Cerebral Protection Research Articles

Brain protective effect of dexmedetomidine vs propofol for sedation during prolonged mechanical ventilation in non-brain injured patients.

Dexmedetomidine and propofol are two sedatives used for long-term sedation. It remains unclear whether dexmedetomidine provides superior cerebral protection for patients undergoing long-term mechanical ventilation. To compare the neuroprotective effects of dexmedetomidine and propofol for sedation during prolonged mechanical ventilation in patients without brain injury. Patients who underwent mechanical ventilation for > 72 h were randomly assigned to receive sedation with dexmedetomidine or propofol. The Richmond Agitation and Sedation Scale (RASS) was used to evaluate sedation effects, with a target range of -3 to 0. The primary outcomes were serum levels of S100-β and neuron-specific enolase (NSE) every 24 h. The secondary outcomes were remifentanil dosage, the proportion of patients requiring rescue sedation, and the time and frequency of RASS scores within the target range. A total of 52 and 63 patients were allocated to the dexmedetomidine group and propofol group, respectively. Baseline data were comparable between groups. No significant differences were identified between groups within the median duration of study drug infusion [52.0 (IQR: 36.0-73.5) h vs 53.0 (IQR: 37.0-72.0) h, P = 0.958], the median dose of remifentanil [4.5 (IQR: 4.0-5.0) μg/kg/h vs 4.6 (IQR: 4.0-5.0) μg/kg/h, P = 0.395], the median percentage of time in the target RASS range without rescue sedation [85.6% (IQR: 65.8%-96.6%) vs 86.7% (IQR: 72.3%-95.3), P = 0.592], and the median frequency within the target RASS range without rescue sedation [72.2% (60.8%-91.7%) vs 73.3% (60.0%-100.0%), P = 0.880]. The proportion of patients in the dexmedetomidine group who required rescue sedation was higher than in the propofol group with statistical significance (69.2% vs 50.8%, P = 0.045). Serum S100-β and NSE levels in the propofol group were higher than in the dexmedetomidine group with statistical significance during the first six and five days of mechanical ventilation, respectively (all P < 0.05). Dexmedetomidine demonstrated stronger protective effects on the brain compared to propofol for long-term mechanical ventilation in patients without brain injury.

Left Atrial Appendage Closure in Patients With a Mechanical Mitral Valve Prosthesis: A Multicentre Italian Pilot Study

BackgroundIn patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy and therapeutic international normalized ratio (INR) range, the incidence of cardiac thromboembolism is not negligible, and the subgroup of patients who have a mechanical prosthetic mitral valve (PMV) has the highest risk. We aimed to assess the long-term effects of left atrial appendage closure (LAAC) in AF patients with a mechanical PMV who experienced a failure of VKA therapy. MethodsIn this retrospective, multicentre study, patients underwent LAAC because of thrombotic events including transient ischemic attack and/or stroke, systemic embolism, and evidence of left atrial appendage thrombosis and/or sludge, despite VKA therapy, were enrolled. Patients with a mechanical PMV were included and compared with those affected by nonvalvular AF. The primary endpoint was the composite of all-cause death, major cardiovascular events, and major bleedings at follow-up. The feasibility and safety of LAAC also were assessed. ResultsA total of 55 patients (42% female; mean age, 70 ± 9 years), including 12 with a mechanical PMV, were enrolled. The most-frequent indication to LAAC (71%) was LAA thrombosis or sludge. Procedural success was achieved in 96% of overall cases, and in 100% of patients with a PMV. In 35 patients, a cerebral protection device was used. During a median follow-up of 6.1 ± 4.3 years, 4 patients with a PMV, and 20 patients without a PMV, reported adverse events (hazard ratio 0.73 [95% confidence interval 0.25-2.16, P = 0.564]). ConclusionsLAAC seems to be a valuable alternative in patients with AF who have a mechanical PMV, with failure of VKA therapy. This off-label, real-world clinical practice indication deserves validation in further studies.

Cerebral Embolic Protection Devices for Transcatheter Aortic Valve Replacement: Review of the Literature and Future Perspectives.

Transcatheter aortic valve replacement (TAVR) has been a revolutionary therapy in the treatment of aortic valve stenosis. The risk of stroke associated with TAVR has decreased significantly since its introduction; however, it remains a devastating complication when it does occur. Many of the strokes associated with TAVR occur peri-procedurally and are thought to be due to embolic debris entering the cerebrovascular circulation. A number of different cerebral embolic protection devices (CEPD) have been developed and are in various stages of testing and use. The results from clinical trials evaluating the role for CEPD to reduce the risk of stroke have been mixed. As a result, their uptake has been very heterogeneous. This review provides a summary of the diverse CEPD devices available for use and outlines the clinical evidence available to date.

Suppression of microRNA-320 Induces Cerebral Protection Against Ischemia/Reperfusion Injury by Targeting HMGB1/NF-kappaB Axis.

MicroRNAs have been shown to potentially function in cerebral ischemia/reperfusion (IR) injury. This study aimed to examine the expression of microRNA-320 (miR-320) in cerebral IR injury and its involvement in cerebral mitochondrial function, oxidative stress, and inflammatory responses by targeting the HMGB1/NF-kappaB axis. Sprague-Dawley rats were subjected to middle cerebral artery occlusion to simulate cerebral IR injury. The cerebral expression of miR-320 was assessed using qRT-PCR. Neurological function, cerebral infarct volume, mitochondrial function, oxidative stress, and inflammatory cytokines were evaluated using relevant methods, including staining, fluorometry, and ELISA. HMGB1 expression was analyzed through Western blotting. The levels of miR-320, HMGB1, neurological deficits, and cerebral infarction were significantly higher after IR induction. Intracerebral overexpression of miR-320 resulted in substantial neurological deficits, increased infarct volume, elevated levels of 8-isoprostane, NF-kappaBp65, TNF-alpha, IL-1beta, ICAM-1, VCAM-1, and HMGB1 expression. It also promoted the loss of mitochondrial membrane potential and ROS levels while reducing MnSOD and GSH levels. Downregulation of miR-320 and inhibition of HMGB1 activity significantly reversed the outcomes of cerebral IR injury. MiR-320 plays a negative role in regulating cerebral inflammatory/oxidative reactions induced by IR injury by enhancing HMGB1 activity and modulating mitochondrial function.

Examining the Role of Cerebral Embolic Protection Devices in Preventing Postoperative Stroke in Patients with a History of Stroke or Transient Ischemic: Insights from the National Inpatient Sample.

Cerebral embolic protection devices (CEPD) during transcatheter aortic valve replacement (TAVR) have been shown to lower the risk of stroke during the procedure. However, their long-term and clinical effects on neuro-cognition are unknown. Therefore, we hypothesized the benefit of CEPD in TAVR patients with a prior history of stroke or transient ischemic attack (TIA). National Inpatient Sample (2019) and International Classification of Diseases, 10th Revision codes were used to identify patients undergoing TAVR with prior stroke or TIA. Propensity-matched analysis was performed to adjust for baseline characteristics and comorbidities. Primary outcome measures were postoperative stroke and all-cause mortality. Length of stay and hospital cost were secondary outcomes. Of 8450 unmatched TAVR patients with prior stroke or TIA in 2019, 1095 (13%) utilized CEPD. After propensity matching previous myocardial infarction (MI), coronary artery bypass grafting, and drug abuse were higher in the TAVR-only cohort. Postoperative stroke rate (1.4% vs 2.2%; P = 0.081) and odds [adjusted odds ratio (aOR), 0.48; 95% confidence interval (CI), 0.11-2.17; P = 0.341] were lower in the CEPD group. There was no difference in all-cause in-hospital mortality between the 2 groups (0.9% vs 1.0%). Length of stay (3 vs 2 days, P <0.001) and hospital expenditure ($172,711 vs $162,284; P = 0.002) were higher for the TAVR-only cohort. CEPD in TAVR patients with prior stroke or TIA did not show statistically significant postoperative stroke benefits. However, further larger-scale prospective studies are needed to evaluate the long-term neurocognitive benefits of CEPD in these patients. As the use of TAVR continues to expand, optimizing peri-procedural strategies such as the use of CEPD remains a critical area of research to improve patient outcomes.

Uncommon Carotid Artery Stenting Complications: A Series by Images.

To describe through emblematic images rare but clinically relevant carotid artery stenting complications that occurred at two high-volume centres for carotid artery stenting (CAS). CAS is an alternative to carotid endarterectomy (CEA) for the treatment of carotid artery stenosis in patients judged to be at high risk for CEA. CAS complications range between 1 and 9% and are higher in older patients complaining of neurological symptoms at the time of presentation. Besides periprocedural or early-after-procedure stroke, which remains the true Achilles' heel of CAS, other dramatic complications might compromise the clinical outcomes of this procedure. Five infrequent complications, out of more than 1000 CAS performed in the years 2016-2021, have been described. Among CAS complications, acute carotid stent thrombosis, rescue retrieval of a disconnected distal cerebral embolic protection device, plaque prolapse after carotid stenting, cerebral hyperperfusion syndrome (CHS), and radial artery long sheath entrapment requiring surgical intervention were found to account for 0.3% of the total number of procedures performed by operators with high CAS volume. Unusual CAS complications may infrequently occur, even in hands of expert operators. To know how to deal with such complications might help interventionalists to improve CAS performance.

The efficacy of different types of cerebral embolic protection device during transcatheter aortic valve implantation: a meta-analysis.

Perioperative stroke remains a devastating complication after transcatheter aortic valve implantation (TAVI), and using a cerebral embolic protection device (CEPD) during TAVI may reduce the occurrence of stroke according to some studies. Therefore, we conducted this meta-analysis to determine whether CEPD should be routinely used during TAVI. The inclusion criteria for this study were randomized controlled trials (RCTs) that examined the outcome of stroke with or without CEPD during TAVI, with a minimum follow-up period of 30 days. The primary endpoint was the occurrence of stroke (including both cerebrovascular accidents and death due to cerebrovascular accidents). The risk of stroke was lower in the CEPD group: RR 0.68, 95% CI 0.49-0.96, p = 0.03, I2 = 0%. A subgroup analysis was conducted according to the type of CEPD. The risk of stroke was lower in the I&LCCA (filter cover the innominate and the left common carotid arteries) type CEPD group: RR 0.66, 95% CI 0.49-0.96, p = 0.03, I2 = 36%. However, there was no statistically significant difference in the risk of stroke in the TMCA [filter cover the three major cerebral arteries (innominate, left common carotid, and subclavian arteries)] type CEPD group: RR 0.81, 95% CI 0.36-1.80, p = 0.60, I2 = 0%. In this meta-analysis, the I&LCCA-type CEPD can reduce the risk of stroke within 30 days following TAVI, but the TMCA type cannot.

Cerebral Embolic Protection in Transcatheter Aortic Valve Implantation Using the Sentinel Cerebral Protection System: A Systematic Review and Meta-Analysis.

Transcatheter aortic valve implantation (TAVI) plays a vital role in patients with symptomatic aortic stenosis. Despite the mortality benefit of TAVI, embolic stroke remains a feared complication. As a result, transcatheter cerebral embolic protection (TCEP) devices have been developed to reduce this risk. Given the ongoing debate of TCEP in TAVI, we performed a systematic review and meta-analysis of all randomized controlled trials to date to identify outcomes of periprocedural stroke using the Sentinel™ cerebral protection system (CPS). MEDLINE, Cochrane, and Scopus databases were utilized from inception until 12/2023. PRISMA criteria was utilized. Keywords included "cerebral embolic protection", "sentinel cerebral protection system", "transcatheter aortic valve implantation", and "transcatheter aortic valve replacement". Primary outcome was periprocedural stroke. Secondary outcomes included periprocedural disabling and non-disabling stroke, all-cause mortality, transient ischemic attack, delirium, acute kidney injury, vascular complications, bleeding, and pacemaker implantation. Risk ratios (RR) were measured via Mantel-Haenszel method with fixed analysis. Heterogeneity was assessed via chi-squared and Higgin's I2 test. Four trials with 3528 patients were assessed. SAPIEN 3 was the most common bioprosthetic valve used. The average age was 79.4years with 41.9% of the sample size being females. The most prevalent comorbidities were hypertension, diabetes mellitus, and coronary artery disease. There was no difference in periprocedural stroke in patients who underwent TAVI with the Sentinel™ CPS compared to no TCEP (RR 0.75, P = 0.12). Periprocedural disabling strokes were less likely in those who underwent TAVI with the Sentinel™ CPS compared to no TCEP (RR 0.41, P = 0.02) with a number needed to treat (NNT) of 123. All other outcomes did not reach statistical significance. In our analysis, there was no difference between TAVI with the Sentinel™ CPS compared to TAVI without TCEP in regard to risk of periprocedural stroke; however, it was associated with a decreased risk of periprocedural disabling stroke.

Safety and efficacy of cerebral embolic protection in transcatheter aortic valve implantation: an updated meta-analysis.

The use of cerebral embolic protection devices during transcatheter aortic valve implantation (TAVI) reveals conflicting data. This updated meta-analysis aims to evaluate the efficacy and safety of the SENTINEL Cerebral Protection System. A literature search for relevant studies up to September 2022 was performed. Study outcomes were divided based on time period - overall (up to 30 days) and short (≤7 days). The outcomes studied include stroke (disabling, non-disabling), mortality, neuroimaging findings, transient ischaemic attack, acute kidney injury and major vascular and bleeding complications. A total of 15 studies involving 294,134 patients were included. Regarding overall outcomes, significant reductions were noted for mortality (odds ratio [OR] 0.60, 95% confidence interval [CI]: 0.41-0.88; p=0.008), all stroke (OR 0.64, 95% CI: 0.46-0.88; p=0.006) and disabling stroke (OR 0.42, 95% CI: 0.23-0.74; p=0.003) using the SENTINEL device. No significant differences were noted for other outcomes. There was significant heterogeneity across the studies for mortality (p=0.013) and all stroke (p=0.003). Including only randomised data (n=4), there was only significant reduction in the incidence of disabling stroke (OR 0.39, 95% CI: 0.17-0.89; p=0.026) in the SENTINEL group. In studies reporting ≤7-day outcomes (n=8), use of the SENTINEL device demonstrated significantly lower rates of all stroke (p<0.001), disabling stroke (p<0.001) and major bleeding complications (p=0.02). No differences in neuroimaging outcomes were noted. In this updated meta-analysis, use of the SENTINEL Cerebral Protection System was associated with lower rates of mortality, all stroke and disabling stroke, although significant heterogeneity was noted for mortality and all stroke. Including exclusively randomised data, there was only significant reduction in the incidence of disabling stroke. No significant adverse outcomes with device use were noted.

Cerebral protection in acute type A aortic dissection surgery: a systematic review and meta-analysis.

Acute type A aortic dissection (ATAAD) still challenges physicians and warrants emergent surgical management. Two main methods to reduce cerebrovascular events in ATAAD surgeries are antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP). We conducted a systematic review and meta-analysis to compare the outcomes of ACP and RCP methods during the ATAAD surgery. In this study, we searched the databases until March 29th, 2023. Studies that reported the data for comparison of different types of brain perfusion protection during aortic surgery in patients with ATAAD were included. Twenty-six studies met the eligibility criteria. All studies had a low risk of bias as they were evaluated by the Joanna Briggs Institute (JBI) critical appraisal tool. Eventually, we included 26 studies in the current meta-analysis, and a total of 13,039 patients were evaluated. The calculated risk ratio (RR) for permanent neurologic dysfunction (PND) in ACP and RCP comparison was RR =1.23, 95% confidence interval (CI): (0.84, 1.80) (P value =0.2662), and in unilateral ACP (uACP) and bilateral ACP (bACP) was RR =1.2786, 95% CI: (0.7931, 2.0615) (P value =0.3132). When comparing the ACP-RCP and uACP-bACP groups, significant differences were found between ACP-RCP the groups in terms of circulatory arrest time (P value =0.0017 and P value =0.1995, respectively), cardiopulmonary bypass time (P value =0.5312 and P value =0.7460, respectively), intensive care unit (ICU)-stay time (P value =0.2654 and P value =0.0099), crossclamp time (P value =0.6228 and P value =0.2625), and operative mortality (P value =0.9368 and P value =0.2398, respectively), and when comparing the u-ACP and b-ACP groups for transient neurologic deficit (TND), an RR of 1.32, 95% CI: (1.05, 1.67) (P value =0.0199). The results showed high heterogeneity and no publication bias. This study demonstrated that the ACP and RCP are both safe and acceptable techniques to use in emergent settings. The uACP technique is equivalent to bACP in terms of PND and mortality, however, uACP is preferred over bACP in terms of TND.

Final report of the PROTEMBO C Trial: a prospective evaluation of a novel cerebral protection device during TAVI.

Final report of the PROTEMBO C Trial: a prospective evaluation of a novel cerebral protection device during TAVI.

Cerebral embolic protection with filters and an occlusion balloon catheter during transcatheter aortic valve replacement

Cerebral embolic protection with filters and an occlusion balloon catheter during transcatheter aortic valve replacement

Clinical impact of cerebral protection during transcatheter aortic valve implantation.

Embolization of debris can complicate transcatheter aortic valve implantation (TAVI) causing stroke. Cerebral embolism protection (CEP) devices can divert or trap debris. To evaluate the efficacy of CEP during TAVI vs the standard procedure. PubMed, SCOPUS and DOAJ 1/01/2014-04/12/2023. Randomized and observational studies comparing CEP versus standard TAVI, according to PRISMA. stroke. death, bleeding, vascular access complications, acute kidney injury and infarct area. Two investigators independently assessed study quality and extracted data. Twenty-six articles were included (540.247 patients). The primary endpoint was significantly lower (RR = 0.800 95%CI:0.682-0.940; p = 0.007) with CEP. Similarly, death rates were significantly lower with CEP (RR = 0.610 95%CI:0.482-0.771; p < 0.001). No difference was found for bleeding (RR = 1.053 95%CI:0.793-1.398; p = 0.721), vascular complications (RR = 0.937 95%CI:0.820-1.070; p = 0.334) or AKI (RR = 0.982 95%CI:0.754-1.279; p = 0.891). Use of CEP during TAVI is associated with improved outcomes. Future studies will identify patients who benefit most from CEP.

Left atrial appendage closure in patients with left atrial appendage thrombus guided by intracardiac echocardiography

BackgroundData regarding left atrial appendage closure (LAAC) in patients with left atrial appendage (LAA) thrombus are limited. Recently published cases have mostly been guided by transesophageal echocardiography. Intracardiac echocardiography (ICE) is now widely used during LAAC procedures. ObjectiveThis is the first study to report the feasibility of LAAC in patients with LAA thrombus guided by ICE. MethodsPatients with persistent LAA thrombus despite anticoagulation or contraindications to anticoagulation who underwent a modified ICE-guided LAAC procedure between June 2021 and April 2023 were included. Periprocedural events and clinical outcomes during follow-up were recorded. ResultsA total of 12 patients (mean age 65 ± 7 years; 92% male) were included: 10 with persistent LAA thrombus and 2 with contraindications to anticoagulation. Most of the thrombus was at the apex (n = 6), followed by the body (n = 3) and the ostium (n = 3). A LAmbre device was used and successfully implanted in all patients with the guidance of ICE. No thrombotic material was retrieved from patients with the protection of cerebral protection device (n = 11). No patient experienced severe periprocedural complications. All patients completed transesophageal echocardiography follow-up, and no device-related thrombus or peridevice leak > 3 mm was detected. None of the patients experienced stroke/transient ischemic attack, systemic embolism, or major bleeding events during a median follow-up of 147 days (interquartile range 80–306 days). ConclusionLAAC using the LAmbre device guided by ICE may be feasible in patients with LAA thrombus when performed by experienced operators.

Cerebral Protection in Trans-Catheter Aortic Valve Replacement: Review and Contemporary Assessment of Randomized Trial Data.

As the population has aged and as aortic valve therapies have evolved, the use of trans-catheter aortic valve replacement (TAVR) has grown dramatically over the past decade. A well-known complication of percutaneous cardiac intervention is embolic phenomena, and TAVR is among the highest risk procedures for clinical and subclinical stroke. As indications for TAVR expand to lower-risk and ultimately younger patients, the long-term consequences of stroke are amplified. Cerebral embolic protection (CEP) devices have taken a on unique preventative role following the Food and Drug Administration approval of the SentinelTM Cerebral Protection System (CPS). More recently, the PROTECTED TAVR study has spurred extensive debate in the neuro-cardiac community. In this review we describe the contemporary literature regarding stroke risk associated with TAVR, the history and role of CEP devices, a PROTECTED TAVR sub-group analysis, and implications for next steps in the field. Lastly, we explore the unique need for CEP in a younger TAVR population, as well as directions for future research.

Mid-Term Results of an Italian Multicentric Experience with the RoadsaverTM Dual-Layer Carotid Stent System.

Carotid artery stenting (CAS) using first-generation single-layer stents is widely accepted as a good alternative to standard carotid endarterectomy (CEA) but it is associated with worse outcomes in terms of both plaque prolapse and cerebral embolization. To evaluate the perioperative and midterm outcomes of CAS using the new-generation RoadsaverTM dual-layer micromesh-covered carotid stent. Herein, we present the results of an observational, retrospective, multicentric study on non-consecutive patients who underwent the CAS procedure between January 2017 and December 2022 at three Italian, high-volume vascular surgery centers. The inclusion criteria were the patients' eligibility for the CAS procedure in accordance with the current Italian guidelines, and the implantation of a Roadsaver stent. Both symptomatic and asymptomatic patients were included in the study. The patients requiring reintervention for carotid restenosis following CEA were also included. Perioperative data regarding procedural success was defined as the successful implantation of the device in the desired position, less than 30% residual stenosis, and the absence of intraoperative neurological complications. The primary outcome was any adverse cerebrovascular event such as stroke or transient ischemic attack (TIA) during the procedure and/or after discharge. The secondary outcomes were the need for further intervention, and all-cause death following procedure. Three-hundred-fifty-three (353) patients were included in our study; the mean age was 74.3 years. A total of 5.9% of the patients were symptomatic on their operated side, while 7.3% had contralateral carotid occlusion. A cerebral embolic protection device (CPD) was employed in all patients. A total of 13.3% of the patients were operated on for restenosis after CEA Technical success was achieved in 96.9% of the cases with an intraoperative report of six TIAs (1.7%) and six ipsilateral strokes (1.7%). The mean hospital stay was 1.8 days. The thirty-day follow up showed one TIA and one more stroke. At the mean 35-month follow-up time, the primary outcome was present in six patients (1.7%), where four TIAs (1.1%) and two strokes (0.5%) were reported. Restenosis occurred in five patients (1.4%). Death for any cause was reported in 11 patients (3.1%). As most recent, high-quality studies show, the CAS procedure with second-generation devices such as the Roadsaver stent is safe and effective in preventing carotid-related cerebrovascular events in both symptomatic and asymptomatic patients. The intraoperative and postoperative cerebrovascular complication rate in high volume centers is very low, ensuring confidence in its employment for the CAS procedure along with a CPD as a valid alternative to CEA.

Patient Characteristics and Outcomes Associated with Sentinel Protection Device Use in Patients with Aortic Valve Disease Undergoing TAVR in a "Real-World" Setting.

Transcatheter aortic valve replacement (TAVR) has become the dominant treatment for aortic valve disease. While TAVR safety has improved over time, concern remains over the occurrence of cerebrovascular accidents (CVA) secondary to device placement, which is associated with increased morbidity and mortality. The Sentinel Cerebral Protection System (CPS) was developed to reduce the risk of embolic strokes associated with debris produced during TAVR. Studies evaluating Sentinel CPS efficacy have produced conflicting results, and there is little understanding of which patients are selected for device placement in "real-world" settings. With no existing guidelines on device use, the purpose of this study was to describe and compare the characteristics of patients who receive CPS with those who do not in a "real-world" setting of consecutive TAVR patients and evaluate its impact on postoperative complications, namely stroke. This was a single-center, retrospective study of all patients undergoing TAVR between July 1, 2019, and December 31, 2020. Patient demographics, baseline, and perioperative characteristics were collected prospectively using the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry and our institution's TAVR database for analysis. Postoperative outcomes were assessed using primary endpoints of in-hospital/30-day stroke and the composite of death, stroke, and bleeding/vascular events at one-year. To adjust for baseline differences, a propensity score was developed including all factors that were different between groups, and Multivariate Cox Regression analysis was used to control for these differences. Patient follow-up was 97% complete at 12 months with 100% echocardiographic follow-up. A total of 242 consecutive patients (57.9% male) were analyzed, with a mean age of 79.9 9 years. Of these patients, 134 (55.4%) received the Sentinel CPS and 108 (44.6%) did not. Sentinel CPS patients were more likely to be male, not on dialysis, without prior CVA or pacemaker, had less severe chronic lung disease, and were lower operative risk compared to concurrent non-CPS patients. CPS patients were also found to have higher hemoglobin and albumin levels, lower creatinine, and were less likely to be on immunosuppressant therapy. The incidence of in-hospital/30-day stroke after TAVR did not differ between CPS and non-CPS patients (0.0% vs. 1.9%; p = 0.198). Unadjusted analyses at one-year showed a lower occurrence of the composite endpoint in CPS patients compared non-CPS patients (8.3% vs. 17.0%; p = 0.034). After adjustment, the hazard ratio (Adj HR) for the CPS group was no longer significantly associated with a lower composite endpoint (Adj HR = 0.609, 95% CI 0.244-1.523; p = 0.289). Both unadjusted (p = 0.233) and adjusted (p = 0.132) analyses showed no difference in the incidence of stroke at one-year. Our study demonstrates that in a "real-world" setting, the Sentinel CPS device is more likely to be used in healthier and less complex patients. In analyses adjusted for illness severity and patient complexity, CPS use did not have a significant effect on the incidence of in-hospital/30-day stroke or the composite endpoint of death, stroke, and bleeding/vascular events at one-year.

Ozone-mediated cerebral protection: Unraveling the mechanism through ferroptosis and the NRF2/SLC7A11/GPX4 signaling pathway

BackgroundThe pathogenesis of brain ischemic/reperfusion (I/R) insult is characterized by neuronal loss due to excessive oxidative stress responses. Ferroptosis, a form of oxidative cell death, can be triggered when the balance between antioxidants and pro-oxidants in cells is disrupted. Ozone, a natural bioactive molecule with antioxidant/anti-apoptotic and pro-autophagic properties, has been shown to enhance the antioxidant system's capacity and ameliorate oxidative stress. However, its role in neuronal ferroptosis remains unclear. Therefore, we investigated the functions and possible mechanisms of ozone in cerebral I/R-induced ferroptotic neuronal death. MethodsA cerebral ischemia-reperfusion injury model was induced in Sprague-Dawley (SD) rats pre-treated with ozone. Intraperitoneal administration of the NRF2 inhibitor ML385, the SLC7A11 inhibitor Erastin, and the GPX4 inhibitor RSL3 was performed one hour prior to model establishment. ResultsOur results showed that ozone preconditioning mitigated neuronal damage caused by cerebral I/R, reduced the severity of neurological deficits, lowered cerebral infarct volume in middle cerebral artery occlusion (MCAO) rats, and decreased the volume of cerebral infarcts. Transmission electron microscopy, immunofluorescence, and Western blotting indicated ferroptosis following MCAO-induced brain damage. MCAO resulted in morphological damage to neuronal mitochondria, increased lipid peroxidation accumulation, and elevated malondialdehyde (MDA) production. Furthermore, MCAO decreased levels of FTH1 and GPX4 (negative regulators of ferroptosis) and increased ACSL4 levels (a positive regulator of ferroptosis). Ozone preconditioning demonstrated a neuroprotective effect by increasing NRF2 nuclear translocation and the expression of SLC7A11 and GPX4. Treatment with ML385, Erastin, and RSL3 significantly reversed ozone preconditioning's protective effect on neuronal ferroptosis. ConclusionOur findings demonstrated that ozone treatment attenuates ferroptosis in a cerebral ischemia/reperfusion injury rat model via the NRF2/SLC7A11/GPX4 pathway, providing a theoretical basis for ozone's potential use as a therapy to prevent ischemic stroke.

The Anti-Apoptotic Effect of Ranolazine on Cerebral Protection during Cardiopulmonary Bypass and Carotid Artery Surgery.

We aimed to determine the usability of ranolazine (Rn) as a neuroprotective during cardiac surgeries and carotid artery interventions where cerebral blood flow is interrupted. Female Wistar albino rats were used. The rats were divided into 4 groups of 8 rats each. The first group (Group 1) was the control group. Group 2 underwent ischemia induction but was not treated with Rn. Group 3 received 25 mg/kg/day and Group 4 50 mg/kg/day Rn intraperitoneally, starting 3 days before ischemia induction. Bilateral carotid arteries were explored and clamped simultaneously. Ischemia was induced for 15 minutes. After 72 hours, the experimental animals were sacrificed. Superoxide dismutase, alkaline phosphatase, and interleukin 6 levels were similar among the 4 groups. Acetylcholine esterase (Group 3: p = 0.007, Group 4: p = 0.002), tumor necrosis factor-alpha (Group 4: p = 0.01), and annexin V (Group 3: p = 0.001) levels were statistically significantly lower in the Rn-treated groups. Malondialdehyde (Group 3: p = 0.003, Group 4: p = 0.009), reduced glutathione (Group 4: p = 0.04), acid phosphatase (Group 3: p = 0.04), noradrenaline (Group 3: p = 0.01), and Bcl-2 (Group 4: p = 0.004) levels were significantly higher in the Rn-treated groups. The results of this study demonstrated the antiapoptotic effect of Rn in a brain ischemia-reperfusion model of rats receiving Rn before the procedure.

Predictive factors for cranioplasty complications – A decade's experience

IntroductionCranioplasty (CP) following craniectomy provides cerebral protection, improves cerebrospinal fluid dynamics, and restores cosmesis. Although often viewed as minor, CP can have major complications. Research questionThis study aims to identify the predictive factors for post-operative complications in patients undergoing CP after decompressive craniectomy. MethodsWe conducted a retrospective study at a tertiary hospital, analyzing patients who underwent CP after decompressive craniectomy (DC) from 2008 to 2019. Patient demographics, medical history, and surgery details were retrieved from hospital records. Complications included symptomatic intracerebral haemorrhage, extradural or subdural haemorrhage, hydrocephalus, infection, or bone resorption. ResultsThe study included 168 patients: 139 adults (mean age 47.6 ± 12.68 years) and 29 pediatric patients (mean age 11.8 ± 5.62 years), with a slight male predominance. The overall complication rate was 26.2%, with infection being the most common (8.9%). Predictive factors for CP complications identified by binomial logistic regression, controlling for age and sex, included primary coagulopathy (14.3-fold risk increase, p = 0.034), intraoperative ventricular puncture (7.9-fold risk increase, p = 0.009), and intraoperative dural layer breach (2.8-fold risk increase, p = 0.033). Pre-CP home living was a protective factor. ConclusionsCP requires vigilant management to prevent complications. Primary coagulopathy, intraoperative ventricular puncture, and dural layer breach are significant risk factors for complications.