Acute stress differently modulates interneurons excitability and synaptic plasticity in the primary motor cortex of wild-type and SOD1G93A mouse model of ALS.

Primary motor cortex (M1) network stability depends on activity of inhibitory interneurons, for which susceptibility to stress was previously demonstrated in limbic regions. Hyperexcitability in M1 following changes in the excitatory/inhibitory balance is a key pathological hallmark of amyotrophic lateral sclerosis (ALS). Using electrophysiological approaches, we assessed the impact of acute restraint stress on inhibitory interneurons excitability and global synaptic plasticity in M1 of the SOD1G93A ALS mouse model at a late pre-symptomatic stage (10-12.5 weeks). Based on their firing type (continuous, discontinuous, with accommodation or not) and electrophysiological characteristics (resting potential, rheobase, firing frequency), interneurons from M1 slices were separated into four clusters, labelled from 1 to 4. Among them, only interneurons from the first cluster, presenting continuous firing with few accommodations, tended to show increased excitability in wild-type (WT) and decreased excitability in SOD1G93A animals following stress. In vivo analyses of evoked field potentials showed that stress suppressed the theta burst-induced plasticity of an excitatory component (N1) recorded in the superficial layers of M1 in WT, with no impact on an inhibitory complex (N2-P1) from the deeper layers. In SOD1G93A mice, stress did not affect N1 but suppressed the N2-P1 plasticity. These data suggest that stress can alter M1 network functioning in a different manner in WT and SOD1G93A mice, possibly through changes of inhibitory interneurons excitability and synaptic plasticity. This suggests that stress-induced activity changes in M1 may therefore influence ALS outcomes. KEY POINTS: Disruption of the excitatory/inhibitory balance in the primary motor cortex (M1) has been linked to cortical hyperexcitability development, a key pathological hallmark of amyotrophic lateral sclerosis (ALS). Psychological stress was reported to influence excitatory/inhibitory balance in limbic regions, but very little is known about its influence on the M1 functioning under physiological or pathological conditions. Our study revealed that acute stress influences the excitatory/inhibitory balance within the M1, through changes in interneurons excitability along with network plasticity. Such changes were different in pathological (SOD1G93A ALS mouse model) vs. physiological (wild-type) conditions. The results of our study help us to better understand how stress modulates the M1 and highlight the need to further characterize stress-induced motor cortex changes because it may be of importance when evaluating ALS outcomes.

BiœmuS: A new tool for neurological disorders studies through real-time emulation and hybridization using biomimetic Spiking Neural Network.

Characterization and modeling of biological neural networks has emerged as a field driving significant advancements in our understanding of brain function and related pathologies. As of today, pharmacological treatments for neurological disorders remain limited, pushing the exploration of promising alternative approaches such as electroceutics. Recent research in bioelectronics and neuromorphic engineering have fostered the development of the new generation of neuroprostheses for brain repair. However, achieving their full potential necessitates a deeper understanding of biohybrid interaction. In this study, we present a novel real-time, biomimetic, cost-effective and user-friendly neural network capable of real-time emulation for biohybrid experiments. Our system facilitates the investigation and replication of biophysically detailed neural network dynamics while prioritizing cost-efficiency, flexibility and ease of use. We showcase the feasibility of conducting biohybrid experiments using standard biophysical interfaces and a variety of biological cells as well as real-time emulation of diverse network configurations. We envision our system as a crucial step towards the development of neuromorphic-based neuroprostheses for bioelectrical therapeutics, enabling seamless communication with biological networks on a comparable timescale. Its embedded real-time functionality enhances practicality and accessibility, amplifying its potential for real-world applications in biohybrid experiments.

Acute Type B Aortic Dissection: Insights From a Single-Center Retrospective Experience Over 12 Years.

INTRODUCTION: The treatment of acute type B aortic dissection (ATBAD) is currently a challenge for vascular surgeons, because of the early morbidity and mortality rates and the high risk of late aortic events up to 50% at 5 years. This study presents the initial outcomes of ATBAD treatment using optimal medical therapy alone or combined with proximal entry tear stent-graft coverage. Additionally, it provides an analysis of the evolution of the aortic diameter and its clinical consequences during the chronic phase in each group. MATERIALS AND METHODS: Conducted as a retrospective, single-center study, we enrolled all consecutive ATBAD patients (n=130) treated between 2008 and 2020. The primary analysis studies the entire patient cohort based on their initial management approach, namely, medical treatment alone for uncomplicated ATBAD (n=67) or combined with stent-graft entry tear coverage (n=63). We also conducted a subgroup analysis to investigate factors associated with disease progression in the medical management group. RESULTS: Median follow-up was 29.5 months. During this time aneurysmal evolution was observed in: 42.4% of cases in the medical group compared with 21.8% in the stent-graft group, primarily affecting the thoracic aorta. The stent-graft group exhibited significant aortic remodeling, with a decrease in false lumen (FL) and thoracic aortic diameters. Initial aortic diameter ≥40 mm and FL ≥22 mm were independent risk factors for aneurysmal degeneration. Five-year survival was consistent at 76.1% in both groups. CONCLUSION: This study confirms the safety and efficacy of stent-graft entry tear coverage for ATBAD. Initial thoracic endovascular aortic repair (TEVAR) appears to reduce late aortic events by promoting aortic remodeling. Considering TEVAR's safety and potential to prevent late aortic complications, it may be considered for uncomplicated ATBAD patients with an initial aortic diameter ≥40 mm or an FL ≥22 mm. CLINICAL IMPACT: This study validates the efficacy and safety of using endovascular stent grafts to seal the proximal entry tear in cases of acute type B aortic dissections, compared to optimal medical therapy. Aortic remodelling significantly benefits from endovascular stent graft coverage of the proximal entry tear. Given the heightened risk of late aortic events observed in the medical therapy cohort, there appears to be a necessity for including endovascular interventions in the management of uncomplicated acute type B aortic dissections, particularly when aortic diameter is ≥40 mm and false lumen diameter is ≥22 mm.

Editor's Choice - Outcomes of Cold Stored Saphenous Vein Allografts for Haemodialysis Vascular Access.

OBJECTIVE: The aim of this study was to evaluate the outcomes of cold stored saphenous vein allografts (CSVAs) for haemodialysis vascular access. METHODS: A retrospective, two centre study was conducted between January 2016 and December 2020 of all patients who had CSVA placement for haemodialysis vascular access. Primary, primary assisted, and secondary patency were analysed, as well as procedural complications and re-interventions. RESULTS: One hundred and nine patients (n = 55 women) with a mean age of 67.2 ± 13.6 years, with no options for creating an autogenous arteriovenous fistula, were included in the study. At one year, primary, primary assisted, and secondary patency were 37.6%, 59.0%, and 73.3%, respectively; and at two years 19.9%, 42.5%, and 54.9%, respectively. During a mean follow up period of 26 ± 18 months, five patients (4.6%) had an access infection, with no related death. During the follow up period, 32 patients (29.4%) died and 13 patients (11.9%) underwent a kidney transplant. None of these patients showed immunoconversion before transplantation. The cumulative incidence of adverse events by the Fine-Gray method was calculated. Considering competing risks (death and renal transplantation), 9.2% of patients lost their vascular access at one year and 18% at two years. Moreover, 57.8% patients had stenosis, mainly on the outflow (45.9%), and 49.5% had thrombosis. CONCLUSION: With a comparable patency rate associated with a low infection rate, CSVA offers a potential alternative to expanded polytetrafluoroethylene grafts. This creates haemodialysis vascular access when the venous capital is exhausted in patients with reported risk factors for vascular access infection, i.e., insertion in the thigh, advanced age, diabetes mellitus, immunocompromised state, obesity, or revision of an infected prosthetic graft.

Excitatory action of low frequency depolarizing GABA/glycine synaptic inputs is prevalent in prenatal spinal SOD1G93A motoneurons.

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease characterized by progressive motor neuron degeneration and muscle paralysis. Recent evidence suggests the dysfunction of inhibitory signalling in ALS motor neurons. We have shown that embryonic day (E)17.5 spinal motoneurons (MNs) of the SOD1G93A mouse model of ALS exhibit an altered chloride homeostasis. At this prenatal stage, inhibition of spinal motoneurons (MNs) is mediated by depolarizing GABAergic/glycinergic postsynaptic potentials (dGPSPs). Here, using an ex vivo preparation and patch clamp recording from MNs with a chloride equilibrium set below spike threshold, we report that low input resistance (Rin ) E17.5 MNs from the SOD1G93A ALS mouse model do not correctly integrate dGPSPs evoked by electrical stimulations of GABA/glycine inputs at different frequencies. Indeed, firing activity of most wild-type (WT) MNs with low Rin was inhibited by incoming dGPSPs, whereas low Rin SOD1G93A MNs were excited or exhibited a dual response (excited by low frequency dGPSPs and inhibited by high frequency dGPSPs). Simulation highlighted the importance of the GABA/glycine input density and showed that pure excitation could be obtained in SOD-like MNs by moving GABA/glycine input away from the cell body to dendrites. This was in agreement with confocal imaging showing a lack of peri-somatic inhibitory terminals in SOD1G93A MNs compared to WT littermates. Putative fast ALS-vulnerable MNs with low Rin are therefore lacking functional inhibition at the near-term prenatal stage. KEY POINTS: We analysed the integration of GABAergic/glycinergic synaptic events by embryonic spinal motoneurons (MNs) in a mouse model of the amyotrophic lateral sclerosis (ALS) neurodegenerative disease. We found that GABAergic/glycinergic synaptic events do not properly inhibit ALS MNs with low input resistance, most probably corresponding to future vulnerable MNs. We used a neuron model to highlight the importance of the GABA/glycine terminal location and density in the integration of the GABAergic/glycinergic synaptic events. Confocal imaging showed a lack of GABA/glycine terminals on the cell body of ALS MNs. The present study suggests that putative ALS vulnerable MNs with low Rin lack functional inhibition at the near-term stage.

Chloride Homeostasis in Developing Motoneurons.

Maturation of GABA/Glycine chloride-mediated synaptic inhibitions is crucial for the establishment of a balance between excitation and inhibition. GABA and glycine are excitatory neurotransmitters on immature neurons that exhibit elevated [Cl-]i. Later in development [Cl-]i drops leading to the occurrence of inhibitory synaptic activity. This ontogenic change is closely correlated to a differential expression of two cation-chloride cotransporters that are the Cl- channel K+/Cl- co-transporter type 2 (KCC2) that extrudes Cl- ions and the Na+-K+-2Cl- cotransporter NKCC1 that accumulates Cl- ions. The classical scheme built from studies performed on cortical and hippocampal networks proposes that immature neurons display high [Cl-]i because NKCC1 is overexpressed compared to KCC2 and that the co-transporters ratio reverses in mature neurons, lowering [Cl-]i. In this chapter, we will see that this classical scheme is not true in motoneurons (MNs) and that an early alteration of the chloride homeostasis may be involved in pathological conditions.

From real-time single to multicompartmental Hodgkin-Huxley neurons on FPGA for bio-hybrid systems.

Modeling biological neural networks has been a field opening to major advances in our understanding of the mechanisms governing the functioning of the brain in normal and pathological conditions. The emergence of real-time neuromorphic platforms has been leading to a rising significance of bio-hybrid experiments as part of the development of neuromorphic biomedical devices such as neuroprosthesis. To provide a new tool for the neurological disorder characterization, we design real-time single and multicompartmental Hodgkin-Huxley neurons on FPGA. These neurons allow biological neural network emulation featuring improved accuracy through compartment modeling and show integration in bio-hybrid system thanks to its real-time dynamics.

Two opposite voltage-dependent currents control the unusual early development pattern of embryonic Renshaw cell electrical activity.

Renshaw cells (V1R) are excitable as soon as they reach their final location next to the spinal motoneurons and are functionally heterogeneous. Using multiple experimental approaches, in combination with biophysical modeling and dynamical systems theory, we analyzed, for the first time, the mechanisms underlying the electrophysiological properties of V1R during early embryonic development of the mouse spinal cord locomotor networks (E11.5-E16.5). We found that these interneurons are subdivided into several functional clusters from E11.5 and then display an unexpected transitory involution process during which they lose their ability to sustain tonic firing. We demonstrated that the essential factor controlling the diversity of the discharge pattern of embryonic V1R is the ratio of a persistent sodium conductance to a delayed rectifier potassium conductance. Taken together, our results reveal how a simple mechanism, based on the synergy of two voltage-dependent conductances that are ubiquitous in neurons, can produce functional diversity in embryonic V1R and control their early developmental trajectory.

Elective late open conversion after endovascular aneurysm repair is associated with comparable outcomes to primary open repair of abdominal aortic aneurysms.

OBJECTIVE: Three of four patients with infrarenal abdominal aortic aneurysm are now treated with endovascular aneurysm repair (EVAR). The incidence of secondary procedures and surgical conversions is increasing for a population theoretically unfit for open surgery. The indications and outcomes of late open surgical conversions after EVAR in a high-volume tertiary vascular unit are reported. METHODS: This retrospective single-center study includes all patients who underwent a late open conversion between January 1996 and July 2018. Data were collected from records on patient demographics, operative indications, surgical strategy, perioperative outcomes, and medium-term survival. RESULTS: Sixty-two consecutive patients (88.7% male) with a mean age of 77.5 years are included. The median duration since index EVAR was 38.5 months; 65% of stent grafts requiring late open conversion had suprarenal fixation. Indications included 22.6% type IA, 16.1% type IB, and 45.2% type II endoleaks; 12.9% graft thrombosis; and 14.5% endoprosthesis infection. Complete endograft explantation was performed in 37.1% of patients and a partial explantation in 54.8%, whereas 8.1% of stent grafts were wholly preserved in situ. Overall 30-day mortality was 12.9% (n = 8) in the cohort and 2.7% for elective patients. The all-cause morbidity rate was 40.1%, and the median length of hospital stay was 9 days. After follow-up of 28.4 months (range, 1.8-187.3 months), all-cause survival was 58.8%. Avoidance of aortic clamping (P = .006) and elective procedures (P = .019) were associated with a significant reduction in the length of hospital stay. Moreover, the 30-day mortality (P = .002), occurrence of postoperative renal dysfunction (P = .004), and intestinal ischemia (P = .017) were increased in the emergency setting. Excluding cases with rupture or infection, survival estimates were 97%, 97%, and 71% at 1 year, 2 years, and 5 years, respectively. CONCLUSIONS: Technically more complex than primary open surgery, late open conversion is a procedure that generates an acceptable perioperative risk when it is performed in a high-volume aortic surgical center. Elective open conversion is associated with excellent early and late outcomes. Endograft preservation strategies decrease perioperative morbidity.

Implication of 5-HT in the Dysregulation of Chloride Homeostasis in Prenatal Spinal Motoneurons from the G93A Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration and muscle paralysis. The early presymptomatic onset of abnormal processes is indicative of cumulative defects that ultimately lead to a late manifestation of clinical symptoms. It remains of paramount importance to identify the primary defects that underlie this condition and to determine how these deficits lead to a cycle of deterioration. We recently demonstrated that prenatal E17.5 lumbar spinal motoneurons (MNs) from SOD1G93A mice exhibit a KCC2-related alteration in chloride homeostasis, i.e., the EGABAAR is more depolarized than in WT littermates. Here, using immunohistochemistry, we found that the SOD1G93A lumbar spinal cord is less enriched with 5-HT descending fibres than the WT lumbar spinal cord. High-performance liquid chromatography confirmed the lower level of the monoamine 5-HT in the SOD1G93A spinal cord compared to the WT spinal cord. Using ex vivo perforated patch-clamp recordings of lumbar MNs coupled with pharmacology, we demonstrated that 5-HT strongly hyperpolarizes the EGABAAR by interacting with KCC2. Therefore, the deregulation of the interplay between 5-HT and KCC2 may explain the alteration in chloride homeostasis detected in prenatal SOD1G93A MNs. In conclusion, 5-HT and KCC2 are two likely key factors in the presymptomatic phase of ALS, particular in familial ALS involving the SOD1G93A mutation.

Relaxation of synaptic inhibitory events as a compensatory mechanism in fetal SOD spinal motor networks.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting motor neurons (MNs) during late adulthood. Here, with the aim of identifying early changes underpinning ALS neurodegeneration, we analyzed the GABAergic/glycinergic inputs to E17.5 fetal MNs from SOD1G93A (SOD) mice in parallel with chloride homeostasis. Our results show that IPSCs are less frequent in SOD animals in accordance with a reduction of synaptic VIAAT-positive terminals. SOD MNs exhibited an EGABAAR10 mV more depolarized than in WT MNs associated with a KCC2 reduction. Interestingly, SOD GABAergic/glycinergic IPSCs and evoked GABAAR-currents exhibited a slower decay correlated to elevated [Cl-]i. Computer simulations revealed that a slower relaxation of synaptic inhibitory events acts as compensatory mechanism to strengthen GABA/glycine inhibition when EGABAAR is more depolarized. How such mechanisms evolve during pathophysiological processes remain to be determined, but our data indicate that at least SOD1 familial ALS may be considered as a neurodevelopmental disease.

[Acute and chronic pathologies of the thoracic aorta: From diagnosis to treatment]. / Pathologie aortique thoracique aiguë et chronique : du diagnostic au traitement.

Aortic pathologies benefit from imaging innovation and interventional radiology developments in order to improve patient management. At the early phase, vital risk should be considered. Whole body CT scan evaluate the complete aorta and its branches to assess the pathology and to choose the best approach between surgery or interventional radiology (fenestration, stentgraft, peripheral stenting). Algorithms, based on the understanding of the complications mechanisms and evolutive risk, modified the management specifically for aortic dissection. At chronic phase, GPs and angiologists should follow their patients in order to detect aortic complications and to treat cardiovascular risk factors. MRA is well indicated if possible.

Persistent Sodium Current Drives Excitability of Immature Renshaw Cells in Early Embryonic Spinal Networks.

Spontaneous network activity (SNA) emerges in the spinal cord (SC) before the formation of peripheral sensory inputs and central descending inputs. SNA is characterized by recurrent giant depolarizing potentials (GDPs). Because GDPs in motoneurons (MNs) are mainly evoked by prolonged release of GABA, they likely necessitate sustained firing of interneurons. To address this issue we analyzed, as a model, embryonic Renshaw cell (V1R) activity at the onset of SNA (E12.5) in the embryonic mouse SC (both sexes). V1R are one of the interneurons known to contact MNs, which are generated early in the embryonic SC. Here, we show that V1R already produce GABA in E12.5 embryo, and that V1R make synaptic-like contacts with MNs and have putative extrasynaptic release sites, while paracrine release of GABA occurs at this developmental stage. In addition, we discovered that V1R are spontaneously active during SNA and can already generate several intrinsic activity patterns including repetitive-spiking and sodium-dependent plateau potential that rely on the presence of persistent sodium currents (INap). This is the first demonstration that INap is present in the embryonic SC and that this current can control intrinsic activation properties of newborn interneurons in the SC of mammalian embryos. Finally, we found that 5 µm riluzole, which is known to block INaP, altered SNA by reducing episode duration and increasing inter-episode interval. Because SNA is essential for neuronal maturation, axon pathfinding, and synaptogenesis, the presence of INaP in embryonic SC neurons may play a role in the early development of mammalian locomotor networks.SIGNIFICANCE STATEMENT The developing spinal cord (SC) exhibits spontaneous network activity (SNA) involved in the building of nascent locomotor circuits in the embryo. Many studies suggest that SNA depends on the rhythmic release of GABA, yet intracellular recordings of GABAergic neurons have never been performed at the onset of SNA in the SC. We first discovered that embryonic Renshaw cells (V1R) are GABAergic at E12.5 and spontaneously active during SNA. We uncover a new role for persistent sodium currents (INaP) in driving plateau potential in V1R and in SNA patterning in the embryonic SC. Our study thus sheds light on a role for INaP in the excitability of V1R and the developing SC.

Depolarizing GABA/glycine synaptic events switch from excitation to inhibition during frequency increases.

By acting on their ionotropic chloride channel receptors, GABA and glycine represent the major inhibitory transmitters of the central nervous system. Nevertheless, in various brain structures, depolarizing GABAergic/glycinergic postsynaptic potentials (dGPSPs) lead to dual inhibitory (shunting) and excitatory components, the functional consequences of which remain poorly acknowledged. Indeed, the extent to which each component prevails during dGPSP is unclear. Understanding the mechanisms predicting the dGPSP outcome on neural network activity is therefore a major issue in neurobiology. By combining electrophysiological recordings of spinal embryonic mouse motoneurons and modelling study, we demonstrate that increasing the chloride conductance (g(Cl)) favors inhibition either during a single dGPSP or during trains in which g(Cl) summates. Finally, based on this summation mechanism, the excitatory effect of EPSPs is overcome by dGPSPs in a frequency-dependent manner. These results reveal an important mechanism by which dGPSPs protect against the overexcitation of neural excitatory circuits.

Thoracic endovascular aortic repair: A single center's 15-year experience.

OBJECTIVE: Specific complications of thoracic endovascular aortic repair (TEVAR) exist and long-term data are lacking. The purpose of this study was to evaluate our long-term TEVAR results. METHODS: This is a single-center retrospective study of 223 patients undergoing TEVAR from 1998 to 2013. Indication was aneurysm (45%), traumatic (26%), dissection (23%), and septic (6%). RESULTS: Patients' mean age was 62.7 ± 17.9 years, 84% of them had an American Society of Anesthesiologists score ≥3, and 42% had an aortic rupture. TEVAR was performed in zone 0 (n = 17), 1 (n = 17), or 2 (n = 59) in 42% of patients. Technical success rate was 96.4%. Overall 30-day mortality was 11.7% (elective aneurysm, 11.6%; emergent aneurysm, 34.3%; acute type B dissection, 14.8%; chronic dissection, 4.2%; septic, 8.3%; and traumatic, 1.7%). Major adverse events included stroke in 4.5%, spinal cord ischemia in 1.8%, and retrograde aortic dissection in 2.7%. Mean follow-up was 43.4 ± 38 months. Estimated aortic complications-free survivals at 12, 36, 60, and 120 months were (% ± standard error) 73% ± 3%, 64% ± 4%, 62% ± 4% and 57% ± 5%, respectively. Multivariate analysis showed that patients treated for a chronic aortic dissection had a significant risk of late reintervention (P = .001) CONCLUSIONS: Because of its simplicity and low morbimortality rate, TEVAR has become the first-line approach for thoracic aortic diseases. Mortality outcomes are related to aortic pathology, emergent status, and proximal landing zone. To improve long-term results, rigorous patient selection and follow-up, development of referral centers, and technologic evolution of materials have to be reached.

Nonsynaptic glycine release is involved in the early KCC2 expression.

The cation-chloride co-transporters are important regulators of the cellular Cl(-) homeostasis. Among them the Na(+) -K(+) -2Cl(-) co-transporter (NKCC1) is responsible for intracellular chloride accumulation in most immature brain structures, whereas the K(+) -Cl(-) co-transporter (KCC2) extrudes chloride from mature neurons, ensuring chloride-mediated inhibitory effects of GABA/glycine. We have shown that both KCC2 and NKCC1 are expressed at early embryonic stages (E11.5) in the ventral spinal cord (SC). The mechanisms by which KCC2 is prematurely expressed are unknown. In this study, we found that chronically blocking glycine receptors (GlyR) by strychnine led to a loss of KCC2 expression, without affecting NKCC1 level. This effect was not dependent on the firing of Na(+) action potentials but was mimicked by a Ca(2+) -dependent PKC blocker. Blocking the vesicular release of neurotransmitters did not impinge on strychnine effect whereas blocking volume-sensitive outwardly rectifying (VSOR) chloride channels reproduced the GlyR blockade, suggesting that KCC2 is controlled by a glycine release from progenitor radial cells in immature ventral spinal networks. Finally, we showed that the strychnine treatment prevented the maturation of rhythmic spontaneous activity. Thereby, the GlyR-activation is a necessary developmental process for the expression of functional spinal motor networks. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 764-779, 2016.

Outcomes of cold-stored venous allograft for below-knee bypasses in patients with critical limb ischemia.

OBJECTIVE: Critical limb ischemia (CLI), the most advanced form of peripheral arterial disease, is associated with strikingly high morbidity and mortality rates. Autogenous single-segment great saphenous vein (GSV) remains the optimal conduit for infrainguinal revascularization. Unfortunately, GSV is unavailable in up to 20% of patients. There is no consensus about the alternative graft that should be used for infragenicular bypass grafting when the GSV is unavailable. Currently, there are no outcome data for cold-stored venous allograft use in regard to recent safety and efficacy objective performance goals described by the Society for Vascular Surgery. METHODS: This is a retrospective analysis of 118 infragenicular revascularizations performed for CLI with cold-stored venous allografts obtained from varicose vein stripping surgery in a single institution from November 2002 to August 2013. RESULTS: Mean age (± standard deviation) was 75 ± 12 years (male, 76%; diabetes, 73%; dialysis, 16%), and 38% (n = 45) had a history of failed ipsilateral revascularization. None had suitable autogenous conduit for even composite vein bypass. The distal anastomosis was performed to an infrapopliteal artery in 85 cases (72%). At 30 days, perioperative death rate was 6.8%, major adverse cardiovascular event rate was 7.6%, and major adverse limb event rate was 11.9%. Mean follow-up was 34 ± 29 months (range, 1-113 months). At 1 year, freedom from major adverse limb event or perioperative death, limb salvage, survival, amputation-free survival, and secondary patency rates were, respectively, 64.9%, 82.5%, 85.4%, 73.3%, and 58.3%. Ejection fraction <45% and dialysis were the most significant factors predicting failure of revascularization. CONCLUSIONS: Cold-stored venous allografts may be used for performing infragenicular revascularization for CLI with acceptable safety and efficacy results despite poor long-term patency. Their level of performance remains inferior to autologous vein sources but seems comparable to alternative allografts or prosthetic conduit. Their availability is a major advantage compared with other biologic alternative sources.

Minimum 10-year follow-up of endovascular repair for acute traumatic transection of the thoracic aorta.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) for traumatic rupture of the descending thoracic aorta seems, in the short term, to be associated with better outcomes than open repair, but long-term data are lacking. METHODS: A review was conducted of a prospectively maintained database of patients who underwent TEVAR for traumatic rupture of the descending thoracic aorta in our unit, with a minimum 10-year follow-up. Follow-up computed tomography scans were performed at 1 week, 3 and 6 months, and annually thereafter. Particular attention was focused on device-related issues. RESULTS: Among the 53 patients, 17 had a minimum 10-year follow-up: mean age was 45.8 ± 17 years (range: 18-78 years); 4 were women. Mean follow-up was 11.6 years (range: 10.1-13.1 years). Technical success was achieved in 100% of cases. The distribution of the proximal landing zone was zone 2 in 4 cases, zone 3 in 13 cases. A case of inadvertent coverage of supra-aortic trunks occurred intraoperatively. An early proximal type I endoleak was successfully treated by proximal implantation of an additional second stent-graft. No perioperative death was observed, and none of the patients suffered transient or permanent paraplegia, or cerebral complication. After a minimum 10-year follow-up, all patients were still alive. Follow-up computed tomography scans did not reveal any stent-graft migration or collapse, or secondary endoleaks. However, we observed that the proximal and distal aortic neck dilated to some extent, as is the natural history of the thoracic aorta. This dilation was more marked in patients aged <30 years. CONCLUSIONS: Our minimum 10-year follow-up study of endovascular repair for acute traumatic transection of the thoracic aorta demonstrated that the reduction in the operative mortality rate of TEVAR, compared with open repair, lasts over time, without any device-related issues. Longer-term follow-up is necessary to determine whether the thoracic aorta expansion continues and becomes clinically significant.

Experimental evaluation of complete endovascular arch reconstruction by in situ retrograde fenestration.

BACKGROUND: The aim of this experimental study was to assess the feasibility of complete endovascular arch reconstruction by in situ retrograde fenestration and to investigate the impact of stent-graft material on stent-graft fenestrations. METHODS: The experiments were performed using 8 cadaveric human thoracic aortas (aortic arch) using 2 different stent-graft types: woven polyester (Valiant Captivia; Medtronic Vascular, Santa Rosa, CA) and expanded polytetrafluoroethylene (conformable [C]-TAG; W.L. Gore & Associates, Flagstaff, AZ). A benchtop aortic pulsatile flow model was used. Stent-grafts were deployed into the aortic arch, covering the ostia of the supraaortic trunks. A 5-mm 30-degree angioscope was introduced into the ascending aorta to monitor the procedure. Retrograde fenestration and deployment of the balloon expandable stent-graft was performed sequentially for each supraaortic trunk. Subsequent to stent-graft explantation, macroscopic evaluation of each fenestration was performed. RESULTS: All attempts to fenestrate the C-TAG and Valiant stent-grafts and implant the covered stent through the supraaortic trunks were successful. In all cases, branch stents were patent and no endoleak was evident. The Valiant stent-graft was easier to puncture because of the higher radial force of the stent-graft providing better counterpressure; however, stent-graft material had no impact on the quality of fenestrations. CONCLUSIONS: Total endovascular repair of the aortic arch through in situ retrograde fenestration of stent-grafts is feasible. The behavior of the 2 types of stent-graft was significantly different while the fenestrations were fashioned, but stent-graft material had no impact on the quality of fenestrations.

VEGF modulates synaptic activity in the developing spinal cord.

Although it has been documented that the nervous and the vascular systems share numerous analogies and are closely intermingled during development and pathological processes, interactions between the two systems are still poorly described. In this study, we investigated whether vascular endothelial growth factor (VEGF), which is a key regulator of vascular development, also modulates neuronal developmental processes. We report that VEGF enhances the gamma-aminobutyric acid (GABA)/glycinergic but not glutamatergic synaptic activity in embryonic spinal motoneurons (MNs), without affecting MNs excitability. In response to VEGF, the frequency of these synaptic events but not their amplitude was increased. Blocking endogenous VEGF led to an opposite effect by decreasing frequency of synaptic events. We found that this effect occurred specifically at early developmental stages (E13.5 and E15.5) and vanished at the prenatal stage E17.5. Furthermore, VEGF was able to increase vesicular inhibitory amino acid transporter density at the MN membrane. Inhibition of single VEGF receptors did not modify electrophysiological parameters indicating receptor combinations or an alternative pathway. Altogether, our findings identify VEGF as a modulator of the neuronal activity during synapse formation and highlight a new ontogenic role for this angiogenic factor in the nervous system.