Mechanical Thrombectomy for Ischemic Stroke Secondary to Large Vessel Occlusions in Patients on Extracorporeal Membrane Oxygenation.

INTRODUCTION: The use of short-term mechanical circulatory support (MCS) devices and procedures for function- and life-sustaining therapy is becoming a routine practice at many centers. Concomitant with the increasing use of MCS is the increasing recognition of acute brain injuries, including acute ischemic stroke, which may be caused by a myriad of MCS-driven factors. The aim of this case series was to document our experience with mechanical thrombectomy (MT) for ischemic stroke in extracorporeal membrane oxygenation (ECMO) patients. METHODS: We retrospectively reviewed a prospectively maintained database of patients undergoing endovascular thrombectomy for large vessel occlusion at our institution. We identified patients that were on ECMO and underwent thrombectomy. Baseline demographics and procedural and functional outcomes were collected. RESULTS: Three patients on ECMO were identified to have a large vessel occlusion and underwent thrombectomy. Two patients had an internal carotid artery terminus occlusion and one had a basilar artery occlusion. An mTICI 3 recanalization was achieved in all patients without postoperative hemorrhagic complications. Two patients achieved a 3-month mRS of 1, while one had mRS 4. CONCLUSION: Ischemic stroke can be associated with significant morbidity in MCS patients. We demonstrate that MT can be safely performed in this patient population with good outcomes.

Learning curve for endoscopic posterior cervical foraminotomy.

PURPOSE: While anterior cervical discectomy and fusion as well as cervical disk arthroplasty are gold standard treatments for the surgical treatment of cervical radiculopathy, posterior endoscopic cervical foraminotomy (PECF) as a substitute procedure is gaining popularity. To date, studies investigating the number of surgeries needed to achieve proficiency in this procedure are lacking. The purpose of the study is to examine the learning curve for PECF. METHODS: The learning curve in operative time for two fellowship-trained spine surgeons at independent institutions was retrospectively assessed for 90 uniportal PECF procedures (PBD: n = 26, CPH: n = 64) performed from 2015 to 2022. Operative time was assessed across consecutive cases using a nonparametric monotone regression, and a plateau in operative time was used as a proxy to define the learning curve. Secondary outcomes assessing achievement of endoscopic prowess before and after the initial learning curve included number of fluoroscopy images, visual analog scale (VAS) for neck and arm, Neck Disability Index (NDI), and the need for reoperation. RESULTS: There was no significant difference in operative time between surgeons (p = 0.420). The start of a plateau for Surgeon 1 occurred at 9 cases and 111.6 min. The start of a plateau for Surgeon 2 occurred at 29 cases and 114.7 min. A second plateau for Surgeon 2 occurred at 49 cases and 91.8 min. Fluoroscopy use did not significantly change before and after surmounting the learning curve. The majority of patients achieved minimally clinically important differences in VAS and NDI after PECF, but postoperative VAS and NDI did not significantly differ before and after achieving the learning curve. There were no significant differences in revisions or postoperative cervical injections before and after reaching a steady state in the learning curve. CONCLUSION: PECF is an advanced endoscopic technique with an initial improvement in operative time that occurred after as few as 8 cases to as many as 28 cases in this series. A second learning curve may occur with additional cases. Patient-reported outcomes improve following surgery, and these outcomes are independent of the surgeon's position on the learning curve. Fluoroscopy use does not change significantly along the learning curve. PECF is a safe and effective technique that current and future spine surgeons should consider as part of their armamentarium.

Cognitive, Psychiatric, and Quality of Life Outcomes in Adult Survivors of Extracorporeal Membrane Oxygenation Therapy: A Scoping Review of the Literature.

OBJECTIVES: To perform a scoping literature review of cognitive, psychiatric, and quality of life outcomes in adults undergoing extracorporeal membrane oxygenation for any indication. DATA SOURCES: We searched PubMed, EMBASE, Cochrane Library, Web of Science, CINAHL, and PsycINFO from inception to June 2019. STUDY SELECTION: Observational studies, clinical trials, qualitative studies, and case series with at least 10 adult subjects were included for analysis. Outcomes of interest consisted of general or domain-specific cognition, psychiatric illness, and quality of life measures that included both mental and physical health. DATA EXTRACTION: Study selection, data quality assessment, and interpretation of results were performed by two independent investigators in accordance with the PRISMA statement. DATA SYNTHESIS: Twenty-two articles were included in this review. Six described cognitive outcomes, 12 described psychiatric outcomes of which two were qualitative studies, and 16 described quality of life outcomes. Cognitive impairment was detected in varying degrees in every study that measured it. Three studies examined neuroimaging results and found neurologic injury to be more frequent in venoarterial versus venovenous extracorporeal membrane oxygenation, but described a variable correlation with cognitive impairment. Rates of depression, anxiety, and post-traumatic stress disorder were similar to other critically ill populations and were related to physical disability after extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation survivors' physical quality of life was worse than population norms but tended to improve with time, while mental quality of life did not differ significantly from the general population. Most studies did not include matched controls and instead compared outcomes to previously published values. CONCLUSIONS: Extracorporeal membrane oxygenation survivors experience cognitive impairment, psychiatric morbidity, and worse quality of life compared with the general population and similar to other survivors of critical illness. Physical disability in extracorporeal membrane oxygenation patients plays a significant role in psychiatric morbidity. However, it remains unclear if structural brain injury plays a role in these outcomes and whether extracorporeal membrane oxygenation causes secondary brain injury.

Mechanical ventilation in aneurysmal subarachnoid hemorrhage: systematic review and recommendations.

OBJECTIVE: Mechanical ventilation (MV) has a complex interplay with the pathophysiology of aneurysmal subarachnoid hemorrhage (aSAH). We aim to provide a review of the physiology of MV in patients with aSAH, give recommendations based on a systematic review of the literature, and highlight areas that still need investigation. DATA SOURCES: PubMed was queried for publications with the Medical Subject Headings (MeSH) terms "mechanical ventilation" and "aneurysmal subarachnoid hemorrhage" published between January 1, 1990, and March 1, 2020. Bibliographies of returned articles were reviewed for additional publications of interest. STUDY SELECTION: Study inclusion criteria included English language manuscripts with the study population being aSAH patients and the exposure being MV. Eligible studies included randomized controlled trials, observational trials, retrospective trials, case-control studies, case reports, or physiologic studies. Topics and articles excluded included review articles, pediatric populations, non-aneurysmal etiologies of subarachnoid hemorrhage, mycotic and traumatic subarachnoid hemorrhage, and articles regarding tracheostomies. DATA EXTRACTION: Articles were reviewed by one team member, and interpretation was verified by a second team member. DATA SYNTHESIS: Thirty-one articles met the inclusion criteria for this review. CONCLUSIONS: We make recommendations on oxygenation, hypercapnia, PEEP, APRV, ARDS, and intracranial pressure monitoring.

Proceedings from the Neurotherapeutics Symposium on Neurological Emergencies: Shaping the Future of Neurocritical Care.

Effective treatment options for patients with life-threatening neurological disorders are limited. To address this unmet need, high-impact translational research is essential for the advancement and development of novel therapeutic approaches in neurocritical care. "The Neurotherapeutics Symposium 2019-Neurological Emergencies" conference, held in Rochester, New York, in June 2019, was designed to accelerate translation of neurocritical care research via transdisciplinary team science and diversity enhancement. Diversity excellence in the neuroscience workforce brings innovative and creative perspectives, and team science broadens the scientific approach by incorporating views from multiple stakeholders. Both are essential components needed to address complex scientific questions. Under represented minorities and women were involved in the organization of the conference and accounted for 30-40% of speakers, moderators, and attendees. Participants represented a diverse group of stakeholders committed to translational research. Topics discussed at the conference included acute ischemic and hemorrhagic strokes, neurogenic respiratory dysregulation, seizures and status epilepticus, brain telemetry, neuroprognostication, disorders of consciousness, and multimodal monitoring. In these proceedings, we summarize the topics covered at the conference and suggest the groundwork for future high-yield research in neurologic emergencies.

Emergent carotid stenting and intra-arterial abciximab in acute ischemic stroke due to tandem occlusion.

OBJECTIVE: Acute occlusions of the extracranial internal carotid artery (ICA) and a major intracranial artery respond poorly to intravenous tissue plasminogen activator (tPA) and present an endovascular challenge. The aim of our study was to retrospectively delineate the feasibility of the combined use of emergent carotid stenting and intra-arterial (IA) Abciximab with intracranial revascularization in the setting of acute ischemic stroke and carotid occlusions at our institution. METHODS: Eleven patients with complete cervical carotid occlusion with or without concomitant intracranial ICA and/or MCA occlusion were identified from a single center, retrospective review of patients admitted to the Stroke unit. We evaluated all cases for complications of emergent cervical ICA recanalization employing carotid stenting and IA Abciximab. RESULTS: All patients had complete cervical carotid occlusion with (n = 8) or without (n = 3) concomitant intracranial ICA and/or MCA occlusion. Successful emergent cervical ICA recanalization was achieved in all cases. All patients were administered IA Abciximab (dose range 6-17 mg, average 11.4 mg) immediately following the cervical carotid stenting. There was complete recanalization in all patients with no procedural morbidity or mortality. A single case (1/11, 9%) developed asymptomatic hemorrhagic transformation. Upon discharge, 9 patients (9/11, 82%) had a mRS of 0-2 and 2 patients (2/11, 18%) had a mRS of 3. CONCLUSIONS: In acute ICA-MCA/distal ICA occlusions, extracranial stenting followed by intracranial IA Abciximab and thrombectomy appears feasible, effective, and safe. Further evaluation of this treatment strategy is warranted.

Activation of PPARα by Oral Clofibrate Increases Renal Fatty Acid Oxidation in Developing Pigs.

The objective of this study was to evaluate the effects of peroxisome proliferator-activated receptor α (PPARα) activation by clofibrate on both mitochondrial and peroxisomal fatty acid oxidation in the developing kidney. Ten newborn pigs from 5 litters were randomly assigned to two groups and fed either 5 mL of a control vehicle (2% Tween 80) or a vehicle containing clofibrate (75 mg/kg body weight, treatment). The pigs received oral gavage daily for three days. In vitro fatty acid oxidation was then measured in kidneys with and without mitochondria inhibitors (antimycin A and rotenone) using [1-14C]-labeled oleic acid (C18:1) and erucic acid (C22:1) as substrates. Clofibrate significantly stimulated C18:1 and C22:1 oxidation in mitochondria (p < 0.001) but not in peroxisomes. In addition, the oxidation rate of C18:1 was greater in mitochondria than peroxisomes, while the oxidation of C22:1 was higher in peroxisomes than mitochondria (p < 0.001). Consistent with the increase in fatty acid oxidation, the mRNA abundance and enzyme activity of carnitine palmitoyltransferase I (CPT I) in mitochondria were increased. Although mRNA of mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (mHMGCS) was increased, the ß-hydroxybutyrate concentration measured in kidneys did not increase in pigs treated with clofibrate. These findings indicate that PPARα activation stimulates renal fatty acid oxidation but not ketogenesis.

Imaging of amide proton transfer and nuclear Overhauser enhancement in ischemic stroke with corrections for competing effects.

Chemical exchange saturation transfer (CEST) potentially provides the ability to detect small solute pools through indirect measurements of attenuated water signals. However, CEST effects may be diluted by various competing effects, such as non-specific magnetization transfer (MT) and asymmetric MT effects, water longitudinal relaxation (T1 ) and direct water saturation (radiofrequency spillover). In the current study, CEST images were acquired in rats following ischemic stroke and analyzed by comparing the reciprocals of the CEST signals at three different saturation offsets. This combined approach corrects the above competing effects and provides a more robust signal metric sensitive specifically to the proton exchange rate constant. The corrected amide proton transfer (APT) data show greater differences between the ischemic and contralateral (non-ischemic) hemispheres. By contrast, corrected nuclear Overhauser enhancements (NOEs) around -3.5 ppm from water change over time in both hemispheres, indicating whole-brain changes that have not been reported previously. This study may help us to better understand the contrast mechanisms of APT and NOE imaging in ischemic stroke, and may also establish a framework for future stroke measurements using CEST imaging with spillover, MT and T1 corrections.

Isolation and characterization of stem cells from human central nervous system malignancies.

Central Nervous System (CNS) tumors include some of the most invasive and lethal tumors in humans. The poor prognosis in patients with CNS tumors is ascribed to their invasive nature. After the description of a stem cell-like cohort in hematopoietic cancers, tumor stem cells (TSCs) have been isolated from a variety of solid tumors, including brain tumors. Further research has uncovered the crucial role these cells play in the initiation and propagation of brain tumors. More importantly, TSCs have also been shown to be relatively resistant to conventional cytotoxic therapeutics, which may also account for the alarmingly high rate of CNS tumor recurrence. In order to elucidate prospective therapeutic targets it is imperative to study these cells in detail and to accomplish this, we need to be able to reliably isolate and characterize these cells. This chapter will therefore, provide an overview of the methods used to isolate and characterize stem cells from human CNS malignancies.

Laboratory models for central nervous system tumor stem cell research.

Central nervous system (CNS) tumors are complex organ systems comprising of a neoplastic component with associated vasculature, inflammatory cells, and reactive cellular and extracellular components. Research has identified a subset of cells in CNS tumors that portray defining properties of neural stem cells, namely, that of self-renewal and multi-potency. Growing evidence suggests that these tumor stem cells (TSC) play an important role in the maintenance and growth of the tumor. Furthermore, these cells have also been shown to be refractory to conventional therapy and may be crucial for tumor recurrence and metastasis. Current investigations are focusing on isolating these TSC from CNS tumors to investigate their unique biological processes. This understanding will help identify and develop more effective and comprehensive treatment strategies. This chapter provides an overview of some of the most commonly used laboratory models for CNSTSC research.

Emerging strategies for the treatment of tumor stem cells in central nervous system malignancies.

High-grade central nervous system (CNS) tumors are notorious for high rates of recurrence and poor outcomes. A small cohort of tumor cells, dubbed tumor stem cells (TSC), are now being recognized as an important subset of the tumor that is resistant to chemotherapy and radiotherapy and account for the high recurrence rates. Recent research is developing modalities to target TSCs specifically in a bid to improve the response of the tumor as a whole. The methods being employed to target TSCs include targeting TSC-specific pathways or receptors, TSC-sensitizing agents to chemotherapy and radiotherapy, immunotherapy, TSC-differentiating agents, and viral therapy. This chapter provides an overview of strategies that are expected to help develop new and more effective treatments for CNS tumors.

Inverse Z-spectrum analysis for spillover-, MT-, and T1 -corrected steady-state pulsed CEST-MRI--application to pH-weighted MRI of acute stroke.

Endogenous chemical exchange saturation transfer (CEST) effects are always diluted by competing effects, such as direct water proton saturation (spillover) and semi-solid macromolecular magnetization transfer (MT). This leads to unwanted T2 and MT signal contributions that lessen the CEST signal specificity to the underlying biochemical exchange processes. A spillover correction is of special interest for clinical static field strengths and protons resonating near the water peak. This is the case for all endogenous CEST agents, such as amide proton transfer, -OH-CEST of glycosaminoglycans, glucose or myo-inositol, and amine exchange of creatine or glutamate. All CEST effects also appear to be scaled by the T1 relaxation time of water, as they are mediated by the water pool. This forms the motivation for simple metrics that correct the CEST signal. Based on eigenspace theory, we propose a novel magnetization transfer ratio (MTRRex ), employing the inverse Z-spectrum, which eliminates spillover and semi-solid MT effects. This metric can be simply related to Rex , the exchange-dependent relaxation rate in the rotating frame, and ka , the inherent exchange rate. Furthermore, it can be scaled by the duty cycle, allowing for simple translation to clinical protocols. For verification, the amine proton exchange of creatine in solutions with different agar concentrations was studied experimentally at a clinical field strength of 3 T, where spillover effects are large. We demonstrate that spillover can be properly corrected and that quantitative evaluation of pH and creatine concentration is possible. This proves that MTRRex is a quantitative and biophysically specific CEST-MRI metric. Applied to acute stroke induced in rat brain, the corrected CEST signal shows significantly higher contrast between the stroke area and normal tissue, as well as less B1 dependence, than conventional approaches.

Targeting glioblastoma cancer stem cells: the next great hope?

Glioblastoma multiforme (GBM) is the most common primary brain tumor and is notorious for its poor prognosis. The highly invasive nature of GBM and its inherent resistance to therapy lead to very high rates of recurrence. Recently, a small cohort of tumor cells, called cancer stem cells (CSCs), has been recognized as a subset of tumor cells with self-renewal ability and multilineage capacity. These properties, along with the remarkable tumorigenicity of CSCs, are thought to account for the high rates of tumor recurrence after treatment. Recent research has been geared toward understanding the unique biological characteristics of CSCs to enable development of targeted therapy. Strategies include inhibition of CSC-specific pathways and receptors; agents that increase sensitivity of CSCs to chemotherapy and radiotherapy; CSC differentiation agents; and CSC-specific immunotherapy, virotherapy, and gene therapy. These approaches could inform the development of newer therapeutics for GBM.

After ECMO Decannulation, Are Patients Thriving or Just Surviving?

The use of extracorporeal membrane oxygenation (ECMO) to support patients with cardiac arrest, cardiogenic shock, and acute respiratory distress syndrome is rising worldwide.1 While ECMO may save the lives of some of our sickest patients, the outlook of ECMO survivorship remains uncertain. Defining longer-term functional and neuropsychiatric outcomes in ECMO survivors is important for 3 reasons. First, critically ill patients are at high risk of experiencing postintensive care syndrome (PICS), defined as new physical, cognitive, or psychological impairments that present in survivors of critical illness after hospital discharge.2 PICS is associated with more severe illness and longer intensive care unit length of stay.3 Because ECMO is reserved for patients with refractory shock or hypoxia, patients treated with ECMO represent a severely ill patient population with prolonged length of stay, putting them at particularly high risk of developing PICS. Second, ECMO is associated with direct neurologic injury, including both macrohemorrhages and microhemorrhages, infarcts, and diffuse hypoxic-ischemic brain injury that likely contribute to long-term outcomes.4 Finally, ECMO is very expensive. A recent study determined that the average cost per admission for patients with COVID-19 placed on ECMO was nearly $850,000 more than those who received only mechanical ventilation.5 Understanding patient-centered outcomes will be an integral part of future cost-effectiveness analyses.

Parameter free AEWMA control chart for dispersion in semiconductor manufacturing.

The study presents a new parameter free adaptive exponentially weighted moving average (AEWMA) control chart tailored for monitoring process dispersion, utilizing an adaptive approach for determining the smoothing constant. This chart is crafted to adeptly detect shifts within anticipated ranges in process dispersion by dynamically computing the smoothing constant. To assess its effectiveness, the chart's performance is measured through concise run-length profiles generated from Monte Carlo simulations. A notable aspect is the incorporation of an unbiased estimator in computing the smoothing constant through the suggested function, thereby improving the chart's capability to identify different levels of increasing and decreasing shifts in process dispersion. The comparison with an established adaptive EWMA-S2 dispersion chart highlights the considerable efficiency of the proposed chart in addressing diverse magnitudes of process dispersion shifts. Additionally, the study includes an application to a real-life dataset, showcasing the practicality and user-friendly nature of the proposed chart in real-world situations.

Memory type Bayesian adaptive max-EWMA control chart for weibull processes.

The simultaneous monitoring of both the process mean and dispersion has gained considerable attention in statistical process control, especially when the process follows the normal distribution. This paper introduces a novel Bayesian adaptive maximum exponentially weighted moving average (Max-EWMA) control chart, designed to jointly monitor the mean and dispersion of a non-normal process. This is achieved through the utilization of the inverse response function, particularly suitable for processes conforming to a Weibull distribution. To assess the effectiveness of the proposed control chart, we employed the average run length (ARL) and the standard deviation of run length (SDRL). Subsequently, we compared the performance of our proposed control chart with that of an existing Max-EWMA control chart. Our findings suggest that the proposed control chart demonstrates a higher level of sensitivity in detecting out-of-control signals. Finally, to illustrate the effectiveness of our Bayesian Max-EWMA control chart under various Loss Functions (LFs) for a Weibull process, we present a practical case study focusing on the hard-bake process in the semiconductor manufacturing industry. This case study highlights the adaptability of the chart to different scenarios. Our results provide compelling evidence of the exceptional performance of the suggested control chart in rapidly detecting out-of-control signals during the hard-bake process, thereby significantly contributing to the improvement of process monitoring and quality control.

Memory type Max-EWMA control chart for the Weibull process under the Bayesian theory.

The simultaneous monitoring of both process mean and dispersion, particularly in normal processes, has garnered significant attention within the field. In this article, we present a new Bayesian Max-EWMA control chart that is intended to track a non-normal process mean and dispersion simultaneously. This is accomplished through the utilization of the inverse response function, especially in cases where the procedure follows a Weibull distribution. We used the average run length (ARL) and the standard deviation of run length (SDRL) to assess the efficacy of our suggested control chart. Next, we contrast our suggested control chart's performance with an already-existing Max-EWMA control chart. Our results show that compared to the control chart under consideration, the proposed control chart exhibits a higher degree of sensitivity. Finally, we present a useful case study centered around the hard-bake process in the semiconductor manufacturing sector to demonstrate the performance of our Bayesian Max-EWMA control chart under different Loss Functions (LFs) for a Weibull process. The case study highlights how flexible the chart is to various situations. Our results offer strong proof of the outstanding ability of the Bayesian Max-EWMA control chart to quickly identify out-of-control signals during the hard-bake procedure. This in turn significantly contributes to the enhancement of process monitoring and quality control.

Risk adjusted EWMA control chart based on support vector machine with application to cardiac surgery data.

In the current study, we demonstrate the use of a quality framework to review the process for improving the quality and safety of the patient in the health care department. The researchers paid attention to assessing the performance of the health care service, where the data is usually heterogeneous to patient's health conditions. In our study, the support vector machine (SVM) regression model is used to handle the challenge of adjusting the risk factors attached to the patients. Further, the design of exponentially weighted moving average (EWMA) control charts is proposed based on the residuals obtained through SVM regression model. Analyzing real cardiac surgery patient data, we employed the SVM method to gauge patient condition. The resulting SVM-EWMA chart, fashioned via SVM modeling, revealed superior shift detection capabilities and demonstrated enhanced efficacy compared to the risk-adjusted EWMA control chart.

An adaptive Bayesian approach for improved sensitivity in joint monitoring of mean and variance using Max-EWMA control chart.

This article introduces an adaptive approach within the Bayesian Max-EWMA control chart framework. Various Bayesian loss functions were used to jointly monitor process deviations from the mean and variance of normally distributed processes. Our study proposes the mechanism of using a function-based adaptive method that picks self-adjusting weights incorporated in Bayesian Max-EWMA for the estimation of mean and variance. This adaptive mechanism significantly enhances the effectiveness and sensitivity of the Max-EWMA chart in detecting process shifts in both the mean and dispersion. The Monte Carlo simulation technique was used to calculate the run-length profiles of different combinations. A comparative performance analysis with an existing chart demonstrates its effectiveness. A practical example from the hard-bake process in semiconductor manufacturing is presented for practical context and illustration of the chart settings and performance. The empirical results showcase the superior performance of the Adaptive Bayesian Max-EWMA control chart in identifying out-of-control signals. The chart's ability to jointly monitor the mean and variance of a process, its adaptive nature, and its Bayesian framework make it a useful and effective control chart.

A novel flexible exponent power-X family of distributions with applications to COVID-19 mortality rate in Mexico and Canada.

This paper aims to introduce a novel family of probability distributions by the well-known method of the T-X family of distributions. The proposed family is called a "Novel Generalized Exponent Power X Family" of distributions. A three-parameters special sub-model of the proposed method is derived and named a "Novel Generalized Exponent Power Weibull" distribution (NGEP-Wei for short). For the proposed family, some statistical properties are derived including the hazard rate function, moments, moment generating function, order statistics, residual life, and reverse residual life. The well-known method of estimation, the maximum likelihood estimation method is used for estimating the model parameters. Besides, a comprehensive Monte Carlo simulation study is conducted to assess the efficacy of this estimation method. Finally, the model selection criterion such as Akaike information criterion (AINC), the correct information criterion (CINC), the Bayesian information criterion (BINC), the Hannan-Quinn information criterion (HQINC), the Cramer-von-Misses (CRMI), and the ANDA (Anderson-Darling) are used for comparison purpose. The comparison of the NGEP-Wei with other rival distributions is made by Two COVID-19 data sets. In terms of performance, we show that the proposed method outperforms the other competing methods included in this study.