Survival of In-Hospital Cardiopulmonary Arrest in Trauma Patients.

INTRODUCTION: Relative to other hospitalized patients, trauma patients are younger with fewer comorbidities, but the incidence and outcomes of in-hospital cardiopulmonary arrest (IHCA) with cardiopulmonary resuscitation (CPR) in this population is unknown. Therefore, we aimed to investigate factors associated with survival in trauma patients after IHCA to test the hypothesis that compared to other hospitalized patients, trauma patients with IHCA have improved survival. METHODS: Retrospective review of the Trauma Quality Improvement Program database 2017 to 2019 for patients who had IHCA with CPR. Primary outcome was survival to hospital discharge. Secondary outcomes were in-hospital complications, hospital length of stay, intensive care unit length of stay, and ventilator days. Data were compared with univariate and multivariate analyses at P < 0.05. RESULTS: In 22,346,677 admitted trauma patients, 14,056 (0.6%) received CPR. Four thousand three hundred seventy-seven (31.1%) survived to discharge versus 26.4% in a national sample of all hospitalized patients (P < 0.001). In trauma patients, median age was 55 y, the majority were male (72.2%). Mortality was higher for females versus males (70.3% versus 68.3%, P = 0.026). Multivariate regression showed that older age 1.01 (95% confidence interval (CI) 1.01-1.02), Hispanic ethnicity 1.21 (95% CI 1.04-1.40), and penetrating trauma 1.51 (95% CI 1.32-1.72) were risk factors for mortality, while White race was a protective factor 0.36 (95% CI 0.14-0.89). CONCLUSIONS: This is the first study to show that the incidence of IHCA with CPR is approximately six in 1000 trauma admissions and 31% survive to hospital discharge, which is higher than other hospitalized patients. Age, gender, racial, and ethnic disparities also influence survival.

Should VV ECMO be considered as treatment option in COVID-19 infection after kidney transplant? A word of caution.

Several reports have shown that hospitalized kidney transplant recipients (KTR) had high mortality rates when infected with COVID-19. Extracorporeal Membrane Oxygenation (ECMO) has been shown to be an option for refractory respiratory failure in COVID-19 patients with variable rates of recovery. The outcome of ECMO in respiratory failure is highly related to cohort investigated and patient selection. Over a 10-month period in the height of COVID-19 pandemic 5 KTR patients were placed on ECMO with none of the patients surviving to discharge. All patients experienced multisystem organ failure (MSOF) and hematologic pathology while on ECMO. We concluded that COVID-19 in KTR patients presents with a refractory MSOF that is not well supported with ECMO in a traditional approach. Future work is needed to determine how to best support refractory respiratory failure in KTR patients with COVID-19.

Administration and Scoring Errors on the Woodcock-Johnson IV Tests of Achievement: Before and During COVID-19.

Eighty Woodcock-Johnson IV Tests of Achievement protocols from 40 test administrators were examined to determine the types and frequencies of administration and scoring errors made. Non-critical errors (e.g., failure to record verbatim) were found on every protocol (M = 37.2). Critical (e.g., standard score, start point) errors were found on 98.8% of protocols (M = 15.3). Additionally, a series of paired samples t-test were conducted to determine differences in total, critical, and non-critical errors pre- and during-COVID-19. No statistic differences were found. Our findings add to a growing body of research that suggests that errors on norm-referenced tests of achievement are pervasive. However, the frequency of errors did not appear to be affected by COVID-19 stressors or social distancing requirements. Implications of these findings for training and practice are discussed. Suggestions for future research are also provided.

Arterial or cuff pressure: Clinical predictors among patients in shock in a critical care resuscitation unit.

OBJECTIVES: Blood pressure (BP) measurement is essential for managing patients with hypotension. There are differences between invasive arterial blood pressure (IABP) and noninvasive blood pressure (NIBP) measurements. However, the clinical applicability of these differences in patients with shock [need for vasopressor or serum lactate ≥ 4 millimole per liter (mmol/L)] has not been reported. This study investigated differences in IABP and NIBP as well as changes in clinical management in critically ill patients with shock. METHODS: This was a retrospective study involving adult patients admitted to the Critical Care Resuscitation Unit (CCRU). Adult patients who received IABP upon admission between 01/01/2017-12/31/2017 with non-hypertensive diseases were eligible. The primary outcome, clinically relevant difference (CRD), was defined as difference of 10 mm of mercury (mmHg) between IABP and NIBP and change of blood pressure management according to goal mean arterial pressure (MAP) ≥ 65 mmHg. We performed forward stepwise multivariable logistic regression to measure associations. RESULTS: Sample size calculation recommended 200 patients, and we analyzed 263. 121 (46%) patients had shock, 23 (9%) patients had CRD. Each mmol/L increase in serum lactate was associated with 11% higher likelihood of having CRD (OR 1.11, 95%CI 1.002-1.2). Peripheral artery disease and any kidney disease was significantly associated with higher likelihood of MAP difference ≥ 10 mmHg. CONCLUSION: Approximately 9% of patients with shock had clinically-relevant MAP difference. Higher serum lactate was associated with higher likelihood of CRD. Until further studies are available, clinicians should consider using IABP in patients with shock.

Predictors of clinically relevant differences between noninvasive versus arterial blood pressure.

OBJECTIVE: Blood pressure (BP) measurements are important for managing patients with hypertensive emergencies (HE). Previous studies showed that there was significant difference between IABP and NIBP but no information whether these differences changed management. Our study investigated the factors associated with the differences affecting BP management of patients with HE. METHODS: This was a retrospective study involving adult patients admitted to a resuscitation unit. We screened all patients who received IABP upon admission between 06/01/2017 and 12/31/2017 as sample size calculation recommended 64 patients. Primary outcome was the clinical relevance of the difference of IABP vs. NIBP, which was defined as having both: a) difference of 10 mm of mercury (mmHg), and b) resulting in possible change of blood pressure managements according to treatment guidelines. We performed backward stepwise multivariable logistic regression to measure associations. RESULTS: We analyzed 147 patients whose mean age was 69 (±16) years and included 69 (47%) patients with spontaneous intracerebral hemorrhage (sICH). Mean difference between IABP and NIBP was 21 (±16) mmHg while 41 (28%) patients who had difference affecting managements. In multivariable regression, sICH (Odd Ratios 13.5, 95%CI 2.3-79.5, p-value < 0.001) was significantly associated with clinically relevant difference between the two modalities of BP monitoring. CONCLUSIONS: There was a large difference between IABP and NIBP among patients with hypertensive emergencies. Up to 30% of patients had clinically relevant differences. Patients with sICH were more likely to have differences affecting BP management. Further studies are needed to confirm our observation.

Don't pig(!) the wrong heart!

Cardiac xenotransplantation is believed to have approached clinical application. However, this approach to advanced heart failure is burdened with a multitude of ethical issues. These issues need to be addressed openly and be broadly discussed in public. Only through an honest and transparent approach, it will be possible to engage the lay audience in the evaluation of pig to human transplant.

Intoxication and overdose should not preclude veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: Acute intoxication (AI) related morbidity and mortality are increasing in the United States. For patients with severe respiratory failure in the setting of an acute ingestion, veno-venous extracorporeal membrane oxygenation (VV ECMO) can provide salvage therapy. The purpose of this study was to evaluate outcomes in patients with overdose-related need for VV ECMO. METHODS: We performed a retrospective review of all patients admitted to a specialty VV ECMO unit between August 2014 and August 2018. Patients were stratified by those whose indication for VV ECMO was directly related to an acute ingestion (alcohol, illicit drug, or prescription drug overdose) and those with unrelated diagnoses. Demographics, pre-cannulation clinical characteristics, ECMO parameters, and outcomes data was collected and analyzed with parametric and non-parametric statistics as indicated. RESULTS: 189 patients were enrolled with 27 (14%) diagnosed with AI. Patients requiring VV ECMO for an AI were younger, had lower median BMI and PaO2/FiO2, and higher RESP scores than non-AI patients (p = 0.002, 0.01, 0.03 and 0.01). There was no difference in pre-cannulation pH, lactate, or SOFA scores between the two groups (p = 0.24, 0.5, 0.6). There was no difference in survival to discharge (p = 0.95). Among survivors, there was no difference in ECMO time or hospital stay (p = 0.24, 0.07). CONCLUSION: We demonstrate no survival difference for patients with and without an AI-related need for VV ECMO. AI patients should be supported with VV ECMO when traditional therapies fail despite potential stigma against acceptance on referral.

Evolutionary genomics of three agricultural pest moths reveals rapid evolution of host adaptation and immune-related genes.

BACKGROUND: Understanding the genotype of pest species provides an important baseline for designing integrated pest management (IPM) strategies. Recently developed long-read sequence technologies make it possible to compare genomic features of nonmodel pest species to disclose the evolutionary path underlying the pest species profiles. Here we sequenced and assembled genomes for 3 agricultural pest gelechiid moths: Phthorimaea absoluta (tomato leafminer), Keiferia lycopersicella (tomato pinworm), and Scrobipalpa atriplicella (goosefoot groundling moth). We also compared genomes of tomato leafminer and tomato pinworm with published genomes of Phthorimaea operculella and Pectinophora gossypiella to investigate the gene family evolution related to the pest species profiles. RESULTS: We found that the 3 solanaceous feeding species, P. absoluta, K. lycopersicella, and P. operculella, are clustered together. Gene family evolution analyses with the 4 species show clear gene family expansions on host plant-associated genes for the 3 solanaceous feeding species. These genes are involved in host compound sensing (e.g., gustatory receptors), detoxification (e.g., ABC transporter C family, cytochrome P450, glucose-methanol-choline oxidoreductase, insect cuticle proteins, and UDP-glucuronosyl), and digestion (e.g., serine proteases and peptidase family S1). A gene ontology enrichment analysis of rapid evolving genes also suggests enriched functions in host sensing and immunity. CONCLUSIONS: Our results of family evolution analyses indicate that host plant adaptation and pathogen defense could be important drivers in species diversification among gelechiid moths.

CRISPR-based diagnostics detects invasive insect pests.

Rapid identification of organisms is essential for many biological and medical disciplines, from understanding basic ecosystem processes, disease diagnosis, to the detection of invasive pests. CRISPR-based diagnostics offers a novel and rapid alternative to other identification methods and can revolutionize our ability to detect organisms with high accuracy. Here we describe a CRISPR-based diagnostic developed with the universal cytochrome-oxidase 1 gene (CO1). The CO1 gene is the most sequenced gene among Animalia, and therefore our approach can be adopted to detect nearly any animal. We tested the approach on three difficult-to-identify moth species (Keiferia lycopersicella, Phthorimaea absoluta and Scrobipalpa atriplicella) that are major invasive pests globally. We designed an assay that combines recombinase polymerase amplification (RPA) with CRISPR for signal generation. Our approach has a much higher sensitivity than real-time PCR assays and achieved 100% accuracy for identification of all three species, with a detection limit of up to 120 fM for P. absoluta and 400 fM for the other two species. Our approach does not require a sophisticated laboratory, reduces the risk of cross-contamination, and can be completed in less than 1 h. This work serves as a proof of concept that has the potential to revolutionize animal detection and monitoring.

Admission to a Verified Pediatric Trauma Center is Associated With Improved Outcomes in Severely Injured Children.

BACKGROUND: Previous studies have shown improved survival for severely injured adult patients treated at American College of Surgeons verified level I/II trauma centers compared to level III and undesignated centers. However, this relationship has not been well established in pediatric trauma centers (PTCs). We hypothesize that severely injured children will have lower mortality at verified level I/II PTCs compared to centers without PTC verification. METHODS: All patients 1-15 years of age with ISS >15 in the 2017-2019 American College of Surgeons Trauma Quality Programs (ACS TQP) dataset were reviewed. Patients with pre-hospital cardiac arrest, burns, and those transferred out for ongoing inpatient care were excluded. Logistic regression models were used to assess the effects of pediatric trauma center verification on mortality. RESULTS: 16,301 patients were identified (64 % male, median ISS 21 [17-27]), and 60 % were admitted to verified PTCs. Overall mortality was 6.0 %. Mortality at centers with PTC verification was 5.1 % versus 7.3 % at centers without PTC verification (p < 0.001). After controlling for injury mechanism, sex, age, pediatric-adjusted shock index (SIPA), ISS, arrival via interhospital transfer, and adult trauma center verification, pediatric level I/II trauma center designation was independently associated with decreased mortality (OR 0.72, 95 % CI 0.61-0.85). CONCLUSIONS: Treatment at ACS-verified pediatric trauma centers is associated with improved survival in critically injured children. These findings highlight the importance of PTC verification in optimizing outcomes for severely injured pediatric patients and should influence trauma center apportionment and prehospital triage. LEVEL OF EVIDENCE: Level IV - Retrospective review of national database.

Improved survival for severely injured patients receiving massive transfusion at US teaching hospitals: A nationwide analysis.

BACKGROUND: Previous studies have shown improved survival for patients treated at American College of Surgeons (ACS)-verified level I trauma centers compared with level II, level III, and undesignated centers. This mortality difference is more pronounced in severely injured patients. However, a survival benefit for severely injured trauma patients has not been established at teaching institutions compared with nonteaching centers. Because massive transfusion (MT) is associated with high mortality, we hypothesize that patients receiving MT have lower mortality at teaching hospitals than at nonteaching hospitals. METHODS: All adult ACS Trauma Quality Improvement Program-eligible patients who underwent MT, defined as >10 U of packed red blood cells in the first 4 hours after arrival, in the 2019 ACS Trauma Quality Programs participant use file were eligible. Patients with severe head injury (head Abbreviated Injury Scale score, ≥3), prehospital cardiac arrest, and interhospital transfers were excluded. Logistic regression models were used to assess the effects of trauma center hospital teaching status on the adjusted odds of 3-hour, 6-hour, and 24-hour mortality. RESULTS: A total of 1,849 patients received MT (81% male; median Injury Severity Score, 26 [18-35]), 72% were admitted to level I trauma centers, and 28% were admitted to level II centers. Overall hospital mortality was 41%; 17% of patients died in 3 hours, 25% in 6 hours, and 33% in 24 hours. Teaching hospitals were associated with decreased 3-hour (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.27-0.75), 6-hour (OR, 0.37; 95% CI, 0.24-0.56), 24-hour (OR, 0.50; 95% CI, 0.34-0.75), and overall mortality (OR, 0.66; 95% CI, 0.44-0.98), compared with nonteaching hospitals, controlling for sex, age, heart rate, injury severity, injury mechanism, and trauma center verification level. CONCLUSION: Severely injured patients requiring MT experience significantly lower mortality at teaching hospitals compared with nonteaching hospitals, independently of trauma center verification level. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

CRISPR-based diagnostics detects invasive insect pests.

Rapid identification of organisms is essential across many biological and medical disciplines, from understanding basic ecosystem processes and how organisms respond to environmental change, to disease diagnosis and detection of invasive pests. CRISPR-based diagnostics offers a novel and rapid alternative to other identification methods and can revolutionize our ability to detect organisms with high accuracy. Here we describe a CRISPR-based diagnostic developed with the universal cytochrome-oxidase 1 gene (CO1). The CO1 gene is the most sequenced gene among Animalia, and therefore our approach can be adopted to detect nearly any animal. We tested the approach on three difficult-to-identify moth species (Keiferia lycopersicella, Phthorimaea absoluta, and Scrobipalpa atriplicella) that are major invasive pests globally. We designed an assay that combines recombinase polymerase amplification (RPA) with CRISPR for signal generation. Our approach has a much higher sensitivity than other real time-PCR assays and achieved 100% accuracy for identification of all three species, with a detection limit of up to 120 fM for P. absoluta and 400 fM for the other two species. Our approach does not require a lab setting, reduces the risk of cross-contamination, and can be completed in less than one hour. This work serves as a proof of concept that has the potential to revolutionize animal detection and monitoring.

Defining pediatric sepsis by different criteria: discrepancies in populations and implications for clinical practice.

OBJECTIVE: Pediatric patients with sepsis are identified using related but distinct criteria for clinical, research, and administrative purposes. The overlap between these criteria will affect the validity of extrapolating data across settings. We sought to quantify the extent of agreement among different criteria for pediatric severe sepsis/septic shock and to detect systematic differences between these cohorts. DESIGN: Observational cohort study. SETTING: Forty-two bed pediatric intensive care unit at an academic medical center. PATIENTS: A total of 1,729 patients ≤ 18 yrs-old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were screened for severe sepsis or septic shock using consensus guidelines (research criteria), diagnosis by healthcare professionals (clinical criteria), and International Classification of Diseases, Ninth Revision, Clinical Modification codes (administrative criteria). Cohen's κ determined the level of agreement among criteria, and patient characteristics were compared between cohorts. Ninety (5.2%) patients were identified by research, 96 (5.6%) by clinical, and 103 (6.0%) by administrative criteria. The κ ± standard error for pair-wise comparisons was 0.67 ± 0.04 for research-clinical, 0.52 ± 0.05 for research-administrative, and 0.55 ± 0.04 for clinical-administrative. Of the patients in the clinical cohort, 67% met research and 58% met administrative criteria. The research cohort exhibited a higher Pediatric Index of Mortality-2 score (median, interquartile range 5.2, 1.6-13.3) than the clinical (3.6, 1.1-6.2) and administrative (3.9, 1.0-6.0) cohorts (p = .005), an increased requirement for vasoactive infusions (74%, 57%, and 45%, p < .001), and a potential bias toward an increased proportion with respiratory dysfunction compared with clinical practice. CONCLUSIONS: Although research, clinical, and administrative criteria yielded a similar incidence (5%-6%) for pediatric severe sepsis/septic shock, there was only a moderate level of agreement in the patients identified by different criteria. One third of patients diagnosed clinically with sepsis would not have been included in studies based on consensus guidelines or International Classification of Diseases, Ninth Revision, Clinical Modification codes. Differences in patient selection need to be considered when extrapolating data across settings.

The genome sequence of the sallow kitten, Furcula furcula (Clerck, 1759).

We present a genome assembly from an individual male Furcula furcula (the sallow kitten; Arthropoda; Insecta; Lepidoptera; Notodontidae). The genome sequence is 736 megabases in span. The entire assembly (100%) is scaffolded into 29 chromosomal pseudomolecules, with the Z sex chromosome assembled. The complete mitochondrial genome was also assembled and is 17.2 kilobases in length.

Single Center Experience With Veno-Venous Extracorporeal Membrane Oxygenation in Patients With Traumatic Brain Injury.

METHODS: We retrospectively reviewed TBI patients ≥ 18 years of age treated with VV-ECMO. The primary outcome was survival to discharge. Secondary outcomes included progression of intracranial hemorrhage, bleeding complications, and episodes of oxygenator thrombosis requiring exchange. Medians and interquartile ranges were reported where appropriate. RESULTS: 13 TBI patients received VV-ECMO support during the study period. The median age was 28 years (Interquartile range (IQR) 25-37.5) and 85% were men. Median admission Glasgow coma scale was 5 (IQR 3-13.5). Median injury severity score (ISS) was 48 (IQR 33.5-66). Median pre-ECMO PaO2:FiO2 ratio was 58 (IQR 47-74.5). Five (38.4%) patients survived to discharge. Six patients (46%) received systemic A/C while on ECMO. No patient had worsening of intracranial hemorrhage on computed tomography imaging. There were two bleeding complications in patients on A/C, neither was related to TBI. Four patients required an oxygenator change; 2 in patients on A/C. CONCLUSION: VV-ECMO appears safe with TBI. We have demonstrated that A/C can be withheld without increased complications. Traumatic brain injury should not be considered an absolute contraindication to the use of VV-ECMO for severe respiratory failure and should be decided on a case by case basis. Additional research is needed to confirm these preliminary findings.

Ticks as novel sentinels to monitor environmental levels of per- and polyfluoroalkyl substances (PFAS).

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent, ubiquitous pollutants. It is important to continuously monitor the presence of PFAS contamination, utilizing both legacy and new sentinels. In this study, environmental PFAS levels were evaluated using ticks as a sentinel model due to their world-wide distribution, hematophagous nature, and ease of collection and sampling. Hematophagy in discrete blood meals, from a suite of vertebrates, allows ticks to sample dozens of species of consumers and bioaccumulation across communities. Four different species of ticks, across two states (NY, n = 28 in mid-April of 2020 and FL, n = 32 between 2015 and 2020) with two sampling sites in each state were analyzed for the presence of 53 PFAS. The total PFAS concentration in ticks was the lowest at Newburgh (NY), a site that has been undergoing remediation efforts, while the highest total PFAS concentrations were measured in ticks at the Sweetwater site, a wastewater treatment wetland. Detection of PFAS and the potential for variation between tick species and between locations are necessary to establish the utility of ticks as sentinels, in addition to assessing additional environmental factors, such as other wildlife, water, or soil.

Dispersal and Land Cover Contribute to Pseudorabies Virus Exposure in Invasive Wild Pigs.

We investigated the landscape epidemiology of a globally distributed mammal, the wild pig (Sus scrofa), in Florida (U.S.), where it is considered an invasive species and reservoir to pathogens that impact the health of people, domestic animals, and wildlife. Specifically, we tested the hypothesis that two commonly cited factors in disease transmission, connectivity among populations and abundant resources, would increase the likelihood of exposure to both pseudorabies virus (PrV) and Brucella spp. (bacterial agent of brucellosis) in wild pigs across the Kissimmee Valley of Florida. Using DNA from 348 wild pigs and sera from 320 individuals at 24 sites, we employed population genetic techniques to infer individual dispersal, and an Akaike information criterion framework to compare candidate logistic regression models that incorporated both dispersal and land cover composition. Our findings suggested that recent dispersal conferred higher odds of exposure to PrV, but not Brucella spp., among wild pigs throughout the Kissimmee Valley region. Odds of exposure also increased in association with agriculture and open canopy pine, prairie, and scrub habitats, likely because of highly localized resources within those land cover types. Because the effect of open canopy on PrV exposure reversed when agricultural cover was available, we suggest that small-scale resource distribution may be more important than overall resource abundance. Our results underscore the importance of studying and managing disease dynamics through multiple processes and spatial scales, particularly for non-native pathogens that threaten wildlife conservation, economy, and public health.

Albert Wojciech Adamkiewicz (1850-1921): unsung hero behind the eponymic artery.

The artery of Adamkiewicz is an important radiculomedullary artery supplying the spinal cord, especially the lumbar enlargement. Anatomical knowledge of this artery is important for avoiding serious neurological complications during surgery performed in this region--for neurosurgeons and interventional radiologists treating intramedullary tumors and spinal arteriovenous malformations, traumatologists performing spinal fusions, thoracic surgeons treating aortic aneurysms, and urologists and pediatric surgeons conducting retroperitoneal dissections. However, the biography of the talented Polish pathologist Albert Adamkiewicz, after whom the landmark artery is named, has not been described adequately in the existing neurosurgical literature. The authors bring to light the historical perspective of the eponymic artery and provide a recapitulation of other significant contributions made by Adamkiewicz, mostly involving the nervous system. His research papers on the histology of neuronal tissues and neurodegenerative diseases had high scientific merit, but the discovery of the anticancer antitoxin "cancroin" and his postulation of a cancer-causing parasite he named "Coccidium sarcolytus" met with harsh criticism and eventually led to his ill fame. The biography is supplemented with a brief overview of the important surgical implications of the artery of Adamkiewicz.

Loperamide induced cardiac arrhythmia successfully supported with veno-arterial ECMO (VA-ECMO), molecular adsorbent recirculating system (MARS) and continuous renal replacement therapy (CRRT).

Introduction: This case of Loperamide misuse had refractory ventricular arrhythmias and was successfully supported by VA ECMO. Loperamide is currently available without prescription and can be obtained in large quantities over the internet despite Food and Drug Administration (FDA) 2016 black box warning noting cardiac toxicity. This case illustrates the life-threatening toxicity of loperamide and suggests a supportive modality to provide clinical time while the drug is cleared endogenously or exogenously. Case report: A 36-year-old female was found minimally responsive. Vital signs and monitoring revealed wide complex bradycardia, undetectable blood pressure, hypothermia, bradypnea, and hypoglycemia. The rhythm degenerated to polymorphic ventricular tachycardia cardia refractory to multiple ACLS protocols. VA-ECMO was initiated with immediate stabilization. Subsequent history revealed massive consumption of loperamide taking 400-600 mg daily. Highest known loperamide and N-desmethyl-loperamide levels were 32 and 500 ng/ml respectively. Since loperamide and metabolites are known to be protein bound, molecular adsorbent recirculating system (MARS) was initiated for toxin clearance. Additionally, she developed acute renal failure supported by CRRT. She was ultimately weaned from ECMO, MARS, and CRRT and discharged neurologically intact on hospital day 12. Discussion: VA ECMO for hemodynamic support provided the needed time for natural resolution of the cardiac toxicity while providing adequate perfusion. MARS was used in the setting of highly protein bound toxins, but drug clearance could not be demonstrated through serial levels. VA ECMO (or referral to a center with VA ECMO) should be considered with lethal loperamide-induced cardiotoxicity and perhaps other cardio-toxins.

The legendary contributions of Thomas Willis (1621-1675): the arterial circle and beyond.

Thomas Willis established neurology as a distinct discipline and made significant original contributions to many related fields including anatomy, pathology, cardiology, endocrinology, and gastroenterology. He is most remembered for his work in elucidating the function and anatomy of the circle of Willis. Willis' accomplishments and research methods can be credited in large part to his unconventional medical education which did not include traditional teachings, but rather emphasized learning through clinical practice. Although Willis was not the first to describe the arterial circle, he was the first to describe its function and provide a complete, undisputed illustration through his own innovative use of dye studies. The Willis classification of cranial nerves was still in use over 100 years after its original description. He has also described several disease entities and named many brain structures. Willis' accomplishments in comparative anatomy and understanding the pathophysiology of various diseases through original multidisciplinary experimental work in a clinical setting reveal that he was a true pioneer in translational research.