Risk of infective endocarditis after hybrid melody mitral valve replacement in infants: the French experience.

OBJECTIVES: Surgical management of mitral valve disease is challenging in infants <1 year old. We aimed at reviewing the French experience with Melody mitral valve replacement in critically ill infants. METHODS: A retrospective cohort study reporting the French experience with Melody mitral valve replacement. RESULTS: Seven symptomatic infants [complete atrioventricular septal defect (n = 4, Down syndrome: n = 3), hammock valve (n = 3)] underwent Melody mitral valve replacement [age: 3 months (28 days to 8 months), weight: 4.3 kg (3.2-6.4 kg)] because of severe mitral valve regurgitation (6) or mixed valve disease (1) and 14 mm (11-16 mm) mitral valve annulus. In 2 patients whose valve was felt irreparable, Melody mitral valve replacement was performed straightaway. The others underwent 2 (1-3) previous attempts of valve repair; 3 were on extracorporeal membrane oxygenation. Melody mitral valve replacement led to competent valve and low gradient [3 mmHg, (1-4 mmHg)]. One patient died 3 days post-implant from extracorporeal membrane oxygenation-related stroke. Of the 6 discharged home patients, 3 (50%) were readmitted for a definite diagnosis (1) or high suspicion (2) of infective endocarditis, of which 2 died. Over the follow-up, 1 underwent balloon expansions of the valve at 9- and 16-months post-implant, and mechanical mitral valve replacement at 2 years; another is currently planned for transcatheter Melody valve dilation. CONCLUSIONS: Melody mitral valve replacement may be considered in selected infants with small mitral valve annulus as an alternative to mechanical mitral valve replacement. Our experience highlights a high-risk of late infective endocarditis that deserves further consideration.

Long-term results of the Warden procedure for right partial anomalous pulmonary venous connection.

INTRODUCTION: Surgery is considered as the first-line therapeutic strategy of partial anomalous pulmonary venous connection. The Warden technique has very good short-term results. The aim of this study is to evaluate the stability of these good results over a long period of follow-up. MATERIALS AND METHODS: We reviewed all patients who underwent a Warden procedure for partial anomalous pulmonary venous connection between 1997 and 2017 in our centre. A total of 73 patients were included. The median age was 14 years (5 months-72 years). Post-operative data were obtained through our hospital network. Late follow-up data were obtained through referrals, cardiologist letters and directly from the patient. RESULTS: The mean length of follow-up was 8 years and the longest time was 22 years (range, 1-22). Twenty-five percent of our cohort had more than 10 years of follow-up. There were no cardio-vascular deaths. Eight (11.6%) patients suffered from post-operative rhythm disturbances, 5 (7.2%) of which were permanent. Two (2.9%) patients required a pacemaker implantation. At the end of the follow-up period, only one patient remained pacemaker dependent. There were no pulmonary vein obstructions. Two (2.9%) caval vein stenosis were detected, one at 7 months and the other at 7 years. These patients were treated by angioplasty alone. Five (6.8%) patients were lost to follow-up. CONCLUSIONS: The good short-term results of the Warden procedure for right partial anomalous pulmonary venous connection appear to persist in the long term, with excellent freedom from pulmonary and caval stenosis in adolescence through to adulthood.

Generation of CD34+CD43+ Hematopoietic Progenitors to Induce Thymocytes from Human Pluripotent Stem Cells.

Immunotherapy using primary T cells has revolutionized medical care in some pathologies in recent years, but limitations associated to challenging cell genome edition, insufficient cell number production, the use of only autologous cells, and the lack of product standardization have limited its clinical use. The alternative use of T cells generated in vitro from human pluripotent stem cells (hPSCs) offers great advantages by providing a self-renewing source of T cells that can be readily genetically modified and facilitate the use of standardized universal off-the-shelf allogeneic cell products and rapid clinical access. However, despite their potential, a better understanding of the feasibility and functionality of T cells differentiated from hPSCs is necessary before moving into clinical settings. In this study, we generated human-induced pluripotent stem cells from T cells (T-iPSCs), allowing for the preservation of already recombined TCR, with the same properties as human embryonic stem cells (hESCs). Based on these cells, we differentiated, with high efficiency, hematopoietic progenitor stem cells (HPSCs) capable of self-renewal and differentiation into any cell blood type, in addition to DN3a thymic progenitors from several T-iPSC lines. In order to better comprehend the differentiation, we analyzed the transcriptomic profiles of the different cell types and demonstrated that HPSCs differentiated from hiPSCs had very similar profiles to cord blood hematopoietic stem cells (HSCs). Furthermore, differentiated T-cell progenitors had a similar profile to thymocytes at the DN3a stage of thymic lymphopoiesis. Therefore, utilizing this approach, we were able to regenerate precursors of therapeutic human T cells in order to potentially treat a wide range of diseases.

Medium-term follow-up of autologous pericardial patches for pediatric aortic arch reconstruction.

OBJECTIVES: Direct anastomosis, like end-to-end anastomosis or end-to-side anastomosis, is commonly employed to repair aortic coarctation or interrupted aortic arch. Direct anastomosis of the aorta, however, may result in restenosis or bronchial compression. To circumvent these complications, we have applied a technique consisting of aortic reconstruction using glutaraldehyde-fixed autologous pericardial patches. METHODS: Our database was queried for infants who underwent aortic arch reconstruction using autologous pericardial patches from 2007 to 2019. Medical records, including echography imaging, were reviewed, and Z-scores of aortic arch diameters were retrospectively assessed at baseline, immediately after surgery, and at follow-up end. RESULTS: Overall, 58 patients met the inclusion criteria, with a median age of 9.8 days at surgery and median postoperative follow-up of 46 months. Re-coarctation requiring re-intervention by either surgery or percutaneous angioplasty was documented in 14.7% of patients. Overall, 9% of patients died of all-cause mortality. The Z-scores evolved favorably from baseline, which clearly indicated hypoplastic aortic arch, to early postoperative status, which clearly showed values close to those obtained in normal infants, with likewise normal values obtained at median 46-month follow-up. CONCLUSIONS: Glutaraldehyde-fixed autologous pericardial patches were shown to provide correct medium-term results for aortic arch reconstruction. The incidence of restenosis requiring re-intervention was shown to be low. Autologous pericardial patches can be considered as an acceptable and easily available solution for aortic arch repair surgery.

Frequency of Extracorporeal Membrane Oxygenation Support and Outcomes After Implementation of a Structured PICU Network in Neonates and Children: A Prospective Population-Based Study in the West of France.

OBJECTIVES: To describe the frequency and outcomes on the use of extracorporeal membrane oxygenation (ECMO) among critically ill neonates and children within a structured pediatric critical care network in the West of France. To assess the optimality of decision-making process for patients primarily admitted in non-ECMO centers. DESIGN: Observational prospective population-based study from January 2015 to December 2019. PATIENTS: Neonates over 34 weeks of gestational age, weighing more than 2,000 g and children under 15 years and 3 months old admitted in one of the 10 units belonging to a Regional Pediatric Critical Care Network. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight-thousand one hundred eighty-nine children and 3,947 newborns were admitted within one of the 10 units of the network over the study period. Sixty-five children (8.1% [95% CI, 6.2-10‰]) and 35 newborns (9.4% [95% CI, 6.4-12%]) required ECMO support. Of these patients, 31 were first admitted to a non-ECMO center, where 20 were cannulated in situ (outside the regional ECMO center) and 11 after transfer to the ECMO regional center. Cardiogenic shock, highest serum lactate level, and cardiac arrest prior to first phone call with the regional ECMO center were associated with higher rate of in situ cannulation. During the study period, most of the patients were cannulated for underlying cardiac issue (42/100), postoperative cardiac surgery instability (38/100), and pediatric (10/100) and neonatal (10/100) respiratory distress syndrome. Patients primarily admitted in non-ECMO centers or not had similar 28-day post-ICU survival rates compared with those admitted in the referral ECMO center (58% vs 51%; p = 0.332). Pre-ECMO cardiac arrest, ECMO, and lower pH at ECMO onset were associated with lower 28-day post-ICU survival. CONCLUSIONS: Our local results suggest that a structured referral network for neonatal and pediatric ECMO in the region of Western France facilitated escalation of care with noninferior (or similar) early mortality outcome. Our data support establishing referral networks in other equivalent regions.

Outcome analysis of a conservative approach to diaphragmatic paralysis following congenital cardiac surgery in neonates and infants: a bicentric retrospective study.

OBJECTIVES: Diaphragmatic paralysis following congenital cardiac surgery is associated with significant morbidity and mortality. Spontaneous recovery of diaphragmatic function has been described, contrasting with centres providing early diaphragmatic plication. We aimed to describe the outcomes of a conservative approach, as well as to identify factors associated with a failure of the strategy. METHODS: This is a retrospective study of patients admitted after cardiac surgery and suffering unilateral diaphragmatic paralysis within 2 French Paediatric Cardiac Surgery Centers. The conservative approach, defined by the prolonged use of ventilation until successful weaning from respiratory support, was the primary strategy adopted in both centres. In case of unsuccessful evolution, a diaphragmatic plication was scheduled. Total ventilation time included invasive and non-invasive ventilation. Diaphragm asymmetry was defined by the number of posterior rib segments counted between the 2 hemi-diaphragms on the chest X-ray after cardiac surgery. RESULTS: Fifty-one neonates and infants were included in the analysis. Patients' median age was 12.0 days at cardiac surgery (5.0-82.0), and median weight was 3.5 kg (2.8-4.9). The conservative approach was successful for 32/51 patients (63%), whereas 19/51 patients (37%) needed diaphragm plication. There was no difference in patients' characteristics between groups. Respiratory support prolonged for 21 days or more and diaphragm asymmetry more than 2 rib segments were independently associated with the failure of the conservative strategy [odds ratio (OR) 6.9 (1.29-37.3); P = 0.024 and OR 6.0 (1.4-24.7); P = 0.013, respectively]. CONCLUSIONS: The conservative approach was successful for 63% of the patients. We identified risk factors associated with the strategy's failure.

Results of large pulmonary homograft implantation for right ventricular outflow tract reconstruction.

BACKGROUND: To evaluate the long-term results of implantation of homogeneous large size of pulmonary homograft (PH) for reconstruction of the right ventricular outflow tract (RVOT). METHODS: Between January 2000 and December 2017, 107 patients were implanted with PH for reconstruction of the RVOT. Data were collected retrospectively in this single-center study. PH failure was defined as a peak of gradient greater than 40 mmHg and/or as a pulmonary regurgitation greater than Grade 2. Primary endpoint was the reoperation of the RVOT during follow-up. Secondary endpoints were overall survival, occurrence of PH failure and the rate of reoperation for all cause. RESULTS: Mean age of the recipients was 26.1 ± 13.6 years. Median follow-up interval was 2.99 years (interquartile range [IQR]: 6.2). Mean size of PH was 24.9 ± 1.9 mm. Reoperation of the RVOT occurred in eight patients (7.8%). Time before reoperation was 2.74 years (IQR: 6.4). Freedom from reoperation for RVOT at 5 and 10 years was respectively 95.7% and 90.0%. Overall survival at 10 years was 95.2%. PH failure occurred in 13 patients (12.0%). Median time before PH failure was 6.7 years (IQR: 9.6). Freedom from PH failure at 10 years was 81.6%. Reoperation for PH failure occurred in four patients (3.9%). Concomitant tricuspid surgery (p = .01; 95% confidence interval [CI]: 1.9-319.6) and undersized PH (p = .01; 95% CI: 2.06-719.8) were independent risk factors of late reoperation. CONCLUSION: Implantation of large PH for RVOT reconstruction provides excellent midterm results in terms of reoperation.

Rapid and Reproducible Differentiation of Hematopoietic and T Cell Progenitors From Pluripotent Stem Cells.

Cell therapy using T cells has revolutionized medical care in recent years but limitations are associated with the difficulty of genome editing of the cells, the production of a sufficient number of cells and standardization of the product. Human pluripotent stem cells (hPSCs) can self-renew and differentiate into T cells to provide a standardized homogenous product of defined origin in indefinite quantity, therefore they are of great potential to alleviate limitations of therapeutic T cell production. The differentiation of hPSCs takes place in two steps: first the induction of hematopoietic stem/progenitor cells (HSPCs), then the induction of lymphopoiesis by Notch signaling. However, the differentiation of T cells from hPSCs can be difficult and lack reproducibility. One parameter that needs to be better assessed is the potential of DLL1 vs. DLL4 ligands of the Notch pathway to induce T cells. In addition, culture of hPSCs is labor-intensive and not compatible with GMP production, especially when they are cultured on feeder cells. Thus, the definition of a robust GMP-compatible differentiation protocol from hPSCs cultured in feeder-free conditions would increase the accessibility to off-the-shelf hematopoietic and T cell progenitors derived from hPSCs. In this article, we describe an efficient, rapid and reproducible protocol for the generation of hematopoietic and T cell progenitors in two steps: (1) generation of HSPCs from embryoid bodies (EB) in serum free medium and GMP-compatible feeder-free systems, (2) directed differentiation of hPSC-derived HSPCs into T-cell progenitors in the presence of bone marrow stromal cells expressing Notch-ligands OP9-DLL1 vs. OP9-DLL4.

Continuous cerebral and myocardial selective perfusion in neonatal aortic arch surgery.

BACKGROUND: To assess the feasibility and early outcome of continuous cerebral and myocardial selective perfusion (CCMSP) during aortic arch surgery in neonates. METHODS: We performed a single-center retrospective study between 2008 and 2019 on neonates who underwent aortic arch surgery with or without associated heart lesion repair. CCMSP with moderate hypothermia levels (28°C) was achieved using selective brachiocephalic artery and ascending aorta cannulation. Target rates of cerebral and myocardial perfusion were 25 to 35 mL/kg/min and 150 ml/m2/min. Cardiopulmonary bypass (CPB) variables and clinical outcomes were analyzed. RESULTS: Overall, 69 neonates underwent either isolated aortic arch repair (n = 31) or aortic arch repair with ventricular septal defect (VSD) closure (n = 38). Age and weight medians were 8 [6 to 15] days and 3.4 [2.9-3.5] kg, respectively. Mean CPB and aortic clamping times were 134 ± 47 and 26 ± 5 minutes for isolated aortic arch repair, and 159 ± 47 and 75 ± 30 minutes for aortoplasty accompanied by VSD closure. Mean CCMSP time was 52 ± 21 minutes with cerebral rate of 32.6 ± 10 mL·kg-1 ·min-1 . Overall in hospital survival was 98.5% (68/69). Major complications were: postoperative cardiac failure requiring mechanical support followed by stroke (n = 1; 1.44%) and transient renal failure requiring dialysis (n = 2; 2.89%). Neither myocardial nor digestive complication occurred. CONCLUSION: CCMSP is a safe and reproducible strategy for cerebral, myocardial and visceral protection in neonatal aortic arch repair, with or without VSD closure, resulting in low complication and mortality.

Clinical performance of a three-dimensional saddle-shaped, rigid ring for mitral valve repair.

OBJECTIVES: The Profile 3D annuloplasty ring is a complete, rigid, saddle-shaped ring indicated for reconstruction and/or remodelling of the pathological mitral valve (MV) in patients with mitral insufficiency. METHODS: This prospective, non-randomized, observational, postmarket release study characterized the patient population for which the study ring was chosen for MV repair, assessed the relief from MV dysfunction and determined the level of mitral regurgitation (MR) at follow-up (6-12 months postimplant). RESULTS: Between February 2013 and July 2015, 151 patients were enrolled at 7 centres; data were excluded for 3 patients. The mean age of the remaining 148 patients was 63.8 ± 12.3 years, and 85 patients (57.4%) were men. Ischaemic cardiomyopathy was present in 15 patients (10.1%) and dilated cardiomyopathy in 12 patients (8.1%). MR was severe in 86 of 145 patients with available data (59.3%). Implantation was successful in 141 of 147 attempted procedures. Two deaths (n = 148, 1.4%) occurred within 30 days, and 1 death (0.7%) occurred >30 days after implant. Analysis of patients with data from both visits (n = 111) demonstrated that MR was none or mild in 94.5% of patients, moderate in 3.6% and moderate to severe in 1.8% at follow-up. Nearly all (104 of 109, 95.4%) patients were in New York Heart Association Class I/II. Among patients with ischaemic cardiomyopathy or dilated cardiomyopathy preoperatively, 16 of 19 patients with available data (84.2%) had no or mild MR at follow-up. CONCLUSIONS: MV repair using the Profile 3D annuloplasty ring is a safe and effective treatment for MR. Further investigation is warranted to determine whether patients with ischaemic cardiomyopathy or dilated cardiomyopathy derive unique benefit from this saddle-shaped ring. Clinical trial registration number: www.clinicaltrials.gov, NCT01112566.

Right partial anomalous pulmonary venous connection to the superior vena cava following the Warden procedure.

BACKGROUND AND AIMS: Surgical repair of right partial pulmonary anomalous connection to the superior vena cava (SVC) with the Warden procedure can be complicated by SVC obstruction, pulmonary veins obstruction, and sinus node dysfunction. We review our 20 years of experience with Warden procedures for the repair of right partial pulmonary venous connection to the SVC. METHODS: This was a single-center retrospective study of all patients (pediatric and adult) with right partial pulmonary abnormal venous connections who underwent a complete repair with the Warden procedure between 1997 and 2016. A total of 59 patients were included. The median age was 14 years (5 months to 61 years) and the median weight was 44 kg (4.9-92 kg). RESULTS: The mean term follow-up was 7 (±5) years. No deaths were reported. One (1.7%) patient required a pacemaker implantation; two (3.4%) suffered from a SVC stenosis successfully treated with balloon dilatation and stent implantation; and eight (13.6%) patients had transient rhythm disturbances, one had junctional ectopic tachycardia, three had sick sinus syndrome, three had an atrial flutter, and one had an atrioventricular block. None suffered from pulmonary vein obstruction. CONCLUSION: The Warden procedure is safe and can be performed with very low morbidity, mortality, rhythm disturbances, and decreased pulmonary and SVC obstructions.

Strategy to identify the causes and to solve a sludge granulation problem in methanogenic reactors: application to a full-scale plant treating cheese wastewater.

Granulation of biomass is at the basis of the operation of the most successful anaerobic systems (UASB, EGSB and IC reactors) applied worldwide for wastewater treatment. Despite of decades of studies of the biomass granulation process, it is still not fully understood and controlled. "Degranulation/lack of granulation" is a problem that occurs sometimes in anaerobic systems resulting often in heavy loss of biomass and poor treatment efficiencies or even complete reactor failure. Such a problem occurred in Mexico in two full-scale UASB reactors treating cheese wastewater. A close follow-up of the plant was performed to try to identify the factors responsible for the phenomenon. Basically, the list of possible causes to a granulation problem that were investigated can be classified amongst nutritional, i.e. related to wastewater composition (e.g. deficiency or excess of macronutrients or micronutrients, too high COD proportion due to proteins or volatile fatty acids, high ammonium, sulphate or fat concentrations), operational (excessive loading rate, sub- or over-optimal water upflow velocity) and structural (poor hydraulic design of the plant). Despite of an intensive search, the causes of the granulation problems could not be identified. The present case remains however an example of the strategy that must be followed to identify these causes and could be used as a guide for plant operators or consultants who are confronted with a similar situation independently of the type of wastewater. According to a large literature based on successful experiments at lab scale, an attempt to artificially granulate the industrial reactor biomass through the dosage of a cationic polymer was also tested but equally failed. Instead of promoting granulation, the dosage caused a heavy sludge flotation. This shows that the scaling of such a procedure from lab to real scale cannot be advised right away unless its operability at such a scale can be demonstrated.

Development of a spherically focused phased array transducer for ultrasonic image-guided hyperthermia.

A 1.5 MHz prolate spheroidal therapeutic array with 128 circular elements was designed to accommodate standard imaging arrays for ultrasonic image-guided hyperthermia. The implementation of this dual-array system integrates real-time therapeutic and imaging functions with a single ultrasound system (Vantage 256, Verasonics). To facilitate applications involving small animal imaging and therapy the array was designed to have a beam depth of field smaller than 3.5 mm and to electronically steer over distances greater than 1 cm in both the axial and lateral directions. In order to achieve the required f number of 0.69, 1-3 piezocomposite modules were mated within the transducer housing. The performance of the prototype array was experimentally evaluated with excellent agreement with numerical simulation. A focal volume (2.70 mm (axial) × 0.65 mm (transverse) × 0.35 mm (transverse)) defined by the -6 dB focal intensity was obtained to address the dimensions needed for small animal therapy. An electronic beam steering range defined by the -3 dB focal peak intensity (17 mm (axial) × 14 mm (transverse) × 12 mm (transverse)) and -8 dB lateral grating lobes (24 mm (axial) × 18 mm (transverse) × 16 mm (transverse)) was achieved. The combined testing of imaging and therapeutic functions confirmed well-controlled local heating generation and imaging in a tissue mimicking phantom. This dual-array implementation offers a practical means to achieve hyperthermia and ablation in small animal models and can be incorporated within protocols for ultrasound-mediated drug delivery.

Neonatal Marfan Syndrome: Report of a Case with an Inherited Splicing Mutation outside the Neonatal Domain.

We report a child and her mother affected by Marfan syndrome. The child presented with a phenotype of neonatal Marfan syndrome, revealed by acute and refractory heart failure, finally leading to death within the first 4 months of life. Her mother had a common clinical presentation. Genetic analysis revealed an inherited FBN1 mutation. This intronic mutation (c.6163+3_6163+6del), undescribed to date, leads to exon 49 skipping, corresponding to in-frame deletion of 42 amino acids (p.Ile2014_Asp2055del). FBN1 next-generation sequencing did not show any argument for mosaicism. Association in the same family of severe neonatal and classical Marfan syndrome illustrates the intrafamilial phenotype variability.

Role of the MHC restriction during maturation of antigen-specific human T cells in the thymus.

In the thymus, a T-cell repertoire able to confer protection against infectious and noninfectious agents in a peptide-dependent, self-MHC-restricted manner is selected. Direct detection of Ag-specific thymocytes, and analysis of the impact of the expression of the MHC-restricting allele on their frequency or function has never been studied in humans because of the extremely low precursor frequency. Here, we used a tetramer-based enrichment protocol to analyze the ex vivo frequency and activation-phenotype of human thymocytes specific for self, viral and tumor-antigens presented by HLA-A*0201 (A2) in individuals expressing or not this allele. Ag-specific thymocytes were quantified within both CD4CD8 double or single-positive compartments in every donor. Our data indicate that the maturation efficiency of Ag-specific thymocytes is poorly affected by HLA-A2 expression, in terms of frequencies. Nevertheless, A2-restricted T-cell lines from A2(+) donors reacted to A2(+) cell lines in a highly peptide-specific fashion, whereas their alloreactive counterparts showed off-target activity. This first ex vivo analysis of human antigen-specific thymocytes at different stages of human T-cell development should open new perspectives in the understanding of the human thymic selection process.

Late repair of tetralogy of Fallot during childhood in patients from developing countries.

OBJECTIVES: Although the current surgical approach of tetralogy of Fallot (TOF) is primary complete repair in infancy, late diagnosis and lack of surgical facilities in developing countries may delay surgical treatment. Some of these patients exposed to prolonged chronic hypoxaemia are transferred to more privileged countries to undergo surgical repair with the support of non-governmental organizations. The objective of this single-centre retrospective study was to compare the postoperative outcomes of these foreign patients undergoing delayed repair with those of patients born in France undergoing timely repair during the same time period. METHODS: The computer database of our institution was searched for all cases of TOF in foreign patients younger than 15 years, supported by two non-profit organizations, who underwent complete repair between January 2007 and December 2013. The control population consisted of the patients with TOF born in France, who underwent timely complete repair during the same period. RESULTS: The 47 foreign children were older (57.6 ± 38.4 vs 8.3 ± 9.1 months, P < 0.0001), more hypoxaemic (SaO2 79 ± 11 vs 91 ± 8%, P < 0.0001), more growth-retarded (body mass index Z-score -1.35 ± 1.5 vs -0.46 ± 1.3, P = 0.0034), and had higher haematocrit level (52.5 ± 11.7 vs 37.5 ± 6.1%, <0.0001) and worse left ventricular ejection fraction (LVEF 62 ± 8 vs 69 ± 3.8%, P < 0.0001) than the 90 French patients. Postoperative mortality and morbidity (sepsis, arrhythmia, bleeding and need for surgical revision) were similar in the two groups, except for a higher rate of pericardial and/or pleural effusion in foreign children (36 vs 17%, P = 0.02). Length of stay was shorter in foreign than in French patients (11 ± 6 vs 15 ± 15 days, P = 0.0012). CONCLUSIONS: In our experience, despite the presence of several risk factors (growth retardation, chronic hypoxaemia, polycythaemia and left ventricular dysfunction), late repair of TOF was undertaken during childhood in patients from developing countries with no difference in postoperative morbidity and mortality compared with that of timely repair during infancy. These older patients can be discharged sooner. However, patients undergoing late surgery may be at higher risk of complications of right ventricular failure, such as pleural and/or pericardial effusion.

Early structural valve deterioration of Mitroflow aortic bioprosthesis: mode, incidence, and impact on outcome in a large cohort of patients.

BACKGROUND: Structural valve deterioration (SVD) is a major flaw of bioprostheses. Early SVD has been suspected in the last models of Mitroflow bioprosthesis. We sought to assess the incidence, mode, and impact of SVD on outcome in a large series of Mitroflow aortic valve replacement. METHODS AND RESULTS: Six hundred seventeen consecutive patients (aged 76.1±6.3 years) underwent aortic valve replacement with a Mitroflow prosthesis (models 12A/LX) between 2002 and 2007. By echocardiography, 39 patients developed early SVD (1.66% per patient-year), with stenosis as the main mode (n=36). Mean delay to SVD was only 3.8±1.4 years, and 5-year SVD-free survival was 91.6% (95% confidence interval [CI], 88.7-94.7) for the whole cohort and 79.8% (95% CI, 71.2-89.4) and 94.0% (95% CI, 90.3-97.8) for 19- and 21-mm sizes, respectively. Among the 39 patients with SVD, 13 patients (33%) had an accelerated SVD once the mean gradient exceeded 30 mm Hg. Valve-related death was 46.2% in this SVD subgroup. Five-year overall survival was 69.6% (95% CI, 65.7-73.9). In multivariable analysis, SVD was the strongest correlate of overall mortality (hazard ratio=7.7; 95% CI, 4.4-13.6). CONCLUSIONS: Early SVD is frequent in Mitroflow bioprosthesis (models 12A/LX), especially for small sizes (19 and 21 mm), and reduces overall survival. An unpredictable accelerated pattern of SVD constitutes a life-threatening condition. In view of the large number of Mitroflow valves implanted worldwide, one can expect an epidemic of SVD and valve-related deaths, which represents a major public health issue, especially in the elderly. Hence, a close follow-up with yearly echocardiography after Mitroflow implantation is advisable. An urgent reoperation should be discussed in patients with severe SVD even though they are still asymptomatic.

Human comparative experimental study of surgical treatment of atrial fibrillation by epicardial techniques.

BACKGROUND: To set up an experimental model of cadaveric heart in order to evaluate and compare histologic transmurality of lesions immediately caused by different energy sources of anti-arrhythmic epicardial devices. METHODS: Procedures were performed on a cadaveric human heart in orthotopic position with an ischemic time of 48 h at 37° and supported through the use of cardiopulmonary bypass. Three anti-arrhythmic epicardial devices were studied: the bipolar forceps Cardioblate BP (Medtronic) for the radiofrequency, the Epicor Ultracinch LP Ablation device (St. Jude) for ultrasound and the Cardioblate CryoFlex (Medtronic) device for cryoablation. Histological features of lesions made at the pulmonary venous confluence assessed the effectiveness of different energy sources. RESULTS: Over 45 experimentations performed, only 28 were considered correct and retained for histological analysis. Three distinct groups were studied according to the type of procedure performed: group 1 (Radiofrequency, n = 12), group 2 (ultrasound, n = 4), group 3 (cryoablation, n = 10) and controls (n = 2). All analysed samples showed histological changes with a success rates of transmurality of 33% for radiofrequency, 25% for ultrasound and 90% for cryotherapy (p <0.001). The average length of transmurality, when it was reached and the proportion of transmurality over the total length of the lesion were respectively 12 ± 6 mm and 37 ± 18% for group 1, 10 mm and 33% for group 2 and 11.1 ± 1.1 mm and 35 ± 5% for group 3. CONCLUSION: Immediate detectable histological transmural lesions after epicardial procedure are discontinuous whatever the kind of energy source tested in this work and it strongly encourages the repetition of radiofrequency procedures. Nevertheless, our experimental model seems inadequate to assess ultrasound energy efficacy.

[Pediatric heart surgery in developing countries. Twenty years experience of La Chaine de L'espoir (Chain of Hope)]. / La chirurgie cardiaque pédiatrique dans les pays en voie de développement. Vingt ans d'expérience de la chaîne de l'Espoir.

Because of their high incidence, cardiac disorders in children are now a public health issue. These children require multidisciplinary management, but surgery is sometimes unavoidable. The two most frequent types of cardiac disorder in children are congenital defects and rheumatic valve disease. La Chaine de l'Espoir (Chain of Hope) is present in more than 30 countries in Africa, Asia and the Middle East. Due to the socio-economic context and lack of technical resources, pediatric heart surgery has several particular characteristics in developing countries. Infants rarely undergo cardiac surgery, given the complexity of their management and particularly the need for intensive care. Another specificity is the need to limit treatment to reparatory or conservative methods. Surgery is rarely attempted in terminally ill patients. Costs must be kept to a minimum, and this is why we have optedfor local manufacture of mitral rings, led by Daniel Roux. After 20 years of practice we have found that regional hospitals are the smallest structures that can offer acceptable results in terms of patient care and professional training

ClbP is a prototype of a peptidase subgroup involved in biosynthesis of nonribosomal peptides.

The pks genomic island of Escherichia coli encodes polyketide (PK) and nonribosomal peptide (NRP) synthases that allow assembly of a putative hybrid PK-NRP compound named colibactin that induces DNA double-strand breaks in eukaryotic cells. The pks-encoded machinery harbors an atypical essential protein, ClbP. ClbP crystal structure and mutagenesis experiments revealed a serine-active site and original structural features compatible with peptidase activity, which was detected by biochemical assays. Ten ClbP homologs were identified in silico in NRP genomic islands of closely and distantly related bacterial species. All tested ClbP homologs were able to complement a clbP-deficient E. coli mutant. ClbP is therefore a prototype of a new subfamily of extracytoplasmic peptidases probably involved in the maturation of NRP compounds. Such peptidases will be powerful tools for the manipulation of NRP biosynthetic pathways.