopenie a 3400/mm 3 , une elevation des LDH a 241 UI/L, une hyponatremie a 133 mmol/L et une CRP a 70 mg/L. Deux hemocultures etaient positives a S. epidermidis sur le port-a-cath. Le bilan auto-immun etait negatif. Le scanner abdominal et l’IRM cerebrale etaient normaux. La biopsie hepatique ne montrait pas de signe d’hepatite medicamenteuse ou auto-immune. L’antibiotherapie par vancomycine etait inefficace. Finalement, l’apparition d’un rash aspecifique, d’une hyperferritinemie a 2384 μg/L et d’une hypertriglyceridemie a 3,66 g/L permettait de poser le diagnostic de SAM malgre la normalite du myelogramme. Une corticotherapie a 1 mg/kg/j permettait la regression de l’ensemble des symptomes des 48 h. Discussion Le SAM se caracterise par l’apparition brutale de fievre, AEG, hepatosplenomegalie, adenopathies. Des atteintes cutanees, pulmonaires, neurologiques et renales sont possibles. La biologie peut montrer une bi- ou pancytopenie, une elevation des LDH, une perturbation du bilan hepatique, une hypertriglyceridemie, une hyponatremie, une hyperferritinemie et une hypofibrinogenemie. Le diagnostic est confirme par la presence inconstante d’hemophagocytose sur le myelogramme ou la biopsie osteomedullaire. Le SAM est lie a une reaction immunitaire excessive en reponse a une stimulation immune. Son traitement est symptomatique (corticotherapie) et etiologique. Des cas de SAM sous interferon ont ete decrits. De rares cas secondaires a un melanome, avec parfois une bacteriemie associee, ont egalement ete publies. Il n’y a, a ce jour, aucun cas rapporte de SAM sous anti-PD-1 ou anti-CTLA4. Le role declencheur de l’ipilimumab est hautement suspecte chez notre malade en raison de la chronologie des evenements, de l’echec des antibiotiques et d’un melanome peu evolutif. Conclusion Il s’agit ici du premier cas decrit de SAM survenant sous ipilimumab.

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.

The L3 experiment is one of the six large detectors designed for the new generation of electron-positron accelerators. It is the only detector that concentrates its efforts on limited goals of measuring electrons, muons and photons. By not attempting to identify hadrons, L3 has been able to provide an order of magnitude better resolution for electrons, muons and photons. Vertices and hadron jets are also studied. The construction of L3 has involved much state of the art technology in new principles of vertex detection and in new crystals for large scale electromagnetic shower detection and ultraprecise muon detection. This paper presents a summary of the construction of L3.

A survey into the implantation of cardiac pacemakers during 2001 in the Ile-de-France area was carried out by the French National Insurance Medical Service in order to evaluate performance in all centres performing more than 10 primary implantations per year.In 2001, 12 centres out of a total of 49 performed less than 50 primary implantations per year, representing 5% of the total regional activity, which was estimated to be 6414 procedures. The remaining 95% of procedures were spread evenly among 8 high-throughput centres (200 primary implantations per year) and 29 medium-throughput centres (50 to 200 primary implantations per year). Indications for pacing were analysed retrospectively by a team of regulatory doctors on a sample of 2176 patients with reference to the ACC/AHA/NASPE guidelines. After examination of the medical records, the indication was ranked as being class I, II or Ill (absence of indication). A valid indication was lacking in 8.2% of cases. Sinus node dysfunction represented 74.6% of the non-indications, and this classification had the predictive factors of asymptomatic dysfunction, and treatment with anti-arrhythmic or bradycardic medication. The proportion of class III interventions was significantly lower in the high-throughput centres (5.8 vs 9.9%, p0.05).8.2% of primary pacing procedures were not indicated and resulted principally from asymptomatic sinus node dysfunction.

Atrial flutter with 1/1 nodo-ventricular conduction is a classical complication of Vaughan-Williams's Class I antiarrhythmic drugs. The increase of the flutter cycle and weak action of the antiarrhythmic on the atrioventricular node leads to 1/1 conduction of atrial depolarisation to the ventricles. In view of their marked action on the atrioventricular node, this type of pro-arrhythmic effect is very unexpected with Class III antiarrhythmics. The authors report 7 cases of 1/1 atrial flutter with oral amiodarone observed between 1994 and 2001. The patients were 6 men and 1 woman with an average age of 58 +/- 14 years. Four of them had underlying cardiac disease; none were hyperthyroid. The initial arrhythmia was 2/1 atrial flutter (n = 4), 1/1 atrial flutter (n = 2) and atrial fibrillation (n = 1). Treatment was preventive with doses of 400 mg/day associated with carvedilol in one patient and 200 mg/day in another. The other five patients all received loading doses of 9200 +/- 2400 mg over 10 +/- 4 days. The symptoms were palpitations (n = 2) associated in one patient with hypotension, one syncope, one near syncope and one cardiogenic shock. The ventricular cycle of the 1/1 flutter was 287 +/- 33 ms. The QRS duration was 136 +/- 35 ms with ventricular tachycardia-like appearances in 3 cases. An adrenergic trigger factor was noted in 5 patients. One patient required emergency cardioversion. The authors discuss the physiopathology of 1/1 flutter and theoretical diagnostic methods are proposed. In conclusion, amiodarone does not always prevent the occurrence of 1/1 nodo-ventricular conduction in atrial flutter.

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.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.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.

A sparteine test was carried out in 14 patients suffering from acute schizophrenic psychoses before and 1-2 times during oral haloperidol treatment in doses of 10-40 mg day-1. In patients classified as extensive metabolisers (sparteine MR less than 20 before treatment), haloperidol treatment resulted in a rise in sparteine MR that correlated with the serum-haloperidol concentration both within and between patients. At the highest serum haloperidol concentrations (60-80 nM) an increase in sparteine MR by a factor 15-50 was seen, but no patients were transformed into phenotypically poor metabolisers. The steady state concentration of haloperidol on the initial standard dose of 10 mg day-1 was the same in one patient classified as a sparteine poor metaboliser (MR = 112) as in eleven patients classified as extensive metabolisers (MR:0.22-1.47).

The symptoms of acute poisoning after accidental administration of ten times the usually prescribed dosage of caffeine in a premature infant included the following neurological signs: incessant tremors, hypertonia, continuous opisthotonos posture, whining and crying and digestive disturbances. The very high serum caffeine levels, 160 mg/l, determined 66 hours after the first administration was confirmed by the very high cerebrospinal fluid caffeine concentration 115 mg/l. Two exchange transfusions performed at an interval of 16 hours produced a large decrease in serum caffeine levels of approximately 40 mg/l each time, and a similar decrease in the cerebrospinal fluid concentration. The clinical status of the infant improved very rapidly and the child's psychomotor development was normal at 3 months of age.

Single dose disposition of oral quinidine (400 mg sulfate) was studied in a control group of subjects (No. = 6) and in hospitalized alcoholic patients involving one group with (No. = 6) and one group without (No. = 11) hepatic cirrhosis. All subjects also underwent an antipyrine and a debrisoquine test. Patients with cirrhosis had a prolonged elimination half-life (29.5 +/- 5.9 h) and low clearance (24 +/- 7 ml.kg-1.h-1) of antipyrine and also a considerably higher debrisoquine metabolic ratio (18.8 +/- 3.3) than the controls, whereas the alcoholics without cirrhosis had metabolic patterns for these two test compounds comparable to those seen in the controls (antipyrine half-life: 8.8 +/- 1.1 h and 9.8 +/- 2.0 h; debrisoquine metabolic ratio: 3.6 +/- 0.7 and 3.8 +/- 1.2 for alcoholics and controls respectively). In patients with cirrhosis the apparent elimination half-life of quinidine was longer (12.8 +/- 1.8 h) whereas after oral administration clearance of quinidine (15.6 +/- 3.5 l.h-1) and quinidine/3-hydroxyquinidine ratio (9.9 +/- 2.1) were not different from controls (quinidine clearance: 13.45 +/- 1.9 l.h-1; quinidine/3-hydroxyquinidine: 10.3 +/- 2.7). A possible change in distribution patterns of quinidine in cirrhotics may explain these findings.