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As crucial stages in the plant ontogeny, germination and seedling establishment under adverse conditions greatly determine staple crop growth and productivity. In the context of green technologies aiming to improve crop yield, seed priming is emerging as an effective approach to enhance seed vigor and germination performance under salt stress. In this study, we assess the efficiency of seed priming with indole-3-acetic acid (IAA) in mitigating the adverse effects of salt stress on maize (Zea mays L.) seedlings during germination and early seedling stages. In unprimed seeds, salt stress reduced germination indices, and seedling (both radicle and coleoptile) growth, together with decreased tissue hydration. However, seed priming using IAA significantly improved maize salt response, as reflected by the increased seed germination dynamics, early seedling establishment, and water status. Besides, seedlings from IAA-primed seeds showed a higher activity of α-amylase, resulting in increased sugar contents in roots and coleoptiles of salt-stressed plants. Further, IAA-seed priming stimulated the accumulation of endogenous IAA in salt-stressed seedlings, in concomitance with a significant effect on reactive oxygen species detoxification and lipid peroxidation prevention. Indeed, our data revealed increased antioxidant enzyme activities, differentially regulated in roots and coleoptiles, leading to increased activities of the antioxidant enzymes (SOD, CAT and GPX). In summary, data gained from this study further highlight the potential of IAA in modulating early interactions between multiple signaling pathways in the seed, endowing maize seedlings with enhanced potential and sustained tolerance to subsequent salt stress., (© 2024. The Author(s).)

Plants are highly sensitive to various environmental stresses, which can hinder their growth and reduce yields. In this study, we investigated the potential of seed priming with salicylic acid (SA), gibberellic acid (GA 3 ), and sodium chloride (NaCl) to mitigate the adverse effects of salinity stress in Hordeum vulgare at the germination and early seedling stages. Exposing H. vulgare seeds to salt stress reduced the final germination percentage and seedling shoot and root growth. Interestingly, all seed treatments significantly improved salt-induced responses, with GA 3 being more effective in terms of germination performance, plant growth, and photosynthesis. SA priming exhibited promising effects on antioxidant defense mechanisms, proline, sugar, and ascorbic acid production. Notably, SA priming also suppressed reactive oxygen species accumulation and prevented lipid peroxidation. These findings highlight the ability of SA to manage crosstalk within the seed, coordinating many regulatory processes to support plant adaptation to salinity stress.

Background: CLOSE-guided pulmonary vein isolation (PVI) is based on contiguous and optimized (Ablation Index-guided) radiofrequency lesions. The efficacy of CLOSE-guided PVI in persistent atrial fibrillation (AF) treatment has been poorly evaluated., Methods: In two centers, 50 patients eligible for persistent AF ablation underwent CLOSE-guided PVI (Ablation Index ≥ 450 at the anterior wall, ≥300 at posterior wall, intertag distance ≤ 6 mm). If PVI failed to restore sinus rhythm (SR), electrical cardioversion (ECV) was performed. Atrial substrate modification (ASM) was performed only if PVI and ECV failed to restore SR. Recurrence was defined as any recorded episode of AF, atrial tachycardia (AT) or atrial flutter (AFL) > 30 s on Holter electrocardiographs at 3, 6 and 12 months., Results: From the 50 patients (64 ± 10 years, 14% long-standing persistent AF), SR was restored by ECV in 34 patients (68%) 56 ± 38 days prior to ablation. On the day of ablation, 42 patients (84%) were on class I-III anti-arrhythmic drug therapy (ADT) and the rhythm was AF in 23/50 patients. PVI was achieved in all patients; after PVI, ECV was required in 21 patients and ASM in 1 patient. The mean procedure time, radiofrequency time and fluoroscopy time were 141 ± 33 min, 23 ± 7 min and 7 ± 6 min, respectively. At 12 months, single-procedure freedom from AF/AT/AFL was 80%, with 19 patients (38%) receiving class I-III ADT., Conclusions: In a population of patients with persistent AF monitored with intermittent cardiac rhythm recordings, CLOSE-guided PVI resulted in high single-procedure arrhythmia-free survival at 1 year. Future large-scale studies involving continuous cardiac monitoring are necessary.

HIV-2 infection is characterized by low viremia and slow disease progression as compared to HIV-1 infection. Circulating CD14 ++ CD16 + monocytes were found to accumulate and CD11c + conventional dendritic cells (cDC) to be depleted in a Portuguese cohort of people living with HIV-2 (PLWHIV-2), compared to blood bank healthy donors (HD). We studied more precisely classical monocytes; CD16 + inflammatory (intermediate, non-classical and slan + monocytes, known to accumulate during viremic HIV-1 infection); cDC1, important for cross-presentation, and cDC2, both depleted during HIV-1 infection. We analyzed by flow cytometry these PBMC subsets from Paris area residents: 29 asymptomatic, untreated PLWHIV-2 from the IMMUNOVIR-2 study, part of the ANRS-CO5 HIV-2 cohort: 19 long-term non-progressors (LTNP; infection ≥8 years, undetectable viral load, stable CD4 counts≥500/μL; 17 of West-African origin -WA), and 10 non-LTNP (P; progressive infection; 9 WA); and 30 age-and sex-matched controls: 16 blood bank HD with unknown geographical origin, and 10 HD of WA origin (GeoHD). We measured plasma bacterial translocation markers by ELISA. Non-classical monocyte counts were higher in GeoHD than in HD (54 vs. 32 cells/μL, p = 0.0002). Slan + monocyte counts were twice as high in GeoHD than in HD (WA: 28 vs. 13 cells/μL, p = 0.0002). Thus cell counts were compared only between participants of WA origin. They were similar in LTNP, P and GeoHD, indicating that there were no HIV-2 related differences. cDC counts did not show major differences between the groups. Interestingly, inflammatory monocyte counts correlated with plasma sCD14 and LBP only in PLWHIV-2, especially LTNP, and not in GeoHD. In conclusion, in LTNP PLWHIV-2, inflammatory monocyte counts correlated with LBP or sCD14 plasma levels, indicating a potential innate immune response to subclinical bacterial translocation. As GeoHD had higher inflammatory monocyte counts than HD, our data also show that specific controls are important to refine innate immunity studies., (Copyright © 2020 Iannetta, Isnard, Manuzak, Guillerme, Notin, Bailly, Andrieu, Amraoui, Vimeux, Figueiredo, Charmeteau-de Muylder, Vaton, Hatton, Samri, Autran, Thiébaut, Chaghil, Glohi, Charpentier, Descamps, Brun-Vézinet, Matheron, Cheynier and Hosmalin.)

The endoplasmic reticulum (ER) is the site for Zika virus (ZIKV) replication and is central to the cytopathic effects observed in infected cells. ZIKV induces the formation of ER-derived large cytoplasmic vacuoles followed by "implosive" cell death. Little is known about the nature of the ER factors that regulate flavivirus replication. Atlastins (ATL1, -2, and -3) are dynamin-related GTPases that control the structure and the dynamics of the ER membrane. We show here that ZIKV replication is significantly decreased in the absence of ATL proteins. The appearance of infected cells is delayed, the levels of intracellular viral proteins and released virus are reduced, and the cytopathic effects are strongly impaired. We further show that ATL3 is recruited to viral replication sites and interacts with the nonstructural viral proteins NS2A and NS2B3. Thus, proteins that shape and maintain the ER tubular network ensure efficient ZIKV replication. IMPORTANCE Zika virus (ZIKV) is an emerging virus associated with Guillain-Barré syndrome, and fetal microcephaly as well as other neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We found that endoplasmic reticulum (ER)-shaping atlastin proteins (ATL1, -2, and -3), which induce ER membrane fusion, facilitate ZIKV replication. We show that ATL3 is recruited to the viral replication site and colocalize with the viral proteins NS2A and NS2B3. The results provide insights into host factors used by ZIKV to enhance its replication., (Copyright © 2019 American Society for Microbiology.)

Objectives: This study sought to assess the relationship between fibrosis and re-entrant activity in persistent atrial fibrillation (AF)., Background: The mechanisms involved in sustaining re-entrant activity during AF are poorly understood., Methods: Forty-one patients with persistent AF (age 56 ± 12 years; 6 women) were evaluated. High-resolution electrocardiographic imaging (ECGI) was performed during AF by using a 252-chest electrode array, and phase mapping was applied to locate re-entrant activity. Sites of high re-entrant activity were defined as re-entrant regions. Late gadolinium-enhanced (LGE) cardiac magnetic resonance (CMR) was performed at 1.25 × 1.25 × 2.5 mm resolution to characterize atrial fibrosis and measure atrial volumes. The relationship between LGE burden and the number of re-entrant regions was analyzed. Local LGE density was computed and characterized at re-entrant sites. All patients underwent catheter ablation targeting re-entrant regions, the procedural endpoint being AF termination. Clinical, CMR, and ECGI predictors of acute procedural success were then analyzed., Results: Left atrial (LA) LGE burden was 22.1 ± 5.9% of the wall, and LA volume was 74 ± 21 ml/m 2 . The number of re-entrant regions was 4.3 ± 1.7 per patient. LA LGE imaging was significantly associated with the number of re-entrant regions (R = 0.52, p = 0.001), LA volume (R = 0.62, p < 0.0001), and AF duration (R = 0.54, p = 0.0007). Regional analysis demonstrated a clustering of re-entrant activity at LGE borders. Areas with high re-entrant activity showed higher local LGE density as compared with the remaining atrial areas (p < 0.0001). Failure to achieve AF termination during ablation was associated with higher LA LGE burden (p < 0.001), higher number of re-entrant regions (p < 0.001), and longer AF duration (p = 0.008)., Conclusions: The number of re-entrant regions during AF relates to the extent of LGE on CMR, with the location of these regions clustering to LGE areas. These characteristics affect procedural outcomes of ablation.

Background: Trials using echocardiographic mechanical dyssynchrony (MD) parameters in narrow QRS patients have shown a negative response to CRT. We hypothesized MD in these patients may relate to myocardial scar rather than electrical dyssynchrony., Methods: We determined the prevalence of cardiac magnetic resonance (CMR) derived measures of MD in 130 systolic heart failure patients with both broad (≥ 130 ms - BQRS) and narrow QRS duration (< 130 ms - NQRS). We assessed whether late gadolinium enhancement derived scar might explain the presence of MD amongst narrow QRS patients. Dyssynchrony was calculated on the basis of a systolic dyssynchrony index (SDI)., Results: Fifty-nine patients (45%) had a NQRS and the remaining had QRS ≥ 130 ms (BQRS group). 25% of NQRS patients had MD based on SDI. In all narrow and broad QRS patients with MD there was a significantly lower scar volume than those without MD (7.4 ± 10.5% vs 13.7 ± 13.3% vs. p < 0.01). This was the case in the BQRS group with a significantly lower scar burden in patients with MD (5.0 ± 7.7% vs 15.4 ± 15.6%, p < 0.01). Notably in the NQRS group this difference was absent with an equal scar burden in patients with MD 13.3 ± 13.9% and without MD 12.5 ± 11%, p = 0.92., Conclusions: 25% of patients with systolic heart failure and a NQRS (< 130 ms) have CMR derived mechanical dyssynchrony. Our findings suggest MD in this group may be secondary to myocardial scar rather than electrical dyssynchrony and therefore not amenable to correction by CRT. This may give insight into non-response and potential harm from CRT in this group.

The DNA-mediated innate immune response underpins anti-microbial defenses and certain autoimmune diseases. Here we used immunoprecipitation, mass spectrometry, and RNA sequencing to identify a ribonuclear complex built around HEXIM1 and the long non-coding RNA NEAT1 that we dubbed the HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein complex (HDP-RNP). The HDP-RNP contains DNA-PK subunits (DNAPKc, Ku70, and Ku80) and paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATRIN3). We show that binding of HEXIM1 to NEAT1 is required for its assembly. We further demonstrate that the HDP-RNP is required for the innate immune response to foreign DNA, through the cGAS-STING-IRF3 pathway. The HDP-RNP interacts with cGAS and its partner PQBP1, and their interaction is remodeled by foreign DNA. Remodeling leads to the release of paraspeckle proteins, recruitment of STING, and activation of DNAPKc and IRF3. Our study establishes the HDP-RNP as a key nuclear regulator of DNA-mediated activation of innate immune response through the cGAS-STING pathway., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The cytopathic effects of Zika virus (ZIKV) are poorly characterized. Innate immunity controls ZIKV infection and disease in most infected patients through mechanisms that remain to be understood. Here, we studied the morphological cellular changes induced by ZIKV and addressed the role of interferon-induced transmembrane proteins (IFITM), a family of broad-spectrum antiviral factors, during viral replication. We report that ZIKV induces massive vacuolization followed by "implosive" cell death in human epithelial cells, primary skin fibroblasts and astrocytes, a phenomenon which is exacerbated when IFITM3 levels are low. It is reminiscent of paraptosis, a caspase-independent, non-apoptotic form of cell death associated with the formation of large cytoplasmic vacuoles. We further show that ZIKV-induced vacuoles are derived from the endoplasmic reticulum (ER) and dependent on the PI3K/Akt signaling axis. Inhibiting the Sec61 ER translocon in ZIKV-infected cells blocked vacuole formation and viral production. Our results provide mechanistic insight behind the ZIKV-induced cytopathic effect and indicate that IFITM3, by acting as a gatekeeper for incoming virus, restricts virus takeover of the ER and subsequent cell death., (© 2017 Institut Pasteur.)

Aims: Cardiac perforations caused by pacemaker or implantable cardioverter-defibrillator (ICD) leads are uncommon but potentially fatal events. The optimal approach to such cases is unclear. The aim of this study was to identify the optimal imaging modality and management strategy for cardiac perforation., Methods and Results: All patients presenting to a single institution with cardiac perforation >24 h since implant between 2011 and 2015 were identified retrospectively. Assessment of the diagnostic performance of pre-extraction chest radiography, transthoracic echocardiography (TTE), and computed tomography (CT) was carried out by blinded review. The method of lead extraction and any associated complications were examined. Eighteen cases of cardiac perforation were identified from 426 lead extraction procedures. Sixteen patients had abnormal electrical parameters at device interrogation. In all cases, the perforating lead was an active fixation model, and in four cases, this was an ICD coil. The accuracy of CT imaging for the diagnosis of cardiac perforation was 92.9%, with sensitivity and specificity of 100 and 85.7%, respectively. This was superior to both TTE (accuracy 62.7%, sensitivity and specificity 41.2 and 84.2%, respectively) and chest radiography (accuracy 61.1%, sensitivity and specificity 27.7 and 94.4%, respectively). Transvenous lead extraction (TLE) was performed in 17 patients, and a hybrid surgical approach in 1 patient. Of those who underwent TLE, there was 100% complete procedural success as per Heart Rhythm Society definitions., Conclusion: In the setting of cardiac perforation, CT is the imaging modality of choice. Transvenous lead extraction can be recommended as a safe, efficacious, and versatile intervention., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: In contrast to patients with left bundle branch block (LBBB), heart failure patients with narrow QRS and nonspecific intraventricular conduction delay (NICD) display a relatively limited response to cardiac resynchronization therapy. We sought to compare left ventricular (LV) activation patterns in heart failure patients with narrow QRS and NICD to patients with LBBB using high-density electroanatomic activation maps., Methods and Results: Fifty-two heart failure patients (narrow QRS [n=18], LBBB [n=11], NICD [n=23]) underwent 3-dimensional electroanatomic mapping with a high density of mapping points (387±349 LV). Adjunctive scar imaging was available in 37 (71%) patients and was analyzed in relation to activation maps. LBBB patients typically demonstrated (1) a single LV breakthrough at the septum (38±15 ms post-QRS onset); (2) prolonged right-to-left transseptal activation with absence of direct LV Purkinje activity; (3) homogeneous propagation within the LV cavity; and (4) latest activation at the basal lateral LV. In comparison, both NICD and narrow QRS patients demonstrated (1) multiple LV breakthroughs along the posterior or anterior fascicles: narrow QRS versus LBBB, 5±2 versus 1±1; P =0.0004; NICD versus LBBB, 4±2 versus 1±1; P =0.001); (2) evidence of early/pre-QRS LV electrograms with Purkinje potentials; (3) rapid propagation in narrow QRS patients and more heterogeneous propagation in NICD patients; and (4) presence of limited areas of late activation associated with LV scar with high interindividual heterogeneity., Conclusions: In contrast to LBBB patients, narrow QRS and NICD patients are characterized by distinct mechanisms of LV activation, which may predict poor response to cardiac resynchronization therapy., (© 2017 American Heart Association, Inc.)

Background: The underlying mechanisms sustaining human persistent atrial fibrillation (PsAF) is poorly understood., Objectives: This study sought to investigate the complexity and distribution of AF drivers in PsAF of varying durations., Methods: Of 135 consecutive patients with PsAF, 105 patients referred for de novo ablation of PsAF were prospectively recruited. Patients were divided into 3 groups according to AF duration: PsAF presenting in sinus rhythm (AF induced), PsAF <12 months, and PsAF >12 months. Patients wore a 252-electrode vest for body surface mapping. Localized drivers (re-entrant or focal) were identified using phase-mapping algorithms., Results: In this patient cohort, the most prominent re-entrant driver regions included the pulmonary vein (PV) regions and inferoposterior left atrial wall. Focal drivers were observed in 1 or both PV regions in 75% of patients. Comparing between the 3 groups, with longer AF duration AF complexity increased, reflected by increased number of re-entrant rotations (p < 0.05), number of re-entrant rotations and focal events (p < 0.05), and number of regions harboring re-entrant (p < 0.01) and focal (p < 0.05) drivers. With increased AF duration, a higher proportion of patients had multiple extra-PV driver regions, specifically in the inferoposterior left atrium (p < 0.01), superior right atrium (p < 0.05), and inferior right atrium (p < 0.05). Procedural AF termination was achieved in 70% of patients, but decreased with longer AF duration., Conclusions: The complexity of AF drivers increases with prolonged AF duration. Re-entrant and focal drivers are predominantly located in the PV antral and adjacent regions. However, with longer AF duration, multiple drivers are distributed at extra-PV sites. AF termination rate declines as patients progress to longstanding PsAF, underscoring the importance of early intervention., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Left ventricular (LV) lead implantation through the coronary sinus (CS) can be limited and sometimes not possible-alternative approaches are needed. Minimally invasive, robotically guided LV lead implantation has major advantages, but there are little published data about the short- and long-term follow-ups, in terms of feasibility, safety, electrical performance, and impact on clinical outcome., Methods and Results: A total of 21 heart failure patients underwent robotically guided LV lead implantation using the Da Vinci Robotic System. Indications were failed implant with conventional approach through the CS (n = 16) and non-response to conventional cardiac resynchronization therapy (n = 5). During the procedure, the entire LV free wall was exposed through 3 transthoracic ports (10 mm diameter each) allowing ample choice of stimulation site and the ability to implant 2 LV leads via a Y connector. Patients were prospectively followed up for 1 year. The two LV leads were successfully implanted in all patients. No peri-procedural complications were observed. After a mean stay in the intensive care unit of 1.2 ± 4 days, the 21 patients were hospitalized in the EP department for 6.7 ± 2.9 days. Acute LV thresholds were excellent (1.0 V ± 0.6/0.4 ms) and stayed stable at 1-year follow-up (1.5 V ± 0.6/0.4 ms, P = 0.21). Four patients demonstrated an increased threshold (>2 V/0.4 ms). There was no phrenic nerve stimulation. After 12 months, in the failed implant group, 69% of the patients were echocardiographic and clinical responders., Conclusion: The robotic approach was feasible, safe, and minimally invasive. Accordingly, robotically guided LV lead implantation seems to offer a new alternative when conventional approaches are not suitable., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Currently, no non-invasive cardiac pacing device acceptable for prolonged use in conscious patients exists. High Intensity Focused Ultrasound (HIFU) can be used to perform remote pacing using reversibility of electromechanical coupling of cardiomyocytes. Here we described an extracorporeal cardiac stimulation device and study its efficacy and safety. We conducted experiments ex vivo and in vivo in a large animal model (pig) to evaluate clinical potential of such a technique. The stimulation threshold was determined in 10 different ex vivo hearts and different clinically relevant electrical effects such as consecutive stimulations of different heart chambers with a single ultrasonic probe, continuous pacing or the inducibility of ventricular tachycardia were shown. Using ultrasonic contrast agent, consistent cardiac stimulation was achievable in vivo for up to 1 hour sessions in 4 different animals. No damage was observed in inversion-recovery MR sequences performed in vivo in the 4 animals. Histological analysis revealed no differences between stimulated and control regions, for all ex vivo and in vivo cases.

Background : Rates of pacemaker implantation are steadily increasing and as patients are living longer, endovenous leads remain implanted for an extended period of time thereby increasing the risk of cardiac implantable electronic device (CIED) infection. Investigating fever of unknown origin in patients with implanted pacemakers can be challenging. Recently, 18 F-fluorodeoxyglucose positron emission tomography/computerised tomography ( 18 F-FDG-PET/CT) scanning has been used as a diagnostic tool for lead endocarditis in small studies. Objectives : ENDOTEP is a prospective and multicentre study designed to evaluate the accuracy of 18 F-FDG-PET/CT scanning in the diagnosis of lead endocarditis. Methods : A total of 250 patients referred for pacemaker extraction due to suspicion of an infected device will be prospectively enrolled in six French regional centres for investigation and treatment of CIED infection. 18 F-FDG-PET/CT scanning (index test) will be performed in each patient in the 48 hours preceding lead extraction. Bacteriological cultures (reference standard) will assess the presence of lead endocarditis, blind to 18 F-FDG-PET/CT results. Enrolment started in June 2015 and is expected to end by June 2017. The primary objective will be to establish the sensitivity of the 18 F-FDG-PET/CT scan for lead endocarditis. Secondary objectives will include other accuracy parameters, inter-observer agreement in the interpretation of 18 F-FDG-PET/CT scanning, the influence of previous antibiotic therapy on 18 F-FDG-PET/CT diagnostic accuracy and assessment of septic emboli associated to lead endocarditis. Conclusion : The ENDOTEP study will examine the ability of 18 F-FDG-PET/CT scanning to avoid possible false-positive results, as is common using the current usual diagnostic strategy and may lead to unnecessary extraction of implants in patients with suspected lead infection., Competing Interests: Disclosure: This research was conducted with the financing of Bordeaux University Hospital (source of grants: PHRC Hospital Program of Clinical Research).

Background: During the past years, many innovations have been introduced to facilitate catheter ablation of post-myocardial infarction ventricular tachycardia. However, the predictors of outcome after ablation were not thoroughly studied., Methods and Results: From 2009 to 2013, consecutive patients referred for post-myocardial infarction ventricular tachycardia ablation were included. The end point of the procedure was complete elimination of local abnormal ventricular activities (LAVA) and ventricular tachycardia (VT) noninducibility. The predictors of outcome with primary end point of VT recurrence were assessed. A total of 125 patients were included (age: 64±11 years; 7 women) for 142 procedures. The left ventricle was accessed via transseptal, retrograde aortic, and epicardial approaches in 87%, 33%, and 37% of patients, respectively. Three-dimensional electroanatomical mapping system was used in 70%, multipolar catheter in 51%, and real-time image integration in 38% (from magnetic resonance imaging in 39% and multidetector computed tomography in 93%) of patients. Before ablation, VT was inducible in 75%, and endocardial/epicardial LAVA were present in 88%/75%. After ablation, complete LAVA elimination was achieved in 60%, and VT noninducibility in 83%. During a median follow-up of 850 days (interquartile range, 439-1707), VT recurrence was observed in 36%. Multivariable analysis identified 3 independent outcome predictors: the ability to achieve complete LAVA elimination (R(2)=0.29; P<0.0001; risk ratio=0.52 [0.38-0.70]), the use of real-time image integration (R(2)=0.21; P=0.0006; risk ratio=0.49 [0.33-0.74]), and the use of multipolar catheters (R(2)=0.08; P=0.05; risk ratio=0.75 [0.56-1.00])., Conclusions: Achievement of complete LAVA elimination and use of scar integration from imaging and multipolar catheters to focus high-density mapping are independent predictors of VT-free survival after catheter ablation for post-myocardial infarction ventricular tachycardia., (© 2016 American Heart Association, Inc.)

Objectives: This study sought to characterize the clinical characteristics, atrial substrate, and prognosis in a subgroup of patients with persistent atrial fibrillation (AF) from the onset (PsAFonset)., Background: Patients with AF frequently progress from trigger-driven paroxysmal arrhythmias to substrate-dependent persistent arrhythmias., Methods: Patients referred for persistent AF (PsAF) ablation were enrolled from 3 centers. Consecutive patients with PsAFonset (n = 129) were compared with patients with PsAF that progressed from paroxysmal AF (n = 231). In addition, 90 patients (30 patients with PsAFonset and 60 control subjects) were studied with noninvasive mapping to characterize the AF drivers. The degree of fractionation and endocardial voltages were assessed invasively., Results: Patients with PsAFonset were younger (p = 0.047) and more obese (p < 0.001); there were more men (p = 0.034), more patients with hypertension (p = 0.044), and these patients had larger left (p < 0.05) and right atria (p < 0.05). Baseline AF cycle length was shorter in the PsAFonset group (p < 0.01); the degree of fractionation was higher (p < 0.001 for both atria), and the endocardial voltage was lower (p < 0.05 for both atria). Patients with PsAFonset had higher a number of re-entrant driver regions (p < 0.001) and extrapulmonary vein regions that had re-entrant drivers (p < 0.05), whereas control subjects displayed more focal driver regions (p = 0.029). The acute AF termination rate was lower in the PsAFonset group (42% vs. 81%; p < 0.001). During a mean follow-up of 17 ± 11 months from the last procedure, patients with PsAFonset had significantly higher AF, atrial tachycardia (AT), and AF/AT recurrence rates (p < 0.01)., Conclusions: Patients with PsAFonset represent a distinct subgroup defined by specific demographics, underlying diffuse biatrial substrate disease, and worse clinical outcome. The findings highlight the importance of defining criteria for early detection of atrial substrate disease., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Unlabelled: In a previous screen of putative interferon-stimulated genes, SUN2 was shown to inhibit HIV-1 infection in an uncharacterized manner. SUN2 is an inner nuclear membrane protein belonging to the linker of nucleoskeleton and cytoskeleton complex. We have analyzed here the role of SUN2 in HIV infection. We report that in contrast to what was initially thought, SUN2 is not induced by type I interferon, and that SUN2 silencing does not modulate HIV infection. However, SUN2 overexpression in cell lines and in primary monocyte-derived dendritic cells inhibits the replication of HIV but not murine leukemia virus or chikungunya virus. We identified HIV-1 and HIV-2 strains that are unaffected by SUN2, suggesting that the effect is specific to particular viral components or cofactors. Intriguingly, SUN2 overexpression induces a multilobular flower-like nuclear shape that does not impact cell viability and is similar to that of cells isolated from patients with HTLV-I-associated adult T-cell leukemia or with progeria. Nuclear shape changes and HIV inhibition both mapped to the nucleoplasmic domain of SUN2 that interacts with the nuclear lamina. This block to HIV replication occurs between reverse transcription and nuclear entry, and passaging experiments selected for a single-amino-acid change in capsid (CA) that leads to resistance to overexpressed SUN2. Furthermore, using chemical inhibition or silencing of cyclophilin A (CypA), as well as CA mutant viruses, we implicated CypA in the SUN2-imposed block to HIV infection. Our results demonstrate that SUN2 overexpression perturbs both nuclear shape and early events of HIV infection., Importance: Cells encode proteins that interfere with viral replication, a number of which have been identified in overexpression screens. SUN2 is a nuclear membrane protein that was shown to inhibit HIV infection in such a screen, but how it blocked HIV infection was not known. We show that SUN2 overexpression blocks the infection of certain strains of HIV before nuclear entry. Mutation of the viral capsid protein yielded SUN2-resistant HIV. Additionally, the inhibition of HIV infection by SUN2 involves cyclophilin A, a protein that binds the HIV capsid and directs subsequent steps of infection. We also found that SUN2 overexpression substantially changes the shape of the cell's nucleus, resulting in many flower-like nuclei. Both HIV inhibition and deformation of nuclear shape required the domain of SUN2 that interacts with the nuclear lamina. Our results demonstrate that SUN2 interferes with HIV infection and highlight novel links between nuclear shape and viral infection., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

The Fc region of HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) is required for suppressing viraemia, through mechanisms which remain poorly understood. Here, we identify bNAbs that exert antibody-dependent cellular cytotoxicity (ADCC) in cell culture and kill HIV-1-infected lymphocytes through natural killer (NK) engagement. These antibodies target the CD4-binding site, the glycans/V3 and V1/V2 loops on gp120, or the gp41 moiety. The landscape of Env epitope exposure at the surface and the sensitivity of infected cells to ADCC vary considerably between viral strains. Efficient ADCC requires sustained cell surface binding of bNAbs to Env, and combining bNAbs allows a potent killing activity. Furthermore, reactivated infected cells from HIV-positive individuals expose heterogeneous Env epitope patterns, with levels that are often but not always sufficient to trigger killing by bNAbs. Our study delineates the parameters controlling ADCC activity of bNAbs, and supports the use of the most potent antibodies to clear the viral reservoir.

Objectives: The aim of this study was to investigate the role of 18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scanning in identifying septic embolism in patients with lead endocarditis., Background: Lead endocarditis may be associated with septic embolism, in which case the administration mode, type, and duration of antibiotic therapy must be adapted. However, diagnosis can be challenging: magnetic resonance imaging (MRI) cannot be performed in the vast majority of patients with cardiac implantable electronic devices (CIEDs). FDG PET/CT scanning has been proposed as a diagnostic tool for suspected CIED infection., Methods: Thirty-five consecutive patients with lead endocarditis were prospectively studied. FDG PET/CT scanning was performed and analyzed blindly by experienced nuclear medicine physicians to assess for the presence of septic embolism 2 days before lead extraction., Results: FDG PET/CT scanning identified septic emboli in 10 patients (29%): 7 with spondylodiscitis, 2 with septic pulmonary emboli, and 1 with an infected vascular prosthesis. Among the 7 patients with occult spondylodiscitis, 4 were asymptomatic, and 3 had back pain with negative CT imaging, MRI being contraindicated due to non MRI-compatible CIEDs. Antimicrobial therapy was adapted (double antibiotic therapy with good bone penetration) and prolonged. Among other important ancillary findings, 3 patients presented focal FDG uptake in the colon (1 adenocarcinoma, and 2 resected polyps) and 2 in the esophagus (both cases confirmed as neoplasia)., Conclusions: This study emphasizes the potential utility of FDG PET/CT scanning as a diagnostic tool for septic emboli in patients with pacing lead endocarditis. This promising diagnostic tool may be integrated in the diagnostic algorithm of patients with lead endocarditis because diagnosis of septic embolisms has a direct and significant impact on the therapeutic care pathway., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Ventricular tachycardia (VT) ablation for ventricular arrhythmias is a validated approach, typically performed endocardially, or combined with an epicardial approach if endocardial ablation failed or in case of non-ischaemic cardiomyopathy. We report our experience with epicardial only procedure in a subset of patients with incessant VT or VT storm., Methods and Results: This was a single centre retrospective study. Between 2011 and 2014, all patients referred for VT ablation were reviewed at CHU Bordeaux. All patients with an epicardial only (anterior percutaneous approach) mapping and ablation procedure were included. In total, 296 patients underwent a VT ablation and 4 (all male, 70 ± 7 years, 27 ± 11% left ventricular ejection fraction) of them underwent an epicardial only procedure: two ischaemic patients had an endocardial left ventricular thrombus and incessant VT. One patient post-myocarditis had a failed a previous endocardial procedure without local abnormal ventricular activity (LAVA). The fourth patient had a dilated cardiomyopathy and a complicated epicardial puncture followed by mild continuous bleeding (200 mL) precluding anticoagulation associated with left ventricular endocardial access. Local abnormal ventricular activity elimination was verified only epicardially in all and obtained in two patients and non-inducibility was tested and achieved in the two patients without thrombus. No further complications occurred. After a mean follow-up of 21 ± 12 months, one patient (25%) had recurrence of VT and no patient death was observed., Conclusion: Epicardial only ablation seems feasible and effective and useful in a limited subset of patients with incessant VT. However, endpoints are more difficult to evaluate and long-term follow-up is needed., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

The copper-catalyzed asymmetric conjugate addition (ACA) of nucleophiles onto polyenic Michael acceptors represents an attractive and powerful methodology for the synthesis of relevant chiral molecules, as it enables in a straightforward manner the sequential generation of two or more stereogenic centers. In the last decade, various chiral copper-based catalysts were evaluated in combination with different nucleophiles and Michael acceptors, and have unambiguously demonstrated their usefulness in the control of the regio- and enantioselectivity of the addition. The aim of this review is to report recent breakthroughs achieved in this challenging field.

Background: The correlates of left ventricular (LV) substrate in arrhythmogenic right ventricular (RV) cardiomyopathy are largely unknown., Methods and Results: Thirty-two patients with arrhythmogenic RV cardiomyopathy (47±14 years; 6 women) were included. RV and LV dysplasia were defined from multidetector computed tomography and cardiac magnetic resonance imaging. Arrhythmias were characterized as right-sided or left-sided on 12-lead ECG recordings at baseline and during isoproterenol testing. In 14 patients, the imaging substrate was compared with voltage mapping and local abnormal ventricular activity. Imaging abnormalities were found in 32 (100%) and 21 (66%) patients on the RV and LV, respectively, intramyocardial fat on multidetector computed tomography being the most sensitive feature. LV involvement related to none of the Task Force criteria. Right-sided arrhythmias were more frequent than left-sided arrhythmias (P=0.003) although the latter were more frequent in case of LV involvement (P=0.02). The agreement between low voltage and fat on multidetector computed tomography was high on the RV when using either endocardial unipolar or epicardial bipolar data (κ=0.82 and κ=0.78, respectively) but lower on the LV (κ=0.54 for epicardial bipolar). LV local abnormal ventricular activity was found in all patients with LV involvement, and none of the others. The density of local abnormal ventricular activity within fat areas was similar between the RV and LV (P=0.57)., Conclusions: LV substrate is frequent in arrhythmogenic RV cardiomyopathy, but poorly identified by current diagnostic strategies. Left-sided arrhythmias are more frequent in case of LV involvement. LV fat hosts the same density of local abnormal ventricular activity as RV fat, but is less efficiently detected by voltage mapping. These results support the need for alternative diagnostic strategies to identify LV dysplasia., (© 2015 American Heart Association, Inc.)

Atrial fibrillation (AF) is the most common rhythm disorder, and is strongly associated with thromboembolic events and heart failure. Over the past decade, catheter ablation of AF has advanced considerably with progressive improvement in success rates. However, interventional treatment is still challenging, especially for persistent and long-standing persistent AF. Recently, AF analysis using a non-invasive body surface mapping technique has been shown to identify localised reentrant and focal sources, which play an important role in driving and perpetuating AF. Non-invasive mapping-guided ablation has also been reported to be effective for persistent AF. In this review, we describe new clinical insights obtained from non-invasive mapping of persistent AF to guide catheter ablation.

Over the past few decades, significant progress has been made in understanding the mechanistic basis of atrial fibrillation (AF). One of the most important discoveries in this context has been that pulmonary veins (PV) play a prominent role in the pathogenesis of AF. PV isolation has since become the most widely used technique for treatment of paroxysmal AF. Multiple studies have demonstrated that the electrophysiological and anatomical characteristics of PVs create a proarrhythmogenic substrate. The following review discusses the mechanistic links between PVs and AF.

Background: Epicardial ventricular tachycardia (VT) ablation is associated with risks of coronary artery (CA) and phrenic nerve (PN) injury. We investigated the role of multidetector computed tomography in visualizing CA and PN during VT ablation., Methods and Results: Ninety-five consecutive patients (86 men; age, 57 ± 15) with VT underwent cardiac multidetector computed tomography. The PN detection rate and anatomic variability were analyzed. In 49 patients undergoing epicardial mapping, real-time multidetector computed tomographic integration was used to display CAs/PN locations in 3-dimensional mapping systems. Elimination of local abnormal ventricular activities (LAVAs) was used as ablation end point. The distribution of CAs/PN with respect to LAVA was analyzed and compared between VT etiologies. Multidetector computed tomography detected PN in 81 patients (85%). Epicardial LAVAs were observed in 44 of 49 patients (15 ischemic cardiomyopathy, 15 nonischemic cardiomyopathy, and 14 arrhythmogenic right ventricular cardiomyopathy) with a mean of 35 ± 37 LAVA points/patient. LAVAs were located within 1 cm from CAs and PN in 35 (80%) and 18 (37%) patients, respectively. The prevalence of LAVA adjacent to CAs was higher in nonischemic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy than in ischemic cardiomyopathy (100% versus 86% versus 53%; P < 0.01). The prevalence of LAVAs adjacent to PN was higher in nonischemic cardiomyopathy than in ischemic cardiomyopathy (93% versus 27%; P < 0.001). Epicardial ablation was performed in 37 patients (76%). Epicardial LAVAs could not be eliminated because of the proximity to CAs or PN in 8 patients (18%)., Conclusions: The epicardial electrophysiological VT substrate is often close to CAs and PN in patients with nonischemic cardiomyopathy. High-resolution image integration is potentially useful to minimize risks of PN and CA injury during epicardial VT ablation., (© 2015 American Heart Association, Inc.)

In recent years, the early repolarization pattern has emerged as a risk factor for malignant ventricular arrhythmias and sudden cardiac death. The identification of the subset of patients who are at high risk of sudden death represents a significant challenge to the clinician. Multiple clinical and ECG features have been associated with an increased risk of sudden deathin however the majority of risk factors confer a small increase in absolute risk. The present article reviews current evidence and potential management strategies in patients with early repolarization.

Introduction: This study aimed to compare the functional capacity and gene expression profile of monocyte-derived dendritic cells (MD-DCs) in HLA-B27+ axial spondyloarthritis (SpA) patients and healthy controls., Methods: MD-DCs were differentiated with interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for seven days, starting from purified CD14+ monocytes and stimulated with lipopolysaccharide (LPS) for six and twenty four hours. Their capacity to stimulate allogeneic CD4+ T cells from unrelated healthy donor was tested. Transcriptomic study was performed with Affymetrix HuGene 1.0 ST microarrays. Gene expression levels were compared between patients and controls using a multivariate design under a linear model (LIMMA). Real-time quantitative PCR (qRT-PCR) was performed for validation of the most striking gene expression differences., Results: The stimulatory capacity of allogeneic CD4+ T cells by MD-DCs from SpA patients was decreased. Transcriptomic analysis revealed 81 genes differentially expressed in MD-DCs between SpA patients and controls (P <0.01 and fold-change <0.66 or >1.5). Four selected genes were validated by q, Rt-Pcr: ADAMTS15, CITED2, F13A1 and SELL. Expression levels of ADAMTS15 and CITED2, encoding a metallopeptidase and a transcription factor, respectively, were inversely correlated with each other (R = 0.75, P = 0.0003). Furthermore, in silico analysis identified several genes of the Wnt signaling pathway having expression co-regulated with CITED2., Conclusion: This study revealed altered function and gene expression pattern in MD-DCs from HLA-B27+ axial SpA. Co-expression study showed an inverse correlation between ADAMTS15 and CITED2. Moreover, the Wnt signaling pathway appeared as deregulated in SpA MD-DCs, a finding which may be connected to Th17-driven inflammatory responses.

Background: Specific noninvasive signal processing was applied to identify drivers in distinct categories of persistent atrial fibrillation (AF)., Methods and Results: In 103 consecutive patients with persistent AF, accurate biatrial geometry relative to an array of 252 body surface electrodes was obtained from a noncontrast computed tomography scan. The reconstructed unipolar AF electrograms acquired at bedside from multiple windows (duration, 9±1 s) were signal processed to identify the drivers (focal or reentrant activity) and their cumulative density map. The driver domains were catheter ablated by using AF termination as the procedural end point in comparison with the stepwise-ablation control group. The maps showed incessantly changing beat-to-beat wave fronts and varying spatiotemporal behavior of driver activities. Reentries were not sustained (median, 2.6 rotations lasting 449±89 ms), meandered substantially but recurred repetitively in the same region. In total, 4720 drivers were identified in 103 patients: 3802 (80.5%) reentries and 918 (19.5%) focal breakthroughs; most of them colocalized. Of these, 69% reentries and 71% foci were in the left atrium. Driver ablation alone terminated 75% and 15% of persistent and long-lasting AF, respectively. The number of targeted driver regions increased with the duration of continuous AF: 2 in patients presenting in sinus rhythm, 3 in AF lasting 1 to 3 months, 4 in AF lasting 4 to 6 months, and 6 in AF lasting longer. The termination rate sharply declined after 6 months. The mean radiofrequency delivery to AF termination was 28±17 minutes versus 65±33 minutes in the control group (P<0.0001). At 12 months, 85% patients with AF termination were free from AF, similar to the control population (87%,); P=not significant., Conclusions: Persistent AF in early months is maintained predominantly by drivers clustered in a few regions, most of them being unstable reentries., (© 2014 American Heart Association, Inc.)

Catheter ablation is an established treatment strategy for a range of different cardiac arrhythmias. Over the past decade two major areas of expansion have been ablation of atrial fibrillation (AF) and ventricular tachycardia (VT) in the context of structurally abnormal hearts. In parallel with the expanding role of catheter ablation for AF and VT, multiple novel technologies have been developed which aim to increase safety and procedural success. Areas of development include novel catheter designs, novel navigation technologies and higher resolution imaging techniques. The aim of the present review is to provide an overview of novel developments in AF ablation and VT ablation in patients with of structural cardiac diseases.

Background: Although the Task Force Criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) have recently been updated, the diagnosis remains challenging in the early stages. The aim of this study was to evaluate the diagnostic value of β-adrenergic stimulation in ARVC., Methods and Results: We evaluated 412 consecutive patients (213 men, age 41.5±16 years) referred for premature ventricular contractions evaluation or suspected ARVC. Isoproterenol testing was performed with continuous infusion of isoproterenol (45 μg/min) for 3 minutes. It was considered positive if there were either (1) polymorphic premature ventricular contractions with ≥1 couplet or (2) sustained or nonsustained ventricular tachycardia with left bundle branch block excluding right ventricular outflow tract ventricular tachycardia. ARVC was diagnosed in 35 patients at initial evaluation (23 men, aged 42±15 years). Isoproterenol testing was positive in 32 of 35 (91.4%) patients with ARVC and in 42 of 377 (11.1%) patients without ARVC (P<0.0001). Sensitivity, specificity, positive, and negative predictive values of isoproterenol testing to diagnose ARVC were 91.4%, 88.9%, 43.2%, and 99.1%, respectively. During a mean follow-up period of 5.6±4.4 years, 6 additional patients met diagnostic criteria for ARVC. Importantly, initial isoproterenol testing was positive in 6 of 6 (100%) of these patients. Survival free from ARVC diagnosis was significantly lower in the positive isoproterenol group than in the negative isoproterenol group (P<0.0001, exact log-rank test)., Conclusions: Ventricular arrhythmogenicity during isoproterenol testing is highly sensitive (sensitivity, 91.4%) for the diagnosis of ARVC, particularly in its early stages., (© 2014 American Heart Association, Inc.)

Aims: Alternative forms of cardiac resynchronization therapy (CRT), including biventricular endocardial (BV-Endo) and multisite epicardial pacing (MSP), have been developed to improve response. It is unclear which form of stimulation is optimal. We aimed to compare the acute haemodynamic response (AHR) and electrophysiological effects of BV-Endo with MSP via two separate coronary sinus (CS) leads or a single-quadripolar CS lead., Methods and Results: Fifteen patients with a previously implanted CRT system received a second temporary CS lead and left ventricular (LV) endocardial catheter. A pressure wire and non-contact mapping array were placed into the LV cavity to measure LVdP/dtmax and perform electroanatomical mapping. Conventional CRT, BV-Endo, and MSP were then performed (MSP-1 via two epicardial leads and MSP-2 via a single-quadripolar lead). The best overall AHR was found using BV-Endo pacing with a 19.6 ± 13.6% increase in AHR at the optimal endocardial site over baseline (P < 0.001). There was an increase in LVdP/dtmax with MSP-1 and MSP-2 compared with conventional CRT, but this was not statistically significant. Biventricular endocardial pacing from the optimal site was significantly superior to conventional CRT (P = 0.039). The AHR achieved when BV-Endo pacing was highly site specific. Within individuals, the best pacing modality varied and was affected by the underlying substrate. Left ventricular activation times did not predict the optimal haemodynamic configuration., Conclusion: Biventricular endocardial pacing and not MSP was superior to conventional CRT, but was highly site specific. Within individuals, however, different methods of stimulation are optimal and may need to be tailored to the underlying substrate., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: The classification of atrial fibrillation as paroxysmal or persistent (PsAF) is clinically useful, but does not accurately reflect the underlying pathophysiology and is therefore a suboptimal guide to selection of ablation strategy., Aim: To determine if additional substrate ablation is beneficial for a subset of patients with PsAF, in whom long periods of sinus rhythm (SR) can be maintained., Methods: We included patients presenting with PsAF in whom continuous periods of SR>3months were documented. All patients were in SR on the day of the procedure. Electrical pulmonary vein isolation (PVI) was performed in all patients. Additional electrogram (EGM)-guided ablation was left to the discretion of the operator. Patient characteristics and follow-up were analysed with respect to presence or absence of additional EGM-guided ablation., Results: Sixty-five patients (mean age 60.1±8.9years; 81.5% men) met the inclusion criteria. EGM-guided ablation was performed in 32 (49%) patients. Patients with and without EGM-guided ablation had similar baseline characteristics. Absence of EGM-guided ablation was one of the independent predictors for arrhythmia recurrences after the index procedure (hazard ratio 0.24; confidence interval 0.12-0.47). After a median follow-up of 18±10months, the number of procedures required was significantly higher in the 'PVI-only' group (2.24±0.75 vs. 1.84±0.81; P=0.04) to achieve a similar success rate (84% vs. 81%; P=0.833)., Conclusion: The addition of EGM-guided ablation requires fewer procedures to achieve similar clinical efficacy in mid-term follow-up compared with a PVI-only strategy in patients with PsAF presenting for ablation in SR., (Copyright © 2013. Published by Elsevier Masson SAS.)

Objectives: Type II activation describes the U-shaped electrical activation of the left ventricle (LV) with a line of block in patients with left bundle branch block (LBBB). We sought to determine if a corresponding pattern of contraction could be identified using cardiac magnetic resonance (CMR) cine imaging and whether this predicted response to cardiac resynchronization therapy (CRT)., Background: U-shaped LV electrical activation in LBBB has been shown to predict favorable response to CRT. It is not known if the degree of electromechanical coupling is such that the same is true for LV contraction patterns., Methods: A total of 52 patients (48% ischemic) scheduled for CRT implantation prospectively underwent pre-implantation CMR cine analysis using endocardial contour tracking software to generate time-volume curves and contraction propagation maps. These were analyzed to assess the contraction sequence of the LV. The effect of contraction pattern on CRT response in terms of reverse remodeling (RR) and clinical parameters (New York Heart Association functional class, 6-min walk distance and Heart Failure Questionnaire score) was assessed at 6 months., Results: Two types of contraction pattern were identified; homogenous spread from septum to lateral wall (type I, n = 27) and presence of block with a subsequent U-shaped contraction pattern (type II, n = 25). Rates of RR in those with a type 2 pattern were significantly greater at 6 months (80% vs. 26%, p < 0.001) as was mean increase in 6-min walk distance (126 ± 106 m vs. 55 ± 60 m; p = 0.004)., Conclusions: Cine CMR can identify a U-shaped pattern of contraction which predicts increased echocardiographic and clinical response rates to CRT in patients with LBBB., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Management of pacemaker infection in pacing-dependent patients is often challenging. Typically, temporary pacing is used while antibiotic therapy is given for a number of days before reimplantation of a new endocardial system. This results in a prolonged hospital stay and complications associated with temporary pacing. In this study, we examine the feasibility of performing a single combined procedure of epicardial pacemaker implantation followed by system extraction., Methods: One hundred consecutive infected pacemaker-dependent patients underwent implantation of 2 epicardial ventricular leads and were converted to a ventricular demand pacing system. The infected pacing system was then extracted during the same procedure. Patients were followed up for 12 months., Results: Significant pericardial bleeding developed during the procedure in 3 patients. The presence of the pericardial drain positioned during the implantation of the epicardial pacing system meant that cardiac tamponade did not occur, allowing surgical repair with sternotomy to be carried out under stable hemodynamic conditions. Two of these 100 patients died in the 30-day postoperative period; 1 death was due to septic shock and 1 to pulmonary distress. Median 1-year epicardial pacing thresholds were stable and excellent (1.4 ± 0.9 volts). However, 1 of the 2 leads developed increased thresholds in 6 patients, which led to the exclusive use of other ventricular lead., Conclusions: A single combined procedure of surgical epicardial pacemaker implantation and pacemaker system extraction appears to be a safe and effective method for managing pacemaker-dependent patients with infected pacemakers., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

HIV infects activated CD4⁺ T cells and induces their depletion. Progressive HIV infection leading to AIDS is fueled by chronic immune hyperactivation, mediated by inflammatory cytokines like TNFα. This has been related to intestinal epithelial damage and microbial LPS translocation into the circulation. Using 11-color flow cytometry, cell sorting, and cell culture, we investigated the numbers and TNFα production of fully defined circulating dendritic cell and monocyte populations during HIV-1 infection. In 15 viremic, untreated patients, compared with 8 treated, virologically suppressed patients or to 13 healthy blood donors, circulating CD141 (BDCA-3)⁺ and CD1c (BDCA-1)⁺ dendritic cell counts were reduced. Conversely, CD14⁺ CD16⁺⁺ monocyte counts were increased, particularly those expressing M-DC8, while classical CD14⁺⁺ CD16⁻ M-DC8⁻ monocyte numbers were unchanged. Blood mononuclear cells from viremic patients produced more TNFα in response to LPS than those from virologically suppressed patients. M-DC8⁺ monocytes were mostly responsible for this overproduction. Moreover, M-DC8⁺ monocytes differentiated in vitro from classical monocytes using M-CSF and GM-CSF, which is increased in viremic patient's plasma. This M-DC8⁺ monocyte population, which is involved in the pathogenesis of chronic inflammatory diseases like Crohn disease, might thus be considered as a major actor in the immune hyperactivation fueling HIV infection progression.