Pragmatic Approach to In Situ Simulation to Identify Latent Safety Threats Before Moving to a Newly Built ICU.

OBJECTIVES: Transitions to new care environments may have unexpected consequences that threaten patient safety. We undertook a quality improvement project using in situ simulation to learn the new patient care environment and expose latent safety threats before transitioning patients to a newly built adult ICU. DESIGN: Descriptive review of a patient safety initiative. SETTING: A newly built 24-bed neurocritical care unit at a tertiary care academic medical center. SUBJECTS: Care providers working in neurocritical care unit. INTERVENTIONS: We implemented a pragmatic three-stage in situ simulation program to learn a new patient care environment, transitioning patients from an open bay unit to a newly built private room-based ICU. The project tested the safety and efficiency of new workflows created by new patient- and family-centric features of the unit. We used standardized patients and high-fidelity mannequins to simulate patient scenarios, with "test" patients created through all electronic databases. Relevant personnel from clinical and nonclinical services participated in simulations and/or observed scenarios. We held a debriefing after each stage and scenario to identify safety threats and other concerns. Additional feedback was obtained via a written survey sent to all participants. We prospectively surveyed for missed latent safety threats for 2 years following the simulation and fixed issues as they arose. MEASUREMENTS AND MAIN RESULTS: We identified and addressed 70 latent safety threats, including issues concerning physical environment, infection prevention, patient workflow, and informatics before the move into the new unit. We also developed an orientation manual that highlighted new physical and functional features of the ICU and best practices gleaned from the simulations. All participants agreed or strongly agreed that simulations were beneficial. Two-year follow-up revealed only two missed latent safety threats. CONCLUSIONS: In situ simulation effectively identifies latent safety threats surrounding the transition to new ICUs and should be considered before moving into new units.

A Modified Delphi Consensus Approach to Define Entrustable Professional Activities for Neurocritical Care Advanced Practice Providers.

OBJECTIVES: To define consensus entrustable professional activities (EPAs) for neurocritical care (NCC) advanced practice providers (APPs), establish validity evidence for the EPAs, and evaluate factors that inform entrustment expectations of NCC APP supervisors. DESIGN: A three-round modified Delphi consensus process followed by application of the EQual rubric and assessment of generalizability by clinicians not affiliated with academic medical centers. SETTING: Electronic surveys. SUBJECTS: NCC APPs ( n = 18) and physicians ( n = 12) in the United States with experience in education scholarship or APP program leadership. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The steering committee generated an initial list of 61 possible EPAs. The panel proposed 30 additional EPAs. A total of 47 unique nested EPAs were retained by consensus opinion. The steering committee defined six core EPAs addressing medical knowledge, procedural competencies, and communication proficiency which encompassed the nested EPAs. All core EPAs were retained and subsequently met the previously described cut score for quality and structure using the EQual rubric. Most clinicians who were not affiliated with academic medical centers rated each of the six core EPAs as very important or mandatory. Entrustment expectations did not vary by prespecified groups. CONCLUSIONS: Expert consensus was used to create EPAs for NCC APPs that reached a predefined quality standard and were important to most clinicians in different practice settings. We did not identify variables that significantly predicted entrustment expectations. These EPAs may aid in curricular design for an EPA-based assessment of new NCC APPs and may inform the development of EPAs for APPs in other critical care subspecialties.

Smartphone Use in the Management of Neurological Emergencies: A Simulation-Based Study.

BACKGROUND: Smartphone use in medicine is nearly universal despite a dearth of research assessing utility in clinical performance. We sought to identify and define smartphone use during simulated neuroemergencies. METHODS: In this retrospective review of a prospective observational single-center simulation-based study, participants ranging from subinterns to attending physicians and stratified by training level (novice, intermediate, and advanced) managed a variety of neurological emergencies. The primary outcome was frequency and purpose of smartphone use. Secondary outcomes included success rate of smartphone use and performance (measured by completion of critical tasks) of participants who used smartphones versus those who did not. In subgroup analyses we compared outcomes across participants by level of training using t-tests and χ2 statistics. RESULTS: One hundred and three participants completed 245 simulation scenarios. Smartphones were used in 109 (45%) simulations. Of participants using smartphones, 102 participants looked up medication doses, 52 participants looked up management guidelines, 11 participants looked up hospital protocols, and 13 participants used smartphones for assistance with an examination scale. Participants found the correct answer 73% of the time using smartphones. There was an association between participant level and smartphone use with intermediate participants being more likely to use their smartphones than novice or advanced participants, 53% versus 29% and 26%, respectively (p < 0.05). Of the intermediate participants, those who used smartphones did not perform better during the simulation scenario than participants who did not use smartphones (smartphone users' mean score [standard deviation] = 12.3 [2.9] vs. nonsmartphone users' mean score [standard deviation] = 12.9 (2.7), p = 0.85). CONCLUSIONS: Participants commonly used smartphones in simulated neuroemergencies but use didn't confer improved clinical performance. Less experienced participants were the most likely to use smartphones and less likely to arrive at correct conclusions, and thus are the most likely to benefit from an evidence-based smartphone application for neuroemergencies.

Intensive Blood Pressure Control After Mechanical Thrombectomy for Acute Ischemic Stroke.

Optimal blood pressure targets following successful mechanical thrombectomy remain uncertain. While some observational studies suggest that the relationship between blood pressure and outcomes follows a U-shaped curve, others suggest a linear relationship where lower is better. The recent BP-TARGET study (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy) did not find a benefit to intensive blood pressure lowering regarding the risk of symptomatic intracranial hemorrhage, but it was not sufficiently powered to detect differences in functional outcomes. On its heels arrived the ENCHANTED2 (Enhanced Control of Hypertension and Thrombectomy Stroke Study)/mechanical thrombectomy trial, the first trial of intensive blood pressure lowering in patients with hypertension following successful mechanical thrombectomy powered to detect a difference in functional outcomes. The trial randomized patients to either a systolic blood pressure less than 120 or 140 to 180 mm Hg. The trial was terminated early due to safety concerns in the more intensive blood pressure-lowering group. In this emerging therapy critique, we explore concerns regarding the generalizability of ENCHANTED2/mechanical thrombectomy, including the high prevalence of intracranial atherosclerosis in the studied population. We survey mechanisms for poor outcomes in patients who receive overly aggressive blood pressure reduction following successful thrombectomy, such as poststroke autoregulatory compromise and persistent microcirculatory hypoperfusion. Finally, we advocate for a more moderate approach, pending further research.

Evaluating salvage electroconvulsive therapy for the treatment of prolonged super refractory status epilepticus: A case series.

BACKGROUND AND OBJECTIVES: Clinicians have treated super refractory status epilepticus (SRSE) with electroconvulsive therapy (ECT); however, data supporting the practice are scant and lack rigorous evaluation of continuous electroencephalogram (cEEG) changes related to therapy. This study aims to describe a series of patients with SRSE treated at our institution with ECT and characterize cEEG changes using a blinded review process. METHODS: We performed a single-center retrospective study of consecutive patients admitted for SRSE and treated with ECT from January 2014 to December 2022. Our primary outcome was the resolution of SRSE. Secondary outcomes included changes in ictal-interictal EEG patterns, anesthetic burden, treatment-associated adverse events, and changes in clinical examination. cEEG was reviewed pre- and post-ECT by blinded epileptologists. RESULTS: Ten patients underwent treatment with ECT across 11 admissions (8 female, median age 57 years). At the time of ECT initiation, nine patients had ongoing SRSE while two had highly ictal patterns and persistent encephalopathy following anesthetic wean, consistent with late-stage SRSE. Super-refractory status epilepticus resolution occurred with a median time to cessation of 4 days (interquartile range [IQR]: 3-9 days) following ECT initiation. Background continuity improved in five patients and periodic discharge frequency decreased in six. There was a decrease in anesthetic use following the completion of ECT and an improvement in neurological exams. There were no associated adverse events. DISCUSSION: In our cohort, ECT was associated with improvement of ictal-interictal patterns on EEG, and resolution of SRSE, and was not associated with serious adverse events. Further controlled studies are needed.

Acute Headache Management for Patients with Subarachnoid Hemorrhage: An International Survey of Health Care Providers.

BACKGROUND: Severe headaches are common after subarachnoid hemorrhage. Guidelines recommend treatment with acetaminophen and opioids, but patient data show that headaches often persist despite multimodal treatment approaches. Considering an overall slim body of data for a common complaint affecting patients with SAH during their intensive care stay, we set out to assess practice patterns in headache management among clinicians who treat patients with SAH. METHODS: We conducted an international cross-sectional study through a 37-question Web-based survey distributed to members of five professional societies relevant to intensive and neurocritical care from November 2021 to January 2022. Responses were characterized through descriptive analyses. Fisher's exact test was used to test associations. RESULTS: Of 516 respondents, 329 of 497 (66%) were from North America and 121 of 497 (24%) from Europe. Of 435 respondents, 379 (87%) reported headache as a major management concern for patients with SAH. Intensive care teams were primarily responsible for analgesia during hospitalization (249 of 435, 57%), whereas responsibility shifted to neurosurgery at discharge (233 of 501, 47%). Most used medications were acetaminophen (90%), opioids (66%), corticosteroids (28%), and antiseizure medications (28%). Opioids or medication combinations including opioids were most frequently perceived as most effective by 169 of 433 respondents (39%, predominantly intensivists), followed by corticosteroids or combinations with corticosteroids (96 of 433, 22%, predominantly neurologists). Of medications prescribed at discharge, acetaminophen was most common (303 of 381, 80%), followed by opioids (175 of 381, 46%) and antiseizure medications (173 of 381, 45%). Opioids during hospitalization were significantly more prescribed by intensivists, by providers managing higher numbers of patients with SAH, and in Europe. At discharge, opioids were more frequently prescribed in North America. Of 435 respondents, 299 (69%) indicated no change in prescription practice of opioids with the opioid crisis. Additional differences in prescription patterns between continents and providers and while inpatient versus at discharge were found. CONCLUSIONS: Post-SAH headache in the intensive care setting is a major clinical concern. Analgesia heavily relies on opioids both in use and in perception of efficacy, with no reported change in prescription patterns for opioids for most providers despite the significant drawbacks of opioids. Responsibility for analgesia shifts between hospitalization and discharge. International and provider-related differences are evident. Novel treatment strategies and alignment of prescription between providers are urgently needed.

Verticalization for Refractory Intracranial Hypertension: A Case Series.

BACKGROUND: Severe intracranial hypertension is strongly associated with mortality. Guidelines recommend medical management involving sedation, hyperosmotic agents, barbiturates, hypothermia, and surgical intervention. When these interventions are maximized or are contraindicated, refractory intracranial hypertension poses risk for herniation and death. We describe a novel intervention of verticalization for treating intracranial hypertension refractory to aggressive medical treatment. METHODS: This study was a single-center retrospective review of six cases of refractory intracranial hypertension in a tertiary care center. All patients were treated with a standard-of-care algorithm for lowering intracranial pressure (ICP) yet maintained an ICP greater than 20 mmHg. They were then treated with verticalization for at least 24 h. We compared the median ICP, the number of ICP spikes greater than 20 mmHg, and the percentage of ICP values greater than 20 mmHg in the 24 h before verticalization vs. after verticalization. We assessed the use of hyperosmotic therapies and any changes in the mean arterial pressure and cerebral perfusion pressure related with the intervention. RESULTS: Five patients were admitted with subarachnoid hemorrhage and one with intracerebral hemorrhage. All patients had ICP monitoring by external ventricular drain. The median opening pressure was 30 mmHg (25th-75th interquartile range 22.5-30 mmHg). All patients demonstrated a reduction in ICP after verticalization, with a significant decrease in the median ICP (12 vs. 8 mmHg; p < 0.001), the number of ICP spikes (12 vs. 2; p < 0.01), and the percentage of ICP values greater than 20 mmHg (50% vs. 8.3%; p < 0.01). There was a decrease in total medical interventions after verticalization (79 vs. 41; p = 0.05) and a lower total therapy intensity level score after verticalization. The most common adverse effects included asymptomatic bradycardia (n = 3) and pressure wounds (n = 4). CONCLUSIONS: Verticalization is an effective noninvasive intervention for lowering ICP in intracranial hypertension that is refractory to aggressive standard management and warrants further study.

Dynamic Intracranial Pressure Waveform Morphology Predicts Ventriculitis.

BACKGROUND: Intracranial pressure waveform morphology reflects compliance, which can be decreased by ventriculitis. We investigated whether morphologic analysis of intracranial pressure dynamics predicts the onset of ventriculitis. METHODS: Ventriculitis was defined as culture or Gram stain positive cerebrospinal fluid, warranting treatment. We developed a pipeline to automatically isolate segments of intracranial pressure waveforms from extraventricular catheters, extract dominant pulses, and obtain morphologically similar groupings. We used a previously validated clinician-supervised active learning paradigm to identify metaclusters of triphasic, single-peak, or artifactual peaks. Metacluster distributions were concatenated with temperature and routine blood laboratory values to create feature vectors. A L2-regularized logistic regression classifier was trained to distinguish patients with ventriculitis from matched controls, and the discriminative performance using area under receiver operating characteristic curve with bootstrapping cross-validation was reported. RESULTS: Fifty-eight patients were included for analysis. Twenty-seven patients with ventriculitis from two centers were identified. Thirty-one patients with catheters but without ventriculitis were selected as matched controls based on age, sex, and primary diagnosis. There were 1590 h of segmented data, including 396,130 dominant pulses in patients with ventriculitis and 557,435 pulses in patients without ventriculitis. There were significant differences in metacluster distribution comparing before culture-positivity versus during culture-positivity (p < 0.001) and after culture-positivity (p < 0.001). The classifier demonstrated good discrimination with median area under receiver operating characteristic 0.70 (interquartile range 0.55-0.80). There were 1.5 true alerts (ventriculitis detected) for every false alert. CONCLUSIONS: Intracranial pressure waveform morphology analysis can classify ventriculitis without cerebrospinal fluid sampling.

Effect of Early vs Standard Approach to Tracheostomy on Functional Outcome at 6 Months Among Patients With Severe Stroke Receiving Mechanical Ventilation: The SETPOINT2 Randomized Clinical Trial.

Importance: Many patients with severe stroke have impaired airway protective reflexes, resulting in prolonged invasive mechanical ventilation. Objective: To test whether early vs standard tracheostomy improved functional outcome among patients with stroke receiving mechanical ventilation. Design, Setting, and Participants: In this randomized clinical trial, 382 patients with severe acute ischemic or hemorrhagic stroke receiving invasive ventilation were randomly assigned (1:1) to early tracheostomy (≤5 days of intubation) or ongoing ventilator weaning with standard tracheostomy if needed from day 10. Patients were randomized between July 28, 2015, and January 24, 2020, at 26 US and German neurocritical care centers. The final date of follow-up was August 9, 2020. Interventions: Patients were assigned to an early tracheostomy strategy (n = 188) or to a standard tracheostomy (control group) strategy (n = 194). Main Outcomes and Measures: The primary outcome was functional outcome at 6 months, based on the modified Rankin Scale score (range, 0 [best] to 6 [worst]) dichotomized to a score of 0 (no disability) to 4 (moderately severe disability) vs 5 (severe disability) or 6 (death). Results: Among 382 patients randomized (median age, 59 years; 49.8% women), 366 (95.8%) completed the trial with available follow-up data on the primary outcome (177 patients [94.1%] in the early group; 189 patients [97.4%] in the standard group). A tracheostomy (predominantly percutaneously) was performed in 95.2% of the early tracheostomy group in a median of 4 days after intubation (IQR, 3-4 days) and in 67% of the control group in a median of 11 days after intubation (IQR, 10-12 days). The proportion without severe disability (modified Rankin Scale score, 0-4) at 6 months was not significantly different in the early tracheostomy vs the control group (43.5% vs 47.1%; difference, -3.6% [95% CI, -14.3% to 7.2%]; adjusted odds ratio, 0.93 [95% CI, 0.60-1.42]; P = .73). Of the serious adverse events, 5.0% (6 of 121 reported events) in the early tracheostomy group vs 3.4% (4 of 118 reported events) were related to tracheostomy. Conclusions and Relevance: Among patients with severe stroke receiving mechanical ventilation, a strategy of early tracheostomy, compared with a standard approach to tracheostomy, did not significantly improve the rate of survival without severe disability at 6 months. However, the wide confidence intervals around the effect estimate may include a clinically important difference, so a clinically relevant benefit or harm from a strategy of early tracheostomy cannot be excluded. Trial Registration: ClinicalTrials.gov Identifier: NCT02377167.

The Modified Fisher Scale Lacks Interrater Reliability.

BACKGROUND: The modified Fisher scale (mFS) is a critical clinical and research tool for risk stratification of cerebral vasospasm. As such, the mFS is included as a common data element by the National Institute of Neurological Disorders and Stroke SAH Working Group. There are few studies assessing the interrater reliability of the mFS. METHODS: We distributed a survey to a convenience sample with snowball sampling of practicing neurointensivists and through the research survey portion of the Neurocritical Care Society Web site. The survey consisted of 15 scrollable CT scans of patients with SAH for mFS grading, two questions regarding the definitions of the scale criteria and demographics of the responding physician. Kendall's coefficient of concordance was used to determine the interrater reliability of mFS grading. RESULTS: Forty-six participants (97.8% neurocritical care fellowship trained, 78% UCNS-certified in neurocritical care, median 5 years (IQR 3-6.3) in practice, treating median of 80 patients (IQR 50-100) with SAH annually from 32 institutions) completed the survey. By mFS criteria, 30% correctly identified that there is no clear measurement of thin versus thick blood, and 42% correctly identified that blood in any ventricle is scored as "intraventricular blood." The overall interrater reliability by Kendall's coefficient of concordance for the mFS was moderate (W = 0.586, p < 0.0005). CONCLUSIONS: Agreement among raters in grading the mFS is only moderate. Online training tools could be developed to improve mFS reliability and standardize research in SAH.

Development of Neurological Emergency Simulations for Assessment: Content Evidence and Response Process.

OBJECTIVE: To document two sources of validity evidence for simulation-based assessment in neurological emergencies. BACKGROUND: A critical aspect of education is development of evaluation techniques that assess learner's performance in settings that reflect actual clinical practice. Simulation-based evaluation affords the opportunity to standardize evaluations but requires validation. METHODS: We identified topics from the Neurocritical Care Society's Emergency Neurological Life Support (ENLS) training, cross-referenced with the American Academy of Neurology's core clerkship curriculum. We used a modified Delphi method to develop simulations for assessment in neurocritical care. We constructed checklists of action items and communication skills, merging ENLS checklists with relevant clinical guidelines. We also utilized global rating scales, rated one (novice) through five (expert) for each case. Participants included neurology sub-interns, neurology residents, neurosurgery interns, non-neurology critical care fellows, neurocritical care fellows, and neurology attending physicians. RESULTS: Ten evaluative simulation cases were developed. To date, 64 participants have taken part in 274 evaluative simulation scenarios. The participants were very satisfied with the cases (Likert scale 1-7, not at all satisfied-very satisfied, median 7, interquartile range (IQR) 7-7), found them to be very realistic (Likert scale 1-7, not at all realistic-very realistic, median 6, IQR 6-7), and appropriately difficult (Likert scale 1-7, much too easy-much too difficult, median 4, IQR 4-5). Interrater reliability was acceptable for both checklist action items (kappa = 0.64) and global rating scales (Pearson correlation r = .70). CONCLUSIONS: We demonstrated two sources of validity in ten simulation cases for assessment in neurological emergencies.

Neuromuscular Electrical Stimulation and High-Protein Supplementation After Subarachnoid Hemorrhage: A Single-Center Phase 2 Randomized Clinical Trial.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) survivors live with long-term residual physical and cognitive disability. We studied whether neuromuscular electrical stimulation (NMES) and high-protein supplementation (HPRO) in the first 2 weeks after SAH could preserve neuromotor and cognitive function as compared to standard of care (SOC) for nutrition and mobilization. METHODS: SAH subjects with a Hunt Hess (HH) grade > 1,modified Fisher score > 1 and BMI < 40 kg/m2 were randomly assigned to SOC or NMES + HPRO. NMES was delivered to bilateral quadricep muscles daily during two 30-min sessions along with HPRO (goal:1.8 g/kg/day) between post-bleed day (PBD) 0 and 14. Primary endpoint was atrophy in the quadricep muscle as measured by the percentage difference in the cross-sectional area from baseline to PBD14 on CT scan. All subjects underwent serial assessments of physical (short performance physical battery, SPPB) cognitive (Montreal Cognitive Assessment Scale, MoCA) and global functional recovery (modified Rankin Scale, mRS) at PBD 14, 42, and 90. RESULTS: Twenty-five patients (SOC = 13, NMES + HPRO = 12) enrolled between December 2017 and January 2019 with no between-group differences in baseline characteristics (58 years old, 68% women, 50% HH > 3). Median duration of interventions was 12 days (range 9-14) with completion of 98% of NMES sessions and 83% of goal HPRO, and no reported serious adverse events. There was no difference in caloric intake between groups, but HPRO + NMES group received more protein (1.5 ± 0.5 g/kg/d v 0.9 ± 0.4 g/kg/d, P < 0.01). Muscle atrophy was less in NMES + HPRO than the SOC group (6.5 ± 4.1% vs 12.5 ± 6.4%, P 0.01). Higher atrophy was correlated with lower daily protein intake (ρ = - 0.45, P = 0.03) and lower nitrogen balance (ρ = 0.47, P = 0.02); and worse 3 month SPPB (ρ = -  0.31, P = 0.1) and mRS (ρ = 0.4, P = 0.04). NMES + HPRO patients had a better median [25%,75] SPPB (12[10, 12] v. 9 [4, 12], P = 0.01) and mRS (1[0,2] v.2[1, 3], P = 0.04) than SOC at PBD 90. CONCLUSIONS: NMES + HPRO appears to be feasible and safe acutely after SAH and may reduce acute quadriceps muscle wasting with a lasting benefit on recovery after SAH.

Pain Trajectories Following Subarachnoid Hemorrhage are Associated with Continued Opioid Use at Outpatient Follow-up.

BACKGROUND: Subarachnoid hemorrhage (SAH) is characterized by the worst headache of life and associated with long-term opioid use. Discrete pain trajectories predict chronic opioid use following other etiologies of acute pain, but it is unknown whether they exist following SAH. If discrete pain trajectories following SAH exist, it is uncertain whether they predict long-term opioid use. We sought to characterize pain trajectories after SAH and determine whether they are associated with persistent opioid use. METHODS: We reviewed pain scores from patients admitted to a single tertiary care center for SAH from November 2015 to September 2019. Group-based trajectory modeling identified discrete pain trajectories during hospitalization. We compared outcomes across trajectory groups using χ2 and Kruskal-Wallis tests. Multivariable regression determined whether trajectory group membership was an independent predictor of long-term opioid use, defined as continued use at outpatient follow-up. RESULTS: We identified five discrete pain trajectories among 305 patients. Group 1 remained pain free. Group 2 reported low scores with intermittent spikes and slight increase over time. Group 3 noted increasing pain severity through day 7 with mild improvement until day 14. Group 4 experienced maximum pain with steady decrement over time. Group 5 reported moderate pain with subtle improvement. In multivariable analysis, trajectory groups 3 (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.5-8.3) and 5 (OR 8.0; 95% CI 3.1-21.1), history of depression (OR 3.6; 95% CI 1.3-10.0) and racial/ethnic minority (OR 2.3; 95% CI 1.3-4.1) were associated with continued opioid use at follow-up (median 62 days following admission, interquartile range 48-96). CONCLUSIONS: Discrete pain trajectories following SAH exist. Recognition of pain trajectories may help identify those at risk for long-term opioid use.

Triage of Patients with Intracerebral Hemorrhage to Comprehensive Versus Primary Stroke Centers.

OBJECTIVES: The management of patients admitted with intracerebral hemorrhage (ICH) mostly occurs in an ICU. While guidelines recommend initial treatment of these patients in a neurocritical care or stroke unit, there is limited data on which patients would benefit most from transfer to a comprehensive stroke center where on-site neurosurgical coverage is available 24/7. As neurocritical units become more common in primary stroke centers, it is important to determine which patients are most likely to require neurosurgical intervention and transfer to comprehensive stroke centers. MATERIALS AND METHODS: This is a retrospective observational cohort study conducted at an academic comprehensive stroke center in the United States. Four-hundred-fifty-nine consecutive patients transferred or directly admitted to the neurocritical care unit from 2016-2018 with the primary diagnosis of ICH were included. Univariate statistics and multivariate regression were used to identify clinical characteristics associated with neurosurgical intervention, defined as undergoing craniotomy, ventriculostomy, or endovascular embolization of an arteriovenous malformation (AVM). RESULTS: The following variables were associated with neurosurgical intervention in multivariate analysis: age (OR 0.38, 95% CI 0.27-0.55), admission Glasgow Coma Scale (OR 0.29, 95% CI 0.18-0.48), the presence of intraventricular hemorrhage (OR 2.82, CI 1.71-4.65), infratentorial location of ICH (OR 2.28, 95% CI 1.20-4.31), previous antiplatelet use (OR 2.04, 95% CI 1.24-3.34), and an AVM indicated on CT Angiogram (OR 2.59, 95% CI 1.19-5.63) were independently associated with the need for neurosurgical intervention. This was translated into a scoring system to help make quick triage decisions, with high sensitivity (99%, 95% CI 97-99%) and negative predictive value (98%, 95% CI 89-99%). CONCLUSIONS: Using previously well described predictors of severity in ICH patients, we were able to develop a scoring system to predict the need for neurosurgical intervention with high sensitivity and negative predictive value.

Intraoperative hypotension and perioperative acute ischemic stroke in patients having major elective non-cardiovascular non-neurological surgery.

PURPOSE: The association between intraoperative hypotension and perioperative acute ischemic stroke is not well described. We hypothesized that intraoperative hypotension would be associated with perioperative acute ischemic stroke. METHODS: Four-year retrospective cohort study of elective non-cardiovascular, non-neurological surgical patients. Characteristics of patients who had perioperative acute ischemic stroke were compared against those of patients who did not have acute ischemic stroke. Multivariable logistic regression was used to determine whether hypotension was independently associated with increased odds of perioperative acute ischemic stroke. RESULTS: Thirty-four of 9816 patients (0.3%) who met study inclusion criteria had perioperative acute ischemic stroke. Stroke patients were older and had more comorbidities including hypertension, coronary artery disease, diabetes mellitus, active tobacco use, chronic obstructive pulmonary disease, cerebral vascular disease, atrial fibrillation, and peripheral vascular disease (all P < 0.05). MAP < 65 mmHg was not associated with increased odds of acute ischemic stroke when modeled as a continuous or categorical variable. MAP < 60 mmHg for more than 20 min was independently associated with increased odds of acute ischemic stroke, OR = 2.67 [95% CI = 1.21 to 5.88, P = 0.02]. CONCLUSION: Our analysis suggests that when MAP is less than 60 mmHg for more than 20 min, there is increased odds of acute ischemic stroke. Further studies are needed to determine what MAP should be targeted during surgery to optimize cerebral perfusion and limit ischemic stroke risk.

Multimodal imaging of biological tissues using combined MALDI and NAPA-LDI mass spectrometry for enhanced molecular coverage.

Mass spectrometry imaging (MSI) is a powerful analytical technique that enables detection, discovery, and identification of multiple classes of biomolecules, while simultaneously mapping their spatial distributions within a sample (e.g., a section of biological tissue). The limitation in molecular coverage afforded by any single MSI platform has led to the development of multimodal approaches that incorporate two or more techniques to obtain greater chemical information. Matrix-assisted laser desorption ionization (MALDI) is a preeminent ionization technique for MSI applications because the wide range of available matrices allows some degree of enhancement with respect to the detection of particular molecular classes. Nonetheless, MALDI has a limited ability to detect and image several classes of molecules, e.g., neutral lipids, in complex samples. Laser desorption ionization from silicon nanopost arrays (NAPA-LDI or NAPA) has been shown to offer complementary coverage with respect to MALDI by providing improved detection of neutral lipids and some small metabolites. Here, we present a multimodal imaging method in which a single tissue section is consecutively imaged at low and high laser fluences, generating spectra that are characteristic of MALDI and NAPA ionization, respectively. The method is demonstrated to map the distributions of species amenable to detection by MALDI (e.g., phospholipids and intermediate-mass metabolites) and NAPA (e.g., neutral lipids such as triglycerides and hexosylceramides, and small metabolites) in mouse brain and lung tissue sections.

Remote ablation chamber for high efficiency particle transfer in laser ablation electrospray ionization mass spectrometry.

Laser ablation electrospray ionization (LAESI) driven by mid-infrared laser pulses allows the direct analysis of biological tissues with minimal sample preparation. Dedicated remote ablation chambers have been developed to eliminate the need for close proximity between the sample and the mass spectrometer inlet. This also allows for the analysis of large or irregularly shaped objects, and incorporation of additional optics for microscopic imaging. Here we report on the characterization of a newly designed conical inner volume ablation chamber working in transmission geometry, where a reduced zone of stagnation was achieved by tapering the sample platform and the chamber outlet. As a result, the transmission efficiency of both large (>7.5 µm) and smaller particulates (<6.5 µm) has increased significantly. Improved analytical figures of merit, including 300 fmol limit of detection, and three orders of magnitude in dynamic range, were established. Particle residence time, measured by the FWHM of the analyte signal, was reduced from 2.0 s to 0.5 s enabling higher ablation rates and shorter analysis time. A total of six glucosinolates (sinigrin, gluconapin, progoitrin, glucoiberin, glucoraphanin, and glucohirsutin) were detected in plant samples with ion abundances higher by a factor of 2 to 8 for the redesigned ablation chamber.

Histological demonstration of BSEP/ABCB11 inhibition in transient neonatal cholestasis: a case report.

BACKGROUND: Idiopathic or transient neonatal cholestasis (TNC) represents a group of cholestatic disorders with unidentified origin and remains a diagnosis of exclusion. Dysfunction of hepatobiliary transporters mediating excretion of biliary constituents from hepatocytes may play a central role in the pathogenesis of cholestasis. Despite variants of bile salt (BS) export pump (BSEP/ABCB11) have already been described in TNC, the pathogenic role of BSEP dysfunction in TNC remained so far elusive. CASE PRESENTATION: We report on a newly-identified heterozygous ABCB11 missense variant (c.1345G > A, p.Glu449Lys) which was associated with prolonged cholestasis in a term infant after a complicated neonatal period. Moreover, we show for the first time almost completely abolished BSEP expression on the hepatocellular membrane in TNC. CONCLUSION: This report demonstrates for the first time a close association between the prolonged cholestasis in infancy and impaired BSEP expression on the hepatocyte canalicular membrane in a heterozygous carrier of newly-identified ABCB11 variant.

Factors associated with tracheostomy decannulation in patients with severe traumatic brain injury.

OBJECTIVE: To assess variables associated with decannulation in patients with traumatic brain injury (TBI). PARTICIPANTS: 79 patients with TBI requiring tracheostomy and ICU admission from January 1st to December 31st, 2014. DESIGN: Retrospective analysis. MEASURES: Patients decannulated prior to 90 days were compared with patients who remained cannulated. Two Cox Proportional Hazards models were used to predict decannulation using variables prior to tracheostomy and throughout hospitalization. RESULTS: Median time to decannulation was 37 days (Interquartile Range [IQR] 29-67). Variables prior to tracheostomy associated with decannulation included diabetes (HR, 0.15; 95% CI, 0.03-0.84; p =.03), craniotomy (HR, 0.25; 95% CI, 0.06-1.02; p =.05) and acute kidney injury (AKI) (HR, 0.06; 95% CI, 0.01-0.48; p =.01). Variables present throughout hospitalization included age (HR, 1.12; 95% CI, 1.01-1.21; p =.03), ventilator days (HR, 0.74; 95% CI, 0.57-0.95; p =.02), reintubation (HR, 0.07; 95% CI, 0.01-0.64; p =.02), aspiration (HR, 0.01; 95% CI, 0.0-0.29, p =.01), craniotomy (HR, 0.004; 95% CI, 0.0-0.39; p =.02) and AKI (HR, 0.0; 95% CI, 0.0-0.21; p =.01). CONCLUSION: The presence of diabetes, craniotomy and acute kidney injury may inform the conversation surrounding chances for decannulation prior to tracheostomy.

High Throughput Complementary Analysis and Quantitation of Metabolites by MALDI- and Silicon Nanopost Array-Laser Desorption/Ionization-Mass Spectrometry.

Silicon nanopost array (NAPA) structures have been shown to be effective substrates for laser desorption/ionization-mass spectrometry (LDI-MS) and have been used to analyze a variety of samples including peptides, metabolites, drugs, explosives, and intact cells, as well as to image lipids and metabolites in tissue sections. However, no direct comparison has yet been conducted between NAPA-MS and the most commonly used LDI-MS technique, matrix-assisted laser desorption/ionization (MALDI)-MS. In this work, we compare the utility of NAPA-MS to that of MALDI-MS using two common matrices for the analysis of metabolites in cellular extracts and human urine. Considerable complementarity of molecular coverage was observed between the two techniques. Of 178 total metabolites assigned from cellular extracts, 68 were uniquely detected by NAPA-MS and 62 were uniquely detected by MALDI-MS. NAPA-MS was found to provide enhanced coverage of low-molecular weight compounds such as amino acids, whereas MALDI afforded better detection of larger, labile compounds including nucleotides. In the case of urine, a sample largely devoid of higher-mass labile compounds, 88 compounds were uniquely detected by NAPA-MS and 13 by MALDI-MS. NAPA-MS also favored more extensive alkali metal cation adduction relative to MALDI-MS, with the [M + 2Na/K - H]+ species accounting for as much as 97% of the total metabolite ion signal in positive mode. The capability of NAPA-MS for targeted quantitation of endogenous metabolites in urine via addition of isotopically labeled standards was also examined. Both NAPA-MS and MALDI-MS provided quantitative results in good agreement with one another and the concentrations reported in the literature, as well as good sample-to-sample reproducibility (RSD < 10%).