Neurological Mortality Research Articles

Risk Factors Associated With Neurological and Extra-Neurological Complications and Mortality in Patients With Stroke.

Introduction Understanding when and how systemic complications can occur after an acute stroke is crucial. It is important to identify patients who are at higher risk for these complications. Early and effective treatment based on this knowledge can significantly improve patient outcomes. The objective of this study was to identify the risk factors associated with neurological and extra-neurological complications and mortality in stroke patients treated at a secondary care hospital. Methods Of a total of 170 patients diagnosed with hemorrhagic/ischemic stroke and transient cerebral ischemia at a secondary care hospital in Mexico, the records of 125 were reviewed and of these, 86 were included in the study. The study group comprised 86 adult patients (> 18 years of age) diagnosed with ischemic or hemorrhagic stroke or transient cerebral ischemia. Their demographics, clinical characteristics, in-hospital complications, and mortality were retrospectively analyzed. Results Of the 86 patients examined, 34.9% experienced complications, regardless of the type of stroke. The most significant factor associated with mortality and complications during hospitalization in patients with stroke was previous diseases. Other factors that were linked to higher mortality were pre-existing medical conditions. The most common neurological complication among patients with stroke during hospitalization was intracranial hypertension (3.5%). As for extra-neurological complications, pressure ulcers and nosocomial pneumonia had an occurrence rate of 4.7%. Conclusions The main neurological complication during hospitalization of patients with stroke was intracranial hypertension, while the extra neurological complications were pressure ulcers and nosocomial pneumonia.

Best medical management versus intravenous thrombolysis for mild non-disabling ischemic stroke: A prospective noninferiority registry study

ObjectivesThe efficacy and safety of intravenous thrombolysis uncertain in patients with non-disabling mild ischemic stroke. Our aim was to investigate whether best medical management only is noninferior to intravenous thrombolysis plus best medical management therapy for achieving favorable functional outcome at 90 days. Materials and methodsIn a prospective acute ischemic stroke registry from 2018 through 2020, 314 non-disabling mild ischemic stroke patients received best medical management only and 638 underwent intravenous thrombolysis plus best medical management. The primary outcome was modified Rankin Scale ≤1 at Day 90. The noninferiority margin was −5%. Secondary outcomes of hemorrhagic transformation, early neurologic deterioration and mortality were also evaluated. ResultsThe best medical management only was noninferior to the combined therapy of intravenous thrombolysis and best medical management with regard to the primary outcome (unadjusted risk difference, 1.16%; 95% CI, −3.48% ∼ 5.8%; p = 0.0046 for noninferiority; adjusted risk difference, 3.01%; 95% CI, −3.39% ∼ 9.41%). After propensity score matching, p < 0.0001 for noninferiority. RD, 4.03%; 95% CI, −1.59% ∼ 9.69%. p < 0.0001 for noninferiority. Adjusted RD, 5.23%; 95% CI, −1.88% ∼ 9.97%. The occurrence of hemorrhagic transformation was significantly increased in the group of combination therapy (OR, 4.26; 95% CI, 1.30 to 13.99; p = 0.008), while no significant difference was detected in early neurologic deterioration (OR, 1.11; 95% CI, 0.49–2.52; p = 0.808) and mortality (OR, 0.57; 95% CI, 0.20 to 1.69; p = 0.214) between groups. ConclusionsIn the present study, we found the best medical management only was noninferior to the combination therapy of intravenous thrombolysis plus best medical management for non-disabling mild ischemic stroke within 4.5 h after onset. Best medical management may be a treatment of choice for non-disabling mild ischemic stroke patients. Further randomized controlled studies are warranted.

Multiple meningiomas: Epidemiology, management, and outcomes.

Meningiomas are the most common nonmalignant brain tumor in adults, with an increasing incidence of asymptomatic meningiomas diagnosed on more ubiquitous neuroimaging. A subset of meningioma patients bear 2 or more spatially separated synchronous or metachronous tumors termed "multiple meningiomas" (MM), reported to occur in only 1%-10% of patients, though recent data indicate higher incidence. MM constitute a distinct clinical entity, with unique etiologies including sporadic, familial and radiation-induced, and pose special management challenges. While the pathophysiology of MM is not established, theories include independent origin in disparate locations through unique genetic events, and the "monoclonal hypothesis" of a transformed neoplastic clone with subarachnoid seeding precipitating numerous distinct meningiomas. Patients with solitary meningiomas carry the risk of long-term neurological morbidity and mortality, as well as impaired health-related quality of life, despite being a generally benign and surgically curable tumor. For patients with MM, the situation is even less favorable. MM should be regarded as a chronic disease, and in many cases, the management goal is disease control, as cure is seldom possible. Multiple interventions and lifelong surveillance are sometimes necessary. We aim to review the MM literature and create a comprehensive overview, including an evidence-based management paradigm.

The role of targeted temperature management in 30-day hospital readmissions in cardiac arrest survivors: A national population-based study.

Targeted temperature management (TTM) implementation following resuscitation from cardiac arrest is controversial. Although prior studies have shown that TTMimproves neurological outcomes and mortality, less is known about the rates or causes of readmission in cardiac arrest survivors within 30days. We aimed to determine whether the implementation of TTM improves all-cause 30-day unplanned readmission rates in cardiac arrest survivors. Using the Nationwide Readmissions Database, we identified 353,379 adult cardiac arrest index hospitalizations and discharges using the International Classification of Diseases, 9thand 10thcodes. The primary outcome was 30-day all-cause unplanned readmissions following cardiac arrest discharge. Secondary outcomes included 30-day readmission rates and reasons, including impacts on other organ systems. Of 353,379 discharges for cardiac arrest with 30-day readmission,9,898 (2.80%) received TTM during index hospitalization. TTM implementation was associated with lower 30-day all-cause unplanned readmission rates versus non-recipients(6.30% vs. 9.30%, p<0.001). During index hospitalization, receiving TTM was also associated with higher rates of AKI (41.12% vs. 37.62%, p<0.001) and AHF (20.13% vs. 17.30%, p<0.001). We identified an association between lower rates of 30-day readmission for AKI (18.34% vs. 27.48%, p<0.05) and trend toward lower AHF readmissions (11.32% vs. 17.97%, p=0.05) among TTM recipients. Our study highlights a possible negative association between TTM and unplanned 30-day readmission in cardiac arrest survivors, thereby potentially reducing the impact and burden of increased short-term readmission in these patients. Future randomized studies are warranted to optimize TTM use during post-arrest care.

Single-cell transcriptomics reveal a hyperacute cytokine and immune checkpoint axis after cardiac arrest in patients with poor neurological outcome

Most patients hospitalized after cardiac arrest (CA) die because of neurological injury. The systemic inflammatory response after CA is associated with neurological injury and mortality but remains poorly defined. We determine the innate immune network induced by clinical CA at single-cell resolution. Immune cell states diverge as early as 6h post-CA between patients with good or poor neurological outcomes 30days after CA. Nectin-2+ monocyte and Tim-3+ natural killer (NK) cell subpopulations are associated with poor outcomes, and interactome analysis highlights their crosstalk via cytokines and immune checkpoints. Exvivo studies of peripheral blood cells from CA patients demonstrate that immune checkpoints are a compensatory mechanism against inflammation after CA. Interferon γ (IFNγ)/interleukin-10 (IL-10) induced Nectin-2 on monocytes; in a negative feedback loop, Nectin-2 suppresses IFNγ production by NK cells. The initial hours after CA may represent a window for therapeutic intervention in the resolution of inflammation via immune checkpoints. This work was supported by funding from the American Heart Association, Brigham and Women's Hospital Department of Medicine, the Evergreen Innovation Fund, and the National Institutes of Health.

Hypothermia after extracorporeal cardiopulmonary resuscitation not associated with improved neurologic complications or survival in children: An analysis of the ELSO registry

AimTo analyze the association between hypothermia and neurologic complications among children who were treated with extracorporeal cardiopulmonary resuscitation (ECPR) using the Extracorporeal Life Support Organization (ELSO) international registry. MethodsWe conducted a retrospective, multicenter, database study utilizing ELSO data for ECPR encounters from January 1, 2011, through December 31, 2019. Exclusion criteria included multiple ECMO runs and lack of variable data. The primary exposure was hypothermia under 34 °C for greater than 24 hours. The primary outcome, determined a priori, was a composite of neurologic complications defined by ELSO registry including brain death, seizures, infarction, hemorrhage, diffuse ischemia. Secondary outcomes were mortality on ECMO and mortality prior to hospital discharge. Multivariable logistic regression determined the odds of neurologic complications, mortality on ECMO or prior to hospital discharge associated with hypothermia after adjustment for available pertinent covariables. ResultsOf the 2,289 ECPR encounters, no difference in odds of neurologic complications were found between the hypothermia and non-hypothermia groups (AOR 1.10, 95% CI 0.80–1.51). However, hypothermia exposure was associated with decreased odds of mortality on ECMO (AOR 0.76, 95% CI 0.59–0.97), but no difference in mortality prior to hospital discharge (AOR 0.96, 95% CI 0.76–1.21) ConclusionAnalysis of a large, multicenter, international dataset demonstrates that hypothermia for greater than 24 hours among children who undergo ECPR is not associated with decreased neurologic complications or mortality benefit at time of hospital discharge.

Timing and Outcomes of Precoronary Artery Bypass Grafting Carotid Endarterectomy

The Society for Vascular Surgery Clinical Practice Guidelines suggests the timing of carotid endarterectomy (CEA) in patients with symptomatic or bilateral severe asymptomatic carotid stenosis needing coronary artery bypass grafting (CABG) be performed either with preoperative CEA or concomitantly with CABG. The optimal timing of CEA in patients with high grade unilateral stenosis, however, has been controversial due to equivocal and/or scarce data. This study examines our experience with pre-CABG CEA and timing in this patient population. This is a single-center retrospective review of all patients who underwent CEA before or during CABG between January 2010 and January 2021. All patients receiving CEA were anesthetized by a dedicated cardiac anesthesiologist. Patients were compared based on timing of CEA in relation to CABG: concomitant (CABG day 0 from CEA) and nonconcomitant (CABG day 1-30 after CEA). The nonconcomitant cohort was substratified into hyperacute (CABG within 48 hours), acute (CABG within 2 weeks), and subacute (CABG within 30 days). Demographics and status of carotid disease were collated. Primary outcomes included stroke, defined as new neurologic deficit, myocardial infarction (MI), 30-day readmission, and 30-day mortality. A total of 39 patients were identified in the study population. Of these, 9 (23%) patients underwent CEA and CABG concomitantly, with 30 receiving nonconcomitant CEA (hyperacute [9, 23%]; acute [16, 41%]; subacute [5, 13%]). Baseline demographics and comorbidities were similar between groups. The degree of internal carotid artery stenosis, presence of high-grade contralateral stenosis, and symptomatic carotid presentation did not impact perioperative outcomes. One stroke occurred after a concomitant CEA/CABG that was a bi-hemispheric event believed to be due to cannulating a highly diseased ascending aorta. One patient in the concomitant cohort developed postoperative MI, cardiogenic shock, and subsequent death (Table I). There was no observed stroke, MI, or death in the nonconcomitant cohort. Thirty-day readmission and mortality were similar between all groups (Tables I and II). However, when comparing aggregate stoke/MI (Table I), a statistically significant difference was observed in favor of the nonconcomitant cohort (P = .007). Careful consideration is needed when determining appropriate timing for coronary revascularization in patients with carotid disease. These data suggest that nonconcomitant, preoperative CEA can be performed safely by a dedicated cardiac anesthesiologist before CABG. Concomitant CEA/CABG, as reflected in these data, carries an added procedural risk of stroke and a potentially poor cardiac outcome. Further study is warranted to elucidate the role of timing in perioperative outcomes for patients requiring CEA and CABG.Table IPerioperative outcomes for patients undergoing coronary artery bypass grafting (CABG) within 30 days of carotid endarterectomy (CEA)Concomitant CABG (n = 9)Nonconcomitant CABG (n = 30)P valuePostoperative events (MI, NS), No. (%)2 (22.2)0 (0).007a30-day readmission, No. (%)1 (11.1)3 (10).9330-day mortality, No. (%)1 (11.1)0 (0).07MI, Myocardial infarction; NS, neurologic symptoms. Open table in a new tab Table IIPerioperative outcomes for patients undergoing coronary artery bypass grafting (CABG) within 30 days of carotid endarterectomy (CEA), with the nonconcomitant CEA/CABG cohort substratified by timingConcomitant CABG (n = 9)Hyperacute CABG (n = 9)Acute CABG (n = 16)Subacute CABG (n = 5)P valuePostoperative events (MI, NS), No. (%)2 (11.1)0 (0)0 (0)0 (0).3530-day readmission, No. (%)1 (11.1)0 (0)1 (6.3)2 (40).1130-day mortality, No. (%)1 (11.1)0 (0)0 (0)0 (0).35MI, Myocardial infarction; NS, neurologic symptoms. Open table in a new tab

Outcomes in children after mild neonatal hypoxic ischaemic encephalopathy: A population-based cohort study.

To investigate whether mild neonatal hypoxic ischaemic encephalopathy (HIE) in term born infants is associated with cerebral palsy, epilepsy, mental retardation and death up to 6 years of age. Population-based cohort study. Sweden, 2009-2015. Live term born infants without congenital malformations or chromosomal abnormalities (n = 505 075). Birth and health data were retrieved from Swedish national health and quality registers. Mild HIE was identified by diagnosis in either the Swedish Medical Birth Register or the Swedish Neonatal Quality Register. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). A composite of the outcomes cerebral palsy, epilepsy, mental retardation and death up to 6 years of age. Median follow-up time was 3.3 years after birth. Of 414 infants diagnosed with mild HIE, 17 were classified according to the composite outcome and incidence rates were 12.6 and 2.9 per 1000 child-years in infants with and without HIE respectively. Infants with mild HIE was four times as likely to be diagnosed with the composite outcome (HR 4.42, 95% CI 2.75-7.12) compared with infants without HIE. When analysed separately, associations were found with cerebral palsy (HR 21.50, 95% CI 9.59-48.19) and death (HR 19.10, 95% CI 7.90-46.21). HRs remained essentially unchanged after adjustment for covariates. Mild neonatal HIE was associated with neurological morbidity and mortality in childhood. Challenges include identifying infants who may develop morbidity and how to prevent adverse outcomes.

Long-term outcomes following pipeline embolization of unruptured aneurysms.

Flow diversion using the pipeline embolization device (PED) for unruptured aneurysms is associated with high occlusion and low morbidity and mortality. However, most reports have limited follow-up of 1-2 years. Therefore, we sought to report our outcomes after PED for unruptured aneurysms in patients with at least 5-years of follow-up. Review of patients undergoing PED for unruptured aneurysms from 2009 to 2016. Overall, 135 patients with 138 aneurysms were included for analysis. Seventy-eight percent of aneurysms (n=107) over a median radiographic follow-up of 5.0 years underwent complete occlusion. Among aneurysms with at least 5-years of radiographic follow-up (n=71), 79% (n=56) achieved complete obliteration. No aneurysm recanalized after radiographic obliteration. Furthermore, over a median clinical follow-up period of 4.9 years, 84% of patients (n=115) self-reported mRS scores between 0 and 2. For patients with at least 5-years of clinical follow-up, 88% (n=61) reported mRS between 0 and 2. In total, 3% (n=4) of patients experienced a major, non-fatal neurologic complication related to the PED, 5% (n=7) of patients experienced a minor neurologic complication related to PED placement, and 2% (n=3) died from either delayed aneurysm rupture, delayed ipsilateral hemorrhage after PED placement, or delayed (9 months after treatment) neural compression after progressive thrombosis of a PED-treated dolichoectactic vertebrobasilar aneurysm. Treatment of unruptured aneurysms with the PED is associated with high rates of long-term angiographic occlusion and low, albeit clinically important, rates of major neurologic morbidity and mortality. Thus, flow diversion via PED placement is safe, effective, and durable.

Perioperative Outcomes of Hyperlactatemia during Craniotomy: A Systematic Review and Meta-Analysis of 1,832 Patients

Abstract Background Hyperlactatemia, is common in patients undergoing neurosurgical procedures. Several studies have identified potential risk factors for developing hyperlactatemia in neurosurgical patients, including body mass index, surgery duration, tumour volume, and certain drugs such as volatile anesthetic agents and corticosteroids. This systematic review and meta-analysis examined the evidence of the association between perioperative lactate levels in patients undergoing brain surgery and postoperative morbidity and mortality. Methods Using PubMed, Scopus, Web of Science, Embase, CINAHL, Medline, Google Scholar, and the Cochrane Central Register of Controlled Trials databases, a systematic literature search was conducted for studies examining the association between perioperative hyperlactatemia and postoperative outcomes in patients undergoing brain surgery. Two authors independently evaluated the full-text papers for eligibility, and then data extraction and meta-analyses of similar studies were conducted (using a random effect model for each outcome measure). The Newcastle Ottawa Scale was used to evaluate the risk of bias (NOS scale). Results Seven observational studies were included, and a total of 1,832 patients were assessed in the systematic review and meta-analysis. The quality of the included studies ranged from poor to high quality according to the NOS quality assessment tool. Meta-analysis results revealed no significant association between perioperative hyperlactatemia and postoperative new neurological deficits (five studies: odds ratio [OR] = 0.97, 95% confidence interval [CI] [0.50–1.87], p = 0.92; heterogeneity: I 2 = 38%, p = 0.18). Similarly, perioperative hyperlactatemia was neither significantly associated with increased 30-day postoperative mortality (two studies; OR = 0.20, 95% CI [0.02–2.00], p = 0.17; heterogeneity: I 2 = 0%, p = 0.59) nor 6 months survival rate (three studies; OR = 1.05, 95% CI [0.75–1.47], p = 0.79; heterogeneity: I 2 = 0%, p = 0.51). Moreover, there was no difference in the length of hospital stay between the two groups (four studies: mean difference = –0.85, 95% CI [–1.73 to 0.03], p = 0.06). Pooled studies were not homogenous (I 2 = 68%, p = 0.03). Conclusion Perioperative hyperlactatemia is benign in neurosurgical patients and is not associated with significant postoperative outcomes, such as developing new postoperative neurological deficit, 30-day mortality, 6-month survival, or prolonged hospital stay.

Change in habitual intakes of flavonoid-rich foods and mortality in US males and females

BackgroundHigher baseline intakes of flavonoid-rich foods and beverages are associated with a lower risk of chronic disease and mortality in observational studies. However, associations between changes in intakes and mortality remain unclear. We aimed to evaluate associations between 8-year changes in intakes of (1) individual flavonoid-rich foods and (2) a composite measure (termed the ‘flavodiet’) of foods and beverages that are known to be main contributors to flavonoid intake and subsequent total and cause-specific mortality.MethodsWe evaluated associations between 8-year changes in intakes of (1) individual flavonoid-rich foods and (2) a novel ‘flavodiet’ score and total and cause-specific mortality. We included 55,786 females from the Nurses’ Health Study (NHS) and 29,800 males from the Health Professionals Follow-up Study (HPFS), without chronic disease at baseline in our analyses. Using multivariable-adjusted Cox proportional hazard models, we examined associations of 8-year changes in intakes of (1) flavonoid-rich foods and (2) the flavodiet score with subsequent 2-year lagged 6-year risk of mortality adjusting for baseline intakes. Data were pooled using fixed-effects meta-analyses.ResultsWe documented 15,293 deaths in the NHS and 8988 deaths in HPFS between 1986 and 2018. For blueberries, red wine and peppers, a 5%, 4% and 9% lower risk of mortality, respectively, was seen for each 3.5 servings/week increase in intakes while for tea, a 3% lower risk was seen for each 7 servings/week increase [Pooled HR (95% CI) for blueberries; 0.95 (0.91, 0.99); red wine: 0.96 (0.93, 0.99); peppers: 0.91 (0.88, 0.95); and tea: 0.97 (0.95, 0.98)]. Conversely, a 3.5 servings/week increase in intakes of onions and grapefruit plus grapefruit juice was associated with a 5% and 6% higher risk of total mortality, respectively. An increase of 3 servings per day in the flavodiet score was associated with an 8% lower risk of total mortality [Pooled HR: 0.92 (0.89, 0.96)], and a 13% lower risk of neurological mortality [Pooled HR: 0.87 (0.79, 0.97)], after multivariable adjustments.ConclusionsEncouraging an increased intake of specific flavonoid-rich foods and beverages, namely tea, blueberries, red wine, and peppers, even in middle age, may lower early mortality risk.

Validation of the rCAST score and comparison to the PCAC and FOUR scores for prognostication after out-of-hospital cardiac arrest

AimEarly, accurate outcome prediction after out-of-hospital cardiac arrest (OHCA) is critical for clinical decision-making and resource allocation. We sought to validate the revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST) score in a United States cohort and compare its prognostic performance to the Pittsburgh Cardiac Arrest Category (PCAC) and Full Outline of UnResponsiveness (FOUR) scores. MethodsThis is a single-center, retrospective study of OHCA patients admitted between January 2014-August 2022. Area under the receiver operating curve (AUC) was computed for each score for predicting poor neurologic outcome at discharge and in-hospital mortality. We compared the scores’ predictive abilities via Delong’s test. ResultsOf 505 OHCA patients with all scores available, the medians [IQR] for rCAST, PCAC, and FOUR scores were 9.5 [6.0, 11.5], 4 [3, 4], and 2 [0, 5], respectively. The AUC [95% confidence interval] of the rCAST, PCAC, and FOUR scores for predicting poor neurologic outcome were 0.815 [0.763–0.867], 0.753 [0.697–0.809], and 0.841 [0.796–0.886], respectively. The AUC [95% confidence interval] of the rCAST, PCAC, and FOUR scores for predicting mortality were 0.799 [0.751–0.847], 0.723 [0.673–0.773], and 0.813 [0.770–0.855], respectively. The rCAST score was superior to the PCAC score for predicting mortality (p = 0.017). The FOUR score was superior to the PCAC score for predicting poor neurological outcome (p < 0.001) and mortality (p < 0.001). ConclusionThe rCAST score can reliably predict poor outcome in a United States cohort of OHCA patients regardless of TTM status and outperforms the PCAC score.

Association of intraoperative lactate elevation and postoperative mortality and morbidity in patients undergoing craniotomy: retrospective analysis.

Intraoperative lactate levels increase in patients undergoing craniotomy, but the reason is not yet fully known. High levels of intraoperative lactate are associated with mortality and morbidity in patients with septic shock and abdominal and cardiac surgery. Investigate whether intraoperative lactate elevation is associated with postoperative systemic and neurological complications and mortality in craniotomy. Retrospective study SETTING: University hospital in Turkey. In this study, we included patients who underwent elective intracranial tumor surgery in our hospital between 1 January 2018, and 31 December 2018. According to the level of intraoperative lactate, patients were divided into two groups: high (≥2.1 mmol/L) and normal (<2.1 mmol/L). The groups were compared by the presence of postoperative new neurological deficits, postoperative surgical and medical complications, mechanical ventilation duration, 30-day mortality, in-hospital mortality, and hospital stay length. Cox regression analysis was performed for the 30-day mortality outcome. Association between intraoperative lactate levels and postoperative 30-day mortality. 163 patients with lactate data. While no significant difference was found between the groups regarding age, gender, ASA score, tumor location, operation time and pathology results, preoperative neurologic deficits were higher in the high intraoperative lactate group (P=.017). No statically significant difference was found between the groups for postoperative neurological deficit, need for prolonged mechanical ventilation, and hospital stay length. The postoperative 30-day mortality rate was higher in the group with high intraoperative lactate (P=.028). High lactate and medical complications were significant in the Cox analysis. Intraoperative lactate elevation was associated with postoperative 30-day mortality in patients undergoing craniotomy. The intraoperative level of lactate is an important mortality predictor in patients undergoing craniotomy. Retrospective design and single-centered, missing most data for several variables. None.

Subclavian artery revascularization with subclavian-carotid transposition for TEVAR and non-TEVAR patients.

Subclavian artery revascularization (SAR) has become an increasingly performed technique in patients undergoing thoracic endovascular aortic aneurysm repair (TEVAR), in order to optimize the proximal landing zone, or in patients with significant atherosclerotic diseases. SAR was usually achieved through carotid-subclavian bypass (CSB) which is daunted by graft and patency-related issues, or through subclavian carotid transposition (SCT) which has recently been reconsidered as a potential solution. Nowadays, multiple endovascular strategies including parallel grafts, chimney graft and branch-fenestrated repair, are available in patients unfit for open SAR. However, there is no consensus on the preferable technique in both TEVAR- and non TEVAR-patients. The purpose of this study was to evaluate our experience with SCT in terms of overall postoperative adverse events and mid-term patency rate. We performed a retrospective cohort study, including all patients who underwent SCT between June 2014 and March 2020 at our Division. Preoperative risk factors, symptoms, intraoperative details, postoperative outcomes and follow-up data were collected. A total of 27 patients were included in this study. Indications for SCT included aortic arch debranching for TEVAR for thoracic aortic aneurysm and type B dissection and symptomatic subclavian steal syndrome (SSS). There were no major perioperative adverse events or major neurological complications; five minor adverse events occurred (18.5%) (3 Horner' Syndrome, 1 hematoma requiring reoperation,1 pneumothorax). Peripheral nerve injuries and lymphatic lesions were not recorded. On a mean follow-up of 21±16 months, SCT patency was confirmed in all patients and no deaths occurred. Comparison of baseline and operative characteristics and intraoperative details between groups of patients with or without adverse events did not found differences. SCT should be considered a feasible, effective and safe technique for SAR, with low perioperative complications and optimal mid-term patency. This surgical technique appears to provide a lower risk of neurological events and mortality, particularly in TEVAR patients, reducing the complications caused by the coverage of the left subclavian artery.

Acute ischemic stroke: how to investigate the association between disease etiology and gene expression profiles

Background: Acute ischemic stroke (AIS) represents one of the principal causes of neurological morbidity and mortality worldwide. For a prompt and efficient cerebral blood restoration, intravenous treatment with rt-PA is often combined with mechanical thrombectomy (MT) which provides cerebral thrombi (CT) as study material, allowing the investigation of its cellular composition, morphological and histopathological features. Indeed, the determination of stroke etiology, typically defined by the TOAST classification, is paramount for prognostic factors, outcome, and management of the event. Aim of the study is therefore to highlight and analyze gene expression profiles in thrombotic tissue and peripheral blood (PB) in the comparison between strokes of cardioembolic (CE) and atherosclerotic (LAA) origin. Methods: We performed gene expression profiles of 92 patients. CT were stored in RNA later and RNA was extracted by PAX gene blood miRNA kit. The global gene expression profile was assessed by Affymetrix technology using GeneChip Human Transcriptome Array 2.0 combined with Affymetrix Transcriptome Analysis Console (TAC) Software. Results: Currently, we focused our attention on CT data analysis. The analysis revealed a significant difference (p-value&lt;0.05 and FoldChange=2 as threshold) in gene expression when comparing LAA and CE stroke. In particular, from CT of atherosclerotic origin emerges an overexpression of 1766 genes. Prominent among them are genes such as MMP-9, TGFB, TGFBR and CXCL1, primarily involved in neutrophil-mediated immunity, Blood-Brain Barrier (BBB) disruption processes, and associated with atherosclerotic plaque instability and related to poor neurological outcome, suggesting a deleterious role in human brain injury. As concerns CE patients, 57 genes mainly involved in transcriptional regulatory processes turn out to be significantly overexpressed. Conclusions: Transcriptome profiling is a powerful weapon for revealing expression patterns associated with complex disorders. The variation of gene expression profiles confirmed and extended several known pathophysiological mechanisms and may be one way of delineating different stroke etiology.

Assessment of the Diagnostic Utility of GeneXpert Mycobacterium tuberculosis/Rifampicin (MTB/RIF) Assay in the Suspected Cases of Tuberculous Meningitis.

Tuberculous meningitis (TBM) is a manifestation of extrapulmonary tuberculosis (EPTB) caused by Mycobacterium tuberculosis (MTB). The central nervous system is involved in about 1%-2% of all current tuberculosis (TB) cases and about 7%-8% of all EPTB. if not treated early, TBM leads to a high rate of neurological sequelae and mortality. This study aimed to assess the diagnostic performance of the GeneXpert MTB/rifampicin (RIF) assay in patients with TBM. A total of 100 suspected TBM cases were enrolled from various departments at tertiary care hospital, Bhopal, Madhya Pradesh, India, and classified as definite, possible, or probable TBM. The clinical samples were tested for microbiological and other cerebrospinal fluid(CSF) testing. Out of 100 cases, 14 (14%) were classified as definite TBM, 15 (15%) were having probable TBM, and 71 (71%) were having possible TBM.Out of a total of 100 participants, all were negative for acid-fast bacilli (AFB) staining. Of the 100 cases, 11 (11%) were positive by mycobacterium growth indicator tube (MGIT) culture, of which only four (36.36%) were positive by GeneXpert MTB/RIF. GeneXpert MTB/RIF detected three (3%) cases that were negative by MGIT culture. Ten (90.9%) of the 11 MGIT-positive culture isolates were found to be RIFsensitive while one (9.1%) was found to be RIF resistant. Three cases tested positive/sensitive by the GeneXpert MTB/RIF but negative by MGIT culture. Six (85%) of the seven GeneXpert MTB/RIF positive cases were RIF sensitive while one (15%) was RIF resistant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were 36.36% (95% Confidence Interval (CI) (10.93% to 69.21%)), 96.63% (95% CI (90.46% to 99.30%)), 57.14% (95% CI (25.50% to 83.85%)), 92.47% (95% CI (88.70% to 95.06%)) and 90% (95% CI (82.38% to 95.10%)) for GeneXpert MTB/RIF assay, compared with MGIT culture as the reference standard. Our study found that the sensitivity is lower when compared to culture, so using GeneXpert MTB/RIF alone is not recommended. Overall performance of GeneXpert MTB/RIF assay is noteworthy. The GeneXpert MTB/RIF assay is a potentially accepted test for obtaining an earlier diagnosis, and if it tested positive, the treatment should begin immediately. However, culture must be performed in GeneXpert MTB/RIF negative cases.

Therapeutic Hypothermia Following Cardiopulmonary Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

The risk-benefit profile of therapeutic hypothermia is controversial with several randomized controlled trials providing conflicting results. The purpose of this systematic review and meta-analysis was to determine if therapeutic hypothermia provides beneficial neurologic outcomes relative to adverse effects. MEDLINE and EMBASE databases were searched for randomized controlled trials of post-cardiac arrest patients comparing therapeutic hypothermia (~33 degrees Celsius) to normothermia or the standard of care (36 - 38 degrees Celsius). Data were collected using the Covidence systematic review software. Statistical analysis was performed by Review Manager software. Risk of bias, sensitivity, and heterogeneity were analyzed using the Cochran's Collaboration tool, trial sequential analysis (TSA) software, and I2 statistic respectively. A total of 1825 studies were screened and 5 studies (n=3614) were included. No significant differences existed between the hypothermia group and normothermia for favorable neurologic outcome (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.97 to 1.41) or all-cause mortality (RR 0.97, 95% CI 0.89 to 1.05). When compared to normothermia, the hypothermia group had greater risk of adverse effects (RR 1.16, 95% CI 1.04 to 1.28), which was driven by the onset of arrhythmias. Subgroup analyses revealed that therapeutic hypothermia provided greater neurologic benefit in trials with a higher percentage of subjects with shockable rhythms (RR 0.73, 95% CI 0.6 to 0.88). Trial sequential analysis revealed statistical futility for therapeutic hypothermia and favorable neurologic outcome, mortality, and adverse effects. Therapeutic hypothermia does not provide consistent benefit in neurologic outcome or mortality in the general cardiac arrest population. Patients with shockable rhythms may show favorable neurologic outcome with therapeutic hypothermia and further investigation in this population is warranted. Any potential benefit associated with therapeutic hypothermia must be weighed against the increased risk of adverse effects, particularly the onset of arrhythmias.

309 Mechanical Thrombectomy for Acute Basilar Artery Occlusion, Where Do We Stand? A Safety and Efficacy Analysis

INTRODUCTION: Acute basilar artery occlusion accounts for 1% of all ischemic strokes, but more often than not, leads to devastating neurological injury and mortality. Many institutions still opt for best medical therapy for this type of ischemic stroke, however there is increasing evidence that mechanical thrombectomy for these patients leads to better outcomes. METHODS: This study was a retrospective chart review of a prospectively maintained database for patients with acute basilar artery occlusion treated with mechanical thrombectomy from January 2014 through March 2022. RESULTS: Our study included a total of 74 patients. The mean age was 62.7 years and 55.4% were male. The most common comorbidity was hypertension (73%). The mean door to puncture time was 75 minutes and the mean procedure time was 54 minutes. 86.5% of patients had a good mTICI score (≥ 2b). There were 4 patients who had procedural complications, and symptomatic intracerebral hemorrhage occurred in 3 patients. At 90 days, 62.5% of patients had a favorable functional outcome (mRS, 0 – 3). The mortality rate was 32.4% and 2% during the hospital admission and at 90 days respectively. Finally, on univariate analysis, the need for adjunct treatment and higher presenting NIHSS score was associated with poor functional outcome at 90 days (p-value, 0.03 and &lt;0.001 respectively). Shorter procedure time was associated with better revascularization (mTICI score ≥ 2b) (p-value, 0.0015). CONCLUSIONS: Our findings showed that MT is safe and effective for patients presenting with acute basilar artery conclusion and is in conjunction with previous literature. Final results from upcoming trials should hopefully establish MT as gold standard for these patients.

348 Risk of Rupture and Treatment Outcomes of Giant Pediatric Aneurysms: Multi-Institutional Case Series and Meta-Meta-Analysis

INTRODUCTION: Giant pediatric aneurysms are vascular malformations that can cause significant neurologic morbidity and mortality. Their rarity has precluded large cohort studies to inform their management. METHODS: Multi-institutional cohort study of cases from Boston Children’s Hospital (BCH) and the Barrow Neurologic Institute (BNI) along with systematic review and meta-analysis of previously reported cases. RESULTS: A total of 15 patients were included in the multi-institutional cohort, and an additional 88 patients were included from 14 series to yield 103 patients within the meta-analysis. Amongst the BCH patients, male sex was associated with giant size (OR .2; 95% CI 1.2-162.0).The most common aneurysm locations were in the MCA (38%), ICA (25%), vertebral artery (VA; 11%), and VBJ (8%). Within 69 reports containing radiographic data within the meta-analysis, 38% of aneurysms were saccular. Twenty-eight cases presented with rupture (28%). 0% of cavernous ICA aneurysms, 26% of other anterior circulation aneurysms, and 44% of posterior circulation aneurysms presented with rupture. Increasing age (OR 1.2; 95% CI 1.0-1.4) and saccular morphology (OR 5.3, 95% CI 1.5-18.9) were associated with presentation with rupture, while posterior location trended towards an association (OR 3.1, 95% CI 0.9-11.0). The majority of cases in the systematic review were treated (97%) rather than observed (3%). Endovascular and open treatments were utilized in 40 and 56% of cases. Survival was 97% for unruptured aneurysms and 82% for ruptured aneurysms. A favorable neurologic outcome occurred in 80% of unruptured cases and 54% of ruptured cases. Unruptured presentation (OR 3.7, 95% CI 1.3-11.1) and endovascular treatment modality were associated with a favorable outcome (OR 5.0; 95% CI 1.6-15.8). CONCLUSIONS: Giant pediatric aneurysms are unlikely to be discovered incidentally and often merit treatment. Increasing age and saccular morphology are r predict rupture, and should elevate the concern for semi-urgent treatment.

Regulation of microglia related neuroinflammation contributes to the protective effect of Gelsevirine on ischemic stroke.

Stroke, especially ischemic stroke, is an important cause of neurological morbidity and mortality worldwide. Growing evidence suggests that the immune system plays an intricate function in the pathophysiology of stroke. Gelsevirine (Gs), an alkaloid from Gelsemium elegans, has been proven to decrease inflammation and neuralgia in osteoarthritis previously, but its role in stroke is unknown. In this study, the middle cerebral artery occlusion (MCAO) mice model was used to evaluate the protective effect of Gs on stroke, and the administration of Gs significantly improved infarct volume, Bederson score, neurobiological function, apoptosis of neurons, and inflammation state in vivo. According to the data in vivo and the conditioned medium (CM) stimulated model in vitro, the beneficial effect of Gs came from the downregulation of the over-activity of microglia, such as the generation of inflammatory factors, dysfunction of mitochondria, production of ROS and so on. By RNA-seq analysis and Western-blot analysis, the JAK-STAT signal pathway plays a critical role in the anti-inflammatory effect of Gs. According to the results of molecular docking, inhibition assay, and thermal shift assay, the binding of Gs on JAK2 inhibited the activity of JAK2 which inhibited the over-activity of JAK2 and downregulated the phosphorylation of STAT3. Over-expression of a gain-of-function STAT3 mutation (K392R) abolished the beneficial effects of Gs. So, the downregulation of JAK2-STAT3 signaling pathway by Gs contributed to its anti-inflammatory effect on microglia in stroke. Our study revealed that Gs was benefit to stroke treatment by decreasing neuroinflammation in stroke as a potential drug candidate regulating the JAK2-STAT3 signal pathway.