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Saliva is a biofluid that can be considered as a “mirror” reflecting our body’s health status. Vibrational spectroscopy, Raman and infrared, can provide a detailed salivary fingerprint that can be used for disease biomarker discovery. We propose a systematic literature review based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to evaluate the potential of vibrational spectroscopy to diagnose oral and general diseases using saliva as a biological specimen. Literature searches were recently conducted in May 2020 through MEDLINE-PubMed and Scopus databases, without date limitation. Finally, over a period of 10 years, 18 publications were included reporting on 10 diseases (three oral and seven general diseases), with very high diagnostic performance rates in terms of sensitivity, specificity, and accuracy. Thirteen articles were related to six different cancers of the following anatomical sites: mouth, nasopharynx, lung, esophagus, stomach, and breast. The other diseases investigated and included in this review were periodontitis, Sjögren’s syndrome, diabetes, and myocardial infarction. Moreover, most articles focused on Raman spectroscopy (n = 16/18) and more specifically surface-enhanced Raman spectroscopy (n = 12/18). Interestingly, vibrational spectroscopy appears promising as a rapid, label-free, and non-invasive diagnostic salivary biometric tool. Furthermore, it could be adapted to investigate subclinical diseases—even if developmental studies are required.

Scientific Reports 10(1), 10471 (2020). doi:10.1038/s41598-020-67402-x, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Correction for ‘Confocal Raman microspectroscopy for skin characterization: a comparative study between human skin and pig skin’ by Sana Tfaili et al., Analyst, 2012, 137, 3673–3682, DOI: 10.1039/C2AN16292J.

Background: Dedicated ablation strategies for persistent atrial fibrillation (AF) have shown a limited success rate with frequent atrial tachycardia (AT) occurrence. Recent studies suggest that atrial arrhythmogenic sites are related to tissular heterogeneities and increased fibrosis can be identified as reduced bipolar voltage areas. . Purpose: Targeting low voltage areas (LVA) in addition to PVI may represent an efficient strategy for the ablation of persistent AF, and may limit the risk of AT recurrence. . Methods: We prospectively included consecutive patients with symptomatic persistent AF. The ablation strategy consisted of the following steps: circumferential pulmonary vein isolation (CPVI), Sinus rhythm restoration by electrical cardioversion, voltage map performed in sinus rhythm. Complementary RFA was guided by low voltage areas (0.2-0.4 mV). Success was defined as freedom from AF/ atrial flutter or atrial arrhythmia at 12 months or more. . Results: 101 patients (mean age: 62.5 +/- 10.4 years, men 73%) were included with persistent AF or long standing AF (7%). Procedure time was: 154 ± 25 min and fluoroscopy time: 184 ± 90 sec. Time of RFA was 44.7 +/- 12 min. Mean LA volume was 182 +/- 38 mL. LVA were found in 50 patients (49.5%). The distribution of these areas was: 30 anterior wall 29.7%), 21 septum (20.7%), 19 roof (18.8%), 5 inferior (4.9%), 11 left appendage (10.8%), 6 posterior (5.9%), 3 mitral isthmus (3%). RF ablation was realized for all LVA and homogenisation was attempt. After a single procedure at a mean FU of 12 months, 72.3% of patients were free of symptomatic AF. 27 patients had recurrence of atrial AF: 7 permanent, 15 persistent and 5 paroxysmal AF. Predictive factors of recurrence of AF were: long standing persistent AF, large left atrial volume (> 205 mL), shorts AF cycle length (< 168 ms) and reduce LEVF (< 45%). Atrial tachycardia occurred in 5 patients (4,9%). Mechanisms of AT were: typical cavo-tricuspid flutter in one patient, peri-mitral flutter in 2 patients, and atrial focal tachycardia (close to pulmonary veins) in 2 patients. . Conclusion: These results suggest that PVI with complementary RF ablation guided on low voltage areas is an efficient strategy for symptomatic persistent AF, and reduce the recurrence of AT following this ablation strategy.

International audience; Magnetic resonance imaging (MRI) has become the reference imaging technique for the management of a large number of diseases. The number of MRI examinations increases every year, simultaneously with the number of patients receiving a cardiac electronic implantable device (CEID). The presence of a CEID was considered an absolute contraindication for MRI for many years. The progressive replacement of conventional pacemakers and defibrillators by "magnetic resonance (MR)-conditional" CEIDs and recent data on the safety of MRI in patients with "MR-non-conditional" CEIDs have gradually increased the demand for MRI in patients with a CEID. However, some risks are associated with MRI in CEID carriers, even with MR-conditional devices, because these devices are not "MR safe". Specific programming of the device in "MR mode" and monitoring patients during MRI remain mandatory for all patients with a CEID. A standardized patient workflow based on an institutional protocol should be established in each institution performing such examinations. This joint position paper of the Working Group of Pacing and Electrophysiology of the French Society of Cardiology and the French Society of Diagnostic and Interventional Cardiac and Vascular Imaging describes the effect of and risks associated with MRI in CEID carriers. We propose recommendations for patient workflow and monitoring and CEID programming in MR-conditional, "MR-conditional non-guaranteed" and MR-non-conditional devices.; L’imagerie par résonance magnétique (IRM) est devenue l’imagerie de référence pour le diagnostic d’un grand nombre de pathologies. Le nombre d’examens IRM est en augmentation constante, parallèlement au nombre de patients implantés avec un dispositif électronique cardiaque implantable (DECI). L’IRM était considérée comme une contre-indication absolue à l’IRM jusqu’à il y a quelques années. Le remplacement progressif des stimulateurs et des défibrillateurs conventionnels par des dispositifs « IRM compatibles sous conditions » ainsi que les données récentes sur la sécurité des examens IRM chez les patients porteurs de dispositifs « non-IRM compatible » ont considérablement accru la demande d’examens IRM chez les patients porteurs de DECI. Cependant, les IRM peuvent être associés à certains risques chez les porteurs de DECI, y compris ceux « IRM compatibles sous conditions ». La programmation spécifique de l’appareil en mode « IRM » et la surveillance des patients pendant l’examen restent obligatoires pour tous les patients porteurs de DECI. Une prise en charge standardisée s’appuyant sur un protocole institutionnel est recommandée dans chaque établissement effectuant de tels examens. Ce document conjoint du Groupe Rythmologie et Stimulation Cardiaque de la Société Française de Cardiologie et de la Société Française d’Imagerie Cardiaque et Vasculaire Diagnostique et Interventionnelle décrit les effets et les risques associés à l’IRM chez des porteurs de DECI. Nous proposons des recommandations pour la prise en charge de ces patients, leur surveillance, ainsi que la programmation des dispositifs qu’ils soient « IRM compatibles sous conditions », « IRM compatibles sous conditions hors garantie constructeur » ou « non-IRM compatibles ».

International audience; The population of patients with congenital heart disease (CHD) is continuously increasing, and a significant proportion of these patients will experience arrhythmias because of the underlying congenital heart defect itself or as a consequence of interventional or surgical treatment. Arrhythmias are a leading cause of mortality, morbidity and impaired quality of life in adults with CHD. Arrhythmias may also occur in children with or without CHD. In light of the unique issues, challenges and considerations involved in managing arrhythmias in this growing, ageing and heterogeneous patient population and in children, it appears both timely and essential to critically appraise and synthesize optimal treatment strategies. The introduction of catheter ablation techniques has greatly improved the treatment of cardiac arrhythmias. However, catheter ablation in adults or children with CHD and in children without CHD is more technically demanding, potentially causing various complications, and thus requires a high level of expertise to maximize success rates and minimize complication rates. As French recommendations regarding required technical competence and equipment are lacking in this situation, the Working Group of Pacing and Electrophysiology of the French Society of Cardiology and the Affiliate Group of Paediatric and Adult Congenital Cardiology have decided to produce a common position paper compiled from expert opinions from cardiac electrophysiology and paediatric cardiology. The paper details the features of an interventional cardiac electrophysiology centre that are required for ablation procedures in adults with CHD and in children, the importance of being able to diagnose, monitor and manage complications associated with ablations in these patients and the supplemental hospital-based resources required, such as anaesthesia, surgical back-up, intensive care, haemodynamic assistance and imaging. Lastly, the need for quality evaluations and French registries of ablations in these populations is discussed. The purpose of this consensus statement is therefore to define optimal conditions for the delivery of invasive care regarding ablation of arrhythmias in adults with CHD and in children, and to provide expert and - when possible - evidence-based recommendations on best practice for catheter-based ablation procedures in these specific populations.

Raman spectroscopy is a candidate technique for diagnosis applications in medicine due to its high molecular specificity. Optimizing the pre-treatment applied for Raman data is important for exploiting Raman signals and ensuring their relevance in medical diagnosis. One of the crucial steps in data pre-processing, normalization, can affect significantly the result interpretation. To select the appropriate normalization method, a strategy based on validity indices (VI) is proposed in this study. VI are based on measuring the quality of data partitioning without involving a full sequence of supervised classification. The approach was tested on Raman data acquired from control and in vitro glycated proteins (albumin and collagen). Protein glycation is a process involved in the molecular ageing of tissues that leads to the formation of products altering the functional and structural properties of proteins. Different methods of normalization were applied on the data sets: integrated intensity of the phenylalanine band, integrated intensity of the amide I band, standard normal variate (SNV), multiplicative signal correction (MSC), and extended multiplicative signal correction (EMSC) that performs simultaneously baseline correction and normalization. Following normalization, principal component analysis (PCA) was applied and VI were calculated from PCA scores resulting from each of the normalization methods mentioned. Based on VI quantitative values, our experiments permit to illustrate the effect of normalization on the data separability of control and glycated samples, and to determine the most appropriate normalization and simultaneously the most discriminant principal components to exploit vibrational information associated with glycation-induced modifications. In parallel, principal component analysis - linear discriminant analysis (PCA-LDA) was carried out for positioning the interest of VI in regard to a common chain of data processing.

Correction for ‘Towards normalization selection of Raman data in the context of protein glycation: application of validity indices to PCA processed spectra’ by Fatima Alsamad et al., Analyst, 2020, DOI: 10.1039/c9an02155h.

International audience; Background: According to guidelines, implantable cardioverter defibrillator (ICD) candidates must have a "reasonable expectation of survival with a good functional status >1 year". Identifying risk for early mortality in ICD candidates could be challenging. We aimed to identify factors associated with a =1-year survival among patients implanted with ICDs.Methods: The DAI-PP program was a multicenter, observational French study that included all patients who received a primary prevention ICD in the 2002-2012 period. Characteristics of patients who survived = III), and atrial fibrillation were significantly associatedwith

International audience; Background : The lack of cystic fibrosis transmembrane conductance regulator (CFTR) function causes cystic fibrosis (CF), predisposing to severe lung disease, reduced growth and osteopenia. Both reduced bone content and strength are increasingly recognized in infants with CF before the onset of significant lung disease, suggesting a developmental origin and a possible role in bone disease pathogenesis. The role of CFTR in bone metabolism is unclear and studies on humans are not feasible. Deletion of CFTR in pigs (CFTR −/− pigs) displays at birth severe malformations similar to humans in the intestine, respiratory tract, pancreas, liver, and male reproductive tract. Methods : We compared bone parameters of CFTR −/− male and female pigs with those of their wild-type (WT) littermates at birth. Morphological and microstructural properties of femoral cortical and trabecular bone were evaluated using micro-computed tomography (μCT), and their chemical compositions were examined using Raman microspectroscopy. Results : The integrity of the CFTR −/− bone was altered due to changes in its microstructure and chemical composition in both sexes. Low cortical thickness and high cortical porosity were found in CFTR −/- pigs compared to sex-matched WT littermates. Moreover, an increased chemical composition heterogeneity associated with higher carbonate/phosphate ratio and higher mineral crystallinity was found in CFTR −/− trabecular bone, but not in CFTR −/− cortical bone. Conclusions : The loss of CFTR directly alters the bone composition and metabolism of newborn pigs. Based on these findings, we speculate that bone defects in patients with CF could be a primary, rather than a secondary consequence of inflammation and infection.

Transcatheter left atrial appendage (LAA) closure is an alternative strategy for stroke prevention in atrial fibrillation (AF) patients with an inacceptable risk of bleeding with oral anticoagulation (OAC). A better characterization of major adverse clinical events after LAA closure in daily practice is still needed. Methods We analysed data from all AF patients treated with Watchman or Amplatzer LAA closure according to European guidelines in 8 French cardiology departments. Antithrombotic management was decided for each patient on an individual basis. A Cox regression model was used for multivariable analysis of major adverse events. Yearly rate of ischemic stroke during follow-up was calculated and compared to that expected for a same risk score population. Yearly rate of bleeding was extrapolated from that reported with the HASBLED score. Results A total of 469 consecutive AF patients (299 males, 74.9±8.9 years old, mean CHA2DS2-VASc score 4.5±1.4, HASBLED score 3.7±1.0) received LAA closure from March 2012 to January 2017. There were 272 Watchman devices (58%) and 197 ACP devices (42%) implanted. At discharge, 36% received a single anti platelet therapy (APT), 23% received dual APT, 29% received OAC and no APT, 5% received OAC plus APT and 8% received no antithrombotic therapy. Mean follow up was 11.4 months (median 7, interquartile 3–22 months) during which 70 major adverse events (19 ischemic strokes, 18 major haemorrhages and 33 deaths) were recorded in 69 patients. The annual rate of ischemic stroke was 3.96%, which translates into a 13% relative risk reduction (95% CI −59 to 52%) as compared with the calculated stroke rate for similar CHA2DS2-VASc score after adjustment for exposure to APT and OAC. The annual rate of major bleeding in the study was 3.75%, which corresponds to a 48% relative risk reduction (95% CI 9 to 70%) as compared with the rate that would have been expected based on a comparable HAS-BLED score. Yearly rate of mortality was 7.4% (2.5 to 3 fold higher than in previous randomized trials) and the rate of non-cardiovascular death was 82%. None of the baseline characteristics was predictive of major adverse events, neither in univariate nor in multivariable analysis, which highlights the difficulty in identifying a risk of unfavourable outcome with simple tools. Conclusions AF patients treated with LAA closure may have a lower risk of stroke and bleeding events compared to their theoretical risk. However, our findings indicate that a high rate of major adverse events is observed in these patients during follow-up. This questions the suggested cost-effectiveness of the procedure (with models based on previous trials) for a real-life perspective. A better identification of patients with a relevant benefit of LAA closure is needed among those with long-term anticoagulation contraindication, both for an optimal management of each patient on an individual basis and for a global perspective with limited healthcare resources.

Background Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF), but is limited by a substantial proportion of nonresponders. We hypothesized that adding a second left ventricular (LV) lead to deliver a triple-site CRT (V3 CRT) may improve clinical status of CRT nonresponders. Objective We assessed the feasibility and safety of adding a second LV lead to CRT nonresponders and its clinical impact. Methods Eighty-four recipients of a CRT system and considered as nonresponders as per clinical composite score (CCS) were enrolled in this multicenter study. They were randomized to the V3 arm (implantation of an additional LV lead; n=43) or control arm (no change; n = 41). Implant success rate, incidence of severe adverse events, CCS, and secondary clinical and echocardiographic end points were evaluated at 12 and 24 months. Results Positioning of a second LV lead was successful at first (40 of 44 - 90.9%) or second (4 of 44 - 9.09%) attempt. The perioperative complication rate (infection, system explant, pneumothorax, and hematoma) was high (procedures or system-related complications for 9 patients- 20.4%). After 24 months, 35 systems (79.5%) were working properly. The multinomial logistic regression model showed that V3 treatment had no significant influence (P = .27) on the CCS, number of HF hospitalizations, time to first HF hospitalization, New York Heart Association class, and LV ejection fraction at 12 and 24 months. Conclusion Although addition of a second LV lead in CRT nonresponders is feasible with a high success rate, this approach is associated with a significant rate of severe adverse events and does not provide significant long-term clinical benefits (ClinicalTrials.gov Identifier No. NCT01059175).

Almost 1/3 of heart failure patients fail to respond to cardiac resynchronization therapy (CRT). A simple clinical score to predict who these patients are at the moment of referral or at time of implant may be of importance for early optimization of their management.Observational study. A risk score was derived from factors associated to CRT response. The derivation cohort was composed of 1301 patients implanted with a CRT defibrillator in a multi-center French cohort-study. External validation of this score and assessment of its association with CRT response and all-cause mortality and/or heart transplant was performed in 1959 CRT patients implanted in 4 high-volume European centers.Independent predictors of CRT response in the derivation cohort were: female gender (OR = 2.08, 95% CI 1.26-3.45), NYHA class ≤ III (OR = 2.71, 95% CI 1.63-4.52), left ventricular ejection fraction ≥ 25% (OR = 1.75, 95% CI 1.27-2.41), QRS duration ≥ 150 ms (OR = 1.70, 95% CI 1.25-2.30) and estimated glomerular filtration rate ≥ 60 mL/min (OR = 2.01, 95% CI 1.48-2.72). Each was assigned 1 point. External validation showed good calibration (Hosmer-Lemeshow test-P = 0.95), accuracy (Brier score = 0.19) and discrimination (c-statistic = 0.67), with CRT response increasing progressively from 37.5% in patients with a score of 0 to 91.9% among those with score of 5 (Gamma for trend = 0.44, P 0.001). Similar results were observed regarding all-cause mortality or heart transplant.The ScREEN score (Sex category, Renal function, ECG/QRS width, Ejection fraction and NYHA class) is composed of widely validated, easy to obtain predictors of CRT response, and predicts CRT response and overall mortality. It should be helpful in facilitating early consideration of alternative therapies for predicted non-responders to CRT therapy.

Vibrational spectroscopy has become a valuable tool in many fields as it provides a molecular signature with a non-destructive measurement. Identification and prediction performance of the technique greatly depend on pre-processing steps used to remove unwanted sources of variability, especially for biological matter. However, finding the right combination of pre-processing methods (smoothing, baseline correction and/or normalization) is not a trivial task and usually depends on the operator habits. As testing all possible pre-processing sequences is time consuming, genetic algorithms (GAs) were put forward as a way to quickly find a relatively good sequence. We present here a GA that additionally optimizes the regression model, making the whole data analysis process automated, paving the way to automated machine learning. To make the best of GAs, we determined the optimal GA parameters, based on three datasets of different vibrational spectroscopy modalities (Raman or IR spectra from food industry or biological samples). They depended on the desired quality of the solution, but hardly on the dataset itself, meaning they could be used on new data without further tuning. Our method compares positively with random search, ant colony optimization and tree-structured Parzen Estimator, commonly used in machine learning for tuning hyperparameters. In conclusion, we provide a GA adapted to the simultaneous selection of pre-processing and regression of vibrational spectra.

Background Current ablation strategies for persistent AF have shown a limited success rate with frequent arrhythmia recurrences. Recent studies suggest that the atrial arrhythmogenic sites are related to regions with increased fibrosis detected by reduced bipolar voltage area. Purpose Targeting low voltage areas in addition to PVI may represent an efficient strategy for the ablation of persistent AF. Methods We prospectively included patients with symptomatic persistent AF (mean age: 63 ± 8.8 years, men 69.3%) ( Table 1 ). The ablation strategy consisted in circumferential PVI. Sinus rhythm was restored by electrical cardioversion. A voltage map was performed in sinus rhythm. Complementary ablation was guided by low voltage areas Results In total, 101 patients with persistent AF were included. Low voltage areas ( Fig. 1 ): 32 on anterior wall (30.2%), 25 on septum (23.6%), 8 on posterior (7.5%), 3 on lateral (2.8%), 12 in left appendage (11.3%), 23 on the roofs (21.7%), 3 on inferior (2.8%). RF ablation was performed in all low voltage areas. At the end of procedure, 76 patients (75.2%) were non-inducible. At the end of FU of 18 months, and after a single procedure, 72.3% of patients were free of symptomatic AF (n = 73 patients) and 65.3% of patients (n = 66) were free of AF/AT recurrence. Atrial tachycardia occurred in 9 patients and re-ablated with success ( Table 1 , Fig. 1 ). Conclusion These results suggest that PVI with complementary RF ablation guided on low voltage areas may be an efficient strategy for ablation of persistent AF with low incidence of atrial tachycardia during FU.

Temporal Trends Over a Decade of Defibrillator TherapyBackground Technology and clinical practice surrounding the use of the primary prevention implantable cardioverter defibrillator (ICD) are in a state of constant evolution. The purpose of the study was to test the hypothesis of significant temporal trends in characteristics and outcomes over a decade of ICD therapy. Methods Between 2002 and 2012, 5,539 consecutive patients (age 62.5 ± 11 years, 84.9% male), with ischemic or nonischemic cardiomyopathy, implanted with a primary prevention ICD from 12 centers in France were included. Information on characteristics and outcomes (including causes of death) were evaluated over a median follow-up of 994 days (466-1,667). Results In addition to a shift in the type of devices implanted with a significant increase in cardiac resynchronization therapy-defibrillator (CRT-D) over time (43.6 to 60.4%, P = 0.0001), an increase in mean age (from 61.5 ± 11.6 to 63.2 ± 10.9 years, P = 0.0016), proportion of nonischemic cardiomyopathy (31.0 to 44.7%, P 30 days after implant) complications significantly increased (4.6 to 7.6%, P = 0.003). Conclusion Our findings demonstrate significant changes in patterns of use and outcomes in primary prevention ICD over the last decade with reductions in mortality and appropriate therapies, counterbalanced by an increase in complications.

International audience; Despite the increasingly high rate of implantation of pacemakers (PMs) and implantable cardioverter defibrillators (ICDs) in elderly patients, data supporting their clinical and cost-effectiveness in this age stratum are ambiguous and contradictory. We reviewed the data regarding the applicability, safety and effectiveness of conventional pacing, ICDs and cardiac resynchronization therapy (CRT) in elderly patients. Although periprocedural risk may be slightly higher in the elderly, the implantation procedure for PMs and ICDs is still relatively safe in this age group. In older patients with sinus node disease, the general consensus is that DDD pacing with the programming of an algorithm to minimize ventricular pacing is preferred. In very old patients presenting with intermittent or suspected atrioventricular block, VVI pacing may be appropriate. In terms of correcting potentially life-threatening arrhythmias, the effectiveness of ICD therapy is similar in older and younger individuals. However, the assumption of persistent ICD benefit in the elderly population is questionable, as any advantageous effect of the device on arrhythmic death may be attenuated by higher total non-arrhythmic mortality. While septuagenarians and octogenarians have higher annual all-cause mortality rates, ICD therapy may remain effective in selected patients at high risk of arrhythmic death and with minimum comorbidities despite advanced age. ICD implantation among the elderly, as a group, may not be cost-effective, but the procedure may reach cost-effectiveness in those expected to live more than 5-7years after implantation. Elderly patients usually experience significant functional improvement after CRT, similar to that observed in middle-aged patients. Management of CRT non-responders remains globally the same, while considering a less aggressive approach in terms of reinterventions (revision of left ventricular [LV] lead placement, addition of a right ventricular or LV lead, LV endocardial pacing configuration). Overall, physiological age, general status and comorbidities rather than chronological age per se should be the decisive factors in making a decision about device implantation selection for survival and well-being benefit in elderly patients.

This review summarizes the main findings of the French multicentre DAI-PP pilot programme, and discusses the related clinical and research perspectives. This project included retrospectively (2002–2012 period) more than 5000 subjects with structural heart disease who received an implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death, and were followed for a mean period of 3 years. The pilot phase of the DAI-PP programme has provided valuable information on several practical and clinically relevant aspects of primary prevention ICD implantation in the real-world population, which are summarized in this review. This pilot has led to a prospective evaluation that started in May 2018, assessing ICD therapy in primary and secondary prevention in patients with structural and electrical heart diseases, with remote monitoring follow-up using a dedicated platform. This should further enhance our understanding of sudden cardiac death, to eventually optimize the field of preventative actions. © 2019 Elsevier Masson SAS; Cet article résume les principaux résultats de la phase pilote du programme DAI-PP et discute ses perspectives scientifiques. Ce projet a inclus plus de 5000 sujets (pendant la période 2002–2012) ayant une cardiopathie et implantés d’un défibrillateur automatique implantable (DAI) en prévention primaire de la mort subite avec un suivi moyen de 3 ans. Cette évaluation pilote du programme de recherche DAI-PP, mené dans la vraie vie, a permis d'identifier des messages importants concernant la prévention primaire de la mort subite de patients porteurs de cardiomyopathies dilatées ou cardiopathies ischémiques, résumés dans cet article. Cette phase préliminaire a également permis l'initiation d'une évaluation prospective, débutée en mai 2018, avec pour ambition d'évaluer la prévention primaire et secondaire quelque soit le phénotype sous jacent (structurel ou électrique), en utilisant une nouvelle plateforme de télésurveillance. DAI-PP devrait permettre de mieux comprendre différents aspects de la mort subite cardiaque, pour au final en améliorer la prévention.

The efficiency of Raman spectroscopy for the analysis of biomedical samples has been largely demonstrated at the proof-of-concept stage during one-off measurement campaigns. However, bringing these results to the patient bedside requires to fill the gap for transferability of Raman data acquired in different experimental and instrumental conditions during multicentric measurement campaigns. In this study, we propose to evaluate a solution consisting in the application of Raman data preprocessing specifically developed to remove the spectral variability induced by such different conditions. For this purpose, we compared Raman data of lymphocytes acquired during two independent measurement campaigns from fresh unstained glass blood smears originating from healthy individuals and patients with a B-cell chronic lymphocytic leukemia (CLL) at an advanced stage. The differences between these campaigns were i) the instrumental configuration of the Raman devices, ii) the hospital partner, iii) the smear preparation method. A preprocessing developed previously and efficient for a specific measurement campaign is shown obsolete for these multicentric data. A second preprocessing based on Extended Multiplicative Signal Correction is able to homogenize the data by neutralizing the signal variability between the two measurement campaigns. These conclusions are drawn from the analysis of the data by Principal Component Analysis to study the source of variability between the two campaigns and by Partial Least Squares – Discriminant Analysis to assess the separability between healthy and CLL patients.

Objective In hair care cosmetic products’ evaluation, one commonly used method is to evaluate the hair appearance as a gold standard in order to determine the effect of an active ingredient on the final state of the hair via visual appreciation. Although other techniques have been proposed for a direct analysis of the hair fibres, they give only surface or structural information, without any accurate molecular information. A different approach based on confocal Raman spectroscopy has been proposed for tracking in situ the molecular change in the keratin directly in the human hair fibres. It presents a high molecular specificity to detect chemical interactions between molecules and can provide molecular information at various depths at the cortex and cuticle levels. Methods To evaluate the potential of confocal Raman spectroscopy in testing the efficiency of cosmetic ingredients on keratin structure, we undertook a pilot study on the effectiveness of a smoothing shampoo on natural human hair, by analysing α‐helix and β‐sheet spectral markers in the Amide I band and spectral markers specific to the cystin sulfur content. Results We confirmed that an active proved to be effective on a gold standard decreases α‐helix keratin conformation and promotes β‐sheet keratin conformation in the hair fibres. We also showed that treatment with the effective active decreases the intensity of covalent disulfide (S–S at 510 cm‐1) cross‐linking bands of cysteine. These data confirm that the effective active also acts on the tertiary structure of keratin. Conclusion From these experiments, we concluded that the effective active has a smoothing effect on the human hair fibres by acting on α‐helix and β‐sheet keratin conformation and on the tertiary structure of keratin. Based on these results, confocal Raman spectroscopy can be considered a powerful technique for investigating the influence of hair cosmetic ingredients on keratin structure in human hair fibres. Moreover, this analytical technique has the advantage of being non‐destructive and label free; in addition, it does not require sample extraction or purification and it can be applied routinely in cosmetic laboratories., Confocal Raman spectroscopy can be considered as a powerful technique for investigating the influence of hair cosmetic ingredients on keratin structure in human hair fibres.

Aims Current guidelines do not propose any age cut-off for the primary prevention implantable cardioverter-defibrillator (ICD). However, the risk/benefit balance in the very elderly population has not been well studied. Methods and results In a multicentre French study assessing patients implanted with an ICD for primary prevention, outcomes among patients aged ≥80 years were compared with Conclusion Primary prevention ICD recipients ≥80 years in the real world had relatively low associated comorbidity. Rates of appropriate therapies and device-related complications were similar, compared with younger subjects. Nevertheless, the inherent limitations in interpreting observational data on this particular competing risk situation call for randomized controlled trials to provide definitive answers. Meanwhile, a careful multidisciplinary evaluation is needed to guide patient selection for ICD implantation in the elderly population.

Background RF ablation is a standard practice approach for the symptomatic AF. The interest of substrate ablation, completing pulmonary vein isolation is controversial. The current ablation strategy for persistent AF ablation is a step-by step guided approach: PVI is most often followed by a large ablation of fragmented electrograms identified in AF or completed by linear ablation, but this current ablation strategies have shown a limited success rate with frequent arrhythmia recurrences. Recent studies suggest that the atrial arrhythmogenic sites are related to regions with heterogeneities and increased fibrosis, which is detected by reduced bipolar voltage areas. Objective Defragmentation low voltage areas (LVA) in sinus rhythm (SR) in addition to PVI may represent an efficient strategy for the ablation of persistent AF. Material and methods This is a prospective multicentric interventional study in France. Inclusion criteria: minimum age 18 years, patients with persistent AF ablation, no specific indication restrictions or equipment used regardless of the outcome of the procedure. Number of patients: 210 patients included in 9 centres. Three groups will be constituted: Group 1: PVI without LVA identified, group 2: PVI only, with LVA identified but defragmentation will not be carried out and group 3: PVI with LVA identified and defragmentation will be carried out. Definition of LVA in SR: all potentials 55 ms. Inducibility of AF is realised at the end of the procedure. Usual blanking period of 3 months. Follow-up: clinical evaluation, ECG, and 24h-holter ECG at 6, 12 and 18 months. Outcomes Primary outcome: recurrence of AF at 18 months. Secondary outcomes: comparison of efficiency and safety of the procedures, procedural data (X-ray data, RF duration, AF inducibility), organised atrial tachycaria occurring during FU.

In label-free Fourier-transform infrared histology, spectral images are individually recorded from tissue sections, pre-processed and clustered. Each single resulting color-coded image is annotated by a pathologist to obtain the best possible match with tissue structures revealed after Hematoxylin-Eosin staining. However, the main limitations of this approach are the empirical choice of the number of clusters in unsupervised classification, and the marked color heterogeneity between the clustered spectral images. Here, using normal murine and human colon tissues, we developed an automatic multi-image spectral histology to simultaneously analyze a set of spectral images (8 images mice samples and 72 images human ones). This procedure consisted of a joint Extended Multiplicative Signal Correction (EMSC) to numerically deparaffinize the tissue sections, followed by an automated joint K-Means (KM) clustering using the hierarchical double application of Pakhira-Bandyopadhyay-Maulik (PBM) validity index. Using this procedure, the main murine and human colon histological structures were correctly identified at both the intra- and the inter-individual levels, especially the crypts, secreted mucus, lamina propria and submucosa. Here, we show that batched multi-image spectral histology procedure is insensitive to the reference spectrum but highly sensitive to the paraffin model of joint EMSC. In conclusion, combining joint EMSC and joint KM clustering by double PBM application allows to achieve objective and automated batched multi-image spectral histology.

Parmi les cancers de la peau, les deux types de carcinomes cutanes (basocellulaires et spinocellulaires) sont difficilement distinguables lors de l’examen clinique. Or, il est crucial de les differencier car les seconds necessitent un traitement et une surveillance specifiques. Pour reduire au minimum l’intervention humaine, forcement subjective, la micro-imagerie infrarouge presente un potentiel certain lors du diagnostic… a condition de savoir traiter les images des tissus inclus en paraffine qui ont ete preleves. Ce defi a ete releve et est en passe de devenir la prochaine methode de diagnostic totalement objective et predictive.

BACKGROUND: Pacing in the right ventricle can cause a variety of detrimental effects, including atrial tachyarrhythmias (AT/AF).OBJECTIVE: To evaluate incidence and predictors of persistent AT/AF in patients with long term exposure to ventricular pacing.METHODS: In a multi-center international trial, 605 patients (75±11 years, 240 females), referred for replacement of an implanted pacemaker or cardioverter defibrillator (ICD), with history of high percentage (>40%) ventricular pacing, were randomly allocated to standard dual-chamber pacing or Managed Ventricular Pacing (MVP), a pacing modality which minimizes ventricular pacing. Main end point of this secondary analysis of the PreFER MVP randomized study was persistent AT/AF, defined as ≥7 consecutive days with AT/AF or AT/AF interrupted by atrial cardioversion or AT/AF present during 2 consecutive follow-up visits.RESULTS: Persistent AT/AF was observed in 71 patients (11.7%) after 2 years of follow-up. At multivariable Cox regression analysis, prior AT/AF (hazard ratio (HR)=2.85, 95% confidence intervals (CI)=1.20-6.22, p=0.017) and ventricular pacing percentage, estimated in the first 3 months, ≥10% (HR=3.24, CI=1.13-9.31, p=0.029) resulted as independent predictors for persistent AT/AF. MVP was associated with persistent AT/AF risk (HR=3.41, CI=1.10-10.6, p=0.024) in the subgroup of patients with a baseline long PR interval (PR>230 ms), but not in the whole population.CONCLUSION: In pacemaker and ICD replacement patients, high percentage of ventricular pacing is associated with higher risk of persistent AT/AF. The use of algorithms which minimize right ventricular pacing may benefit patients with normal spontaneous AV conduction but should be evaluated with caution in patients with long PR interval.CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Identifier: NCT00293241.

Background Current ablation strategies for persistent AF have shown a limited success rate with frequent arrhythmia recurrences. STAR-AF 2 trial assessed that PVI-only is as effective as other ablation strategies. Recent studies suggest that the atrial arrhythmogenic sites are related to regions with heterogeneities and increased fibrosis which is detected by reduced bipolar voltage areas. Purpose Targeting low voltage areas in addition to PVI may represent an efficient strategy for the ablation of persistent AF. Methods We prospectively included patients with symptomatic persistent AF (mean age: 60.8 ± 4.2 years, men 78%). The ablation strategy consisted of circumferential pulmonary vein isolation (CPVI). Sinus rhythm was restored by electrical cardioversion. A voltage map was performed in sinus rhythm. Complementary RFA was guided by low voltage areas (0.2–0.4 mV). Success was defined as freedom from AF/atrial flutter or atrial arrhythmia for a period ranging from 3 months to 12 months or more. Results 55 patients were included with persistent AF. Procedure time was: 154 ± 25 min and fluoroscopy time: 184 ± 90 sec. Time of RFA was 44.7 ± 12.7 min. Mean LA volume was 195 ± 35 mL. Low voltage areas were identified in 41.5% of pts. AF was not inducible for 81.8% of pts. After a single procedure at a mean FU of 12 months, 71% of patients were free of symptomatic AF. Predictive factors of recurrence of AF were large left atrial volume (> 205 mL), shorts AF cycle length ( Conclusion These results suggest that PVI with complementary RF ablation guided on low voltage areas is an efficient strategy for symptomatic persistent AF.

Aims The very long-term outcome of patients who survive the first few years after receiving cardiac resynchronization therapy (CRT) has not been well described thus far. We aimed to provide long-term outcomes, especially with regard to the occurrence of sudden cardiac death (SCD), in CRT patients without (CRT-P) and with defibrillator (CRT-D). Methods and results A total of 1775 patients, with ischaemic or non-ischaemic dilated cardiomyopathy, who were alive 5 years after CRT implantation, were enrolled in this multicentre European observational cohort study. Overall long-term mortality rates and specific causes of death were assessed, with a focus on late SCD. Over a mean follow-up of 30 months (interquartile range 10–42 months) beyond the first 5 years, we observed 473 deaths. The annual age-standardized mortality rates of CRT-D and CRT-P patients were 40.4 [95% confidence interval (CI) 35.3–45.5] and 97.2 (95% CI 85.5–109.9) per 1000 patient-years, respectively. The adjusted hazard ratio (HR) for all-cause mortality was 0.99 (95% CI 0.79–1.22). Twenty-nine patients in total died of late SCD (14 with CRT-P, 15 with CRT-D), corresponding to 6.1% of all causes of death in both device groups. Specific annual SCD rates were 8.5 and 5.8 per 1000 patient-years in CRT-P and CRT-D patients, respectively, with no significant difference between groups (adjusted HR 1.0, 95% CI 0.45–2.44). Death due to progressive heart failure represented the principal cause of death (42.8% in CRT-P patients and 52.6% among CRT-D recipients), whereas approximately one-third of deaths in both device groups were due to non-cardiovascular death. Conclusion In this first description of very long-term outcomes among CRT recipients, progressive heart failure death still represented the most frequent cause of death in patients surviving the first 5 years after CRT implant. In contrast, SCD represents a very low proportion of late mortality irrespective of the presence of a defibrillator.

Total human saliva is a biofluid which can be considered as a “mirror” reflecting the state of the body’s health. The “spectral mid-infrared fingerprint” represents a snapshot of the intrinsic biomolecular composition of a saliva sample translating multiple information about the patient, and likely to be related not only to his physiopathological status but also to his behavioral habits or even current medical treatments. These different patient-related characteristics are “confounding factors,” which may strongly affect the infrared data of salivary samples and disrupt the search for specific salivary biomarkers in the detection of diseases, especially in the case of complex pathologies influenced by multiple risk factors such as genetic factors and behavioral factors, and also other comorbidities. In this study, dealing with the processing of infrared saliva spectra from 56 patients, our aim was to highlight spectral features associated with some patient characteristics, namely tobacco smoking, periodontal diseases, and gender. By using multivariate statistical methods of feature selection (principal component analysis coupled with Kruskal–Wallis test, linear discriminant analysis coupled with randfeatures function), we were able to identify the discriminant vibrations associated with a specific factor and to assess the related spectral variability. Based on the methodology demonstrated here, it could be very valuable in the future to develop processing aimed at neutralizing these variabilities, in order to determine specific spectroscopic markers related to a multifactorial disease for diagnostic or follow-up purposes.

Supplemental Digital Content is available in the text., Background: Sudden cardiac death because of ventricular fibrillation (VF) is commonly unexplained in younger victims. Detailed electrophysiological mapping in such patients has not been reported. Methods: We evaluated 24 patients (29±13 years) who survived idiopathic VF. First, we used multielectrode body surface recordings to identify the drivers maintaining VF. Then, we analyzed electrograms in the driver regions using endocardial and epicardial catheter mapping during sinus rhythm. Established electrogram criteria were used to identify the presence of structural alterations. Results: VF occurred spontaneously in 3 patients and was induced in 16, whereas VF was noninducible in 5. VF mapping demonstrated reentrant and focal activities (87% versus 13%, respectively) in all. The activities were dominant in one ventricle in 9 patients, whereas they had biventricular distribution in others. During sinus rhythm areas of abnormal electrograms were identified in 15/24 patients (62.5%) revealing localized structural alterations: in the right ventricle in 11, the left ventricle in 1, and both in 3. They covered a limited surface (13±6 cm2) representing 5±3% of the total surface and were recorded predominantly on the epicardium. Seventy-six percent of these areas were colocated with VF drivers (P

Skin is one of the most important organs of the human body because of its characteristics and functions. There are many alterations, either pathological or physiological, that can disturb its functioning. However, at present all methods used to investigate skin diseases, non-invasive or invasive, are based on clinical examinations by physicians. Thus, diagnosis, prognosis and therapeutic management rely on the expertise of the practitioner, the quality of the method and the accessibility of distinctive morphological characteristics of each lesion. To overcome the high sensitivity of these parameters, techniques based on more objective criteria must be explored. Vibrational spectroscopy has become as a key technique for tissue analysis in the biomedical research field. Based on a non-destructive light/matter interaction, this tool provides information about specific molecular structure and composition of the analyzed sample, thus relating to its precise physiopathological state and permitting to distinguish lesional from normal tissues. This label-free optical method can be performed directly on the paraffin-embedded tissue sections without chemical dewaxing. In this study, the potential of the infrared microspectroscopy, combined with data classification methods was demonstrated, to characterize at the tissular level different types of inflammatory skin lesions, and this independently from conventional histopathology.

Background Transcatheter left atrial appendage (LAA) occlusion is an alternative strategy for stroke prevention in patients with atrial fibrillation (AF). Objectives This study sought to determine the incidence, predictors, and prognosis of thrombus formation on devices in patients with AF who were treated with LAA closure. Methods The study retrospectively analyzed data from patients treated with 2 LAA closure devices seen in 8 centers in France from February 2012 to January 2017. Results A total of 469 consecutive patients with AF underwent LAA closure (272 Watchman devices [Atritech, Boston Scientific, Natick, Massachusetts] and 197 Amplatzer devices [St. Jude Medical, Minneapolis, Minnesota]). Mean follow-up was 13 ± 13 months, during which 339 (72.3%) patients underwent LAA imaging at least once. There were 98 major adverse events (26 thrombi on devices, 19 ischemic strokes, 2 transient ischemic attacks, 18 major hemorrhages, 33 deaths) recorded in 89 patients. The incidence of device-related thrombus in patients with LAA imaging was 7.2% per year. Older age (hazard ratio [HR]: 1.07 per 1-year increase; 95% confidence interval [CI]: 1.01 to 1.14; p = 0.02) and history of stroke (HR: 3.68; 95% CI: 1.17 to 11.62; p = 0.03) were predictors of thrombus formation on the devices, whereas dual antiplatelet therapy (HR: 0.10; 95% CI: 0.01 to 0.76; p = 0.03) and oral anticoagulation at discharge (HR: 0.26; 95% CI: 0.09 to 0.77; p = 0.02) were protective factors. Thrombus on the device (HR: 4.39; 95% CI: 1.05 to 18.43; p = 0.04) and vascular disease (HR: 5.03; 95% CI: 1.39 to 18.23; p = 0.01) were independent predictors of ischemic strokes and transient ischemic attacks during follow-up. Conclusions Thrombus formation on the device is not uncommon in patients with AF who are treated by LAA closure. Such events are strongly associated with a higher risk of ischemic stroke during follow-up. (REgistry on Real-Life EXperience With Left Atrial Appendage Occlusion [RELEXAO]; NCT03279406)

Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF), but is limited by a substantial proportion of nonresponders. We hypothesized that adding a second left ventricular (LV) lead to deliver a triple-site CRT (VWe assessed the feasibility and safety of adding a second LV lead to CRT nonresponders and its clinical impact.Eighty-four recipients of a CRT system and considered as nonresponders as per clinical composite score (CCS) were enrolled in this multicenter study. They were randomized to the VPositioning of a second LV lead was successful at first (40 of 44 - 90.9%) or second (4 of 44 - 9.09%) attempt. The perioperative complication rate (infection, system explant, pneumothorax, and hematoma) was high (procedures or system-related complications for 9 patients- 20.4%). After 24 months, 35 systems (79.5%) were working properly. The multinomial logistic regression model showed that VAlthough addition of a second LV lead in CRT nonresponders is feasible with a high success rate, this approach is associated with a significant rate of severe adverse events and does not provide significant long-term clinical benefits (ClinicalTrials.gov Identifier No. NCT01059175).

ObjectiveIn patients indicated for cardiac resynchronisation therapy (CRT), the choice between a CRT-pacemaker (CRT-P) versus defibrillator (CRT-D) remains controversial and indications in this setting have not been well delineated. Apart from inappropriate therapies, which are inherent to the presence of a defibrillator, whether adding defibrillator to CRT in the primary prevention setting impacts risk of other acute and late device-related complications has not been well studied and may bear relevance for device selection.MethodsObservational multicentre European cohort study of 3008 consecutive patients with ischaemic or non-ischaemic dilated cardiomyopathy and no history of sustained ventricular arrhythmias, undergoing CRT implantation with (CRT-D, n=1785) or without (CRT-P, n=1223) defibrillator. Using propensity score and competing risk analyses, we assessed the risk of significant device-related complications requiring surgical reintervention. Inappropriate shocks were not considered except those due to lead malfunction requiring lead revision.ResultsAcute complications occurred in 148 patients (4.9%), without significant difference between groups, even after considering potential confounders (OR=1.20, 95% CI 0.72 to 2.00, p=0.47). During a mean follow-up of 41.4±29 months, late complications occurred in 475 patients, giving an annual incidence rate of 26 (95% CI 9 to 43) and 15 (95% CI 6 to 24) per 1000 patient-years in CRT-D and CRT-P patients, respectively. CRT-D was independently associated with increased occurrence of late complications (HR=1.68, 95% CI 1.27 to 2.23, p=0.001). In particular, when compared with CRT-P, CRT-D was associated with an increased risk of device-related infection (HR 2.10, 95% CI 1.18 to 3.45, p=0.004). Acute complications did not predict overall late complications, but predicted device-related infection (HR 2.85, 95% CI 1.71 to 4.56, pConclusionsCompared with CRT-P, CRT-D is associated with a similar risk of periprocedural complications but increased risk of long-term complications, mainly infection. This needs to be considered in the decision of implanting CRT with or without a defibrillator.

International audience; Atrial fibrillation (AF) is the most common rhythm disturbance. Among the major thromboembolic complications associated with AF, strokes are foremost, with a 4.4% yearly incidence in the absence of preventive treatment. Therefore, the prevention of these embolic accidents is a priority. While proof of the efficacy of oral anticoagulants (OACs) for this indication is long-standing and convincing, they are associated with haemorrhagic complications. Consequently, their prescription is based on an estimate of the risk (haemorrhagic complications)/benefit (thromboembolic prevention) ratio. In a patient subset at high thromboembolic and haemorrhagic risk, whether to prescribe or abstain from prescribing an OAC is a challenging decision, and an alternative means of thromboembolic prevention is desirable. Percutaneous occlusion of the left atrial appendage (LAA) is an alternative, interventional, non-pharmacological treatment that has been used widely in Europe and for a few years in France, with encouraging results. However, it remains an invasive procedure with a low level of proof in comparison with OACs. Moreover, the indications, the procedural environment and pre-per-post procedural patient management are major questions about this technique, with consequences on its efficacy and risk/benefit ratio. This document, composed by consensus among experts in the field, is an in-depth review of this new therapy.

International audience; To identify and characterize glycation, induced modifications of DNA are crucial toward understanding their functional significance due to their significant role in the long term control of aging and age-related diseases. In this study, we present the ability of Raman microspectroscopy as a novel analytical technique for a rapid and reliable identification of glycated DNA in a reagent-free manner. We have demonstrated that this technique has potential to provide very small conformational modifications. The combination of principal component analysis (PCA) and two-dimensional (2D) correlation spectroscopy has assisted us to explore in vitro DNA-glycation and provide more insights into the dynamics of the DNAglycation process in an easier fashion. PCA analysis of Raman spectra shows a clear discrimination between native and glycated DNA samples. On the other hand, 2D correlation Raman analysis provides sequential order of the mechanism of the DNA-glycation process, and most likely, it occurs in the following sequence: Structural modifications of individual nucleobases (G > A > C) → DNA backbone modifications → partial transition of DNA conformations (A to B form). Our observations clearly suggest that the structure of DNA is altered, i.e., a partial transition of DNA backbone conformation from A to B form when glycated, but does not induce any final transition in DNA double helix conformation, and eventually, DNA presents in an intermediate A−B form, more toward the B form.

This study reports a comprehensive analysis of the effect of 100 μs electric pulses on the biochemical composition of live cells using a label-free approach, confocal Raman microspectroscopy. We investigated different regions of interest around the nucleus of the cells and the dose-effect relationship related to different electric pulse parameters. We also extended the study to another cell type. Membrane resealing was monitored by pulsing the cells in reversible or irreversible electropermeabilization condition at different temperatures. Our results confirmed a previous publication showing that proteins and lipids were highly impacted by the delivery of electric pulses. These chemical changes were similar in different locations around the cell nucleus. By sweeping the field magnitude, the number of electric pulses, or their repetition rate, the Raman signatures of live cells appeared to be related to the electropermeabilization state, verified by Yo-Pro-1 uptake. We also demonstrated that the chemical changes in the Raman signatures were cell-dependent even if common features were noticed between the two cell types used.

Recent studies have shown that in more than half of apparently unexplained sudden cardiac arrests (SCA), a specific aetiology can be unmasked by a careful evaluation. The characteristics and the extent to which such cases undergo a systematic thorough investigation in real-life practice are unknown.Data were analysed from an ongoing study, collecting all cases of out-of-hospital cardiac arrest in Paris area. Investigations performed during the index hospitalization or planned after discharge were gathered to evaluate the completeness of assessment of unexplained SCA. Between 2011 and 2016, among the 18 622 out-of-hospital cardiac arrests, 717 survivors (at hospital discharge) fulfilled the definition of cardiac SCA. Of those, 88 (12.3%) remained unexplained after electrocardiogram, echocardiography, and coronary angiography. Cardiac magnetic resonance imaging yielded the diagnosis in 25 (3.5%) cases, other investigations accounted for 14 (2.4%) additional diagnoses, and 49 (6.8%) patients were labelled as idiopathic ventricular fibrillation (IVF) (48.7 ± 15 years, 69.4% male). Among those labelled IVF, only 8 (16.3%) cases benefited from a complete workup (including pharmacological testing). Younger patients [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.80-22.26] and those admitted to university centres (OR 3.60, 95% CI 1.12-12.45) were more thoroughly investigated. Genetic testing and family screening were initiated in only 9 (18.4%) and 12 (24.5%) cases, respectively.Our findings suggest that complete investigations are carried out in a very low proportion of unexplained SCA. Standardized, systematic approaches need to be implemented to ensure that opportunities for specific therapies and preventive strategies (including relatives) are not missed.

International audience; In the setting of primary prevention of sudden cardiac death, international guidelines (1) recommend an implantable cardioverter-defibrillator (ICD) for symptomatic patients (New York Heart Association [NYHA] functional class II or III) with altered left ventricular ejection fraction (LVEF) (#35%). Our objective was to compare outcomes among patients implanted with a primary prevention ICD according to whether the implantations were guideline-based or not. The DAI-PP (Primary Prevention ICD French Registry) (NCT01992458) enrolled all consecutive patients with ischemic or dilated cardiomyopathy implanted with a primary prevention ICD in 12 French centers between 2002 and 2012 (2). On-guideline patients met both basic criteria, namely, LVEF #35% and NYHA functional class II to III. Off-guideline patients did not meet at least 1 of the 2 criteria. We focused on candidates without an indication for cardiac resynchronization therapy. Vital status and causes of death were ascertained by review of hospital medical files or by communication with primary care physicians, and were corroborated with the French vital status database of the National Institute of Economic Statistics and the French Center on Medical Causes of Death. ICD programming was nonstandardized, although there was a broad consensus between centers (all except 1) concerning the use of high ventricular rates and usually 2 zones (typically ventricular tachycardia >180 beats/min, ventricular fibrillation >220 beats/ min). All data were analyzed using the SAS program version 9.4 (SAS Institute, Cary, North Carolina). Of a total of 5,539 patients enrolled in DAI-PP study, 2,538 were implanted with a single-or double-chamber ICD. Mean age was 60.2 AE 11.7 years, 1,694 (87.4%) were men, 1,379 (71.9%) had ischemic car-diomyopathy, mean LVEF was 28.2 AE 8.6%, and 853 (59.3%) had a QRS width

International audience; AIMS: Implantable cardioverter defibrillators (ICDs) are an effective primary prevention of sudden cardiac death. We examined whether dual-chamber (DC) ICDs confer a greater benefit than single-chamber (SC) ICDs, and compared the long-term outcomes of recipients of each type of device implanted for primary prevention.AbstractAIMS:Implantable cardioverter defibrillators (ICDs) are an effective primary prevention of sudden cardiac death. We examined whether dual-chamber (DC) ICDs confer a greater benefit than single-chamber (SC) ICDs, and compared the long-term outcomes of recipients of each type of device implanted for primary prevention.METHODS AND RESULTS:Between 2002 and 2012, the DAI-PP registry consecutively enrolled 1258 SC- and 1280 DC-ICD recipients at 12 French medical centres. The devices were interrogated at 4- to 6-month intervals during outpatient visits, with a focus on the therapies delivered. The study endpoints were incidence of appropriate therapies, ICD-related morbidity, and deaths from all and from specific causes. The mean age of the SC- and DC-ICD recipients was 59 ± 12 and 62 ± 11 years, respectively (P< 0.0001). The distribution of genders, New York Heart Association functional classes and glomerular filtration rates, and the rates of ischaemic vs. dilated cardiomyopathies and of defibrillation tests at implant, were similar in both study groups. The rates of periprocedural complications were 12.1% in the DC- vs. 8.8% in the SC-ICD groups (P= 0.008). Over a mean follow-up of 3.1 ± 2.2 years, pulse generators were replaced in 21.9% of the DC- vs. 13.6% of the SC-ICD group (P< 0.0001). The proportions of patients treated with ≥1 appropriate therapies (24.7 vs. 23.8%) and ≥1 inappropriate shocks (8.4 vs. 7.8%), and all-cause mortality (12.4 vs. 13.2%) were similar in both groups.CONCLUSION:In this large registry of ICD implanted for primary prevention, DC-ICDs were associated with higher rates of peri-implant complications and generator replacements, whereas the survival and rates of inappropriate shocks were similar in both groups.CLINICAL TRIAL NUMBER:NCT#01992458.Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

International audience; This study evaluated the midterm delivery of doxorubicin in liver specimens from patients (N = 4) with hepatocellular carcinoma treated with drug-eluting embolic (DEE) transarterial chemoembolization. The patients had surgical resection 57, 79, 80 and 105 days after doxorubicin DEE chemoembolization. Doxorubicin concentrations inside embolic particles and in surrounding tissues were assessed by infrared microspectroscopy and microspectrofluorimetry, respectively. Embolic particles still contained doxorubicin and provided sustained drug delivery within targeted tissues 80 days after chemoembolization. Doxorubicin was undetectable after 105 days. In addition, aggregation of embolic particles inside vessel lumina was associated with slower doxorubicin elution and higher tissue concentrations when the number of aggregated embolic particles increased.

International audience; BACKGROUND: Programming implantable cardioverter-defibrillators (ICDs) with a high-rate therapy strategy has proven to be effective in reducing shocks and is associated with a reduced mortality. OBJECTIVE: We sought to determine the impact of a very high rate cutoff programming strategy on outcomes in patients with a primary indication for an ICD due to reduced left ventricular ejection fraction. METHODS: Using data from the multicenter French DAI-PP registry, this cohort-controlled study compared outcomes in 500 patients programmed with a very high rate cutoff (VH-RATE group: monitor zone 170-219 beats/min; ventricular fibrillation zone ≥220 beats/min with 13 ± 4 detection intervals) with 1500 matched control patients programmed with 1 or 2 therapy zone. All ICDs were implanted for primary prevention in patients with systolic dysfunction. Risks of events were compared after propensity score matching of sex, age, ejection fraction, New York Heart Association class, cardiomyopathy, atrial fibrillation, and type of device. RESULTS: After a mean follow-up of 3.6 ± 2.3 years, VH-RATE programming was associated with a reduction of appropriate therapy risk (hazard ratio [HR] 0.40; 95% confidence interval [CI] 0.31-0.51; P < .0001) and inappropriate shock (HR 0.42; 95% CI 0.27-0.63; P < .0001). It was also associated with a decreased risk of sudden cardiac death (HR 0.43; 95% CI 0.17-0.99; P = .04) as compared with patients programmed with 2 therapy zones. There was no significant difference in overall survival between the groups. CONCLUSION: In patients implanted with an ICD in primary prevention with left ventricular dysfunction, very high rate cutoff programming (single therapy zone ≥220 beats/min) was associated with a 60% reduction of appropriate therapies as well as inappropriate shocks, without affecting mortality.

Aim The magnitude of benefit related to implantable cardioverter defibrillator (ICD) therapy for primary prevention of sudden cardiac death (SCD) in non-ischaemic cardiomyopathy (NICM) and ischaemic cardiomyopathy (ICM) has not been evaluated extensively in clinical practice. Methods and results Of the 5539 consecutive patients enrolled in the multicentre Defibrillateur Automatique Implantable-Prevention Primaire (DAI-PP) study (2002-12), 5485 patients (with information on underlying heart disease) were included in the present analysis: 2181 (39.8%) had NICM and 3304 (60.2%) had ICM. ICM patients were older (63.7 ±10.3 vs. 60.6 ± 12.2 years, P

International audience; This paper presents a procedure that digitally neutralizes the contribution of paraffin to FTIR hyperspectral images. A brief mathematical derivation of the procedure is demonstrated and applied on one normal human colon sample to exemplify the de-waxing procedure. The proposed method includes construction of a paraffin model based on PCA, EMSC normalization and application of two techniques for spectral quality control. We discuss every step in which the researcher needs to take a subjective decision during the de-waxing procedure, and we explain how to make an adequate choice of parameters involved. Application of this procedure to 71 hyperspectral images collected from 55 human colon biopsies (20 normal, 17 ulcerative colitis, and 18 adenocarcinoma) showed that paraffin was appropriately neutralized, which made the de-waxed images adequate for analysis by pattern-recognition techniques such as k-means clustering or PCA-LDA.

Complementary diagnostic methods to conventional histopathology are currently being investigated for developing rapid and objective molecular-level understanding of various disorders, especially cancers. Spectral histopathology using vibrational spectroscopic imaging has been put in the frontline as potentially promising in this regard as it provides a “spectral fingerprint” of the biochemical composition of cells and tissues. In order to ascertain the feasible conditions of vibrational spectroscopic methods for tissue-imaging analysis, vibrational multimodal imaging (infrared transmission, infrared-attenuated total reflection, and Raman imaging) of the same colon tissue has been implemented. The spectral images acquired were subjected to multivariate clustering analysis in order to identify on a molecular level the constituent histological organization of the colon tissue such as the epithelium, connective tissue, etc., by comparing the cluster images with the histological reference images. Based on this study, a comparative analysis of important factors involved in the vibrational multimodal imaging approaches such as image resolution, time constraints, their advantages and limitations, and their applicability to biological tissues has been carried out. Out of the three different vibrational imaging modalities tested, infrared-attenuated total reflection mode of imaging appears to provide a good compromise between the tissue histology and the time constraints in achieving similar image contrast to that of Raman imaging at an approximately 33-fold faster measurement time. The present study demonstrates the advantages, the limitations of the important parameters involved in vibrational multimodal imaging approaches, and their potential application toward imaging of biological tissues.