Extracorporeal Life Support for Cardiogenic Shock in Adult Congenital Heart Disease-An ELSO Registry Analysis.

There are minimal data on the use of venoarterial extracorporeal membrane life support (VA-ECLS) in adult congenital heart disease (ACHD) patients presenting with cardiogenic shock (CS). This study sought to describe the population of ACHD patients with CS who received VA-ECLS in the Extracorporeal Life Support Organization (ELSO) Registry. This was a retrospective analysis of adult patients with diagnoses of ACHD and CS in ELSO from 2009-2021. Anatomic complexity was categorized using the American College of Cardiology/American Heart Association 2018 guidelines. We described patient characteristics, complications, and outcomes, as well as trends in mortality and VA-ECLS utilization. Of 528 patients who met inclusion criteria, there were 32 patients with high-complexity anatomy, 196 with moderate-complexity anatomy, and 300 with low-complexity anatomy. The median age was 59.6 years (interquartile range, 45.8-68.2). The number of VA-ECLS implants increased from five implants in 2010 to 81 implants in 2021. Overall mortality was 58.3% and decreased year-by-year (ß= -2.03 [95% confidence interval, -3.36 to -0.70], p = 0.007). Six patients (1.1%) were bridged to heart transplantation and 21 (4.0%) to durable ventricular assist device. Complications included cardiac arrhythmia/tamponade (21.6%), surgical site bleeding (17.6%), cannula site bleeding (11.4%), limb ischemia (7.4%), and stroke (8.7%). Utilization of VA-ECLS for CS in ACHD patients has increased over time with a trend toward improvement in survival to discharge.

Asymptomatic Aorto-Atrial Fistula Secondary to Surgical Repair of Ascending Aortic Dissection: When to Do Nothing.

Secondary aorto-atrial fistula is a rare but potentially life-threatening complication of ascending aortic dissection surgical repair. Secondary aorto-atrial fistulas commonly lead to symptomatic heart failure requiring emergent repair. We present a rare case of secondary aorto-atrial fistula after surgical repair of aortic dissection that remained asymptomatic for a decade. (Level of Difficulty: Intermediate.).

Compound Motor Action Potentials During a Modest Nerve Crush.

Nerve crush injury results in axonotmesis, characterized by disruption of axons and their myelin sheaths with relative sparing of the nerve's connective tissue. Despite the widespread use of crush injury models, no standardized method for producing these lesions has been established. We characterize a crush model in which a narrow forceps is used to induce a modest and controlled compressive injury. The instantaneous compound motor action potential (CMAP) is monitored in situ and in real-time, allowing the characterization of neuromuscular response during and after injury. The tibial nerves of 11 anesthetized rats were surgically isolated. After the placement of electrodes, CMAPs were elicited and registered using a modular-data-acquisition system. Dumont-#5 micro-forceps were instrumented with a force transducer allowing force measurement via a digital sensor. Baseline CMAPs were recorded prior to crush and continued for the duration of the experiment. Nerve crushing commenced by gradually increasing the force applied to the forceps. At a target decrease in CMAP amplitude of 70%-90%, crushing was halted. CMAPs were continually recorded for 5-20 min after the termination of the crushing event. Nerves were then fixed for histological assessment. The following post-crush mean values from 19 trials were reported: peak CMAP amplitude decreased by 81.6% from baseline, duration of crush was 17 sec, rate of applied force was 0.03 N/sec, and maximal applied force was 0.5 N. A variety of agonal phenomena were evident post-lesion. Following the initial decrease in CMAP, 8 of 19 trials demonstrated a partial and transient recovery, followed by a further decline. Thirteen trials exhibited a CMAP amplitude near zero at the end of the recording. Twelve trials demonstrated a superimposed EMG background response during and after the crush event, with disappearance occurring within 4-8 min. Qualitative histology assessment at the lesion site demonstrated a correspondence between CMAP response and partial sparing of nerve fibers. By using a targeted decline in CMAP amplitude as the endpoint, researchers may be able to produce controlled, brief, and reproducible crush injuries. This model can also be used to test interventions aimed at enhancing subsequent regeneration and behavioral recovery.

Comparison of Transcatheter Aortic Valve Implantation Outcomes Between Normal-Flow, Low-Gradient Severe Aortic Stenosis and Normal-Flow, High-Gradient Severe Aortic Stenosis.

BACKGROUND: Normal flow low gradient severe aortic stenosis (NFLG-AS) with preserved ejection fraction is the most prevalent form of low gradient severe aortic stenosis. Despite the increased prevalence, the clinical outcomes and management strategy of NFLG-AS remain controversial. Therefore, our study aimed to evaluate transcatheter aortic valve implantation (TAVI) outcomes of patients with NFLG-AS compared with normal flow high gradient severe aortic stenosis (NFHG-AS). METHODS: We performed a retrospective analysis of 394 patients who underwent TAVI between January 2011 to September 2020. Among 394 patients, 232 patients had NFLG-AS, and 162 patients had NFHG-AS. The primary outcomes included all-cause mortality and cardiovascular mortality. In addition, multiple secondary outcomes were evaluated, including stroke, myocardial infarction, duration of hospital stay, new-onset atrial fibrillation, temporary or permanent pacemaker requirement, major bleeding, blood transfusion, vascular complications, acute kidney injury, hemodialysis requirement, symptom improvement, and repeat hospitalizations due to any cardiac disease. RESULTS: The cumulative six months incidence of all-cause mortality and cardiovascular mortality were similar between and NFLG-AS and NFHG-AS (4.32% vs. 5.17%, P = 0.71 and 2.47% vs. 2.59%, P = 0.94 respectively). There was no difference in the rates of stroke, myocardial infarction, duration of hospital stay, new-onset atrial fibrillation, temporary or permanent pacemaker requirement, major bleeding, blood transfusion, vascular complications, acute kidney injury, hemodialysis requirement, and symptom improvement between the two groups. However, patients with NFLG-AS compared to NFHG-AS had more frequent cardiac-related repeat hospitalizations (19.14% vs. 11.64%, P = 0.04%). CONCLUSION: There was no significant difference in all-cause mortality and cardiovascular mortality between NFLG-AS and NGHG-AS six months post-TAVI. However, patients undergoing TAVI with NFLG-AS had significantly higher rates of cardiac-related repeat hospitalizations.

Left Ventricular Unloading During Extracorporeal Life Support: Current Practice.

Venoarterial extracorporeal life support (VA-ECLS) is a powerful tool that can provide complete cardiopulmonary support for patients with refractory cardiogenic shock. However, VA-ECLS increases left ventricular (LV) afterload, resulting in greater myocardial oxygen demand, which can impair myocardial recovery and worsen pulmonary edema. These complications can be ameliorated by various LV venting strategies to unload the LV. Evidence suggests that LV venting improves outcomes in VA-ECLS, but there is a paucity of randomized trials to help guide optimal strategy and the timing of venting. In this review, we discuss the available evidence regarding LV venting in VA-ECLS, explain important hemodynamic principles involved, and propose a practical approach to LV venting in VA-ECLS.

Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions.

Vascular interventions result in the disruption of the tunica intima and the exposure of sub-endothelial matrix proteins. Nanoparticles designed to bind to these exposed matrices could provide targeted drug delivery systems aimed at inhibiting dysfunctional vascular remodeling and improving intervention outcomes. Here, we present the progress in the development of targeted liposomal nanocarriers designed for preferential collagen IV binding under simulated static vascular flow conditions. PEGylated liposomes (PLPs), previously established as effective delivery systems in vascular cells types, served as non-targeting controls. Collagen-targeting liposomes (CT-PLPs) were formed by conjugating established collagen-binding peptides to modified lipid heads via click chemistry (CTL), and inserting them at varying mol% either at the time of PLP assembly or via micellar transfer. All groups included fluorescently labeled lipid species for imaging and quantification. Liposomes were exposed to collagen IV matrices statically or via hemodynamic flow, and binding was measured via fluorometric analyses. CT-PLPs formed with 5 mol% CTL at the time of assembly demonstrated the highest binding affinity to collagen IV under static conditions, while maintaining a nanoparticle characterization profile of ~50 nm size and a homogeneity polydispersity index (PDI) of ~0.2 favorable for clinical translation. When liposomes were exposed to collagen matrices within a pressurized flow system, empirically defined CT-PLPs demonstrated significant binding at shear stresses mimetic of physiological through pathological conditions in both the venous and arterial architectures. Furthermore, when human saphenous vein explants were perfused with liposomes within a closed bioreactor system, CT-PLPs demonstrated significant ex vivo binding to diseased vascular tissue. Ongoing studies aim to further develop CT-PLPs for controlled targeting in a rodent model of vascular injury. The CT-PLP nanocarriers established here show promise as the framework for a spatially controlled delivery platform for future application in targeted vascular therapeutics.

Advances in the Formulation and Assembly of Non-Cationic Lipid Nanoparticles for the Medical Application of Gene Therapeutics.

Lipid nanoparticles have become increasingly popular delivery platforms in the field of gene therapy, but bench-to-bedside success has been limited. Many liposomal gene vectors are comprised of synthetic cationic lipids, which are associated with lipid-induced cytotoxicity and immunogenicity. Natural, non-cationic PEGylated liposomes (PLPs) demonstrate favorable biocompatibility profiles but are not considered viable gene delivery vehicles due to inefficient nucleic acid loading and reduced cellular uptake. PLPs can be modified with cell-penetrating peptides (CPPs) to enhance the intracellular delivery of liposomal cargo but encapsulate leakage upon CPP-PLP assembly is problematic. Here, we aimed to identify parameters that overcome these performance barriers by incorporating nucleic acid condensers during CPP-PLP assembly and screening variable ethanol injection parameters for optimization. CPP-PLPs were formed with R8-amphiphiles via pre-insertion, post-insertion and post-conjugation techniques and liposomes were characterized for size, surface charge, homogeneity, siRNA encapsulation efficiency and retention and cell associative properties. Herein we demonstrate that pre-insertion of stearylated R8 into PLPs is an efficient method to produce non-cationic CPP-PLPs and we provide additional assembly parameter specifications for a modified ethanol injection technique that is optimized for siRNA encapsulation/retention and enhanced cell association. This assembly technique could provide improved clinical translation of liposomal based gene therapy applications.

Histological Assessment of Wallerian Degeneration of the Rat Tibial Nerve Following Crush and Transection Injuries.

BACKGROUND: Wallerian degeneration (WD) following peripheral nerve injury (PNI) is an area of growing focus for pharmacological developments. Clinically, WD presents challenges in achieving full functional recovery following PNI, as prolonged denervation of distal tissues for an extended period of time can irreversibly destabilize sensory and motor targets with secondary tissue atrophy. Our objective is to improve upon histological assessments of WD. METHODS: Conventional methods utilize a qualitative system simply describing the presence or absence of WD in nerve fibers. We propose a three-category assessment that allows more quantification: A fibers appear normal, B fibers have moderate WD (altered axoplasm), and C fibers have extensive WD (myelin figures). Analysis was by light microscopy (LM) on semithin sections stained with toluidine blue in three rat tibial nerve lesion models (crush, partial transection, and complete transection) at 5 days postop and 5 mm distal to the injury site. The LM criteria were verified at the ultrastructural level. This early outcome measure was compared with the loss of extensor postural thrust and the absence of muscle atrophy. RESULTS: The results showed good to excellent internal consistency among counters, demonstrating a significant difference between the crush and transection lesion models. A significant decrease in fiber density in the injured nerves due to inflammation/edema was observed. The growth cones of regenerating axons were evident in the crush lesion group. CONCLUSION: The ABC method of histological assessment is a consistent and reliable method that will be useful to quantify the effects of different interventions on the WD process.

Effect of Graphene Nanoribbons (TexasPEG) on locomotor function recovery in a rat model of lumbar spinal cord transection.

A sharply transected spinal cord has been shown to be fused under the accelerating influence of membrane fusogens such as polyethylene glycol (PEG) (GEMINI protocol). Previous work provided evidence that this is in fact possible. Other fusogens might improve current results. In this study, we aimed to assess the effects of PEGylated graphene nanoribons (PEG-GNR, and called "TexasPEG" when prepared as 1wt% dispersion in PEG600) versus placebo (saline) on locomotor function recovery and cellular level in a rat model of spinal cord transection at lumbar segment 1 (L1) level. In vivo and in vitro experiments (n = 10 per experiment) were designed. In the in vivo experiment, all rats were submitted to full spinal cord transection at L1 level. Five weeks later, behavioral assessment was performed using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Immunohistochemical staining with neuron marker neurofilament 200 (NF200) antibody and astrocytic scar marker glial fibrillary acidic protein (GFAP) was also performed in the injured spinal cord. In the in vitro experiment, the effects of TexasPEG application for 72 hours on the neurite outgrowth of SH-SY5Y cells were observed under the inverted microscope. Results of both in vivo and in vitro experiments suggest that TexasPEG reduces the formation of glial scars, promotes the regeneration of neurites, and thereby contributes to the recovery of locomotor function of a rat model of spinal cord transfection.

Stimulation of abdominal and upper thoracic muscles with surface electrodes for respiration and cough: Acute studies in adult canines.

OBJECTIVE: To optimize maximal respiratory responses with surface stimulation over abdominal and upper thorax muscles and using a 12-Channel Neuroprosthetic Platform. METHODS: Following instrumentation, six anesthetized adult canines were hyperventilated sufficiently to produce respiratory apnea. Six abdominal tests optimized electrode arrangements and stimulation parameters using bipolar sets of 4.5 cm square electrodes. Tests in the upper thorax optimized electrode locations, and forelimb moment was limited to slight-to-moderate. During combined muscle stimulation tests, the upper thoracic was followed immediately by abdominal stimulation. Finally, a model of glottal closure for cough was conducted with the goal of increased peak expiratory flow. RESULTS: Optimized stimulation of abdominal muscles included three sets of bilateral surface electrodes located 4.5 cm dorsal to the lateral line and from the 8th intercostal space to caudal to the 13th rib, 80 or 100 mA current, and 50 Hz stimulation frequency. The maximal expired volume was 343 ± 23 ml (n=3). Optimized upper thorax stimulation included a single bilateral set of electrodes located over the 2nd interspace, 60 to 80 mA, and 50 Hz. The maximal inspired volume was 304 ± 54 ml (n=4). Sequential stimulation of the two muscles increased the volume to 600 ± 152 ml (n=2), and the glottal closure maneuver increased the flow. CONCLUSIONS: Studies in an adult canine model identified optimal surface stimulation methods for upper thorax and abdominal muscles to induce sufficient volumes for ventilation and cough. Further study with this neuroprosthetic platform is warranted.

Cactus Spine Wounds: A Case Report and Short Review of the Literature.

INTRODUCTION: Cactus plants are commonly seen in arid southwestern regions of the United States. Due to their ready availability, they have become a popular houseplant. The spines or glochidia can easily puncture the skin with only minor pressure (ie, bumping or touching the cactus). Removal of the offending spine is difficult, even with tweezers. CASE: An 18-year-old woman initially self-removed the spines, and marked discomfort and intense erythematous reaction developed within 8 to 10 hours. Patient presented to the emergency room at Mercy Hospital and Trauma Center (Janesville, Wisconsin), where spine removal was unsuccessful. RESULTS: Following emergency room discharge, she had difficulty walking from pain and swelling and was advised to use heat packs, take amoxicillin/clavulanic acid, and rest with her leg elevated for another 7 days along with using eye drops for eye irritation. The lesions slowly improved over the next several months. CONCLUSION: The case of multiple barrel cactus spine injuries with severe pain and swelling is presented herein as well as a review of the treatment options and complications of cactus spine injuries.