Publications by authors named "Sung-Min Cho"

200 Publications

Neurologic Injury in Patients With COVID-19 Who Receive VV-ECMO Therapy: A Cohort Study.

J Cardiothorac Vasc Anesth 2021 May 13. Epub 2021 May 13.

Division of Neurosciences Critical Care, Department of Neurology, Neurosurgery, Anesthesiology and Critical Care Medicine and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD.

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http://dx.doi.org/10.1053/j.jvca.2021.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117479PMC
May 2021

Kinematics after cervical laminoplasty: risk factors for cervical kyphotic deformity after laminoplasty.

Spine J 2021 Jun 9. Epub 2021 Jun 9.

Department of Neurosurgery, Ansan Hospital, Korea University College of Medicine, Ansan, Republic of Korea. Electronic address:

Background Context: Laminoplasty of the cervical spine is widely used as an effective surgical method to treat compressive myelopathy of the cervical spine; however, there is an adverse effect of kyphosis after surgery. The risk factors or predictors of kyphosis have not been sufficiently evaluated.

Purpose: To assess the risk factors for kyphosis following laminoplasty.

Study Design: Retrospective study.

Patient Sample: Patients diagnosed with cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament (OPLL) who underwent laminoplasty between May 2011 and October 2018 were enrolled.

Outcome Measures: Changes in lordosis and range of motion (ROM).

Methods: Radiological imaging data were collected from simple neutral and flexion-extension radiographs at baseline and at 2-year follow-up. The ROM from the neutral position to complete flexion was defined as the flexion capacity, and the ROM from the neutral position to complete extension was defined as the extension capacity.

Results: This study included 53 patients (mean age, 59.3 years). Multivariate linear regression analysis revealed that, the smaller the preoperative extension capacity, the greater was the decrease in lordosis (p = 0.025), while the larger the T1 slope, the greater was the decrease in lordosis following laminoplasty (p = 0.008). Correlation analysis revealed that C2-7 lordosis increased with increasing baseline T1 slope before surgery (p < 0.01). In patients with large preoperative C2-7 lordosis, the postoperative decrease in ROM tended to be greater (p = 0.028). However, the degree of lordosis and ROM reduction did not demonstrate a clear correlation with the clinical outcomes at 2 years after surgery.

Conclusions: Kyphotic changes in the cervical spine following laminoplasty were related to preoperative radiological parameters. The greater the preoperative extension capacity, the lower was the decrease in lordosis, and the greater the T1 slope, the greater was the decrease in lordosis.
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http://dx.doi.org/10.1016/j.spinee.2021.06.010DOI Listing
June 2021

Does Targeted Temperature Management Improve Neurological Outcome in Extracorporeal Cardiopulmonary Resuscitation (ECPR)?

J Intensive Care Med 2021 Jun 11:8850666211018982. Epub 2021 Jun 11.

Division of Neuroscience Critical Care, Departments of Neurology, Neurosurgery, Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.

Purpose: Targeted temperature management (TTM) is a standard of care in patients after cardiac arrest for neuroprotection. Currently, the effectiveness and efficacy of TTM after extracorporeal cardiopulmonary resuscitation (ECPR) is unknown. We aimed to compare neurological and survival outcomes between TTM vs non-TTM in patients undergoing ECPR for refractory cardiac arrest.

Methods: We searched PubMed and 5 other databases for randomized controlled trials and observational studies reporting neurological outcomes or survival in adult patients undergoing ECPR with or without TTM. Good neurological outcome was defined as cerebral performance category <3. Two independent reviewers extracted the data. Random-effects meta-analyses were used to pool data.

Results: We included 35 studies (n = 2,643) with the median age of 56 years (interquartile range [IQR]: 52-59). The median time from collapse to ECMO cannulation was 58 minutes (IQR: 49-82) and the median ECMO duration was 3 days (IQR: 2.0-4.1). Of 2,643, 1,329 (50.3%) patients received TTM and 1,314 (49.7%) did not. There was no difference in the frequency of good neurological outcome at any time between TTM (29%, 95% confidence interval [CI]: 23%-36%) vs. without TTM (19%, 95% CI: 9%-31%) in patients with ECPR ( = 0.09). Similarly, there was no difference in overall survival between patients with TTM (30%, 95% CI: 22%-39%) vs. without TTM (24%, 95% CI: 14%-34%) ( = 0.31). A cumulative meta-analysis by publication year showed improved neurological and survival outcomes over time.

Conclusions: Among ECPR patients, survival and neurological outcome were not different between those with TTM vs. without TTM. Our study suggests that neurological and survival outcome are improving over time as ECPR therapy is more widely used. Our results were limited by the heterogeneity of included studies and further research with granular temperature data is necessary to assess the benefit and risk of TTM in ECPR population.
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http://dx.doi.org/10.1177/08850666211018982DOI Listing
June 2021

Population Characteristics and Markers for Withdrawal of Life-Sustaining Therapy in Patients on Extracorporeal Membrane Oxygenation.

J Cardiothorac Vasc Anesth 2021 May 4. Epub 2021 May 4.

Division of Neuroscience Critical Care, Departments of Neurology and Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address:

Objective: As survival with extracorporeal membrane oxygenation (ECMO) therapy improves, it is important to study patients who do not survive secondary to withdrawal of life-sustaining therapy (WLST). The purpose of the present study was to determine the population and clinical characteristics of those who experienced short latency to WLST.

Design: Retrospective cohort study.

Setting: Single academic hospital center.

Participants: Adult ECMO patients.

Interventions: None.

Measurements And Main Results: During the study period, 150 patients (mean age 54.8 ± 15.9 y, 43.3% female) underwent ECMO (80% venoarterial ECMO and 20% venovenous ECMO). Seventy-three (48.7%) had WLST from ECMO support (median five days), and 33 of those (45.2%) had early WLST (≤five days). Patients who underwent WLST were older (60.3 ± 15.3 y v 49.6 ± 14.7 y; p < 0.001) than those who did not undergo WLST and had greater body mass index (31.7 ± 7.6 kg/mv 28.3 ± 5.5 kg/m; p = 0.002), longer ECMO duration (six v four days; p = 0.01), and higher Acute Physiology and Chronic Health Evaluation (25 v 21; p < 0.001) and Sequential Organ Failure Assessment (12 v 11; p = 0.037) scores. Family request frequently (91.7%) was cited as part of the WLST decision. WLST patients experienced more chaplaincy (89% v 65%; p < 0.001), palliative care consults (53.4% v 29.9%; p = 0.003), and code status change (do not resuscitate: 83.6% v 7.8%; p < 0.001).

Conclusions: Nearly 50% of ECMO patients underwent WLST, with approximately 25% occurring in the first 72 hours. These patients were older, sicker, and experienced a different clinical context. Unlike with other critical illnesses, neurologic injury was not a primary reason for WLST in ECMO patients.
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http://dx.doi.org/10.1053/j.jvca.2021.04.040DOI Listing
May 2021

Embedded Reverse-Offset Printing of Silver Nanowires and Its Application to Double-Stacked Transparent Electrodes with Microscale Patterns.

ACS Appl Mater Interfaces 2021 Jun 25;13(22):26601-26609. Epub 2021 May 25.

Nano-Convergence Mechanical Systems Research Division, Korea Institute of Machinery & Materials, Daejeon 34103, Republic of Korea.

We propose an embedded reverse-offset printing (EROP) method, which generates silver nanowire (AgNW) transparent electrodes for display applications. The proposed EROP method can solve the two critical issues of microscale pattern formation and surface planarization. The AgNW electrode had a transmittance of 82% at 550 nm, a sheet resistance of 12.2 Ω/sq, and a 3.27 nm smooth surface. We realized the roll-based pattern formation of AgNW on a plastic substrate as small as 10 μm with negligible step differences to facilitate the proposed method. The proposed EROP method also produced a double-stacked AgNW electrode, enabling the simultaneous operation of separately micropatterned devices. To verify the usefulness of EROP, we fabricated an organic light-emitting diode (OLED) device to demonstrate leakage current reduction and efficiency improvement compared with a conventional indium tin oxide (ITO)-based OLED device. The EROP-based OLED showed 38 and 25% higher current efficiencies than an insulator-patterned AgNW OLED and a conventional ITO-based OLED, respectively.
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http://dx.doi.org/10.1021/acsami.1c04858DOI Listing
June 2021

Cannabis Use and Stroke: Does a Risk Exist?

J Addict Med 2021 May 17. Epub 2021 May 17.

Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH (CS, IM, ABB), Department of Medicine, University of Connecticut School of Medicine, Hartford, CT (LZH), Welch Medical Library, Johns Hopkins University, Baltimore, MD (CP), Division of Neuroscience Critical Care, Departments of Neurology, Neurosurgery, Anesthesiology, and Critical Care Medicine, Johns Hopkins University, Baltimore, MD (MC).

Aims: Cannabis use has been reported as a risk factor for stroke. We systematically review the prevalence and outcomes of stroke in people with cannabis use.

Methods: We searched MEDLINE and 6 other databases from inception to January 2020 for studies on the relationship between cannabis use and stroke. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations. Two independent reviewers extracted the data. Study quality was assessed by the Newcastle-Ottawa Scale for cohort and case-control studies.

Results: Seventeen studies involving 3,185,560 people with cannabis use were included. Descriptive statistics demonstrated 18,676 (median 1.1%, interquartile range [IQR] 0.3%-1.3%) experienced stroke compared with 0.8% of those without use (Odds Ratio 1.17, 95% CI 1.10-1.25). Among people with cannabis use, median age was 26.2 years (IQR 25.2-34.3 years) and mostly male (median 57.8%). Of stroke subtypes, ischemic stroke was most prevalent (median 1.2%, IQR 0.4%-1.9%), followed by undefined stroke subtype (median 1.2%, IQR 1.1%-1.2%) and hemorrhagic stroke (median 0.3%, IQR 0.1%-0.6%). The majority of people with cannabis use who experienced stroke survived (median: 85.1%, IQR 83%-87.5%) and 64.0% of people experienced a good neurologic outcome, defined as modified Rankin Scale of 0 to 3. Few studies included outcomes of vasospasm or seizure.

Conclusions: In people with cannabis use, the prevalence of ischemic stroke and hemorrhagic stroke was 1.2% and 0.3%, respectively, higher than the prevalence of people without use (0.8% and 0.2%). There is insufficient information on timing, exposure, duration, and dose-responsive relationship.
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http://dx.doi.org/10.1097/ADM.0000000000000870DOI Listing
May 2021

The role of sex and inflammation in cardiovascular outcomes and mortality in COVID-19.

Int J Cardiol 2021 May 8. Epub 2021 May 8.

Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address:

Objective: Higher mortality in COVID-19 in men compared to women is recognized, but sex differences in cardiovascular events are less well established. We aimed to determine the independent contribution of sex to stroke, myocardial infarction and death in the setting of COVID-19 infection.

Methods: We performed a retrospective cohort study of hospitalized COVID-19 patients in a racially/ethnically diverse population. Clinical features, laboratory markers and clinical events were initially abstracted from medical records, with subsequent clinician adjudication.

Results: Of 2060 patients, myocardial injury (32% vs 23%, p = 0.019), acute myocardial infarction (2.7% vs 1.6%, p = 0.114), and ischemic stroke (1.8% vs 0.7%, p = 0.007) were more common in men vs women. In-hospital death occurred in 160 men (15%) vs 117 women (12%, p = 0.091). Men had higher odds of myocardial injury (odds ratio (OR) 2.04 [95% CI 1.43-2.91], p < 0.001), myocardial infarction (1.72 [95% CI 0.93-3.20], p = 0.085) and ischemic stroke (2.76 [95% CI 1.29-5.92], p = 0.009). Despite adjustment for demographics and cardiovascular risk factors, male sex predicted mortality (HR 1.33; 95% CI:1.01-1.74; p = 0.041). While men had significantly higher markers of inflammation, in sex-stratified analyses, increase in interleukin-6, C-reactive protein, ferritin and d-dimer were predictive of mortality and myocardial injury similarly in both sexes.

Conclusions: Adjusted odds of myocardial injury, ischemic stroke and all-cause mortality, but not myocardial infarction, are significantly higher in men compared to women with COVID-19. Higher inflammatory markers are present in men but associated similarly with risk in both men and women. These data suggest that adverse cardiovascular outcomes in men vs. women are independent of cardiovascular comorbidities.
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http://dx.doi.org/10.1016/j.ijcard.2021.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106202PMC
May 2021

Duration of Hyperoxia and Neurologic Outcomes in Patients Undergoing Extracorporeal Membrane Oxygenation.

Crit Care Med 2021 May 3. Epub 2021 May 3.

Neurosciences Critical Care Division, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD. Neurosciences Critical Care Division, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD. Neurosciences Critical Care Division, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. Department of Surgery, Johns Hopkins Surgery Center for Outcomes Research, Johns Hopkins University School of Medicine, Baltimore, MD. Department of Anesthesia and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. Division of Cardiac Surgery, Heart and Vascular Institute, Johns Hopkins University School of Medicine, Baltimore, MD.

Objectives: To evaluate the impact of duration of hyperoxia on neurologic outcome and mortality in patients undergoing venoarterial extracorporeal membrane oxygenation.

Design: A retrospective analysis of venoarterial extracorporeal membrane oxygenation patients admitted to the Johns Hopkins Hospital. The primary outcome was neurologic function at discharge defined by modified Rankin Scale, with a score of 0-3 defined as a good neurologic outcome, and a score of 4-6 defined as a poor neurologic outcome. Multivariable logistic regression analysis was performed to evaluate the association between hyperoxia and neurologic outcomes.

Setting: The Johns Hopkins Hospital Cardiovascular ICU and Cardiac Critical Care Unit.

Interventions: None.

Measurements And Main Results: We measured first and maximum PaO2 values, area under the curve per minute over the first 24 hours, and duration of mild, moderate, and severe hyperoxia. Of 132 patients on venoarterial extracorporeal membrane oxygenation, 127 (96.5%) were exposed to mild hyperoxia in the first 24 hours. Poor neurologic outcomes were observed in 105 patients (79.6%) (102 with vs 3 without hyperoxia; p = 0.14). Patients with poor neurologic outcomes had longer exposure to mild (19.1 vs 15.2 hr; p = 0.01), moderate (14.6 vs 9.2 hr; p = 0.003), and severe hyperoxia (9.1 vs 4.0 hr; p = 0.003). In a multivariable analysis, patients with worse neurologic outcome experienced longer durations of mild (adjusted odds ratio, 1.10; 95% CI, 1.01-1.19; p = 0.02), moderate (adjusted odds ratio, 1.12; 95% CI, 1.04-1.22; p = 0.002), and severe (adjusted odds ratio, 1.19; 95% CI, 1.06-1.35; p = 0.003) hyperoxia. Additionally, duration of severe hyperoxia was independently associated with inhospital mortality (adjusted odds ratio, 1.18; 95% CI, 1.08-1.29; p < 0.001).

Conclusions: In patients undergoing venoarterial extracorporeal membrane oxygenation, duration and severity of early hyperoxia were independently associated with poor neurologic outcomes at discharge and mortality.
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http://dx.doi.org/10.1097/CCM.0000000000005069DOI Listing
May 2021

Transcranial Doppler in Acute COVID-19 Infection: Unexpected Associations.

Stroke 2021 Apr 21:STROKEAHA120032150. Epub 2021 Apr 21.

Dvision of Stroke, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD. (M.C.J., M.N.B.).

Background And Purpose: Stroke may complicate coronavirus disease 2019 (COVID-19) infection based on clinical hypercoagulability. We investigated whether transcranial Doppler ultrasound has utility for identifying microemboli and clinically relevant cerebral blood flow velocities (CBFVs) in COVID-19.

Methods: We performed transcranial Doppler for a consecutive series of patients with confirmed or suspected COVID-19 infection admitted to 2 intensive care units at a large academic center including evaluation for microembolic signals. Variables specific to hypercoagulability and blood flow including transthoracic echocardiography were analyzed as a part of routine care.

Results: Twenty-six patients were included in this analysis, 16 with confirmed COVID-19 infection. Of those, 2 had acute ischemic stroke secondary to large vessel occlusion. Ten non-COVID stroke patients were included for comparison. Two COVID-negative patients had severe acute respiratory distress syndrome and stroke due to large vessel occlusion. In patients with COVID-19, relatively low CBFVs were observed diffusely at median hospital day 4 (interquartile range, 3-9) despite low hematocrit (29.5% [25.7%-31.6%]); CBFVs in comparable COVID-negative stroke patients were significantly higher compared with COVID-positive stroke patients. Microembolic signals were not detected in any patient. Median left ventricular ejection fraction was 60% (interquartile range, 60%-65%). CBFVs were correlated with arterial oxygen content, and C-reactive protein (Spearman ρ=0.28 [=0.04]; 0.58 [<0.001], respectively) but not with left ventricular ejection fraction (ρ=-0.18; =0.42).

Conclusions: In this cohort of critically ill patients with COVID-19 infection, we observed lower than expected CBFVs in setting of low arterial oxygen content and low hematocrit but not associated with suppression of cardiac output.
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http://dx.doi.org/10.1161/STROKEAHA.120.032150DOI Listing
April 2021

Management of syringomyelia associated with tuberculous meningitis: A case report and systematic review of the literature.

J Clin Neurosci 2021 May 5;87:20-25. Epub 2021 Mar 5.

Division of Neurosciences Critical Care, Department of Neurology, Neurosurgery, Anesthesiology and Critical Care Medicine and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address:

Determinants of tuberculosis (TB) syringomyelia, its management options and outcomes are still under investigation. The aim of this study is to present a case of TB syringomyelia with markedly improved symptoms status-post surgery and to understand the clinical characteristics and outcomes of 33 TB syringomyelia cases reported in the literature. Specifically, we examined the differences between patients who were managed medically and those who underwent surgical intervention. Inclusion criteria for the cases were (1) syringomyelia caused by TB infection rather than co-occurrence of these conditions, (2) management protocol described, and (3) post-treatment outcome described. The median age was 30 years (interquartile range (IQR): 23-40) with 55% males. The median time between TB onset to syringomyelia diagnosis was 2 years. Nineteen patients were surgically treated, 11 were medically treated, and 3 received no treatment. Twenty-one patients showed improvement in at least one prior symptom, but no patient experienced a full recovery. Those that underwent surgical intervention were more likely to have TB meningitis (95% vs. 64%, p < 0.05) upon initial TB presentation and have a greater interval between TB onset and syringomyelia presentation (median of 2.6 vs. 0.33 years, ns). A greater proportion of the surgically managed patients experienced improvement in any symptom (74% vs. 45%, ns). Future case-controlled studies with larger sample sizes are required to validate and further understand the outcomes of surgically-managed TB syringomyelia.
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http://dx.doi.org/10.1016/j.jocn.2021.01.052DOI Listing
May 2021

Outcomes, Time-Trends, and Factors Associated With Ancillary Study Use for the Determination of Brain Death.

Crit Care Med 2021 Apr 12. Epub 2021 Apr 12.

Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH. Division of Neurocritical Care, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, OH. Department of Neurointensive Care, Cerebrovascular Center, Cleveland Clinic, Cleveland, OH. Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Department of Neurology, Boston University Medical Center, Boston, MA. Division of Neuroscience Critical Care, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD. Division of Neuroscience Critical Care, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD. Division of Neuroscience Critical Care, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Objectives: Brain death determination often requires ancillary studies when clinical determination cannot be fully or safely completed. We aimed to analyze the results of ancillary studies, the factors associated with ancillary study performance, and the changes over time in number of studies performed at an academic health system.

Design: Retrospective cohort.

Setting: Multihospital academic health system.

Patients: Consecutive adult patients declared brain dead between 2010 and 2020.

Interventions: None.

Measurements And Main Results: Of 140 brain death patients, ancillary studies were performed in 84 (60%). The false negative rate of all ancillary studies was 4% (5% of transcranial Doppler ultrasounds, 4% of nuclear studies, 0% of electroencephalograms, and 17% of CT angiography). In univariate analysis, ancillary study use was associated with female sex (odds ratio, 2.4; 95% CI, 1.21-5.01; p = 0.013) and the etiology of brain death being hypoxic-ischemic brain injury (odds ratio, 2.9; 95% CI, 1.43-5.88; p = 0.003), nontraumatic intracranial hemorrhage (odds ratio, 0.45; 95% CI, 0.21-0.96; p = 0.039), or traumatic brain injury (odds ratio, 0.22; 95% CI, 0.04-0.8; p = 0.031). In multivariable analysis, female sex (odds ratio, 5.7; 95% CI, 2.56-15.86; p = 0.004), the etiology of brain death being hypoxic-ischemic brain injury (odds ratio, 3.2; 95% CI, 1.3-8.8; p = 0.015), and the neurologists performing brain death declaration (odds ratio, 0.08; 95% CI, 0.004-0.64; p = 0.034) were factors independently associated with use of ancillary studies. Over the study period, the total number of ancillary studies performed each year did not significantly change; however, the number of electroencephalograms significantly decreased with time (odds ratio per 1-yr increase, 0.67; 95% CI, 0.49-0.90; p = 0.014).

Conclusions: A large number of ancillary studies were performed despite a clinical determination of brain death; patients with hypoxic-ischemic brain injury are more likely to undergo ancillary studies for brain death determination, and neurologists were less likely to use ancillary studies for brain death. Recently, the use of electroencephalograms for brain death determination has decreased, likely reflecting significant concerns regarding its validity and reliability.
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http://dx.doi.org/10.1097/CCM.0000000000005035DOI Listing
April 2021

A Comprehensive Review of Risk Factor, Mechanism, and Management of Left Ventricular Assist Device-Associated Stroke.

Semin Neurol 2021 Apr 13. Epub 2021 Apr 13.

Neurological Institute, Cleveland Clinic, Cleveland, Ohio.

The use of left ventricular assist devices (LVADs) has been increasing in the last decade, along with the number of patients with advanced heart failure refractory to medical therapy. Ischemic stroke and intracranial hemorrhage remain the leading causes of morbidity and mortality in LVAD patients. Despite the common occurrence and the significant outcome impact, underlying mechanisms and management strategies of stroke in LVAD patients are controversial. In this article, we review our current knowledge on pathophysiology and risk factors of LVAD-associated stroke, outline the diagnostic approach, and discuss treatment strategies.
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http://dx.doi.org/10.1055/s-0041-1726328DOI Listing
April 2021

Brain Injury in Extracorporeal Membrane Oxygenation: A Multidisciplinary Approach.

Semin Neurol 2021 Apr 13. Epub 2021 Apr 13.

Department of Cardiothoracic Surgery, Heart and Vascular Centre, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.

Extracorporeal membrane oxygenation (ECMO) represents an established technique to provide temporary cardiac and/or pulmonary support. ECMO, in veno-venous, veno-arterial or in extracorporeal carbon dioxide removal modality, is associated with a high rate of brain injuries. These complications have been reported in 7 to 15% of adults and 20% of neonates, and are associated with poor survival. Thromboembolic events, loss of cerebral autoregulation, alteration of the blood-brain barrier, and hemorrhage related to anticoagulation represent the main causes of severe brain injury during ECMO. The most frequent forms of acute neurological injuries in ECMO patients are intracranial hemorrhage (2-21%), ischemic stroke (2-10%), seizures (2-6%), and hypoxic-ischemic brain injury; brain death may also occur in this population. Other frequent complications are infarction (1-8%) and cerebral edema (2-10%), as well as neuropsychological and psychiatric sequelae, including posttraumatic stress disorder.
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http://dx.doi.org/10.1055/s-0041-1726284DOI Listing
April 2021

Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome: How Do We Expand Capacity in the COVID-19 Era?

Heart Lung Circ 2021 May 3;30(5):623-625. Epub 2021 Mar 3.

Johns Hopkins School of Nursing, Baltimore, MD, USA. Electronic address: https://twitter.com/nursingdean.

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http://dx.doi.org/10.1016/j.hlc.2021.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927577PMC
May 2021

Neurocritical Care of Mechanical Circulatory Support Devices.

Curr Neurol Neurosci Rep 2021 03 10;21(5):20. Epub 2021 Mar 10.

Departments of Neurology, Neurosurgery, Anesthesiology and Critical Care Medicine, Division of Neuroscience Critical Care, Johns Hopkins University, 600 N. Wolfe Street, Phipps 455, Baltimore, MD, 21287, USA.

Purpose Of Review: Mechanical circulatory support (MCS) devices have demonstrated improved survival outcomes in otherwise refractory cardiopulmonary failure but are associated with significant neurologic morbidity and mortality. This review aims to characterize MCS-associated brain injury and discuss the neurocritical care of this population.

Recent Findings: We found no practice guidelines or specific management strategies for the neurocritical care of patients with MCS devices. Acute brain injury was commonly observed in short-term and durable MCS devices. There is emerging evidence that a standardized neurological monitoring and management algorithm for MCS device-associated brain injury is feasible and potentially improves neurological outcomes. While MCS devices are associated with significant neurologic morbidity and mortality, there is scant evidence regarding optimal neuromonitoring and neurocritical care. With the increase in use of MCS devices for both short-term and durable applications, improved outcomes will depend on early identification and intervention of neurologic complications and further research into their pathophysiology.
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http://dx.doi.org/10.1007/s11910-021-01107-0DOI Listing
March 2021

Cerebral Microbleeds and Intracranial Hemorrhages in Adult Patients on Extracorporeal Membrane Oxygenation-Autopsy Study.

Crit Care Explor 2021 Mar 2;3(3):e0358. Epub 2021 Mar 2.

Department of Neurology, Johns Hopkins Hospital, Baltimore, MD.

Current studies lack robust information on the prevalence and associated factors of cerebral microbleeds in patients who underwent extracorporeal membrane oxygenation.

Design: Retrospective analysis.

Setting: We reviewed patients who underwent (extracorporeal membrane oxygenation) and subsequent brain autopsy with gross and microscopic examinations from January 2009 to December 2018 from a single tertiary center.

Patients: Twenty-five extracorporeal membrane oxygenation patients (median age, 53 yr; interquartile range, 36-61 yr; 17 women and 8 men) underwent brain autopsy.

Interventions: Descriptive analysis of neuropathologic findings. Cerebral microbleed was defined as a small focus (< 10 mm diameter) of accumulation of blood product in the brain tissue. Macrohemorrhage was defined as any of the grossly identifiable epidural, subdural, subarachnoid, or intraparenchymal hemorrhages larger than 10 mm.

Measurement And Main Results: Of 25 (22 venoarterial extracorporeal membrane oxygenation; three venovenous extracorporeal membrane oxygenation), 15 patients (60%) were found to have cerebral microbleeds, whereas 13 (52%) had macrohemorrhages, of whom five (20%) had both. Overall, 92% of brains demonstrated the presence of either cerebral microbleeds or macrohemorrhages after extracorporeal membrane oxygenation support. Of the patients with cerebral microbleeds, lobar cerebral microbleeds (80%) occurred more frequently than deep cerebral microbleeds (60%), with 40% of patients having both types. The cases of macrohemorrhages consisted of one epidural (8%), two subdural (15%), and 10 subarachnoid hemorrhages (77%). In univariate analyses, the presence of macrohemorrhages was significantly associated with the presence of cerebral microbleeds ( = 0.03) with odds ratio of 0.13 (CI, 0.02-0.82). Age, sex, extracorporeal membrane oxygenation duration, extracorporeal membrane oxygenation type, use of aspirin or dialysis during extracorporeal membrane oxygenation support, bloodstream infections, hemoglobin, platelets, and coagulopathy profiles were not associated with cerebral microbleeds.

Conclusions: In patients with postmortem neuropathologic evaluation, 92% sustained acute cerebral microbleeds or macrohemorrhages after extracorporeal membrane oxygenation support. Cerebral microbleeds were commonly present in the majority of extracorporeal membrane oxygenation nonsurvivors. Further research is necessary to study the long-term sequelae, such as cognitive outcome of extracorporeal membrane oxygenation-associated cerebral microbleeds in extracorporeal membrane oxygenation survivors.
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http://dx.doi.org/10.1097/CCE.0000000000000358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929626PMC
March 2021

Building relationships: reimagining the community placement for medical students.

Can Med Educ J 2021 Feb 26;12(1):e107-e108. Epub 2021 Feb 26.

Faculty of Medicine, University of Toronto, Ontario, Canada.

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http://dx.doi.org/10.36834/cmej.70555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931479PMC
February 2021

MACHINE LEARNING COMPARED TO CONVENTIONAL STATISTICAL MODELS FOR PREDICTING MYOCARDIAL INFARCTION READMISSION AND MORTALITY: A SYSTEMATIC REVIEW.

Can J Cardiol 2021 Mar 4. Epub 2021 Mar 4.

Ted Rogers Centre for Heart Research; Peter Munk Cardiac Centre of University Health Network; ICES; Institute for Health Policy, Management and Evaluation; Toronto General Hospital Research Institute; University of Toronto. Electronic address:

Background: To review the performance of machine learning (ML) methods compared to conventional statistical models (CSM) for predicting readmission and mortality in patients with myocardial infarction (MI).

Methods: Following PRISMA guidelines, we systematically reviewed the literature search using MEDLINE, EPUB, Cochrane CENTRAL, EMBASE, INSPEC, ACM Library, and Web of Science. Eligible studies included primary research articles published between January 2000 and March 2020, comparing ML and CSM for prognostication after MI.

Results: Of 7,348 articles, 112 underwent full-text review, with the final set comprised of 24 articles and 374,365 patients. ML methods included artificial neural networks (n=12 studies), random forests (n=11), decision trees (n=8), support vector machines (n=8) and Bayesian techniques (n=7). CSM included logistic regression (n=19 studies), existing CSM-derived risk scores (n=12) and Cox regression (n=2). Thirteen of 19 studies examining mortality reported higher c-indices using ML compared to CSM. One study examined readmissions at two different time points, with c-indices that were higher for ML than CSM. Across all studies, a total of 29 comparisons were performed, but the majority (n=26, 90%) found small (< 0.05) absolute differences in the c-index between ML and CSM. Using a modified CHARMS checklist, sources of bias were identifiable in the majority of studies, and only 2 were externally validated.

Conclusion: Although ML algorithms tended to have higher c-indices than CSM for predicting death or readmission after MI, these studies exhibited threats to internal validity and were often unvalidated. Further comparisons are needed, with adherence to clinical quality standards for prognosis research.
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http://dx.doi.org/10.1016/j.cjca.2021.02.020DOI Listing
March 2021

Tachyarrhythmias and neurologic complications.

Handb Clin Neurol 2021 ;177:151-162

Neurosciences Critical Care, Departments of Anesthesiology and Critical Care Medicine, Neurology, and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address:

Tachyarrhythmias are abnormal heart rhythms with a ventricular rate of 100 or more beats per minute. These rhythms are classified as either narrow or wide-complex tachycardia with further subdivision into regular or irregular rhythm. Patients are frequently symptomatic presenting with palpitations, diaphoresis, dyspnea, chest pain, dizziness, and syncope. Sudden cardiac death may occur with certain arrhythmias. Recognizing tachyarrhythmia and understanding its management is important as a wide spectrum of neurologic complications have been associated with such arrhythmias. The purpose of this chapter is to provide a comprehensive overview on the neurologic complications of tachyarrhythmias, neurologic adverse events of antiarrhythmic interventions, and neurologic conditions that can precipitate tachyarrhythmia.
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http://dx.doi.org/10.1016/B978-0-12-819814-8.00004-4DOI Listing
January 2021

The authors reply.

Crit Care Med 2021 Mar;49(3):e344-e345

Division of Neuroscience Critical Care, Department of Neurology, Johns Hopkins University, Baltimore, MD.

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http://dx.doi.org/10.1097/CCM.0000000000004871DOI Listing
March 2021

New Simple 3-Dimensional Computed Tomogram Classification Leading to Successful Conservative Treatment in 51 Atlanto-Axial Rotatory Fixation Children.

Pediatr Neurosurg 2021 19;56(2):125-132. Epub 2021 Feb 19.

Department of Neurosurgery, Ajou University School of Medicine, Suwon, Republic of Korea.

Objective: to present a new and easy classification of atlanto-axial rotatory fixation (AARF) and to investigate the efficiency of conservative treatment of AARF.

Background: Although there is a precise definition and diagnostic classification of AARF, there is still significant difficulty in measuring the atlas and axis angles because all of the atlas or axis cannot be seen in a certain 2-dimensional computed tomogram image. In addition, some recent case reports showed that long-term conservative treatment can reduce pediatric AARFs, even that are severe or chronic.

Methods: Fifty-one children with AARF were analyzed retrospectively with new 3-dimensional computed tomogram (3DCT)-based AARF classification; the mean age was 72.7 ± 35.2 months (19-139 months). In the new AARF classification, type 1 was defined as that when the C1C2 angle is not 0° on midline and type 2 as that when the C1C2 angle is 0° on the midline.

Results: All 7 children with AARF type 1 were treated successfully only with Halter tractions. Twenty among 44 children with type 2 did not show any difference in improvement compared with not-treated 24 children with type 2.

Conclusion: The first new AARF classification based on 3DCT appears to be easy to use and even the most severe children with AARF may be managed only with conservative treatment such as long-term Halter traction.
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http://dx.doi.org/10.1159/000512368DOI Listing
February 2021

Acute Brain Injury in Postcardiotomy Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation.

J Cardiothorac Vasc Anesth 2021 Jul 25;35(7):1989-1996. Epub 2021 Jan 25.

Neuroscience Critical Care, Departments of Neurology, Neurosurgery, Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address:

Objective: Acute brain injury (ABI) is common in venoarterial extracorporeal membrane oxygenation (VA-ECMO). One of the most common indications for use of VA-ECMO is postcardiotomy shock (PCS). The authors aimed to characterize the prevalence of ABI and its association with outcomes in this population.

Design: prospective observational.

Setting: Single-center tertiary care university hospital.

Participants: Fifty-two consecutive patients treated for PCS with VA-ECMO from November 2017 to March 2020.

Interventions: None.

Measurements And Main Results: The median age of patients was 64 (interquartile range 44-84), 62% were male. Of 52 PCS patients treated with extracorporeal membrane oxygenation, 38% (n = 20) experienced acute brain injury. Ischemic stroke was the most common (n = 13, 25%). Patients with central versus peripheral cannulation experienced more ischemic and hemorrhagic strokes (8% v 38%, p = 0.04). Patients with intracardiac thrombus experienced more brain injury (n = 4, 8% p = 0.02). The in-hospital mortality in patients with brain injury was 90% (n = 18/20) compared to 78% (n = 25/32) in patients without brain injury.

Conclusions: ABI is common in postcardiotomy VA-ECMO and associated with worse outcome. Patients with central recanalization experienced the majority of acute strokes. Intracardiac thrombus was significantly associated with acute brain injury.
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http://dx.doi.org/10.1053/j.jvca.2021.01.037DOI Listing
July 2021

Racism and COVID-19: Are Trainees Prepared?

Acad Med 2021 06;96(6):779

Fourth-year medical student, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; email: Twitter: @stevensmcho; ORCID: http://orcid.org/0000-0001-7751-2539.

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http://dx.doi.org/10.1097/ACM.0000000000003955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140641PMC
June 2021

How Are We Monitoring Brain Injuries in Patients With Left Ventricular Assist Device? A Systematic Review of Literature.

ASAIO J 2021 02;67(2):149-156

Departments of Neurology, Neurosurgery, Anesthesiology and Critical Care Medicine, Neurocritical Care Division, Johns Hopkins Medical Institution, Baltimore, Maryland.

Despite the common occurrence of brain injury in patients with left ventricular assist device (LVAD), optimal neuromonitoring methods are unknown. A systematic review of PubMed and six electronic databases from inception was conducted until June 5, 2019. Studies reporting methods of neuromonitoring while on LVAD were extracted. Of 5,190 records screened, 37 studies met the inclusion criteria. The neuromonitoring methods include Transcranial Doppler ultrasound for emboli monitoring (TCD-e) (n = 13) and cerebral autoregulation (n = 3), computed tomography and magnetic resonance imaging (n = 9), serum biomarkers (n = 7), carotid ultrasound (n = 3), and near-infrared spectroscopy (n = 2). Of 421 patients with TCD-e, thromboembolic events (TEs) were reported in 79 patients (20%) and microembolic signals (MES) were detected in 105 patients (27%). Ischemic stroke was more prevalent in patients with MES compared to patients without MES (43% vs.13%, p < 0.001). Carotid ultrasound for assessing carotid stenosis was unreliable after LVAD implantation. Elevated lactate dehydrogenase (LDH) levels were associated with TEs. Significant heterogeneity exists in timing, frequency, and types of neuromonitoring tools. TCD-e and serial LDH levels appeared to have potential for assessing the risk of ischemic stroke. Future prospective research incorporating protocolized TCD-e and LDH may assist in monitoring adverse events in patients with LVAD.
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http://dx.doi.org/10.1097/MAT.0000000000001204DOI Listing
February 2021

The effect of incorporating an arterial pH target during apnea test for brain death determination.

J Intensive Care 2021 Jan 20;9(1):13. Epub 2021 Jan 20.

Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.

Background: Persistent apnea despite an adequate rise in arterial pressure of CO is an essential component of the criteria for brain death (BD) determination. Current guidelines vary regarding the utility of arterial pH changes during the apnea test (AT). We aimed to study the effect of incorporating an arterial pH target < 7.30 during the AT (in addition to the existing PaCO threshold) on brain death declarations.

Methods: We performed retrospective analysis of consecutive adult patients who were diagnosed with BD and underwent AT at the Cleveland Clinic over the last 10 years. Data regarding baseline and post-AT blood gas analyses were collected and analyzed.

Results: Ninety-eight patients underwent AT in the study period, which was positive in 89 (91%) and inconclusive in 9 (9%) patients. The mean age was 50 years old (standard deviation [SD] 16) and 54 (55%) were female. The most common etiology BD was hypoxic ischemic brain injury (HIBI) due to cardiac arrest (42%). Compared to those with positive AT, patients with inconclusive AT had a higher post-AT pH (7.24 vs 7.17, p = 0.01), lower PaO (47 vs 145, p < 0.01), and a lower PaCO (55 vs 73, p = 0.01). Among patients with a positive AT using PaCO threshold alone, the frequency of patients with post-AT pH < 7.30 was 95% (83/87).

Conclusion: Implementing a BD criteria requiring both arterial pH and PaCO thresholds reduced the total number of positive ATs; these inconclusive cases would have required longer duration of AT to reach both targets, repeated ATs, or ancillary studies to confirm BD. The impact of this on the overall number BD declarations requires further research.
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http://dx.doi.org/10.1186/s40560-020-00522-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816154PMC
January 2021

Diffusion-Weighted Imaging Lesions After Intracerebral Hemorrhage and Risk of Stroke: A MISTIE III and ATACH-2 Analysis.

Stroke 2021 Jan 20;52(2):595-602. Epub 2021 Jan 20.

Division of Neurosciences Critical Care, Johns Hopkins University School of Medicine, Baltimore, MD (S.-M.C., L.R.-L., W.C.Z.).

Background And Purpose: Punctate ischemic lesions noted on diffusion-weighted imaging (DWI) are associated with poor functional outcomes after intracerebral hemorrhage (ICH). Whether these lesions increase long-term risk of stroke is poorly understood.

Methods: We pooled individual patient data from the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) and the MISTIE III trial (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3). We included subjects with a magnetic resonance imaging scan. The exposure was a DWI lesion. The primary outcome was any stroke, defined as a composite of ischemic stroke or recurrent ICH, whereas secondary outcomes were incident ischemic stroke and recurrent ICH. Using multivariate Cox regression analysis, we evaluated the risk of stroke.

Results: Of 505 patients with ICH with magnetic resonance imaging, 466 were included. DWI lesions were noted in 214 (45.9%) subjects, and 34 incident strokes (20 ischemic stroke and 14 recurrent ICH) were observed during a median follow-up of 324 days (interquartile range, 91-374). Presence of a DWI lesion was associated with a 6.9% (95% CI, 2.2-11.6) absolute increase in risk of all stroke (hazard ratio, 2.6 [95% CI, 1.2-5.7]). Covariate adjustment with Cox regression models also demonstrated this increased risk. In the secondary analyses, there was an increased risk of ischemic stroke (hazard ratio, 3.5 [95% CI, 1.1-11.0]) but not recurrent ICH (hazard ratio, 1.7 [95% CI, 0.6-5.1]).

Conclusions: In a heterogeneous cohort of patients with ICH, presence of a DWI lesion was associated with a 2.5-fold heightened risk of stroke among ICH survivors. This elevated risk persisted for ischemic stroke but not for recurrent ICH.
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http://dx.doi.org/10.1161/STROKEAHA.120.031628DOI Listing
January 2021

Functional inhibition of fatty acid binding protein 4 ameliorates impaired ciliogenesis in GCs.

Biochem Biophys Res Commun 2021 02 5;539:28-33. Epub 2021 Jan 5.

Chemical Genomics Global Research Laboratory, Department of Biotechnology, College of Life Science & Biotechnology, Yonsei University, Seoul, 03722, South Korea. Electronic address:

Ciliogenesis is often impaired in some cancer cells, leading to acceleration of cancer phenotypes such as cell migration and proliferation. From the investigation of primary cilia of 16 gastric cancer cells (GCs), we found that GCs could be grouped into four primary cilia (PC)-positive GCs and 12 PC-negative GCs. The proliferation of the PC-positive GCs was lower than that of PC-negative GCs. To explore the role of fatty acid binding protein 4 (FABP4), which is a known oncogenic factor, in ciliogenesis, FABP4 expression and function were inhibited by transfection of cells with short interfering RNA targeting FABP4 (siFABP4) or FABP4 inhibitor treatment. Notably, the proliferation and migration of the cilia-forming GCs was effectively suppressed by inhibition of FABP4. In addition, the primary cilia in GCs were restored by a factor greater than two, suggesting a negative role of FABP4 in ciliogenesis in these GCs and FABP4 as a potential anticancer target.
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http://dx.doi.org/10.1016/j.bbrc.2020.12.083DOI Listing
February 2021

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

ASAIO J 2020 Nov 19. Epub 2020 Nov 19.

Neurosciences Critical Care Division, Departments of Neurology, Neurosurgery, Anesthesiology and Critical Care Medicine and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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.
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http://dx.doi.org/10.1097/MAT.0000000000001317DOI Listing
November 2020

Letter by Uchino and Cho Regarding Article, "Infarction of the Splenium of the Corpus Callosum in the Age of COVID-19: A Snapshot in Time".

Stroke 2020 12 23;51(12):e380. Epub 2020 Nov 23.

Departments of Neurology, Neurosurgery, Anesthesiology, and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (S.-M.C.).

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http://dx.doi.org/10.1161/STROKEAHA.120.032006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678664PMC
December 2020

Therapeutic drug monitoring of valproic acid in extracorporeal membrane oxygenation.

Perfusion 2020 Nov 16:267659120972272. Epub 2020 Nov 16.

Department of Pharmacy, Johns Hopkins Hospital, Baltimore, MD, USA.

Introduction: Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for those in cardiopulmonary failure, including post-cardiac arrest. Despite a high volume of ECMO patients using anti-seizure medication, there is a paucity of data concerning the dosing, levels, and clinical scenarios for their use.

Case Report: We present three cases of ECMO patients post-PEA arrest who were on valproic acid (VPA) for treatment of seizure and/or myoclonus. The total and free levels of VPA are reported.

Discussion: The trough levels are consistent throughout therapy, suggesting VPA is not significantly removed by the ECMO circuitry. Although the total serum levels remained below the toxic range, the free level was elevated in two patients. These patients did not develop signs of toxicity.

Conclusion: VPA may be an effective anti-seizure medication in ECMO patients. Free VPA levels should be more readily available to better quantify efficacy or toxicity, especially in ECMO patients.
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http://dx.doi.org/10.1177/0267659120972272DOI Listing
November 2020