Cerebral Protection Research Articles

Minimally Invasive Access Hemiarch Replacement and Strategies of Cerebral Protection: Early Outcomes

In complex aortic surgery, median sternotomy is still the standard approach. Minimally invasive access techniques are being stablished across the globe. This study aimed to highlight strategies for cerebral protection during minimally invasive access hemiarch replacement surgery, while complementing the existing literature in the viability, safety, and equivalence to the standard approach.

Novel Approach to treating a COVID-19 positive patient with a Complex Arch and Descending Aneurysm and Dissection in whom open surgery is prohibitive.

Ascending aortic and arch aneurysms are a challenging group of pathologies for surgeons. These typically require a complex open repair, including hypothermic circulatory arrest and carry a high peri-operative risk. Outcomes are best when performed in centers with significant experience and expertise. Many patients, because of co-morbidities, are at a prohibitive risk for these open surgeries. Thoracic endovascular aortic repair (TEVAR) has become the preferred treatment of most acute descending thoracic aortic pathologies.[1] However, these require strict anatomic criteria to be successful and are usually confined to the distal arch and descending thoracic aorta. There are no commercially available endovascular devices in the United States to treat this patient population with ascending or proximal arch aneurysms or dissections, especially in an urgent or emergent setting, whose anatomy does not meet criteria for standard TEVAR. We present a novel endovascular approach, including a cerebral protection strategy, to treat a complex arch aneurysm and dissection in a patient who was not a candidate for an open repair.

Frozen elephant trunk technique for aortic arch surgery: the Bordeaux University Hospital experience with Thoraflex hybrid prosthesis.

Aortic arch surgery still represents a challenge, and the frozen elephant trunk (FET) allows a one-step surgery for complex aortic diseases. The aim of the study was to analyze the results of patients undergoing FET procedure for aortic arch surgery at Bordeaux University Hospital. Patients undergoing FET procedure for multisegmented aortic arch pathologies were analyzed in this single-center retrospective study. Further subgroup analyses were performed according to the degree of urgency of the operation (elective versus emergent surgery) and cerebral protection technique: bilateral selective antegrade cerebral perfusion (B-SACP) versus the unilateral one (U-SACP), regardless of the degree of urgency. From August 2018 to August 2022, 77 consecutive patients (64.1±9.9 years, 54 males) were enrolled: 43 (55.8%) for elective surgery and 34 (44.2%) in emergency. Technical success was 100%. 30-day mortality was 15.6% (N.=12, 7% elective vs. 26.5% emergent, P=0.043). Six (7.8%) non-disabling strokes occurred (1.9% B-SACP vs. 20% U-SACP, P=0.021). Median follow-up was 1.11 years (interquartile range, 0.62-2.07). The 1-year overall survival was 81.6±4.45%. The elective group showed a survival trend when compared to the emergency one (P=0.054). However, further examination at landmark analysis elective surgery showed a better survival trend compared to emergency surgery up to 1.78 years (P=0.034), after which significance was lost (P=0.521). Thoraflex hybrid prosthesis for FET technique demonstrated feasibility and satisfactory short-term clinical outcomes, even in emergent settings. In our practice B-SACP seems to offer better protection and less neurological complications compared to U-SACP, nevertheless further analyses are warranted.

The Association of the Cerebral Protection Strategy with Early Mortality and Postoperative Stroke in Acute Type A Aortic Dissection: A Systematic Review and Meta-Analysis

Objective. The optimal cerebral protection strategy in acute type A aortic dissection (ATAAD) is still without a clear consensus. The purpose of this meta-analysis was to compare the outcome of different cerebral protection strategies on ATAAD patients. Materials and Methods. We conducted a systematic review including all studies concerning surgically managed ATAAD patients between 1.1.2010 and 28.2.2022 and reporting the use of cerebral protection strategies in three large databases (Pubmed, Cochrane library, and Scopus). The main outcome events were 30-day mortality and a postoperative stroke rate. The pooled event rates adjusted by age, gender, CPB duration, circulatory arrest duration, and total arch reconstruction rate were calculated. Results. Overall, 39 articles were included covering a total of 16, 876 ATAAD patients. The estimated adjusted pooled early mortality rate was 10.1% (95% confidence interval [CI] 9.1–11.3%) in the ACP group, 15.9% (13.3–18.9%) in the RCP group, and 11.6% (9.2–14.5%) in the HCA group. Compared to the RCP group, ACP and HCA demonstrated lower early mortality (RCP vs. ACP odds-ratio 1.66 [1.28–2.15],p < 0.001; RCP vs. HCA odds-ratio 1.45 [1.02–2.07],p = 0.039). The adjusted pooled stroke rate was 9.0% (8.3–9.8%) in the ACP group, 10.5% (9.3–11.7%) in the RCP group, and 9.1% (8.1–10.2%) in the HCA group. Conclusion. Early mortality might be more common in ATAAD patients treated with RCP compared to ACP and HCA. With regards to postoperative stroke, the results were inconclusive despite the trending inferiority of RCP compared to the other strategies.

Cerebral embolic protection during transcatheter aortic valve replacement: Insights from a consecutive series with the Sentinel cerebral protection device.

Growing interest in neuroprotection in transcatheter aortic valve replacement (TAVR) has catalyzed the development of cerebral protection systems (CPS). Report insights from consecutive real-world patients undergoing TAVR with the Sentinel-CPS. Patients with severe aortic stenosis undergoing TAVR from April 2019 to May 2022 were enrolled in a prospective registry. The reason for unsuccessful Sentinel-CPS deployment and the amount of debris captured by the filters were prospectively recorded. The Sentinal CPS was successfully deployed in 330 patients (85%, Group 1). Deployment was not attempted, unsuccessful or only partially successful in 59 patients (15%, Group 2), caused by anatomical factors such as tortuosity, heavy calcification or small dimensions of radial or brachial artery in 46, technical aspects such as puncture failure or dissection in 5 or use of right radial access for the pigtail in 6. Debris was captured in 98% of patients in Group 1. In 40%, the amount of debris was graded moderate or extensive. Predictors for moderate/extensive debris were moderate/severe aortic calcification (OR 1.50, CI 1.05-2.15, p = 0.03), pre- and postdilatation (OR 1.97, CI 1.02-3.79, p = 0.04 and OR 1.71, CI 1.01-2.89, p = 0.048). The risk of stroke was numerically lower in patients who underwent TAVR with the Sentinel CPS (2.1 vs. 5.1%, respectively, p = 0.15). There was no stroke during CPS deployment, but one patient had a stroke immediately after device retrieval. The Sentinel-CPS was successfully deployed in 85% of patients. Predictors for moderate/extensive debris captured were moderate/severe aortic calcification, pre- and postdilatation.

Assessing for Regional Variation in Carotid Artery Stenting Outcomes—The Influence of Age and Cerebral Protection Modality

Assessing for Regional Variation in Carotid Artery Stenting Outcomes—The Influence of Age and Cerebral Protection Modality

Improving outcomes of surgery for acute type A aortic dissection

Background. It remains equivocal if acute type A aortic dissection (ATAAD) surgical outcomes are improving. We analyzed current outcome trends to evaluate improvements and to identify predicting variables. Methods. From 2015 to 2020, 204 patients underwent surgery for ATAAD and were divided into recent (n = 102) and earlier (n = 102) groups. Uni- and multivariable statistical analysis was performed to identify predictors of 30-day mortality. Results. Thirty-day mortality decreased significantly in the recent group (3.9% vs 14.6%, p = .014). Prevalence of neurological insult also decreased significantly (13% vs 25%, p = .028). Other major complications remained unchanged. There was no statistically significant difference in overall 30-day mortality between low-volume vs high-volume surgeons (12.3% vs 7.3%, p = .21). The number of surgeons performing ATAAD procedures decreased from nine in 2015 to five in 2020. Preoperative lactate (OR 1.24, 95%CI 1.03–1.51), dissection of any arch vessel (OR 14.2, 95%CI 1.79–113), non-normal left ventricular ejection fraction (OR 12.5, 95%CI 2.54–61.6), biological composite graft (OR 19.1, 95%CI 2.75–133), concomitant coronary artery bypass grafting (OR 38.8, 95%CI 2.91–517) and intraoperative adverse event (OR 9.5, 95%CI 2.22–40.9) were statistically significant independent predictors of mortality. Conclusions. Early outcomes after ATAAD improved in the most recent experience. Part of the explanation may be fewer surgeons performing more procedures annually, a relatively conservative approach to the extent of aortic resection and ensuring adequate cerebral protection. Major complications remain prevalent and require attention to be further reduced.

P115 "WHEN THE GOING GETS TOUGH, THE TOUGH GET GOING": LARGE THROMBOSIS ASPIRATION DURING PERCUTANEOUS APPENDAGE OCCLUSION

Abstract Background An 83–year–old woman with permanent atrial fibrillation was referred for percutaneous left atrial appendage closure (LAAC) following a spontaneous intracranial hemorrhage caused by pituitary macroadenomas that the patient refused to excise. Pre–procedural EET revealed no formed thrombus. Intravenous unfractionated heparin (UFH) was administered. After multiple attempts, the device (Amplatzer Amulet) was correctly positioned but before final release, a large thrombus was noted within the left atrium, attached to delivery system. A further 4000 IU of UFH and 300 mg of salicylic acid were administrated, and a subsequent 300 s activated clotting time was recorded. Under continuous negative pressure in the delivery sheath via a 50 mL Luer–Lock syringe, suction of the thrombus was performed. Similarly, the device was released and the delivery system withdrawn into the delivery sheath and removed. Final EET revealed no residual thrombus within the left atrium with adequate device compression and no peri–device leaks. No further aspiration through the sheath was possible, indicating successful thrombus retrieval into the delivery sheath. Discussion Device–related thrombus (DRT) is a possible and terrible complication of percutaneous LAAC due to patient–specific (hypercoagulability disorders, renal insufficiency, nonparoxysmal AF) and/or procedural factors (LAAO depth of implantation >10 mm from the pulmonary vein limbus, pericardial effusion). For this patient, potential causes could be both the long intervention time required for correct positioning of the device and non–optimal pre interventional medical therapy and procedural options included either recapturing the device into the delivery sheath and abandoning the procedure or surgical thrombectomy. Both options would increase the risk of clot dislodgement and embolization. An off–label device deployment under continuous negative pressure was performed reducing embolic risk by minimizing both mechanical forces on the thrombus as well as procedural time. Conclusion Therefore, shorter procedural times and optimized preoperative medical therapy could reduce DRT risk. The evidence for the use of cerebral protection devices in the setting of LAAO insertion is limited to a small single case series. Randomized multicentric studies are necessary to approve routine use of these devices when the patient is deemed to be at high risk of thromboembolism based on clinical or intraprocedural factors.

Cerebral Perfusion and Neuromonitoring during Complex Aortic Arch Surgery: A Narrative Review.

Complex ascending and aortic arch surgery requires the implementation of different cerebral protection strategies to avoid or limit the probability of intraoperative brain damage during circulatory arrest. The etiology of the damage is multifactorial, involving cerebral embolism, hypoperfusion, hypoxia and inflammatory response. These protective strategies include the use of deep or moderate hypothermia to reduce the cerebral oxygen consumption, allowing the toleration of a variable period of absence of cerebral blood flow, and the use of different cerebral perfusion techniques, both anterograde and retrograde, on top of hypothermia, to avoid any period of intraoperative brain ischemia. In this narrative review, the pathophysiology of cerebral damage during aortic surgery is described. The different options for brain protection, including hypothermia, anterograde or retrograde cerebral perfusion, are also analyzed, with a critical review of the advantages and limitations under a technical point of view. Finally, the current systems of intraoperative brain monitoring are also discussed.

E-41 | Role of Cerebral Embolic Protection With Transcatheter Aortic Valve Replacement: An Updated Meta-Analysis of Randomized Controlled Trials

The role of cerebral embolic protection (CEP) in patients undergoing transcatheter aortic valve replacement (TAVR remains a topic of debate despite multiple randomized controlled trials (RCTs). Recently, the PROTECTED TAVR trial was published. The current meta-analysis aimed to aggregate RCTs that examined all available forms of CEP devices to date. PubMed, Cochrane Central, and EMBASE were searched for RCTs comparing CEP versus no CEP in patients undergoing TAVR. The primary outcome was 30-day stroke. The secondary outcome was 30-day all-cause mortality. Search and reporting were according to PRISMA guidelines. Random effects model with DL tau estimator were used for pooled effect. Heterogeneity was assessed using I2 test. All analyses were performed by R studio. Six studies with a total of 3621 patients (CEP n= 1874, no CEP n= 1747) met our inclusion criteria (mean age 79.5 years, 58.6% male, average STS score 3.76). CEP was not associated with a significant reduction of stroke at 30 days (Relative risk RR: 0.75; 95% CI: 0.52, 1.08; P= 0.12; Absolute Risk Difference ARD: -0.75%; 95% CI: -1.8%, 0.3%). No difference in 30-day all-cause mortality with CEP vs no CEP use, RR: 0.93; 95% CI: 0.41, 2.11; P= 0.86. No change in pooled estimate when limiting analysis to trials that utilized Sentinel device. In this meta-analysis of all RCTs to date, use of CEP devices in patients undergoing TAVR was not associated with a significant reduction in 30-day stroke or all-cause mortality.

CE-454611-3 HIGH RISK LEFT ATRIAL APPENDAGE CLOSURE IN PATIENTS WITH A PERSISTENT LEFT ATRIAL APPENDAGE THROMBUS

Left atrial appendage closure (LAAC) in patients with a persistent left atrial appendage (LAA) thrombus is controversial. To introduce a novel utilization of a cerebral protection device during high risk LAAC in patients with a persistent LAA thrombus. N/A Case 1: A 50-year-old male with persistent atrial fibrillation (AF) and remote left ventricular thrombus with a thromboembolic stroke presented for an AF ablation. He was found to have a persistent LAA thrombus on multiple pre-operative CT scans despite changing anticoagulation regimen with rivaroxaban and subsequently warfarin with aspirin. The ablation was aborted. He underwent LAAC (Watchman FLXTM, Boston Scientific) with the cerebral protection device (SentinelTM, Boston Scientific) in place. The transesophageal echocardiogram during the procedure confirmed persistent LAA thrombus (Figure A). At the end of the procedure, embolic debris were identified within the SentinelTM (Figure B). The patient was discharged with no neurologic symptoms at the time of discharge and remains neurologically intact 10 months post procedure. Case 2: A 68-year-old female with persistent AF on a therapeutic warfarin dose presented for an AF ablation. She was noted to have a LAA thrombus on the pre-operative CT scan and the procedure was aborted. Her anticoagulation was switched to apixaban. A repeat CT revealed no change in LAA thrombus, and more aggressive anticoagulation was limited by hematuria. Therefore, she underwent LAAC with the SentinelTM for cerebral protection. Of note, the intraoperative TEE revealed filamentous LAA thrombus (Figure C). The patient tolerated the procedure well and was safely discharged the following day. She had no post-operative changes in her neurologic status and the Watchman FLXTM on routine TEE remained in stable position (Figure D). The presence of LAA thrombus is a common concern in patients referred for LAAC. While classically avoided, this case series suggests that a thrombus being present is not a contraindication for LAAC. A cerebral protection device may be used to prevent cardioembolic stroke in selected patients with a persistent LAA thrombus. Further studies are needed to determine the safety and efficacy of this strategy.

Bespoke Implants for Cranial Reconstructions: Preoperative to Postoperative Surgery Management System.

Traumatic brain injury is a leading cause of death and disability worldwide, with nearly 90% of the deaths coming from low- and middle-income countries. Severe cases of brain injury often require a craniectomy, succeeded by cranioplasty surgery to restore the integrity of the skull for both cerebral protection and cosmetic purposes. The current paper proposes a study on developing and implementing an integrative surgery management system for cranial reconstructions using bespoke implants as an accessible and cost-effective solution. Bespoke cranial implants were designed for three patients and subsequent cranioplasties were performed. Overall dimensional accuracy was evaluated on all three axes and surface roughness was measured with a minimum value of 2.209 μm for Ra on the convex and concave surfaces of the 3D-printed prototype implants. Improvements in patient compliance and quality of life were reported in postoperative evaluations of all patients involved in the study. No complications were registered from both short-term and long-term monitoring. Material and processing costs were lower compared to a metal 3D-printed implants through the usage of readily available tools and materials, such as standardized and regulated bone cement materials, for the manufacturing of the final bespoke cranial implants. Intraoperative times were reduced through the pre-planning management stages, leading to a better implant fit and overall patient satisfaction.

Ageing and Insulin: Inter Alia Diabetes, Obesity and Fitness Concerns

This article argues the essence of insulin sensitivity versus secretion including insulin resistance in the clinical strategy for the treatment, lifestyle changes, prompt interventions and control of diabetes. Progressive decline of glucose tolerance as advanced age occurs has been associated with the pathogenesis of type 2 diabetes due to peripheral insulin resistance and impaired β cell function. In elderly persons, insulin secretion is deranged concomitantly with decreased insulin clearance rate and augmented circulating proinsulin level that ostensibly explicates age-related hyperglycemia. Insulin is associated with numerous pathophysiological processes exhibited during brain function in learning and memory, as well as the regulation of ageing, metabolic syndrome, obesity, diabetes and cardiovascular diseases in Man. Elevated chronic peripheral insulin, decreased insulin action and brain insulin contents are pathognomonic of the insulin resistance syndrome. All these are associated through specific mechanisms in the pathophysiology of ageing and insulin in concert with risk factors and the concomitant complications. Ostensibly, progressive excess insulin induces synchronous elevated levels of oxidative stress and inflammatory impacts which exacerbate or are exacerbated by advancing age, culminating as inimical consequences to healthy lifestyles, longevity or extended lifespan. Therapeutics and other healthcare measures may be beneficial in order to prevent, mitigate or amend insulin aberrations in the elderly and during the ageing process. The mainstay in managing an elderly patient with perturbed insulin action, is control of therapeutic application, as it can reverse acute terminal states. Treatment necessitates stringent and thorough expertise, knowledge and skills for optimum provision and effective cerebral, cardiovascular and skeletal protection for a healthier lifespan and longevity. This article will be of immense contribution in the understanding of the prevention, control and treatment of insulin resistance, metabolic syndrome, diabetes, obesity, cardiovascular and neurological disorders during ageing.

Epimedium Aqueous Extract Ameliorates Cerebral Ischemia/Reperfusion Injury through Inhibiting ROS/NLRP3-Mediated Pyroptosis.

Cerebral ischemia/reperfusion causes exacerbated neuronal damage involving excessive neuroinflammation and oxidative stress. ROS is considered a signal molecule to activate NLRP3; thus, the ROS/NLRP3/pyroptosis axis plays a vital role in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI). Therefore, targeting the inhibition of the ROS/NLRP3/pyroptosis axis may be a promising therapeutic tactic for CIRI. Epimedium (EP) contains many active ingredients (ICA, ICS II, and ICT), which have a wide range of pharmacological activities. However, whether EP can protect against CIRI remains unknown. Thus, in this study, we designed to investigate the effect and possible underlying mechanism of EP on CIRI. The results showed that treatment with EP dramatically mitigated brain damage in rats following CIRI, which was achieved by suppressing mitochondrial oxidative stress and neuroinflammation. Furthermore, we identified the ROS/NLRP3/pyroptosis axis as a vital process and NLRP3 as a vital target in EP-mediated protection. Most interestingly, the main compounds of EP directly bonded with NLRP3, as reflected by molecular docking, which indicated that NLRP3 might be a promising therapeutic target for EP-elicited cerebral protection. In conclusion, our findings illustrate that ICS II protects against neuron loss and neuroinflammation after CIRI by inhibiting ROS/NLRP3-mediated pyroptosis.

The dosage of thiopental as pharmacological cerebral protection during non-shunt carotid endarterectomy: A retrospective study

Background: Thiopental has been used as a pharmacological cerebral protection strategy during carotid endarterectomy surgeries. However, the optimal dosage required to induce burst suppression on the electroencephalogram (EEG) remains unknown. This retrospective study aimed to determine the optimal dosage of thiopental required to induce burst suppression during non-shunt carotid endarterectomy. Methods: The Neurological Institute of Thailand Review Board approved the study. Data were collected from 2009 to 2019 for all non-shunt carotid endarterectomy patients who received thiopental for pharmacological cerebral protection and had intraoperative EEG monitoring. Demographic information, carotid stenosis severity, intraoperative EEG parameters, thiopental dosage, carotid clamp time, intraoperative events, and patient outcomes were abstracted. Results: The study included 57 patients. Among them, 24 patients (42%) achieved EEG burst suppression pattern with a thiopental dosage of 26.3+10.1 mg/kg/hr. There were no significant differences in perioperative events between patients who achieved burst suppression and those who did not. After surgery, 33.3% of patients who achieved burst suppression were extubated and awakened. One patient in the non-burst suppression group experienced mild neurological deficits. No deaths occurred within one month postoperative. Conclusions: The optimal dosage of thiopental required to achieve burst suppression on intraoperative EEG during non-shunt carotid endarterectomy was 26.3+10.1 mg/kg/hr.

An Updated Meta-Analysis on Cerebral Embolic Protection in Patients Undergoing Transcatheter Aortic Valve Intervention Stratified by Baseline Surgical Risk and Device Type

BackgroundTranscatheter aortic valve intervention (TAVI) can lead to the embolization of debris. Capturing the debris by cerebral embolic protection (CEP) devices may reduce the risk of stroke. New evidence has allowed us to examine the effects of CEP in patients undergoing TAVI. We aimed to assess the effects of CEP overall and stratified by the device used (SENTINEL or TriGuard) and the surgical risk of the patients. MethodsWe selected randomized controlled trials using electronic databases through September 17, 2022. We estimated random-effects risk ratios (RR) with (95% confidence interval) and calculated absolute risk differences at 30 days across baseline surgical risks derived from the TAVI trials for any stroke (disabling and nondisabling) and all-cause mortality. ResultsAmong 6 trials (n = 3921), CEP vs. control did not reduce any stroke [RR: 0.95 (0.50-1.81)], disabling [RR: 0.75 (0.18-3.16)] or nondisabling [RR: 0.99 (0.65-1.49)] strokes, or all-cause mortality [RR: 1.23 (0.55-2.77)]. However, when analyzed by device, SENTINEL reduced disabling stroke [RR: 0.46 (0.22-0.95)], translating into 6 fewer per 1000 in high-risk, 3 fewer per 1000 in intermediate-risk, and 1 fewer per 1000 in low surgical-risk patients. CEP vs. control did not reduce the risk of any bleeding [RR: 1.03 (0.44-2.40)], major vascular complications [RR: 1.41 (0.57-3.48)], or acute kidney injury [RR: 1.36 (0.57-3.28)]. ConclusionsThis updated meta-analysis showed that SENTINEL CEP might reduce disabling stroke in patients undergoing TAVI. Patients with high and intermediate surgical risks were most likely to derive benefits.

470 Robotic Transcranial Doppler With Artificial Intelligence for Real-Time Intraoperative Neuromonitoring During Endovascular Carotid Revascularization – A Novel and Autonomous Neuromonitoring Tool

INTRODUCTION: Real-time intraoperative neuromonitoring is crucial to account for cerebral blood flow and embolic protection offered by proximal and distal cerebral protection devices during carotid revascularization procedures. METHODS: All patients diagnosed with high-grade carotid stenosis were prospectively enrolled between October 2021 thru February 2022. The TCD Robot head-brace system was used to secure the patients head, and the robot calibrated to automatically identify ipsilateral MCA or the terminal ICA. Patient demographics and procedural characteristics relevant to the robotic system such as signal strength, time to find signal, intracranial depth of the relevant vessel, cerebral waveform, and emboli count were recorded for the 4 critical phases: i- Access to crossing the lesion, ii- Filter and balloon deployment, iii- Stent placement and implantation, and iv- Removal of delivery system. RESULTS: Eight patients were included in our study (6 males [75%]; mean age 71.5 ± 3.9). Six out of 8 patients were symptomatic with a mean diameter stenosis of 83.5 ± 4.1. Average time taken to find a stable signal was 62 seconds (Range: 10-122). Terminal ICA was the vessel identified in all cases with a mean depth of 64mm (Range: 59-71). Flow arrest was demonstrated in all cases with flow reversal demonstrated in 2. Mean duration for the TCD Robotic surveillance was 23.6 ± 0.9 minutes with an average of 117 distal emboli (Range: 45-143) recorded by the device. Linear regression model identified stent placement and implantation as statistically significant (P = 0.0419) contributor to the final emboli count. CONCLUSIONS: To our knowledge, this is the first case series of real-time comprehensive neuromonitoring using a Robotic Transcranial Doppler system with Artificial Intelligence demonstrating various cerebral blood flow parameters including flow arrest and distal embolic incidence intra-operatively.

Low doses of pharmaceutical formulations loaded with UFMG-V4N2 immunogen induce the production of IgG anti-cocaine antibodies and provide evidence of cerebral protection in the preclinical model

Anti-cocaine vaccines are a promising therapeutic strategy for treating cocaine use disorders. Here we hypothesize that nanoemulsions (NE) or suspensions (SS) loaded with the calix [4]arene-based immunogen UFMG-V4N2 can induce the production of anti-cocaine antibodies and decrease the passage of radiolabeled cocaine analog [99mTc]Trodat-1 through of the brain barrier. UFMG-V4N2 was characterized (solubility, morphology, DSC, XRD) and loaded into NEs and SSs using excipients approved for human use. Immunogenic efficacy was assessed by quantifying the titers and determining the specificity of anti-cocaine IgG antibodies, and by assessing the inhibition of [99mTc]Trodat-1 trafficking across the mice brain-barrier. UFMG-V4N2 is an amorphous, thermally stable molecule with very low hydrophilicity. The immunogenicity of NE or SS was similar, but aluminum phosphate and the lower dose of UFMG-V4N2 induced higher anti-cocaine IgG antibody titers, minimizing [99mTc]Trodat-1 uptake in the brain. Therefore, the UFMG-V4N2 may represent an alternative for the treatment of cocaine use disorder.

Cerebral Embolic Protection Devices: Current State of the Art.

Transcatheter aortic valve replacement (TAVR) has become a first-line treatment for severe aortic stenosis with intermediate to high-risk population with its use increasingly expanding into younger and low-risk cohorts as well. Cerebrovascular events are one of the most serious consequential complications of TAVR, which increase morbidity and mortality. The most probable origin of such neurological events is embolic in nature and the majority occur in the acute phase after TAVR when embolic events are most frequent. Cerebral embolic protection devices have been designed to capture or deflect these emboli, reducing the risk of peri-procedural ischaemic events. They also carry the potential to diminish the burden of new silent ischemic lesions during TAVR. Our review explores different types of these device systems, their rationale, and the established clinical data.

Cerebral Protection Strategies and Stroke in Surgery for Acute Type A Aortic Dissection.

Perioperative stroke remains a devastating complication in the operative treatment of acute type A aortic dissection. To reduce the risk of perioperative stroke, different perfusion techniques can be applied. A consensus on the preferred cerebral protection strategy does not exist. To provide an overview about the different cerebral protection strategies, literature research on Medline/PubMed was performed. All available original articles reporting on cerebral protection in surgery for acute type A aortic dissection and neurologic outcomes since 2010 were included. Antegrade and retrograde cerebral perfusion may provide similar neurological outcomes while outperforming deep hypothermic circulatory arrest. The choice of arterial cannulation site and chosen level of hypothermia are influencing factors for perioperative stroke. Deep hypothermic circulatory arrest is not recommended as the sole cerebral protection technique. Antegrade and retrograde cerebral perfusion are today's standard to provide cerebral protection during aortic surgery. Bilateral antegrade cerebral perfusion potentially leads to superior outcomes during prolonged circulatory arrest times between 30 and 50 min. Arterial cannulation sites with antegrade perfusion (axillary, central or carotid artery) in combination with moderate hypothermia seem to be advantageous. Every concept should be complemented by adequate intraoperative neuromonitoring.