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Background One third of chronic heart failure patients have major intraventricular conduction and uncoordinated ventricular contraction. Non-controlled studies suggest that biventricular pacing may improve haemodynamics and well-being by reducing ventricular asynchrony. The aim of this trial was to assess the clinical efficacy and safety of this new therapy in patients with chronic atrial fibrillation.Methods Fifty nine NYHA class III patients with left ventricular systolic dysfunction, chronic atrial fibrillation, slow ventricular rate necessitating permanent ventricular pacing, and a wide QRS complex (paced width ≥200ms), were implanted with transvenous biventricular-VVIR pacemakers. This single-blind, randomized, controlled, crossover study compared the patients’ parameters, as monitored during two 3-month treatment periods of conventional right-univentricular vs biventricular pacing. The primary end-point was the 6-min walked distance, secondary end-points were peak oxygen uptake, quality-of-life, hospitalizations, patients’ preferred study period and mortality.Results Because of a higher than expected drop-out rate (42%), only 37 patients completed both crossover phases. In the intention-to-treat analysis, we did not observe a significant difference. However, in the patients with effective therapy the mean walked distance increased by 9·3% with biventricular pacing (374±108 vs 342±103m in univentricular;P =0·05). Peak oxygen uptake increased by 13% (P=0·04). Hospitalizations decreased by 70% and 85% of the patients preferred the biventricular pacing period (P<0·001).Conclusion As compared with conventional VVIR pacing, effective biventricular pacing seems to improve exercise tolerance in NYHA class III heart failure patients with chronic atrial fibrillation and wide paced-QRS complexes. Further randomized controlled studies are required to definitively validate this therapy in such patients. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved. [ABSTRACT FROM PUBLISHER]

Aims: Loss of bipolar electrograms immediately after pulsed field ablation (PFA) makes lesion durability assessment challenging., Objective: The aim of this trial (NCT06700226) was to evaluate a novel ablation system that can optically predict lesion durability by detecting structural changes in the tissue during ablation., Methods and Results: Patients with paroxysmal atrial fibrillation underwent pulmonary vein isolation (PVI) using PFA (AblaView®, MedLumics). Using polarization-sensitive optical coherence reflectometry (PS-OCR), reflective characteristics of myocardial tissue and visualization of real-time contrast between healthy tissue and ablated tissue using a drop in tissue birefringence (BiR) was assessed. Wide antral PVI was performed using single point irrigated PFA (unipolar, 1800V, 3 trains, 21 s). Remapping was performed at 3 months. Primary efficacy outcome was the ability of PS-OCR to predict lesion durability at 3-month remapping. Serious adverse events were recorded. Ten patients were included. In total, 38/40 PVs could be isolated with the system. The mean drop of BiR was 17.3 ± 11.5%. Dragging across the ablation lines showed a persistent drop in BiR. During the remap procedures (8/10 patients ablated only with PFA), 12 PVs (37.5%) were found to be electrically reconnected. The mean loss of BiR during all PFA for durable lesions was 20.9%, while only 10.1% BiR loss was observed during the index ablation for reconnected areas (P < 0.001). None of the points with ≥17% loss of birefringence was found to be reconnected., Conclusion: This first-in-human study supports the use of real-time drop in tissue BiR for lesion assessment and durability during PFA delivery, and its procedural safety., Competing Interests: Conflict of interest: D.H. and C.B. are employees of MedLumics; A.V. reports grants/advisory from Medtronic, Biosense Webster, Abbott, and advisory from MedLumics and Adagio Medical; R.P.M. reports grants/advisory from Biosense Webster, Abbott, and advisory from MedLumics; G.P. reports advisory fees from MedLumics, A.S. and S.S. report clinical investigators’ fees from MedLumics., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Pulsed field ablation uses electrical fields to cause nonthermal cell death over several hours. Polarization-sensitive optical coherence reflectometry is an optical imaging technique that can detect changes in the tissue ultrastructure in real time, which occurs when muscular tissue is damaged. The objective of this study was to evaluate the ability of a polarization-sensitive optical coherence reflectometry system to predict the development of chronic lesions based on acute changes in tissue birefringence during pulsed field ablation., Methods: Superior vena cava isolation was performed in 30 swine using a biphasic, bipolar pulsed field ablation system delivered with a nonirrigated focal tip catheter. Acute changes in tissue birefringence and voltage abatement were analyzed for each individual lesion. A high-resolution electroanatomical map was performed at baseline and 4 to 12 weeks after ablation to locate electrical gaps in the ablated area., Results: A total of 141 lesions were delivered and included in the analysis. Acute electrical isolation based on the electroanatomical map was achieved in 96% of the animals, but chronic isolation was only seen in 14 animals (46%). The mean voltage abatement of lesions that showed recovery was 82.8%±14.6% versus 84.4%±17.4% for those that showed fibrosis ( P =0.7). The mean acute reduction in tissue birefringence in points demonstrating fibrosis was 63.8%±11.3% versus 9.1%±0.1% in the points that resulted in electrical gaps. A threshold of acute reduction of birefringence of ≥20% could predict chronic lesion formation with a sensitivity of 96% and a specificity of 83%., Conclusions: Acute tissue birefringence changes assessed with polarization-sensitive optical coherence reflectometry during pulsed field ablation can predict chronic lesion formation and guide the ablation procedure although limited by the tissue thickness., Competing Interests: Disclosures Drs Herranz and Bailleul are employees of MedLumics S.L. Drs Terricabras, Martins, Peinado, Derejko, Mont, Ernst, and Verma are MedLumics S.L. consultants.

Background: Despite advances in asthma treatments, severe asthma exacerbation (SAE) remains a life-threatening condition in adults, and there is a lack of data derived from adult patients admitted to intensive care units (ICUs) for SAE. The current study investigated changes in adult patient characteristics, management, and outcomes of SAE over a 20-year period in 40 ICUs in the greater Paris area., Methods: In this retrospective observational study, admissions to 40 ICUs in the greater Paris area for SAE from January 1, 1997, to December 31, 2016 were analyzed. The primary outcome was the proportion of ICU admissions for SAE during 5-year periods. Secondary outcomes were ICU and hospital mortality, and the use of mechanical ventilation and catecholamine. Multivariate analysis was performed to assess factors associated with ICU mortality., Results: A total of 7049 admissions for SAE were recorded. For each 5-year period, the proportion decreased over time, with SAE accounting for 2.84% of total ICU admissions ( n =2841) between 1997 and 2001, 1.76% ( n =1717) between 2002 and 2006, 1.05% ( n =965) between 2007 and 2011, and 1.05% ( n =1526) between 2012 and 2016. The median age was 46 years (interquartile range [IQR]: 32-59 years), 55.41% were female, the median Simplified Acute Physiology Score II was 20 (IQR: 13-28), and 19.76% had mechanical ventilation. The use of mechanical ventilation remained infrequent throughout the 20-year period, whereas the use of catecholamine decreased. ICU and hospital mortality rates decreased. Factors associated with ICU mortality were renal replacement therapy, catecholamine, cardiac arrest, pneumothorax, acute respiratory distress syndrome, sepsis, and invasive mechanical ventilation (IMV). Non-survivors were older, had more severe symptoms, and were more likely to have received IMV., Conclusion: ICU admission for SAE remains uncommon, and the proportion of cases decreased over time. Despite a slight increase in symptom severity during a 20-year period, ICU and hospital mortality decreased. Patients requiring IMV had a higher mortality rate., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

When it comes to champagne tasting, dissolved CO 2 is a key compound responsible for the very much sought-after effervescence in glasses. Nevertheless, the slow decrease of dissolved CO 2 during prolonged aging of the most prestigious cuvees raises the issue of how long champagne can age before it becomes unable to form CO 2 bubbles during tasting. Measurements of dissolved CO 2 concentrations were done on a collection of 13 successive champagne vintages stored in standard 75 cL bottles and 150 cL magnums showing prolonged aging ranging from 25 to 47 years. The vintages elaborated in magnums were found to retain their dissolved CO 2 much more efficiently during prolonged aging than the same vintages elaborated in standard bottles. A multivariable exponential decay-type model was proposed for the theoretical time-dependent concentration of dissolved CO 2 and the subsequent CO 2 pressure in the sealed bottles during champagne aging. The CO 2 mass transfer coefficient through the crown caps used to seal champagne bottles prior to the 2000s was thus approached in situ with a global average value of K ≈ 7 × 10 -13 m 3 s -1 . Moreover, the shelf-life of a champagne bottle was examined in view of its ability to still produce CO 2 bubbles in a tasting glass. A formula was proposed to estimate the shelf-life of a bottle having experienced prolonged aging, which combines the various relevant parameters at play, including the geometric parameters of the bottle. Increasing the bottle size is found to tremendously increase its capacity to preserve dissolved CO 2 and therefore the bubbling capacity of champagne during tasting. For the very first time, a long time-series dataset combined with a multivariable model indicates that the bottle size plays a crucial role on the progressive decay of dissolved CO 2 experienced by champagne during aging., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: In-hospital cardiac arrest(IHCA) has received little attention compared with out-of-hospital cardiac arrest., Aim: To address the paucity of data on IHCA patients, we examined key features, variations in mortality and predictors of death among patients admitted in French intensive care units(ICUs) from 1997 to 2015., Methods: Using the database of the Collège des Utilisateurs de Bases de données en Réanimation(CUB-Réa) that prospectively collects data from ICUs in the greater Paris area, we determined temporal trends in the incidence of IHCA, patients' outcomes, crude and Simplified Acute Physiology Score(SAPS)-II Standardized mortality and predictors of in-ICU mortality., Results: Of the 376,325 ICU admissions, 15,324(4.08%) had IHCA, with incidence increasing from 2.78% to 3.83%(p < 0.001). Over time, the patient age increased by 0.7 years(p = 0.04) and SAPS-II increased by 2.3%(p < 0.001). Crude in-ICU mortality decreased from 78% to 62.5% over the past 18 years(p < 0.001). The SAPS-II-standardized mortality also decreased over time from 78.4% to 68.3%(p < 0.001) representing a 10.1% relative decrease from 1997 to 2015. In multivariate analysis, admission in a more recent time-period was an independent correlate of decreased mortality(OR 0.40, 95%CI 0.35-0.46)., Conclusion: Occurrence of IHCA increased over time but remains an uncommon reason for being admitted to ICU. From 1997 to 2015, we observed a change in patient profile, with older and more critically ill patients, despite which in-ICU mortality has substantially decreased in IHCA patients, likely resulting from a global improvement in the process of care and more widespread implementation of rapid response teams., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Interval training is a form of exercise that involves intermittent bouts of relatively intense effort interspersed with periods of rest or lower-intensity exercise for recovery. Low-volume high-intensity interval training (HIIT) and sprint interval training (SIT) induce physiological and health-related adaptations comparable to traditional moderate-intensity continuous training (MICT) in healthy adults and those with chronic disease despite a lower time commitment. However, most studies within the field have been conducted in men, with a relatively limited number of studies conducted in women cohorts across the lifespan. This review summarizes our understanding of physiological responses to low-volume interval training in women, including those with overweight/obesity or type 2 diabetes, with a focus on cardiorespiratory fitness, glycemic control, and skeletal muscle mitochondrial content. We also describe emerging evidence demonstrating similarities and differences in the adaptive response between women and men. Collectively, HIIT and SIT have consistently been demonstrated to improve cardiorespiratory fitness in women, and most sex-based comparisons demonstrate similar improvements in men and women. However, research examining insulin sensitivity and skeletal muscle mitochondrial responses to HIIT and SIT in women is limited and conflicting, with some evidence of blunted improvements in women relative to men. There is a need for additional research that examines physiological adaptations to low-volume interval training in women across the lifespan, including studies that directly compare responses to MICT, evaluate potential mechanisms, and/or assess the influence of sex on the adaptive response. Future work in this area will strengthen the evidence-base for physical activity recommendations in women., (© 2021. The Author(s).)

Over the past decade, the zebrafish has been increasingly employed in biomedical neuroscience research due to its numerous evolutionarily conserved features with mammals. Its simple brain and the several molecular tools available for this species make the zebrafish an appealing model to study mechanisms of complex brain functions, including learning and memory. Most learning paradigms developed for the zebrafish have employed visual stimuli as the associative cue. Spontaneous color preference is a potential confound in such studies. It has been analyzed in zebrafish using colored objects, but with conflicting results. It has rarely been explored with colored light, despite the increasing use of computer-generated visual stimuli. Here, we employ a light emitting diode (RGB-system) light-based color preference task in the plus-maze. In two independent experiments, zebrafish were tested in a four-choice or dual-choice condition by using four different-colored lights (red, green, blue and yellow). Our results suggest a light preference hierarchy that depends on context, since yellow was preferred over green in the four-choice condition whereas blue was preferred over all other colors in the two-choice condition. These results are useful for future color-light-based learning experiments in zebrafish.

Background: Complete airway closure during expiration may underestimate alveolar pressure. It has been reported in cases of acute respiratory distress syndrome (ARDS), as well as in morbidly obese patients with healthy lungs. The authors hypothesized that complete airway closure was highly prevalent in obese ARDS and influenced the calculation of respiratory mechanics., Methods: In a post hoc pooled analysis of two cohorts, ARDS patients were classified according to body mass index (BMI) terciles. Low-flow inflation pressure-volume curve and partitioned respiratory mechanics using esophageal manometry were recorded. The authors' primary aim was to compare the prevalence of complete airway closure according to BMI terciles. Secondary aims were to compare (1) respiratory system mechanics considering or not considering complete airway closure in their calculation, and (2) and partitioned respiratory mechanics according to BMI., Results: Among the 51 patients analyzed, BMI was less than 30 kg/m2 in 18, from 30 to less than 40 in 16, and greater than or equal to 40 in 17. Prevalence of complete airway closure was 41% overall (95% CI, 28 to 55; 21 of 51 patients), and was lower in the lowest (22% [3 to 41]; 4 of 18 patients) than in the highest BMI tercile (65% [42 to 87]; 11 of 17 patients). Driving pressure and elastances of the respiratory system and of the lung were higher when complete airway closure was not taken into account in their calculation. End-expiratory esophageal pressure (ρ = 0.69 [95% CI, 0.48 to 0.82]; P < 0.001), but not chest wall elastance, was associated with BMI, whereas elastance of the lung was negatively correlated with BMI (ρ = -0.27 [95% CI, -0.56 to -0.10]; P = 0.014)., Conclusions: Prevalence of complete airway closure was high in ARDS and should be taken into account when calculating respiratory mechanics, especially in the most morbidly obese patients., (Copyright © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.)

FASD results from the developing fetus being exposed to alcohol, and is characterized by morphological, behavioural and cognitive deficits. However, the expression, severity and age of onset of these symptoms has been found to show variation. This variation may partly be due to the developmental stage at which alcohol reached the developing fetus. Previously, alcohol was shown to lead to significant concentration dependent behavioural as well as neurochemical changes detected in adult zebrafish when this substance was administered at 24 h post-fertilization (hpf) for 2 h. This alcohol exposure method arguably mimicked the milder, and more prevalent, forms of human FASD. However, whether the observed changes depended upon the developmental stage, i.e., the timing, of alcohol exposure has not been systematically analyzed. Here, we employ the same alcohol dosing regimen, where zebrafish eggs are immersed into 0% or 1% (vol/vol) alcohol for 2 h, but we perform the immersion at 5, 10, 16, 24, 36, or 48 hpf. We previously developed a sensitive HPLC method to quantify neurochemicals, and found levels of dopamine, serotonin and their metabolites DOPAC and 5-HIAA to be affected by embryonic alcohol treatment. Here, using the same method, we compare whole-brain levels of these neurochemicals in the embryonic alcohol exposed and control zebrafish at their age of 30 days post-fertilization (dpf). Consistent with previous reports, we found significant reduction of levels of dopamine, serotonin and their metabolites in the fish exposed to alcohol at 24 hpf. However, we also found significant dependency on the developmental stage at which alcohol was administered with particularly robust impairments when the exposure was at the early or middle of the developmental periods probed. Our results now demonstrate that one can detect functional abnormalities in the zebrafish brain induced by embryonic alcohol as early as 30 dpf and that the neurochemical deficits are dependent upon the developmental stage at which alcohol is administered., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Oxygen therapy remains a cornerstone of treatment for acute heart failure in patients with pulmonary congestion. While avoiding hypoxaemia has long been a goal of critical care practitioners, less attention has been paid to the potential hazard related to excessive hyperoxia., Aim: To evaluate the impact of early hyperoxia exposure among critically ill patients hospitalized in an intensive care unit for acute heart failure., Methods: In this preliminary study conducted in a Parisian intensive care unit, we assessed patients with acute heart failure admitted with pulmonary congestion and treated with oxygen therapy from 1 January 2015 to 31 December 2016. The hyperoxia group was defined by having at least one partial pressure of oxygen measurement>100mmHg on the first day following admission to the intensive care unit. The primary endpoint was 30-day all-cause mortality. Secondary endpoints were 30-day unplanned hospital admissions, occurrence of infections and intensive care unit and hospital lengths of stay., Results: Seventy-five patients were included. Forty-three patients (57.3%) presented hyperoxia, whereas 32 patients (42.7%) did not (control group). The baseline clinical characteristics did not differ between the two groups. The primary endpoint was not statistically different between the two groups (14.0% in the hyperoxia group vs 18.8% in the control group; P=0.85). The secondary endpoints were also not significantly different between the two groups. In the multivariable analysis, hyperoxia was not associated with increased 30-day mortality (odds ratio 0.77, 95% confidence interval 0.24-2.41)., Conclusion: In patients referred to an intensive care unit for acute heart failure, we did not find any difference in outcomes according to the presence of hyperoxia., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3 before percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) is associated with improved outcomes. However, no recent data are available on its impact beyond 1 year and/or by type of AMI., Aims: To assess the prognostic impact of prePCI TIMI flow at 30 days and 3 years in patients with ST-segment elevation (STEMI) or non-ST-segment elevation (NSTEMI) AMI., Methods: We compared long-term outcomes associated with TIMI flow grade 2/3 versus 0/1 in patients referred for PCI in the nationwide French registry of acute ST-segment elevation or non-ST-segment elevation myocardial infarction (FAST-MI) 2010., Results: TIMI flow grade 2/3 was found in 41% of patients with STEMI and 69% of patients with NSTEMI; it was associated with a lower risk of 30-day death in patients with STEMI (odds ratio 0.30, 95% confidence interval [CI] 0.12-0.77; P=0.01), but not in patients with NSTEMI (odds ratio 0.57, 95% CI 0.22-1.42; P=0.23). TIMI grade flow 2/3 was also associated with a lower risk of 3-year death in patients with STEMI (hazard ratio 0.69, 95% CI 0.49-0.98; P=0.04), but not in patients with NSTEMI (hazard ratio 0.79, 95% CI 0.56-1.11; P=0.17)., Conclusion: TIMI flow grade 2/3 is observed more often in patients with NSTEMI; it is an independent predictor of early and late survival in patients with STEMI, but is not significantly related to early or long-term survival in patients with NSTEMI., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Early infarct-related artery (IRA) patency is associated with better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Using the French Registry of ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2010 registry, we investigated factors related to IRA patency (thrombolysis in myocardial infarction [TIMI] 2/3 flow) at the start of procedure in patients admitted for primary percutaneous coronary intervention. FAST-MI 2010 is a nationwide French registry including 4,169 patients with acute MI. Of 1,452 patients with STEMI with primary percutaneous coronary intervention, 466 (32%) had TIMI 2/3 flow of IRA before the procedure. Mean age (62 ± 14 years in both groups), Global Registry of Acute Coronary Event score (141 ± 31 vs 142 ± 34), and time from onset to angiography (472 ± 499 vs 451 ± 479 minutes) did not differ according to IRA patency (TIMI 2/3 vs TIMI 0/1). Using multivariate logistic regression analysis, IRA patency was more frequently found in patients having called earlier (time from onset to electrocardiogram [ECG] <120 minutes; odds ratio [OR] 1.49; 95% confidence interval [CI] 1.17 to 1.89), or receiving rapid-onset of action (prasugrel or glycoprotein IIb-IIIa) antiplatelet therapy in the prehospital setting (OR 1.59, 95% CI 1.14 to 2.21). Increasing time from diagnostic ECG to angiography was also associated with IRA patency (>90 minutes; OR 1.37, 95% CI 1.08 to 1.75). In conclusion, preprocedural IRA patency is observed in one third of patients with STEMI, it is more frequently found in patients having received fast-acting antiplatelet therapy before angiography, and in patients having called early. Higher IRA patency with increasing time delays from qualifying ECG to angiography suggests an additional role of spontaneous or medication-mediated fibrinolysis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Microtia is a congenital disease with various degrees of severity, ranging from the presence of rudimentary and malformed vestigial structures to the total absence of the ear (anotia). The complex anatomy of the external ear and the necessity to provide good projection and symmetry make this reconstruction particularly difficult. The aim of this work is to report our surgical technique of microtic ear correction and to analyse the short and long term results. From 2000 to 2013, 210 patients affected by microtia were treated at the Maxillo-Facial Surgery Division, Head and Neck Department, University Hospital of Parma. The patient population consisted of 95 women and 115 men, aged from 7 to 49 years. A total of 225 reconstructions have been performed in two surgical stages basing of Firmin's technique with some modifications and refinements. The first stage consists in fabrication and grafting of a three-dimensional costal cartilage framework. The second stage is performed 5-6 months later: the reconstructed ear is raised up and an additional cartilaginous graft is used to increase its projection. A mastoid fascial flap together with a skin graft are then used to protect the cartilage graft. All reconstructions were performed without any major complication. The results have been considered satisfactory by all patients starting from the first surgical step. Low morbidity, the good results obtained and a high rate of patient satisfaction make our protocol an optimal choice for treatment of microtia. The surgeon's experience and postoperative patient care must be considered as essential aspects of treatment.

Background: Atrial-based pacing is associated with lower risk of atrial fibrillation (AF) in sick sinus syndrome compared with ventricular pacing; nevertheless, the impact of site and rate of atrial pacing on progression of AF remains unclear. We evaluated whether long-term atrial pacing at the right atrial (RA) appendage versus the low RA septum with (ON) or without (OFF) a continuous atrial overdrive pacing algorithm can prevent the development of persistent AF., Methods and Results: We randomized 385 patients with paroxysmal AF and sick sinus syndrome in whom a pacemaker was indicated to pacing at RA appendage ON (n=98), RA appendage OFF (n=99), RA septum ON (n=92), or RA septum OFF (n=96). The primary outcome was the occurrence of persistent AF (AF documented at least 7 days apart or need for cardioversion). Demographic data were homogeneous across both pacing site (RA appendage/RA septum) and atrial overdrive pacing (ON/OFF). After a mean follow-up of 3.1 years, persistent AF occurred in 99 patients (25.8%; annual rate of persistent AF, 8.3%). Alternative site pacing at the RA septum versus conventional RA appendage (hazard ratio=1.18; 95% confidence interval, 0.79-1.75; P=0.65) or continuous atrial overdrive pacing ON versus OFF (hazard ratio=1.17; 95% confidence interval, 0.79-1.74; P=0.69) did not prevent the development of persistent AF., Conclusions: In patients with paroxysmal AF and sick sinus syndrome requiring pacemaker implantation, an alternative atrial pacing site at the RA septum or continuous atrial overdrive pacing did not prevent the development of persistent AF., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00419640.

Background: One quarter of strokes are of unknown cause, and subclinical atrial fibrillation may be a common etiologic factor. Pacemakers can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented atrial fibrillation. We evaluated whether subclinical episodes of rapid atrial rate detected by implanted devices were associated with an increased risk of ischemic stroke in patients who did not have other evidence of atrial fibrillation., Methods: We enrolled 2580 patients, 65 years of age or older, with hypertension and no history of atrial fibrillation, in whom a pacemaker or defibrillator had recently been implanted. We monitored the patients for 3 months to detect subclinical atrial tachyarrhythmias (episodes of atrial rate >190 beats per minute for more than 6 minutes) and followed them for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism. Patients with pacemakers were randomly assigned to receive or not to receive continuous atrial overdrive pacing., Results: By 3 months, subclinical atrial tachyarrhythmias detected by implanted devices had occurred in 261 patients (10.1%). Subclinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence interval [CI], 3.78 to 8.17; P<0.001) and of ischemic stroke or systemic embolism (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P=0.007). Of 51 patients who had a primary outcome event, 11 had had subclinical atrial tachyarrhythmias detected by 3 months, and none had had clinical atrial fibrillation by 3 months. The population attributable risk of stroke or systemic embolism associated with subclinical atrial tachyarrhythmias was 13%. Subclinical atrial tachyarrhythmias remained predictive of the primary outcome after adjustment for predictors of stroke (hazard ratio, 2.50; 95% CI, 1.28 to 4.89; P=0.008). Continuous atrial overdrive pacing did not prevent atrial fibrillation., Conclusions: Subclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred frequently in patients with pacemakers and were associated with a significantly increased risk of ischemic stroke or systemic embolism. (Funded by St. Jude Medical; ASSERT ClinicalTrials.gov number, NCT00256152.).

Purpose: Facial paralysis is a congenital or acquired disorder of varying severity leading to an asymmetric or absent facial expression. It represents an important debilitation from both esthetic and functional points of view. In this article we report our experience with patients treated with gracilis muscle transplantation innervated by the motor nerve to the masseter muscle. We discuss the surgical technique and the functional and esthetic results and evaluate the effectiveness of this donor nerve in providing adequate innervation to the muscle transfer for lower facial reanimation., Materials and Methods: Fifteen patients with unilateral facial paralysis were seen and surgically treated at the Department of Maxillofacial Surgery, University of Parma, Parma, Italy, between 2003 and 2007. In this study we report on 8 cases treated with gracilis muscle transfer reinnervated by the motor nerve to the masseter muscle., Results: In this series all free-muscle transplantations survived transfer, and no flap was lost. Facial symmetry at rest and while smiling was excellent or good in all patients, and we observed a significant improvement in speech and oral competence. With practice, the majority of patients developed the ability to smile spontaneously and without jaw movement., Conclusions: We consider the masseter motor nerve a powerful and reliable donor nerve, allowing us to obtain a commissure and upper lip movement similar to those of the normal site for amount and direction. This is why we think that there may be a larger role for the masseter motor nerve for innervation of patients with unilateral facial paralysis who would otherwise have been considered candidates for cross-facial nerve graft innervation of the muscle transfer., (Copyright 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Despite the deleterious effects of cardiac dyssynchrony and the positive effects of cardiac resynchronization therapy, patients with high-degree atrioventricular block continue to receive desynchronizing right ventricular (RV) pacing systems. Although it is unclear whether the negative effects of RV pacing and left bundle branch block (LBBB) are comparable, and whether they depend on the presence and the degree of structural heart disease, one may hypothesize that RV pacing may have similar effects to LBBB. In the BioPace trial, the long-term effects of RV pacing vs. biventricular pacing will be prospectively compared in 1200 pacemaker patients with high likelihood of mostly paced ventricular events, regardless of whether in sinus rhythm or in atrial fibrillation (AF). After echocardiographic examination of left ventricular (LV) function, patients will be randomly assigned to the implantation of an RV vs. a biventricular pacing system and followed for up to 5 years. Primary study endpoints are survival, quality of life (QoL), and the distance covered in a 6-min hall walk (6-MHW) at 24 months after implantation. Secondary endpoints are QoL and the 6-MHW result at 12 months after implantation, hospitalization rate, LV dimensions, LV ejection fraction, and the development of chronic AF and other adverse events.

Background: The clinical value of interventricular (V-V) delay optimization in patients with chronic congestive heart failure (CHF) undergoing implantation of a device for cardiac resynchronization therapy (CRT) has not been clearly demonstrated., Methods: RHYTHM II was a single-blind randomized trial including 121 recipients of a device for CRT with cardioverter/defibrillator capabilities (CRT-D) randomly assigned in a 1:3 ratio to simultaneous (n = 30) versus optimized (OPT) (n = 91) biventricular pacing. V-V delay was optimized by echocardiography. The study end points were (1) freedom from CRT-D system-related complications and (2) changes between preimplant and 6 months of follow-up in (a) New York Heart Association CHF functional class, (b) distance covered during a 6-minute hall walk, and (c) quality of life (QOL)., Results: In the OPT group, the V-V delay ranged from 0 to 80 milliseconds, with 28.4% of patients stimulated at an OPT V-V delay of 0 milliseconds. The overall 6-month survival free of adverse events requiring invasive interventions was 81.8%. In the whole cohort, 6 months of CRT-D was associated with a significant decrease in New York Heart Association class, increase in the distance covered during the 6-minute hall walk, and improvement in QOL (each P < .0001). The effects of CRT-D on these end points were similar in both study groups., Conclusions: Cardioverter-defibrillator capabilities was associated with a significant alleviation of CHF symptoms, increase in functional capacity, and improvement in QOL. The optimization of the V-V delay conferred no additional benefit compared with simultaneous biventricular stimulation.

The atrio-bi-ventricular pacing has been used for hemodynamic improvement since 1994, and the MUSTIC trial is the first controlled study assessing this concept. It collected 67 patients with severe and stable heart failure with optimised medical therapy, with sinus rhythm and without any traditional indication for pacing. After two periods of three months with blinded randomisation and cross-over, the bi-ventricular pacing mode showed its superiority to the inactive mode concerning all study endpoints, for example with an improvement of the functional capacity of 23% assessed by the 6-minutes-walk test. Thus the MUSTIC trial opens up the way for morbidity and mortality studies.

Background: One third of patients with chronic heart failure have electrocardiographic evidence of a major intraventricular conduction delay, which may worsen left ventricular systolic dysfunction through asynchronous ventricular contraction. Uncontrolled studies suggest that multisite biventricular pacing improves hemodynamics and well-being by reducing ventricular asynchrony. We assessed the clinical efficacy and safety of this new therapy., Methods: Sixty-seven patients with severe heart failure (New York Heart Association class III) due to chronic left ventricular systolic dysfunction, with normal sinus rhythm and a duration of the QRS interval of more than 150 msec, received transvenous atriobiventricular pacemakers (with leads in one atrium and each ventricle). This single-blind, randomized, controlled crossover study compared the responses of the patients during two periods: a three-month period of inactive pacing (ventricular inhibited pacing at a basic rate of 40 bpm) and a three-month period of active (atriobiventricular) pacing. The primary end point was the distance walked in six minutes; the secondary end points were the quality of life as measured by questionnaire, peak oxygen consumption, hospitalizations related to heart failure, the patients' treatment preference (active vs. inactive pacing), and the mortality rate., Results: Nine patients were withdrawn from the study before randomization, and 10 failed to complete both study periods. Thus, 48 patients completed both phases of the study. The mean distance walked in six minutes was 22 percent greater with active pacing (399+/-100 m vs. 326+/-134 m, P<0.001), the quality-of-life score improved by 32 percent (P<0.001), peak oxygen uptake increased by 8 percent (P<0.03), hospitalizations were decreased by two thirds (P<0.05), and active pacing was preferred by 85 percent of the patients (P<0.001)., Conclusions: Although it is technically complex, atriobiventricular pacing significantly improves exercise tolerance and quality of life in patients with chronic heart failure and intraventricular conduction delay.

Erythrocytes can be used to entrap drugs, enzymes or other molecules with active properties, with various encapsulation procedures. The method of internalization we are using includes an hypotonic dialysis step. Carrier erythrocytes survival depends on the dialysis process and the carried molecule. Research has led us to perform preclinical trials on animals for several drugs and enzyme therapies and for the improvement of oxyphoric capacity of erythrocytes. There exist many potential clinical applications for each kind of internalized molecules.

Human monoclonal antibodies will be essential in medicine. They are valuable tools for biological diagnosis and therapeutics. Our model, human monoclonal antibodies directed against the Rhesus D antigen can be used for the determination of the Rhesus D phenotype and for the suppression of Rh(D) immunisation in women. These new products require new procedures of preparation, new regulations for the quality controls, which will be discussed in this paper.