Preparing Neurology Residents and Advanced Practice Providers for the COVID-19 ICU-A Neurocritical Care Led Intervention.

BACKGROUND AND PURPOSE: With the surge of critically ill COVID-19 patients, neurology and neurosurgery residents and advanced practice providers (APPs) were deployed to intensive care units (ICU). These providers lacked relevant critical care training. We investigated whether a focused video-based learning curriculum could effectively teach high priority intensive care topics in this unprecedented setting to these neurology providers. METHODS: Neurocritical care clinicians led a multidisciplinary team in developing a 2.5-hour lecture series covering the critical care management of COVID-19 patients. We examined whether provider confidence, stress, and knowledge base improved after viewing the lectures. RESULTS: A total of 88 residents and APPs participated across 2 academic institutions. 64 participants (73%) had not spent time as an ICU provider. After viewing the lecture series, the proportion of providers who felt moderately, quite, or extremely confident increased from 11% to 72% (60% difference, 95% CI 49-72%) and the proportion of providers who felt nervous/stressed, very nervous/stressed, or extremely nervous/stressed decreased from 78% to 48% (38% difference, 95% CI 26-49%). Scores on knowledge base questions increased an average of 2.5 out of 12 points (SD 2.1; p < 0.001). CONCLUSION: A targeted, asynchronous curriculum on critical care COVID-19 management led to significantly increased confidence, decreased stress, and improved knowledge among resident trainees and APPs. This curriculum could serve as an effective didactic resource for neurology providers preparing for the COVID-19 ICU.

Suspected Lower Extremity Ischemia After End-to-Side Femoral Arterial Grafting for VA-ECMO.

Lower extremity ischemic complications are frequently encountered after femoral cannulation for venoarterial extracorporeal membrane oxygenation (VA-ECMO). Many are attributed to mechanical obstruction of distal arterial blood flow related to intraluminal positioning of the arterial cannula. Routine use of distal perfusion catheters is ineffective at eliminating the development of these serious complications. Side- arm grafting instead of direct arterial cannulation is suggested as an alternative. Here, the authors present a case wherein a patient developed suspected lower extremity ischemia from hyperperfusion after femoral VA-ECMO cannulation during use of an arterial side- arm graft, calling into question the benefits of this cannulation strategy.

How Cardiac Anesthesiology Can Help "STEM" the Tide of Under-representation of Minorities in Science and Medicine.

The field of medicine is built upon science, technology, engineering, and math (STEM), yet the United States is rapidly falling behind when it comes to educating the next generation in these disciplines, especially under-represented populations. The authors reflect on existing educational literature surrounding efforts to promote interest in STEM among students and under-represented populations. The authors advocate for greater efforts toward the development of youth programing. Cardiac anesthesia is uniquely positioned as a subspecialty to advance the goal of promoting interest in STEM in diverse groups of young students. The authors describe their development and implementation of a community outreach program to enhance interest in medicine through a cardiac dissection experience.

Use of Methohexital and Dexmedetomidine for Maintenance of Anesthesia in a Patient With Mitochondrial Myopathy: A Case Report.

Provision of anesthesia for patients with mitochondrial disorders is associated with a unique set of challenges. These disorders are rare, which complicates efforts to develop high quality, evidence-based guidelines to inform the perioperative management of those who suffer from them. Accordingly, case reports remain an important source of information regarding their care. Here we present the case of a 27-year-old female patient with mitochondrial myopathy and a history suggestive of malignant hyperthermia susceptibility who received general anesthesia for 2 consecutive surgeries. The induction agents included fentanyl, ketamine, and methohexital. The maintenance agents were methohexital, sufentanil, and dexmedetomidine.

Propofol at clinically relevant concentrations increases neuronal differentiation but is not toxic to hippocampal neural precursor cells in vitro.

BACKGROUND: Propofol in the early postnatal period has been shown to cause brain cell death. One proposed mechanism for cognitive dysfunction after anesthesia is alteration of neural stem cell function and neurogenesis. We examined the effect of propofol on neural precursor or stem cells (NPCs) grown in vitro. METHODS: Hippocampal-derived NPCs from postnatal day 2 rats were exposed to propofol or Diprivan. NPCs were then analyzed for bromodeoxyuridine incorporation to measure proliferation. Cell death was measured by lactate dehydrogenase release. Immunocytochemistry was used to evaluate the expression of neuronal and glial markers in differentiating NPCs exposed to propofol. RESULTS: Propofol dose dependently increases the release of lactate dehydrogenase from NPCs under both proliferating and differentiating conditions at supraclinical concentrations (more than 7.1 µM). Both Diprivan and propofol had the same effect on NPCs. Propofol-mediated release of lactate dehydrogenase is not inhibited by blocking the γ-aminobutyric acid type A receptor or extracellular calcium influx and is not mediated by caspase-3/7. Direct γ-aminobutyric acid type A receptor activation did not have the same effect. In differentiating NPCs, 6 h of propofol at 2.1 µM increased the number neurons but not glial cells 4 days later. Increased neuronal differentiation was not blocked by bicuculline. CONCLUSIONS: Only supraclinical concentrations of propofol or Diprivan kill NPCs in culture by a non-γ-aminobutyric acid type A, noncaspase-3 mechanism. Clinically relevant doses of propofol increase neuronal fate choice by a non-γ-aminobutyric acid type A mechanism.

Networked T cell death following macrophage infection by Mycobacterium tuberculosis.

BACKGROUND: Depletion of T cells following infection by Mycobacterium tuberculosis (Mtb) impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. A number of mechanisms contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs. The extent to which Mtb infection of human macrophages affects T cell viability however, is not well characterised. METHODOLOGY/PRINCIPAL FINDINGS: We found that lymphopenia (<1.5 × 10(9) cells/l) was prevalent among culture-positive tuberculosis patients, and lymphocyte counts significantly improved post-therapy. We previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. In the current study, we sought to examine the influence of infected human alveolar macrophages on T cells. We infected primary human alveolar macrophages (the primary host cell for Mtb) or PMA-differentiated THP-1 cells with Mtb H37Ra, then prepared cell-free supernatants. The supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis. This toxic effect of infected macrophage secreted factors did not require TNF-α or Fas. The supernatant cytotoxic signal(s) were heat-labile and greater than 50 kDa in molecular size. Although ESAT-6 was toxic to T cells, other Mtb-secreted factors tested did not influence T cell viability; nor did macrophage-free Mtb bacilli or broth from Mtb cultures. Furthermore, supernatants from Mycobacterium bovis Bacille de Calmette et Guerin (BCG)- infected macrophages also elicited T cell death suggesting that ESAT-6 itself, although cytotoxic, was not the principal mediator of T cell death in our system. CONCLUSIONS: Mtb-Infected macrophages secrete heat-labile factors that are toxic to T cells, and may contribute to the immunosuppression seen in tuberculosis as well as interfere with microbial eradication in the granuloma.

Delayed environmental enrichment reverses sevoflurane-induced memory impairment in rats.

BACKGROUND: Anesthesia given to immature rodents causes cognitive decline, raising the possibility that the same might be true for millions of children undergoing surgical procedures under general anesthesia each year. We tested the hypothesis that anesthesia-induced cognitive decline in rats is treatable. We also tested if anesthesia-induced cognitive decline is aggravated by tissue injury. METHODS: Seven-day old rats underwent sevoflurane anesthesia (1 minimum alveolar concentration, 4 h) with or without tail clamping. At 4 weeks, rats were randomized to environmental enrichment or normal housing. At 8 weeks rats underwent neurocognitive testing, which consisted of fear conditioning, spatial reference memory, and water maze-based memory consolidation tests, and interrogated working memory, short-term memory, and early long-term memory. RESULTS: Sevoflurane-treated rats had a greater escape latency when the delay between memory acquisition and memory retrieval was increased from 1 min to 1 h, indicating that short-term memory was impaired. Delayed environmental enrichment reversed the effects of sevoflurane on short-term memory and generally improved many tested aspects of cognitive function, both in sevoflurane-treated and control animals. The performance of tail-clamped rats did not differ from those rats receiving anesthesia alone. CONCLUSION: Sevoflurane-induced cognitive decline in rats is treatable. Delayed environmental enrichment rescued the sevoflurane-induced impairment in short-term memory. Tissue injury did not worsen the anesthesia-induced memory impairment. These findings may have relevance to neonatal and pediatric anesthesia.

Selective deficits in the expression of striatal-enriched mRNAs in Huntington's disease.

We have identified and cataloged 54 genes that exhibit predominant expression in the striatum. Our hypothesis is that such mRNA molecules are likely to encode proteins that are preferentially associated with particular physiological processes intrinsic to striatal neurons, and therefore might contribute to the regional specificity of neurodegeneration observed in striatal disorders such as Huntington's disease (HD). Expression of these genes was measured simultaneously in the striatum of HD R6/1 transgenic mice using Affymetrix oligonucleotide arrays. We found a decrease in expression of 81% of striatum-enriched genes in HD transgenic mice. Changes in expression of genes associated with G-protein signaling and calcium homeostasis were highlighted. The most striking decrement was observed for a newly identified subunit of the sodium channel, beta 4, with dramatic decreases in expression beginning at 8 weeks of age. A subset of striatal genes was tested by real-time PCR in caudate samples from human HD patients. Similar alterations in expression were observed in human HD and the R6/1 model for the striatal genes tested. Expression of 15 of the striatum-enriched genes was measured in 6-hydroxydopamine-lesioned rats to determine their dependence on dopamine innervation. No changes in expression were observed for any of these genes. These findings demonstrate that mutant huntingtin protein causes selective deficits in the expression of mRNAs responsible for striatum-specific physiology and these may contribute to the regional specificity of degeneration observed in HD.