Neurological Events In Patients Research Articles

Evaluation of neurological events following minimally invasive mitral valve surgery

Objective: To determine the rate of neurological events in patients undergoing minimally invasive mitral valve surgery and evaluate factors associated with the groups with and without postoperative neurological events. Subjects and Methods: Inclusion Criteria: Patients undergoing minimally invasive mitral valve surgery at the Cardiac Surgery Department, University Medical Center. Exclusion Criteria: Patients with infective endocarditis, patients requiring ECMO support. Study Design: Retrospective case series study. Results: A total of 358 patients underwent minimally invasive mitral valve surgery between 2017 and 2022, with an average age of 50.7 years. Male patients accounted for 53.2%, and the surgical risk according to EuroScore II was 1.6%. Neurological complications occurred in 46 patients, representing 12.8%. Among these, delirium was the most common complication, occurring in 42 patients (91.3%), while stroke with sequelae occurred at a lower rate of 2.2%. The average age of the group with neurological complications was higher than that of the group without complications (53.9 ± 10.8 years vs. 50.2 ± 12.6 years). Additionally, the male proportion in the complication group (63.0%) was higher than in the group without complications (50.6%). The history of stroke in the complication group was 4.3%. The duration of mechanical ventilation and ICU stay was longer in the group with neurological complications, with an average mechanical ventilation time of 36.1 ± 71.3 hours compared to 18.4 ± 24.5 hours in the group without complications. The rate of new-onset atrial fibrillation after surgery was also higher in the complication group (19.6% vs. 10.6%). Conclusion: Neurological complications after surgery are a significant issue, occurring in 12.8% of patients undergoing minimally invasive mitral valve surgery, with delirium and stroke being the most common. Key risk factors include age, hypertension, and atrial fibrillation.

Tocilizumab Prophylaxis Following Axicabtagene Ciloleucel in Relapsed or Refractory Large B-Cell Lymphoma

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Most patients treated with axi-cel experience cytokine release syndrome (CRS) and/or adverse neurologic events (NEs). To explore potential approaches for reducing CAR T-cell-related toxicities with axi-cel, several safety expansion cohorts were added to the pivotal ZUMA-1 trial. ZUMA-1 Cohort 3 was an exploratory safety cohort that investigated the use of the IL-6 receptor-blocking antibody tocilizumab and anticonvulsant levetiracetam as prophylaxis against CRS and NEs in patients treated with axi-cel. Patients with R/R LBCL were enrolled in Cohort 3 and received conditioning chemotherapy on d -5 through -3 followed by a single infusion of axi-cel (2 × 106 cells/kg) on d 0. Prophylactic tocilizumab (8 mg/kg) was administered 48 h after axi-cel infusion. Primary endpoints were incidence and severity of CRS and NEs. Key secondary endpoints included the incidence of adverse events, objective response rate (ORR), duration of response, progression-free survival, overall survival (OS), and biomarker analyses (eg, circulating CAR T cells, cytokines, chemokines). Forty-two patients were enrolled in Cohort 3, 38 of whom received axi-cel. In the 24-month analysis, any-grade CRS and NEs occurred in 92% and 87% of patients, and Grade ≥3 CRS and NEs occurred in 3% and 42% of patients, respectively. One Grade 5 NE (cerebral edema) occurred. With 24-mo minimum follow-up, the ORR was 63%, and 39.5% of patients had ongoing response. With 48-month follow-up, median OS was 34.8 mo (95% CI, 5.4-not estimable). CAR T-cell expansion in ZUMA-1 Cohort 3 was comparable with pivotal Cohorts 1 and 2. Consistent with tocilizumab-mediated inhibition of IL-6R, serum IL-6 levels were increased relative to Cohorts 1 and 2. Grade ≥3 NEs were associated with elevated IL-6 levels, proinflammatory cytokines, and myeloid cells in the cerebrospinal fluid. Based on these findings, prophylactic tocilizumab is not recommended to prevent CAR T-cell-related adverse events, and beneficial effects of prophylactic levetiracetam remain uncertain in patients with R/R LBCL.

Impact of debulking therapy on the clinical outcomes of axicabtagene ciloleucel in the treatment of relapsed or refractory large B-cell lymphoma.

Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, was approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL) based on the results from pivotal Cohorts 1+2 of ZUMA-1 (NCT02348216). ZUMA-1 was expanded to investigate safety management strategies aimed at reducing the incidence and severity of cytokine release syndrome (CRS) and neurologic events (NEs). Prospective safety expansion Cohort 5 evaluated the impact of debulking therapy, including rituximab-containing immunochemotherapy regimens and radiotherapy, in axi-cel-treated patients; the CRS and NE management strategy paralleled those in Cohorts 1+2. Among the 50 patients in Cohort 5 who received axi-cel, 40% received ≥3 prior lines of chemotherapy, and 40% had disease that progressed while on the most recent chemotherapy. Forty-eight patients (96%) received debulking therapy, 14 (28%) radiotherapy only, and 34 (71%) systemic immunochemotherapy. Median decrease in tumor burden (per sum of product of diameters of target lesions) relative to screening was 17.4% with R-ICE/R-GDP, 4.3% with other debulking chemotherapies, and 6.3% with radiotherapy only. All patients were followed for ≥8 months. CRS was reported in 43 patients (86%), with 1 patient (2%) experiencing grade ≥3. NEs were reported in 28 patients (56%), with 6 (12%) experiencing grade ≥3. Cytopenias were the most frequent grade ≥3 adverse event (AE); 19 (38%) and 18 (36%) treated patients had any and grade ≥3 prolonged thrombocytopenia, respectively, and 25 (50%) and 24 (48%) patients had any and grade ≥3 prolonged neutropenia, respectively. Overall, patients who received debulking chemotherapy had higher incidences of serious treatment-emergent AEs than those who received radiotherapy only. At the 24-month analysis, objective response rate was 72%, and complete response rate was 56%. Median duration of response, progression-free survival, and overall survival were 25.8, 3.1, and 20.6 months, respectively. These results from exploratory Cohort 5 demonstrate the feasibility of debulking prior to axi-cel, and together with current real-world evidence, suggest that debulking regimens may help minimize the frequency and severity of CRS and NEs in patients with R/R LBCL. The incidence of other AEs observed in Cohort 5 suggest the risk/benefit profile was not improved via the debulking regimens studied here.

Phase I Study of a CD19-Directed CAR-T Cell Therapy for Relapsed/Refractory Mantle Cell Lymphomas(MCL)

Background: IM19 is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product, which is manufactured in China using a commercial process. We aimed to evaluate the efficacy and safety of IM19 in patients with relapsed or refractory mantle cell lymphomas in a Phase I clinical study. Methods: A phase 1 clinical trial has been launched to evaluate the safety and efficacy of IM19 for the treatment of relapsed/refractory MCL. We enrolled adult patients (aged ≥18 years) with relapsed or refractory MCL who had received at least 2 prior treatment regimens(including BTK inhibitor). Patients were assigned to one of two target dose levels of IM19 as they were sequentially tested in the trial (100×10⁶ CAR+ T cells [one or two doses], 200×10⁶ CAR+ T cells [one or two doses]). Leukapheresed patients could receive bridging chemotherapy based on investigator assessment of disease burden and tumor progression risk. Lymphodepleting (LD) chemotherapy was administered over 3 days, including fludarabine (30 mg/m2 i.v. daily) and cyclophosphamide (300 mg/m 2 i.v. daily), followed 2 days later by intravenous infusion of IM19 at the assigned dose. The first three subjects in each dose group will receive the second LD chemotherapy and infusion of IM19 CAR-T cells for consolidation treatment (with the same dosage as the first treatment) if the efficacy evaluation after the first infusion shows no progression and no DLT occurs. The investigators can determine the start time of consolidation treatment based on the patient's tolerance, but no later than 60 days after the first infusion. Efficacy was assessed at 1, 3, 9, 12, 18, and 24 months post first infusion. Safety events were monitored from beginning of LD through 2 years follow-up. The primary endpoints were adverse events, dose-limiting toxicities, and the objective response rate. Results: Between Mar 3, 2022, and May 5, 2023, Five patients underwent leukapheresis for manufacture of CAR+ T cells (IM19) and all received bridging chemotherapy during the production of IM19. ALL 5 patients received LD and first infusion of IM19 at a dose of 100*10^6 CAR+ cells and no DLTs were observed. CRS was reported only in 1 patient(grade 1) and no patients developed ICANS. ALL 5 patients achieved CR on 28 days after first infusion. The median maximum CAR-T cells expansion (Cmax) was 156×10⁶ CAR+ cells/L, and median area under the curve from 0-28 days post-first infusion (AUC0-28d) was 860 day×CAR+ cells/L. 2 patients received the second LD chemotherapy and infusion of IM19 CAR-T cells for consolidation treatment (with the same dosage as the first treatment) at 44th days post first infusion. No DLTs，CRS or ICANS were observed after second infusion. Meanwhile, CAR-T cells can not be detected at 1, 4, 7, 10, 14, 21 and 28 days post second infusion by Flow cytometry in 2 patients. One patient maintained complete remission after 9 months of follow-up and another patient experience PD at 7th month after first infusion. For three patients who received single infusion of IM19, one maintained complete remission after 6 months of follow-up，one progressed at 3th month after infusion and one are still waiting for second efficacy evaluation. Conclusions: Initial data from this Phase I study demonstrate that use of IM19 resulted in a high objective response rate, with a low incidence of grade 3 or worse cytokine release syndrome and neurological events in patients with relapsed or refractory MCL. We observed that CAR-T cells cannot expand in vivo after secondary infusion. Therefore, secondary infusion may not be necessary.

Neurological event prediction for patients with symptomatic cerebral cavernous malformation: the BLED2 score.

Retrospective patient cohort studies have identified risk factors associated with recurrent focal neurological events in patients with symptomatic cerebral cavernous malformations (CCMs). Using a prospectively maintained database of patients with CCMs, this study identified key risk factors for recurrent neurological events in patients with symptomatic CCM. A simple scoring system and risk stratification calculator was then created to predict future neurological events in patients with symptomatic CCMs. This was a dual-center, prospectively acquired, retrospectively analyzed cohort study. Adult patients who presented with symptomatic CCMs causing focal neurological deficits or seizures were uniformly treated and clinically followed from the time of diagnosis onward. Baseline variables included age, sex, history of intracerebral hemorrhage, lesion multiplicity, location, eloquence, size, number of past neurological events, and duration since last event. Stepwise multivariable Cox regression was used to derive independent predictors of recurrent neurological events, and predictive accuracy was assessed. A scoring system based on the relative magnitude of each risk factor was devised, and Kaplan-Meier curve analysis was used to compare event-free survival among patients with different score values. Subsequently, 1-, 2-, and 5-year neurological event rates were calculated for every score value on the basis of the final model. In total, 126 (47%) of 270 patients met the inclusion criteria. During the mean (interquartile range) follow-up of 54.4 (12-66) months, 55 patients (44%) experienced recurrent neurological events. Multivariable analysis yielded 4 risk factors: bleeding at presentation (HR 1.92, p = 0.048), large size ≥ 12 mm (HR 2.06, p = 0.016), eloquent location (HR 3.01, p = 0.013), and duration ≤ 1 year since last event (HR 9.28, p = 0.002). The model achieved an optimism-corrected c-statistic of 0.7209. All factors were assigned 1 point, except duration from last event which was assigned 2 points. The acronym BLED2 summarizes the scoring system. The 1-, 2-, and 5-year risks of a recurrent neurological event ranged from 0.6%, 1.2%, and 2.3%, respectively, for patients with a BLED2 score of 0, to 48%, 74%, and 93%, respectively, for patients with a BLED2 score of 5. The BLED2 risk score predicts prospective neurological events in symptomatic CCM patients.

Neuroprotective association of preoperative renin-angiotensin system blocking agents use in patients undergoing carotid interventions.

The optimal medical management strategy in the periprocedural period for patients undergoing carotid artery interventions is not well described. Renin-angiotensin-system blocking (RASB) agents are considered to be among the first line anti-hypertensive agents; however, their role in the perioperative period is unclear. The objective of this study was to examine the relationship between the use of RASB agents on periprocedural outcomes in patients undergoing carotid interventions-carotid endarterectomy (CEA), transfemoral carotid artery stenting (CAS), and transcervical carotid artery revascularization (TCAR). The Society for Vascular Surgery Quality Initiative database was queried for all patients undergoing CAS, CEA, and TCAR between 2003 and 2020. Patients were stratified into two groups based upon their use of RASB agents in the periprocedural period. The primary endpoint was periprocedural neurologic events (including both strokes and transient ischemic attacks (TIAs)). The secondary endpoints were peri-procedural mortality and significant cardiac events, including myocardial infarction, dysrhythmia, and congestive heart failure. Over 150,000 patients were included in the analysis: 13,666 patients underwent TCAR, 13,811 underwent CAS, and 125,429 underwent CEA for carotid artery stenosis. Overall, 52.2% of patients were maintained on RASB agents. Among patients undergoing CEA, patients on RASB agents had a significantly lower rate of periprocedural neurologic events (1.7% versus 2.0%, p =0.001). The peri-procedural neurological event rate in the TCAR cohort was similarly reduced in those treated with RASB agents, but did not reach statistical significance (2.0% vs 2.4%, p = 0.162). Among patients undergoing CAS, there was no difference in perioperative neurologic events between the RASB treated and untreated cohorts (3.4% vs 3.2%, p = 0.234); however, the use of RASB agents was significantly associated with lower mortality (1.2% vs 1.7%, p =0.001) with CAS. The use of preoperative RAS-blocking agents did not appear to affect the overall rates of adverse cardiac events with any of the three carotid intervention types, or periprocedural mortality following CEA or TCAR. On multivariable analysis, the use of RAS-blocking agents was independently associated with lower rates of post-procedural neurologic events in patients undergoing CEA (OR 0.819, CI 0.747-0.898; p = 0.01) and TCAR (OR 0.869, CI 0.768-0.984; p = 0.026), but not in those undergoing CAS (OR 0.967, CI 0.884-1.057; p = 0.461). The use of peri-procedural RASB agents was associated with a significantly decreased rate of neurologic events in patients undergoing both CEA and TCAR. This effect was not observed in patients undergoing CAS. As carotid interventions warrant absolute minimization of perioperative complications in order to provide maximum efficacy with regard to stroke protection, the potential neuro-protective effect associated with RASB agents use following CEA and TCAR warrants further examination.

Association of Outflow Cannula Angulation with Adverse Neurological Events in Patients with CF-LVAD

<h3>Purpose</h3> Adverse neurological outcomes are the Achilles heel of the current day LVAD technology and are associated with worse survival. Our previous data suggests that outflow cannula (OFC) angles measured using cardiac CT may correlate with stroke in continuous-flow HeartMate II patients. Therefore, the aim of our study was to assess the relationship of inflow cannula (IFC) and outflow cannula (OFC) position with neurological outcomes centrifugal flow pumps (HM3 and HVAD). <h3>Methods</h3> 108 patients underwent LVAD implantation between 2015 and 2019 at our institution. Of these, 68 patients underwent cardiac CT, and 6 were excluded due to poor image quality. Of these patients, a total of 32 neurological events (NE) occurred in 20 patients. These cases were compared to patients with CT data who did not have NEs. 2D angle measurements were performed on positions of OFC relative to the ascending aorta and IFC relative to the mitral valve. Further we used a novel point-based 3D measurement system to determine the angles in an x-y-z plane. Baseline demographic data and outcome data were collected for all patients. Optimal cut-point of the OFC angle was determined using ROC curve analysis. <h3>Results</h3> Of the 62 patients recruited for this study, 65% had HM3 and 35% had HVAD. The median OFC angle on 2D in patients with NE was 59.8 degrees relative to the aorta, compared with a median angle of 51.7 degrees in patients without NE (p=0.02). Similarly on 3D angle measurements, a median OFC angle of 86.7 degree was observed in patients with NE, compared to a median angle of 77.4 degrees in patients without NE (p=0.01). IFC angle was not associated with an increased risk of NE. The ROC curve analysis showed optimal OFC angle was < 53 degrees in 2D measurements, with sensitivity of 79% and specificity of 61% at predicting NEs. In 3D measurements the optimal OFC angle was less than < 83 degrees with a sensitivity of 79% and a specificity of 61% at predicting NEs. <h3>Conclusion</h3> Optimal angulation of the outflow cannula in LVAD patients can lead to decreased risk for HRAE. Using cardiac CT chest imaging for 2D and 3D measurements, an optimal outflow cannula angulation of < 53 degrees and < 83 degrees, respectively, should be preferred to minimize the risk for HRAE in patients with centrifugal flow LVAD support.

In Vivo Cellular Expansion of Lisocabtagene Maraleucel and Association With Efficacy and Safety in Relapsed/Refractory Large B-Cell Lymphoma.

Lisocabtagene maraleucel (liso‐cel) is an autologous, CD19‐directed, chimeric antigen receptor T‐cell product for the treatment of adult patients with relapsed or refractory large B‐cell lymphoma (LBCL) after 2 or more lines of systemic therapy. In vivo cellular expansion after single‐dose administration of liso‐cel has been characterized. In this article, in vivo liso‐cel expansion in the pivotal study TRANSCEND NHL 001 (ClinicalTrials.gov identifier, NCT02631044) was further characterized to assess the relationship between in vivo cellular expansion after single‐dose administration of liso‐cel and efficacy or safety after adjusting for key baseline characteristics. Two bioanalytical methods, quantitative polymerase chain reaction and flow cytometry, were used for the assessment of cellular kinetics of liso‐cel, which showed high concordance for in vivo cellular expansion. Multivariable logistic regression analyses demonstrated that higher in vivo cellular expansion of liso‐cel was associated with a higher overall response and complete response rate, and a higher incidence of cytokine release syndrome and neurological events in patients with relapsed or refractory LBCL. Age and tumor burden (by sum of the product of perpendicular diameters) were likely to confound the relationship between in vivo cellular expansion and efficacy, where the association became stronger after controlling for these factors. Repeat dosing of liso‐cel was tested in the study; however, in vivo cellular expansion of liso‐cel was lower after repeat dosing than after the initial dose. These findings should enable a comprehensive understanding of the in vivo cellular kinetics of liso‐cel and the association with outcomes in relapsed/refractory LBCL.

406 The BLED2 Neurologic Event Prediction Score for Patients with Symptomatic Cerebral Cavernous Malformation

INTRODUCTION: Studies using retrospective patient cohorts have identified risk factors associated with recurrent focal neurologic events in patients with symptomatic cerebral cavernous malformations (CCMs). METHODS: Adult patients presenting with symptomatic CCMs causing focal neurologic deficits or seizures were included. Baseline variables included age, gender, history of intracerebral hemorrhage, lesion multiplicity, location, eloquence, size, number of past neurologic events, and duration since last event. Stepwise multivariable Cox regression was used to derive independent predictors of recurrent neurologic events, and predictive accuracy was assessed. A scoring system based on the relative magnitude of the risk factors was devised, and Kaplan-Meier curve analysis compared event-free survival between different score values. Subsequently, 1-, 2-, and 5-year neurologic event rates were calculated for every score value based on the final model. RESULTS: 126 (47%) of 270 patients met inclusion criteria. During a mean follow-up of 4.5 years (54.4 months, range 12-66 months), 55 patients (44%) experienced recurrent neurologic events. Multivariable analysis yielded four risk factors: Bleeding at presentation (HR=1.92, p=0.048), Large size =12mm (HR=2.06, p=0.016), Eloquent location (HR=3.01, p=0.013), and Duration of =1 year since last event (HR=9.28, p=0.002). The model achieved an optimism-corrected c-statistic of 0.7209. All factors were assigned 1 point except duration from last event, which was assigned 2 points. The acronym, BLED2 summarizes the scoring system. The 1-, 2-, and 5-year risk of a recurrent neurologic event ranged from 0.6%, 1.2%, and 2.3%, respectively for patients with a BLED2 score of 0, to 48%, 74%, and 93%, respectively for patients with a BLED2 score of 5. CONCLUSION: The BLED2 risk score predicts prospective neurologic events in symptomatic CCM patients.

CT dose management for neurologic events in patients with cardiac devices: Radiation exposure variation in patients with cardiac devices.

To compare the inter-center cranial computed tomography (CT) acquisition rates, CT findings, CT related radiation dose, and variability of CT acquisition parameters for neurologic events among patients with implantable cardioverter-defibrillator (ICD) or left ventricular assist device (LVAD). A total of 224 patients [ICD group (n = 155) and LVAD group (n = 69)] who had at least one cranial CT scan were enrolled from three medical centers. The variability and effect of the number, indication, and findings of cranial CT scans as well as CT acquisition parameters including tube potential, tube current, tube rotation time (TI), slice collimation (cSL), and spiral or sequential scanning techniques on CT dose index volume (CTDIvol), total dose length product (DLP) were analyzed. The mean DLP value of Center A and mean CTDIvol values of Center A and C were significantly lower than Center B (p < 0.001). The mean CTDIvol and DLP values in the ICD group were substantially lower than the LVAD group (p<0.001). The most potent parameters causing the changes in CTDIvol and DLP were kV, mAs values, and CT scanning technique as sequential or spiral according to multivariate linear regression analysis. Cranial CT acquisition parameters and radiation doses vary significantly between centers, which necessitates optimization of cranial CT protocols to overcome the cumulative radiation dose burden in patients with neurologic events.

The HAT2CH2 score predicts neurologic events in patients with cardiac implantable electronic devices without atrial fibrillation

BackgroundThe HAT2CH2 score has been evaluated for predicting new-onset atrial fibrillation (AF) in several clinical conditions but never for adverse neurologic events. We aimed to evaluate the HAT2CH2 score for predicting neurologic events in patients with cardiac implantable electronic devices (CIED). Methods and resultsWe retrospectively reviewed 470 consecutive patients who had CIED without a history of AF. The primary endpoint was a neurologic event, i.e. ischemic stroke or transient ischemic attack. Multivariate Cox regression analysis with time-dependent covariates was used to determine variables associated with independent factors of neurologic events. Patients’ median age was 76 years, and 58.7% were male. During follow-up (median 29 months), 21 neurologic events occurred (incidence rate 1.85/100 patient-years, 95% CI 1.03-3.83). Multivariable Cox regression analysis revealed that the HAT2CH2 score (HR 3.397, 95% CI 2.357-4.895, p < 0.001) was an independent predictor for neurologic events. Optimal HAT2CH2 score cut-off value was 3, with highest Youden index (AUC, 0.923; 95% CI, 0.886–0.959; p < 0.001). The rate of neurologic events increased significantly with increasing HAT2CH2 score (p < 0.001). ConclusionsThe HAT2CH2 score can predict the occurrence of neurologic events in patients with CIED with no history of AF. Further study of the utility of the HAT2CH2 score for the assessment of neurologic event risk and the selection of anti-thrombotic therapy in patients with CIED without prior AF is warranted.

HAT2CH2 score performance predicting neurologic events after cardiac implantable electronic device.

Objectives: The HAT2CH2 score has been evaluated for predicting new-onset atrial fibrillation in several clinical conditions, but never for adverse neurologic events. We aimed to evaluate the effectiveness of HAT2CH2 score in predicting neurologic events in patients with cardiac implantable electronic device (CIED), comparing with atrial high-rate episodes (AHRE).Methods: This case-control study enrolled 314 consecutive patients aged 18 years or older with CIED implantation between January 2015 and April 2021. Patient data were analyzed retrospectively. The primary endpoint was subsequent neurologic events (NE) after implantation. AHRE was defined as > 175 bpm (Medtronic®) lasting ≥ 30 seconds. Variables associated with independent risk of NE were identified using multivariate Cox regression analysis with time-dependent covariates.Results: Patients' median age was 73 years and 61.8% of them were male. During follow-up (median 32 months), 18 NE occurred (incidence rate 2.15/100 patient-years, 95% CI 1.32-4.30). Multiple Cox regression analysis showed that the HAT2CH2 score (HR 2.424, 95% CI 1.683 - 3.492, p < 0.001) was an independent predictor for NE. Optimal HAT2CH2 score cutoff value was 3 with highest Youden index (AUC, 0.923; 95% CI, 0.881-0.966; p < 0.001). Both AHRE ≥ 1 minute and HAT2CH2 score ≥ 3 had the highest AUC of the receiver-operating characteristic (0.898, 95% CI, 0.831-0.965, p < 0.001). Significant increase was observed in NE occurrence rates using the HAT2CH2 score (p < 0.001).Conclusion: The HAT2CH2 score and episodes of AHRE lasting ≥ 1 minute are independent risk factors for NE in patients with CIED.

Preoperative anxiety as predictor of perioperative clinical events following carotid surgery: a prospective observational study

BackgroundPsychological factors like anxiety and depression are recognised to play a causal role in the development of cardiovascular disease and they may also influence outcome after vascular surgery procedures. The aim of this study was to investigate the association of anxiety and depression with postoperative outcome following elective carotid surgery.MethodsSingle centre prospective observational study of patients treated for asymptomatic carotid artery stenosis at an academic vascular surgery centre. Preoperative anxiety and depression were evaluated using self-reporting questionnaires: Spielberger State-Trait Anxiety Inventory (STAI-S/-T) and Hospital Anxiety and Depression Scale (HADS-A/-D). Postoperative morbidity and mortality were assessed with the primary composite endpoint of stroke, myocardial infarction (MI) and death. Standard reporting guidelines for carotid disease were applied.ResultsFrom June 2012 to November 2015, 393 carotid endarterectomies (CEA) were performed at our institution. Out of those, 98 asymptomatic patients were available for analysis (78% male; median age, 71.1 years). Median scores of self-reporting questionnaires did not differ from published data of the general population (STAI-T, trait component, median, 36; IQR, 31-42.75; STAI-S, state component, median, 38; IQR, 32-43; HADS-A median, 6; IQR, 3-8; HADS-D median, 4; IQR, 2-7). Cardiovascular risk factors were similar in anxious and non-anxious patients. The composite endpoint of stroke, MI and death occurred significantly more often in patients presenting with a preoperative HADS-A score higher than 6 (10.5%, 95% CI, 3-25; p =.020).ConclusionsThe present study indicates that preoperative anxiety is associated with the occurrence of intra- and postoperative neurological events in patients undergoing CEA. Patients who had a preoperative HADS-A score of 6 or less had a very low probability of experiencing these complications.

Predicting the Onset of Acute Encephalopathy With Biphasic Seizures and Late Reduced Diffusion by Using Early Laboratory Data.

Background: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) often causes various neurological sequelae, necessitating early and objective differentiation of AESD from a febrile seizure (FS). Therefore, we developed a scoring system that predicts AESD onset using only early laboratory data.Methods: We selected patients with AESD or FS admitted to the Tottori University Hospital between November 2005 and September 2020 and collected laboratory data from onset to discharge in patients with FS and from onset to the second neurological events in patients with AESD.Results: We identified 18 patients with AESD and 181 patients with FS. In comparison with patients with FS, patients with AESD showed statistically significant increases in ammonia (NH3), blood sugar (BS), and serum creatinine (Cr) levels, and the white blood cell (WBC) count, and a significant decrease in pH at <3 h from onset. We set the cut-off values and adjusted the weight of each of these parameters based on data obtained <3 h from onset and proposed a scoring system for predicting AESD. This system showed 91% sensitivity and 94% specificity for distinguishing AESD from FS. These accuracies were only slightly improved by the addition of information related to consciousness and seizure duration (sensitivity, 91%; specificity, 96%).Conclusion: NH3, BS, and Cr levels, WBC count, and pH were significantly different between patients with AESD and patients with FS at <3 h from seizure onset. This scoring system using these data may enable the prediction of AESD onset for patients under sedation or without precise clinical information.

Batch enrollment for an artificial intelligence-guided intervention to lower neurologic events in patients with undiagnosed atrial fibrillation: rationale and design of a digital clinical trial

Clinical trials are a fundamental tool to evaluate medical interventions but are time-consuming and resource-intensive. To build infrastructure for digital trials to improve efficiency and generalizability and test it using a study to validate an artificial intelligence algorithm to detect atrial fibrillation (AF). We will prospectively enroll 1,000 patients who underwent an electrocardiogram for any clinical reason in routine practice, do not have a previous diagnosis of AF or atrial flutter and would be eligible for anticoagulation if AF is detected. Eligible patients will be identified using digital phenotyping algorithms, including natural language processing that runs on the electronic health records. Study invitations will be sent in batches via patient portal or letter, which will direct patients to a website to verify eligibility, learn about the study (including video-based informed consent), and consent electronically. The method aims to enroll participants representative of the general patient population, rather than a convenience sample of patients presenting to clinic. A device will be mailed to patients to continuously monitor for up to 30 days. The primary outcome is AF diagnosis and burden; secondary outcomes include patients' experience with the trial conduct methods and the monitoring device. The enrollment, intervention, and follow-up will be conducted remotely, ie, a patient-centered site-less trial. This is among the first wave of trials to adopt digital technologies, artificial intelligence, and other pragmatic features to create efficiencies, which will pave the way for future trials in a broad range of disease and treatment areas. Clinicaltrials.gov: NCT04208971.

The optimal cutoff of atrial high-rate episodes for neurological events in patients with dual chamber permanent pacemakers.

BackgroundPatients with atrial high‐rate episode (AHRE) are at higher risk of neurological events. This study aimed to identify the optimal cutoff threshold for AHRE duration in patients with dual chamber permanent pacemakers (PPM) without prior atrial fibrillation.MethodsWe included 355 consecutive patients receiving dual chamber pacemaker implantation. Primary outcome was composite endpoint of subsequent neurological events after various AHRE durations. AHRE was defined as >175 bpm (MEDTRONIC) or > 200 bpm (BIOTRONIK) for longer than 30 s. Cox regression analysis with time‐dependent covariates was conducted.ResultsThe mean age of included patients was 75.6 ± 11.3 years. Among 355 included patients, some had multiple AHREs; 125 patients (35.2%) developed AHRE ≥2 min, 107 (30.1%) had ≥5 min, 55 (15.5%) had ≥6 h, and 37 (10.4%) had ≥24 h. The mean follow‐up was 42.1 ± 31.2 months. During follow‐up, 19 neurological events occurred. After adjustment for CHA2DS2‐VASc score and device type, multivariate Cox regression analysis indicated AHRE ≥2 min (HR 13.605, 95% CI 3.010–61.498), and AHRE ≥5 min (HR 5.819, 95% CI 2.056–16.470) were significantly associated with neurological events. Hence, the optimal AHRE cutoff value was 2 min with the highest Youden index (sensitivity, 89.5%; specificity, 67.8%; AUC, 0.823, 95% CI, 0.763–0.884; p < 0.001).ConclusionsPatients with dual chamber PPM who develop AHRE have increased risk of neurological events. Comprehensive assessment of the risks and benefits of prescribing anticoagulants should be considered in PPM patients with AHRE ≥2 min.

Response To "Hemoglobin Concentration May Influence the Incidence of Postoperative Transient Neurological Events in Patients With Moyamoya After Extracranial-intracranial Arterial Bypass: A Retrospective Single Center Experience".

Response To "Hemoglobin Concentration May Influence the Incidence of Postoperative Transient Neurological Events in Patients With Moyamoya After Extracranial-intracranial Arterial Bypass: A Retrospective Single Center Experience".

Modelling the Anatomic Distribution of Neurologic Events in Patients with COVID-19: A Systematic Review of MRI Findings.

Neurologic events have been reported in patients with coronavirus disease 2019 (COVID-19). However, a model-based evaluation of the spatial distribution of these events is lacking. Our aim was to quantitatively evaluate whether a network diffusion model can explain the spread of small neurologic events. The MEDLINE, EMBASE, Scopus, and LitCovid data bases were searched from January 1, 2020, to July 19, 2020. Thirty-five case series and case studies reported 317 small neurologic events in 123 unique patients with COVID-19. Neurologic events were localized to gray or white matter regions of the Illinois Institute of Technology (gray-matter and white matter) Human Brain Atlas using radiologic images and descriptions. The total proportion of events was calculated for each region. A network diffusion model was implemented, and any brain regions showing a significant association (P < .05, family-wise error-corrected) between predicted and measured events were considered epicenters. Within gray matter, neurologic events were widely distributed, with the largest number of events (∼10%) observed in the bilateral superior temporal, precentral, and lateral occipital cortices, respectively. Network diffusion modeling showed a significant association between predicted and measured gray matter events when the spread of pathology was seeded from the bilateral cerebellum (r = 0.51, P < .001, corrected) and putamen (r = 0.4, P = .02, corrected). In white matter, most events (∼26%) were observed within the bilateral corticospinal tracts. The risk of bias was not considered because all studies were either case series or case studies. Transconnectome diffusion of pathology via the structural network of the brain may contribute to the spread of neurologic events in patients with COVID-19.

Clinically Silent Brain Injury and Perioperative Neurological Events in Patients With Left Ventricular Assist Device: A Brain Autopsy Study.

Current studies underestimate the prevalence of brain injury in patients with left ventricular assist devices (LVADs), as CT scans are not sensitive in detecting cerebral ischemia. Using postmortem neuropathological evaluation, we sought to characterize the types and risk factors of brain injury in LVAD patients. We reviewed 24 LVAD patients who underwent brain autopsy with gross and microscopic examinations from 1993 through 2019 at a single tertiary center. Patients who expired less than 7 days after implantation or who underwent explantation more than 7 days before death were excluded. Our study demonstrated that all LVAD nonsurvivors developed brain injury. The most common brain injury was hemorrhage (71%), followed by infarct (42%) and hypoxic ischemic brain injury (HIBI) (33%), and 10 patients (42%) presented with more than 1 brain injury. Cerebral microbleeds (CMBs) and intracranial hemorrhage were present in 33% and 42%, respectively. In those with intracranial hemorrhage, subarachnoid hemorrhage (25%) and intracerebral hemorrhage (25%) were more common than subdural hematoma (4%). Intracranial hemorrhage was associated with driveline infection (P = 0.047), and HIBI was associated with prior history of chronic obstructive pulmonary disease (P = 0.037). Fourteen (60%) had clinically silent brain injury with 65% of hemorrhages and 70% of infarcts being silent. However, the impact of silent brain injury on neurologic outcome and mortality remains unclear. Standardized neurologic monitoring and surveillance are recommended to better detect these clinically silent brain injury.

Hemoglobin Concentration May Influence the Incidence of Postoperative Transient Neurological Events in Patients With Moyamoya After Extracranial-intracranial Arterial Bypass: A Retrospective Single Center Experience.

Moyamoya is a rare condition characterized by cerebral angiographic findings of intracranial carotid artery stenosis with abnormal net-like vessels in the brain, and often presents as transient ischemic attacks or intracranial hemorrhage. Revascularization in the form of extracranial-intracranial (EC-IC) artery bypass has demonstrated efficacy in preventing ischemic attacks and intracranial hemorrhage, although it is associated with a relatively high rate of perioperative ischemic and hemorrhagic stroke. This retrospective analysis aims to evaluate the possible association between postoperative hemoglobin (Hgb) concentration and early postoperative transient neurological events (TNEs) experienced at our center. Consecutive patients undergoing EC-IC bypass between January 1, 2017 and August 31, 2019 were identified, resulting in a study population of 24 patients with 34 individual cases for different cerebral hemispheres. Postoperative Hgb level was evaluated upon arrival to the intensive care unit (ICU) and the primary outcome was the occurrence of TNEs within 24-hours after surgery. The incidence of TNEs within 24 hours postoperatively was 12% (n=4). Statistically significant differences were demonstrated between patients who did and did not experience TNEs in the postoperative period: total Hgb value (mean 9.4 vs. 11.3 g/dL, respectively; P=0.012) and percentage of patients with Hgb <10 g/dL (75% vs. 20%, respectively; P=0.048). Patients with a postoperative Hgb value <10 g/dL upon arrival to the ICU were significantly more likely to experience TNEs (odds ratio, 12; 95% confidence interval, 1.053-136.794; P=0.045). This study reports a possible association between postoperative Hgb level and the occurrence of TNEs within the first 24 hours after surgery in patients undergoing EC-IC for moyamoya.