Symptomatic carotid webs require aggressive intervention.

OBJECTIVE: Carotid web (CaWeb) is a rare form of fibromuscular dysplasia that can produce embolic stroke. Misdiagnosis of symptomatic CaWeb as "cryptogenic stroke" or "embolic stroke of unknown source" is common and can lead to recurrent, catastrophic neurologic events. Reports of CaWeb in the literature are scarce, and their natural history is poorly understood. Appropriate management remains controversial. METHODS: CaWeb was defined as a single, shelf-like, linear projection in the posterolateral carotid bulb causing a filling defect on computed tomography angiography (CTA) or cerebral angiography. Cases of symptomatic CaWeb at a single institution with a high-volume stroke center were identified through collaborative evaluation by vascular neurologists and vascular surgeons. RESULTS: Fifty-two patients with symptomatic CaWeb were identified during a 6-year period (2016-2022). Average age was 49 years (range, 29-73 years), 35 of 52 (67%) were African American, and 18 of 52 (35%) were African American women under age 50. Patients initially presented with stroke (47/52; 90%) or transient ischemic attack (5/52; 10%). Stenosis was <50% in 49 of 52 patients (94%) based on NASCET criteria, and 0 of 52 (0%) CaWebs were identified with carotid duplex. Definitive diagnosis was made by CTA examined in multiple planes or cerebral angiography examined in a lateral projection to adequately assess the posterolateral carotid bulb, where 52 of 52 (100%) of CaWebs were seen. Early in our institutional experience, 10 of 52 patients (19%) with symptomatic CaWeb were managed initially with dual antiplatelet and statin therapy or systemic anticoagulation; all suffered ipsilateral recurrent stroke at an average interval of 43 months (range, 1-89 months), and five were left with permanent deficits. Definitive treatment included carotid endarterectomy in 27 of 50 (56%) or carotid stenting in 23 of 50 (46%). Two strokes were irrecoverable, and intervention was deferred. Web-associated thrombus was observed in 20 of 50 (40%) on angiography or grossly upon carotid exploration. Average interval from initial stroke to intervention was 39 days. After an average follow-up of 38 months, there was no reported postintervention stroke or mortality. CONCLUSIONS: To our knowledge, this is the largest single-institution analysis of symptomatic CaWeb yet reported. Our series demonstrates that carotid duplex is inadequate for diagnosis, and that medical management is unacceptable for symptomatic CaWeb. Recurrent stroke occurred in all patients managed early in our experience with medical therapy alone. We have since adopted an aggressive interventional approach in cases of symptomatic CaWeb, with no postoperative stroke reported over an average follow-up of 38 months. In younger patients presenting with cryptogenic stroke, especially African American women, detailed review of lateral cerebral angiography or multi-planar, fine-cut CTA images is required to accurately rule out or diagnose CaWeb and avoid recurrent neurologic events.

Anesthesia and Developing Brains: Unanswered Questions and Proposed Paths Forward.

Anesthetic agents disrupt neurodevelopment in animal models, but evidence in humans is mixed. The morphologic and behavioral changes observed across many species predicted that deficits should be seen in humans, but identifying a phenotype of injury in children has been challenging. It is increasingly clear that in children, a brief or single early anesthetic exposure is not associated with deficits in a range of neurodevelopmental outcomes including broad measures of intelligence. Deficits in other domains including behavior, however, are more consistently reported in humans and also reflect findings from nonhuman primates. The possibility that behavioral deficits are a phenotype, as well as the entire concept of anesthetic neurotoxicity in children, remains a source of intense debate. The purpose of this report is to describe consensus and disagreement among experts, summarize preclinical and clinical evidence, suggest pathways for future clinical research, and compare studies of anesthetic agents to other suspected neurotoxins.

Prevalence and factors associated with advance health directives in frail older inpatients.

BACKGROUND: Advance health directives (AHD) can be used to explore and document patient preferences for treatment and are therefore an important aspect of care planning. AIMS: To investigate the prevalence and factors associated with AHD among older inpatients. METHODS: This retrospective study included 6449 patients, aged ≥65 years referred for specialist geriatric consultation between 2007 and 2018 in Queensland, Australia. The interRAI-Acute Care Comprehensive Geriatric Assessment tool was used to calculate a frailty index (FI), range 0-1, based on 52 possible deficits, and categorised into intervals of 0.1 for analysis. FI was also grouped according to previously reported cut points: fit (FI ≤0.25), moderately frail (FI >0.25-0.4), frail (FI >0.4-0.6) and severely frail (FI >0.6). RESULTS: An AHD was present in 1032 (16.0%) of 6449 patients. Those with an AHD were significantly frailer than those without an AHD (mean FI 0.52 vs 0.45; P < 0.001). Higher frailty (odds ratio (OR): 1.34 (1.27-1.40)), older age (OR: 1.04 (1.03-1.05)), living in an institution (OR: 1.33 (1.01-1.73)) and recent hospitalisation (OR: 1.42 (1.23-1.62)) were significantly associated with higher prevalence of AHD. Prevalence of AHD increased over time, from 7.6% (n = 66) in 2008 to 35.4% (n = 99) in 2017. CONCLUSIONS: The presence of AHD is associated with sociodemographic factors, as well as higher frailty levels. Prevalence of AHD among inpatients has increased over the past decade but remains modest.

Emergency intraoperative vascular surgery consultations at a tertiary academic center.

OBJECTIVE: Vascular surgeons are frequently called on to provide emergency assistance to surgical colleagues. Whereas previous studies have included elective preoperative vascular consultations, we sought to characterize the breadth of assistance provided during unplanned intraoperative consultations at a single tertiary academic center. METHODS: We queried our institutional billing department during a 15-year period and reviewed the records (January 1, 2002-December 31, 2016) and identified unanticipated unplanned vascular surgery intraoperative consultations from all surgical services. Patients' demographics and comorbidities were recorded along with the consulting services, type of index operation, reasons for vascular consultation, regions of anatomic interventions, type of vascular interventions performed, and outcomes achieved. RESULTS: There were 419 emergency intraoperative consultations identified. Patients were 51% male, with an average age of 57 years and body mass index of 28.3 kg/m2. The most frequently consulting subspecialties included surgical oncology (n = 139 [33.2%]), cardiac surgery (n = 82 [19.6%]), and orthopedics (n = 44 [10.5%]). Index cases were elective/nonurgent (n = 324 [77.3%]), urgent (n = 27 [6.4%]), and emergent (n = 68 [16.2%]), with a majority involving tumor resection (n = 240 [57.3%]). The primary reasons for vascular consultation were revascularization (n = 213 [50.8%]), control of bleeding (n = 132 [31.5%]), assistance with dissection or exposure (n = 46 [11%]), embolic protection (n = 24 [5.7%]), and other (n = 4 [1.1%]). The primary blood vessel and anatomic field of intervention were categorized. Most cases (n = 264 [63%]) included preservation of blood flow, including primary arterial repair (n = 181 [43.2%]), patch angioplasty (n = 83 [19.8%]), bypass (n = 63 [15%]), and thrombectomy (n = 38 [9.1%]). Postoperative mean length of stay was 15 days, with 30-day and 1-year mortality of 7.2% and 26.5%. CONCLUSIONS: Vascular surgeons are called on to provide unplanned open surgical consultations for a wide variety of specialties over wide-ranging anatomic regions, employing a variety of skills and techniques. This study testifies to the essential services supplied to hospitals and our surgical colleagues along with the broad skills and training necessary for modern vascular surgeons.

Chronic intrahippocampal interleukin-1ß overexpression in adolescence impairs hippocampal neurogenesis but not neurogenesis-associated cognition.

Both neuroinflammation and adult hippocampal neurogenesis (AHN) are implicated in many neurodegenerative disorders as well as in neuropsychiatric disorders, which often become symptomatic during adolescence. A better knowledge of the impact that chronic neuroinflammation has on the hippocampus during the adolescent period could lead to the discovery of new therapeutics for some of these disorders. The hippocampus is particularly vulnerable to altered concentrations of the pro-inflammatory cytokine interleukin-1ß (IL-1ß), with elevated levels implicated in the aetiology of neurodegenerative disorders such as Alzheimer's and Parkinson's, and stress-related disorders such as depression. The effect of acutely and chronically elevated concentrations of hippocampal IL-1ß have been shown to reduce AHN in adult rodents. However, the effect of exposure to chronic overexpression of hippocampal IL-1ß during adolescence, a time of increased vulnerability, hasn't been fully interrogated. Thus, in this study we utilized a lentiviral approach to induce chronic overexpression of IL-1ß in the dorsal hippocampus of adolescent male Sprague Dawley rats for 5 weeks, during which time its impact on cognition and hippocampal neurogenesis were examined. A reduction in hippocampal neurogenesis was observed along with a reduced level of neurite branching on hippocampal neurons. However, there was no effect of IL-1ß overexpression on performance in pattern separation, novel object recognition or spontaneous alternation in the Y maze. Our study has highlighted that chronic IL-1ß overexpression in the hippocampus during the adolescent period exerts a negative impact on neurogenesis independent of cognitive performance, and suggests a degree of resilience of the adolescent hippocampus to inflammatory insult.

Association Between Cyanosis, Transfusion, and Thrombotic Complications in Neonates and Children Undergoing Cardiac Surgery.

OBJECTIVE: Children with congenital heart defects are at increased risk for perioperative bleeding and postoperative thrombosis. In this study, the authors sought to develop a predictive model for postoperative thrombotic complications that integrates intraoperative bleeding and the requirement for allogenic blood products in addition to known patient and surgical characteristics. DESIGN: Retrospective cohort. SETTING: Pediatric hospital. PARTICIPANTS: Neonates and children who underwent surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Demographic, laboratory, point-of-care coagulation, surgical, and perioperative transfusion data were collected. Among the 369 participants included in the study, 67 (18%) developed postoperative thrombotic complications. From multivariable logistic regression analyses, preoperative oxygen saturation <85% (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.10-3.85; p = 0.024), surgery in the neonatal period (OR 2.16, 95% CI 1.02-4.55; p = 0.044), use of preoperative antiplatelet or anticoagulation therapy (OR 3.34, 95% CI 1.61-6.96; p = 0.001), and the volume of blood product transfused post-CPB (>80 mL/kg [OR 5.72, 95% CI 1.73-18.91; p = 0.004] and 15-80 mL/kg [OR 3.06, 95% CI 1.24-7.53; p = 0.015]) were independently associated with an increased incidence of thrombotic complications. No statistical differences were observed in available preoperative coagulation tests between children who developed postoperative thrombosis and those who did not. CONCLUSION: This observational cohort study found that cyanosis, surgery in neonates, preoperative anticoagulation or antiplatelet therapy, and the volume of post-CPB transfusion are important predictors of postoperative thrombotic complications in children undergoing cardiac surgery. Additional studies are required to explore the relationship between hypoxia, coagulopathy, and postoperative thrombosis.

Differential effects of adolescent and adult-initiated exercise on cognition and hippocampal neurogenesis.

Adolescence is a critical period for postnatal brain maturation and thus a time when environmental influences may affect cognitive processes in later life. Exercise during adulthood has been shown to increase hippocampal neurogenesis and enhance cognition. However, the impact of exercise initiated in adolescence on the brain and behavior in adulthood is not fully understood. The aim of this study was to compare the impact of voluntary exercise that is initiated during adolescence or early adulthood on cognitive performance in hippocampal-dependent and -independent processes using both object-based and touchscreen operant paradigms. Adult (8 week) and adolescent (4 week) male Sprague-Dawley rats had access to a running wheel (exercise) or were left undisturbed (sedentary control) for 4 weeks prior to behavioral testing and for the duration of the experiment. Results from touchscreen-based tasks showed that reversal learning was enhanced by both adult and adolescent-initiated exercise, while only exercise that began in adolescence induced a subtle but transient increase in performance on a location discrimination task. Spontaneous alternation in the Y-maze was impaired following adolescent onset exercise, while object memory was unaffected by either adult or adolescent-initiated exercise. Adolescent-initiated exercise increased the number of hippocampal DCX cells, an indicator of neurogenesis. It also promoted the complexity of neurites on DCX cells, a key process for synaptic integration, to a greater degree than adult-initiated exercise. Together the data here show that exercise during the adolescent period compared to adulthood differentially affects cognitive processes and the development of new hippocampal neurons in later life.

Hospital admission on weekends for patients who have surgery and 30-day mortality in Ontario, Canada: A matched cohort study.

BACKGROUND: Healthcare interventions on weekends have been associated with increased mortality and adverse clinical outcomes, but these findings are inconsistent. We hypothesized that patients admitted to hospital on weekends who have surgery have an increased risk of death compared with patients who are admitted and have surgery on weekdays. METHODS AND FINDINGS: This matched cohort study included 318,202 adult patients from Ontario health administrative and demographic databases, admitted to acute care hospitals from 1 January 2005 to 31 December 2015. A total of 159,101 patients who were admitted on weekends and underwent noncardiac surgery were classified by day of surgery (weekend versus weekday) and matched 1:1 to patients who both were admitted and had surgery on a weekday (Tuesday to Thursday); matching was based on age (in years), anesthesia basic unit value for the surgical procedure, median neighborhood household income quintile, resource utilization band (a ranking system of overall morbidity), rurality of home location, year of admission, and urgency of admission. Of weekend admissions, 16.2% (25,872) were elective and 53.9% (85,744) had surgery on the weekend of admission. The primary outcome was all-cause mortality within 30 days of the date of hospital admission. The 30-day all-cause mortality for patients admitted on weekends who had noncardiac surgery was 2.6% (4,211/159,101) versus 2.5% (3,901/159,101) for those who were admitted and had surgery on weekdays (adjusted odds ratio [OR] 1.05; 95% CI 1.00 to 1.11; P = 0.03). However, there was significant heterogeneity in the increased odds of death according to the urgency of admission and when surgery was performed (weekend versus weekday). For urgent admissions on weekends (n = 133,229), there was no significant increase in odds of mortality when surgery was performed on the weekend (adjusted OR 1.02; 95% CI 0.95 to 1.09; P = 0.7) or on a subsequent weekday (adjusted OR 1.05; 95% CI 0.98 to 1.12; P = 0.2) compared to urgent admissions on weekdays. Elective admissions on weekends (n = 25,782) had increased risk of death both when surgery was performed on the weekend (adjusted OR 3.30; 95% CI 1.98 to 5.49; P < 0.001) and when surgery was performed on a subsequent weekday (adjusted OR 2.70; 95% CI 1.81 to 4.03; P < 0.001). The main limitations of this study were the lack of data regarding reason for admission and cause of increased time interval from admission to surgery for some cases, the small number of deaths in some subgroups (i.e., elective surgery), and the possibility of residual unmeasured confounding from increased illness severity for weekend admissions. CONCLUSIONS: When patients have surgery during their hospitalization, admission on weekends in Ontario, Canada, was associated with a small but significant proportional increase in 30-day all-cause mortality, but there was significant heterogeneity in outcomes depending on the urgency of admission and when surgery was performed. An increased risk of death was found only for elective admissions on weekends; whether this is a function of patient-level factors or represents a true weekend effect needs to be further elucidated. These findings have potential implications for resource allocation in hospitals and the redistribution of elective surgery to weekends.

Preoperative anemia increases the risk of red blood cell transfusion and prolonged hospital length of stay in children undergoing spine arthrodesis surgery.

BACKGROUND: Preoperative anemia is an important modifiable risk factor for red blood cell (RBC) transfusion in a variety of surgical populations. The primary objective of this study was to examine the association between preoperative anemia and i) transfusion of RBCs within 72 hours of surgery and ii) postoperative clinical outcomes in children undergoing spine arthrodesis surgery. STUDY DESIGN AND METHODS: We assembled a retrospective cohort of children included in the American College of Surgeons National Quality Improvement Program Pediatric database who underwent spine arthrodesis surgery from 2012 to 2016. Anemia was defined using age- and sex-specific hematocrit thresholds. Data collected included demographic and surgical characteristics, RBC transfusion within 72 hours, and 30-day postoperative outcomes (postoperative mechanical ventilation, infection, readmission, hospital length of stay, mortality). Multivariable logistic regression analyses were used to identify independent predictors of RBC transfusion and postoperative outcomes. RESULTS: We included 9,095 patients in the analysis. Preoperative anemia was present in 14% (n = 1,233) of the population and 67% (n = 6,135) of patients were transfused. Our multivariable logistic regression showed anemia, surgical time > 350 minutes, > 7 vertebral levels fused, neuromuscular disease, and cerebral palsy were all independent predictors of RBC transfusion. Preoperative anemia was also associated with prolonged hospital LOS (adjusted OR: 1.31, 95%CI: 1.11-1.54, p = 0.002). CONCLUSIONS: In this study of 9,095 children undergoing spine surgery, preoperative anemia was associated with an increased risk of RBC transfusion and prolonged LOS. Further studies are needed to determine if treatment of preoperative anemia can effectively reduce intraoperative RBC transfusion.

Chronic interleukin-1ß in the dorsal hippocampus impairs behavioural pattern separation.

Understanding the long-term consequences of chronic inflammation in the hippocampus may help to develop therapeutic targets for the treatment of cognitive disorders related to stress, ageing and neurodegeneration. The hippocampus is particularly vulnerable to increases in the pro-inflammatory cytokine interleukin-1ß (IL-1ß), a mediator of neuroinflammation, with elevated levels implicated in the aetiology of neurodegenerative diseases such as Alzheimer's and Parkinson's, and in stress-related disorders such as depression. Acute increases in hippocampal IL-1ß have been shown to impair cognition and reduce adult hippocampal neurogenesis, the birth of new neurons. However, the impact of prolonged increases in IL-1ß, as evident in clinical conditions, on cognition has not been fully explored. Therefore, the present study utilized a lentiviral approach to induce long-term overexpression of IL-1ß in the dorsal hippocampus of adult male Sprague Dawley rats and examine its impact on cognition. Following three weeks of viral integration, pattern separation, a process involving hippocampal neurogenesis, was impaired in IL-1ß-treated rats in both object-location and touchscreen operant paradigms. This was coupled with a decrease in the number and neurite complexity of immature neurons in the hippocampus. Conversely, tasks involving the hippocampus, but not sensitive to disruption of hippocampal neurogenesis, including spontaneous alternation, novel object and location recognition were unaffected. Touchscreen operant visual discrimination, a cognitive task involving the prefrontal cortex, was largely unaffected by IL-1ß overexpression. In conclusion, these findings suggest that chronically elevated IL-1ß in the hippocampus selectively impairs pattern separation. Inflammatory-mediated disruption of adult hippocampal neurogenesis may contribute to the cognitive decline associated with neurodegenerative and stress-related disorders.

Predicting Heparin Responsiveness in Children Before Cardiopulmonary Bypass: A Retrospective Cohort Study.

BACKGROUND: Inadequate or excess administration of unfractionated heparin for cardiopulmonary bypass (CPB) can cause significant harm. Age-dependent differences in the pharmacodynamics and pharmacokinetics of heparin contribute to increased variability of heparin responsiveness in children. The aims of the current study were to (1) examine the correlation between predicted and observed heparin responsiveness in children before CPB measured using the Hemostasis Management System (HMS) Plus (Medtronic, Minneapolis, MN), (2) describe age-specific reference intervals for heparin sensitivity index (HSI) observed in children, and (3) test predictive models of HSI using preoperative clinical and laboratory data. METHODS: In this retrospective cohort study, children (ages ≤17 years) who required therapeutic heparinization for CPB in a 40-month period between September 2010 and December 2013 were investigated. Children weighing ≥45 kg or with a height ≥142 cm were excluded. HSI was defined as the difference between activated clotting time after heparin administration and the baseline activated clotting time divided by the heparin-loading dose (IU) per kilogram. Lin's concordance correlation coefficient was used for the primary analysis of the relationship between predicted and observed HSI. Reference intervals were calculated for HSI using medians and 2.5% and 97.5% percentiles according to established guidelines for clinical and laboratory standards. Nonparametric regression analyses were used to model the relationship between HSI (dependent variable) and preoperative covariates (independent variables). RESULTS: A total of 1281 eligible children were included in the final analysis. Overall, there was a moderate correlation between predicted and observed HSI measured using HMS Plus System (rho_c = 0.46; 95% confidence interval, 0.41-0.50; P < .001). Sixty-five percent (829 of 1281) of predicted HSI values were less than observed. From adjusted regression models, HSI was best predicted by preoperative international normalized ratio, platelet count, and weight, but this model accounted for only 25% of the variance in HSI. CONCLUSIONS: In a large cohort of children, heparin responsiveness before CPB was not reliably predicted by either in vitro measurement using the HMS Plus System or commonly available preoperative clinical and laboratory data. We describe age-specific reference intervals for HSI in children, and we anticipate that these data will aid the identification of heparin resistance in this population.

Incidence of non-physiologically complex surgical procedures performed in children: an Ontario population-based study of health administrative data.

PURPOSE: Quantification of surgical procedures undertaken by hospitals is necessary for informing resource allocation and modelling healthcare services. Our objective was to quantify the incidence, similarity, and diversity of non-physiologically complex surgical procedures performed at pediatric specialist hospitals and other hospitals performing pediatric surgery. METHODS: We conducted a population-based cohort study of children aged 28 days to 18 yr who underwent surgery in the province of Ontario from 2007 to 2015 using healthcare administrative databases. We estimated the incidence of non-physiologically complex procedures (i.e., ≤ 7 basic units in the 2015 Ontario Health Insurance Plan Schedule of Benefits) performed in pediatric specialist hospitals and other hospitals performing pediatric surgery. We used Yue and Clayton's index and the effective number of common procedures (1/Herfindahl index) to quantify the similarity and diversity of pediatric surgical procedures performed in these hospital types. RESULTS: Overall, 830,830 pediatric surgical procedures were performed in 158 Ontario hospitals during the eight-year study period. Most surgical procedures performed at hospitals performing pediatric surgery were non-physiologically complex (vs 50%, P < 0.001). The incidence of non-physiologically complex procedures increased progressively each year at pediatric specialist hospitals and was associated with a reciprocal decline among the other hospitals. Comparing pediatric specialist hospitals with the other hospitals, the mean similarity index for non-physiologically complex procedures was less than moderate (0.52; 95% confidence interval [CI], 0.51 to 0.54). The mean effective number of common non-physiologically complex procedures (i.e., the diversity) among the pediatric specialist hospitals was greater than at the other 154 hospitals performing pediatric surgery (65.3 vs 21.8 procedures, respectively; mean difference, 43.5; 95% CI, 42.2 to 44.8; P < 0.001). CONCLUSIONS: Non-physiologically complex procedures have progressively migrated to pediatric specialist hospitals from other hospitals in Ontario. Specialty pediatric hospitals are principally dissimilar from other hospitals performing pediatric surgery based not on physiological complexity, but on their diversity. These findings suggest that some types of surgical procedures may be redistributed from specialist pediatric hospitals to other hospitals performing pediatric surgery. TRIAL REGISTRATION: www.clinicaltrials.gov , number NCT03144544. Registered 2 May 2016.

Anesthesia and the developing brain: A way forward for laboratory and clinical research.

All commonly used general anesthetics have been shown to cause neurotoxicity in animal models, including nonhuman primates. Opinion, however, remains divided over how cumulative evidence from preclinical and human studies in this field should be interpreted and its translation to current practices in pediatric anesthesia and surgery. A group of international experts in laboratory and clinical sciences recently convened in Genoa, Italy, to evaluate the current state of both laboratory and clinical research and discuss future directions for basic, translational, and clinical studies in this field. This paper describes those discussions and conclusions. A central goal identified was the importance of continuing to pursue laboratory research efforts to better understand the biological pathways underlying anesthesia neurotoxicity. The distinction between basic and translational experimental designs in this field was highlighted, and it was acknowledged that it will be important for future animal research to try to causally link structural changes with long-term cognitive abnormalities. While inherent limitations will continue to affect the ability of even large observational cohorts to determine if anesthesia impacts neurodevelopment or behavioral outcomes, the importance of conducting further large well-designed cohort studies was also emphasized. Adequately powered cohorts could clarify which populations are at increased risk, provide information on environmental and healthcare-related risk modifiers, and guide future interventional trials. If anesthetics cause structural or functional adverse neurological effects in young children, alternative or mitigating strategies need to be considered. While protective or mitigating strategies have been repeatedly studied in animals, there are currently no human data to support alternative anesthetic strategies in clinical practice. Lastly, it was noted that there is still considerable debate over the clinical relevance of anesthesia neurotoxicity, and the need to evaluate the impact of other aspects of perioperative care on neurodevelopment must also be considered.

Symptomatic carotid stenosis and ipsilateral carotid body tumor.

We report an unusual combination of a symptomatic carotid stenosis and ipsilateral carotid body tumor. This patient was successfully treated with simultaneous carotid endarterectomy and tumor resection. Following, the unique challenges and technique are discussed.

A low-cost touchscreen operant chamber using a Raspberry Pi™.

The development of a touchscreen platform for rodent testing has allowed new methods for cognitive testing that have been back-translated from clinical assessment tools to preclinical animal models. This platform for cognitive assessment in animals is comparable to human neuropsychological tests such as those employed by the Cambridge Neuropsychological Test Automated Battery, and thus has several advantages compared to the standard maze apparatuses typically employed in rodent behavioral testing, such as the Morris water maze. These include improved translation of preclinical models, as well as high throughput and the automation of animal testing. However, these systems are relatively expensive, which can impede progress for researchers with limited resources. Here we describe a low-cost touchscreen operant chamber based on the single-board computer, Raspberry PiTM, which is capable of performing tasks similar to those supported by current state-of-the-art systems. This system provides an affordable alternative for cognitive testing in a touchscreen operant paradigm for researchers with limited funding.

The Association Between Cyanosis and Thromboelastometry (ROTEM) in Children With Congenital Heart Defects: A Retrospective Cohort Study.

BACKGROUND: Children with congenital heart defects (CHD) have quantitative and qualitative differences in coagulation compared with healthy children. Secondary to polycythemia and increased deformability of red blood cells, cyanosis may be an important confounding factor for altered whole-blood coagulation in this population with potential implications for interpreting intraoperative thromboelastometry (TEM) for children with CHD undergoing major surgery. The primary aim of the study was to evaluate the association between cyanosis in children with CHD and measures of whole-blood coagulation determined using TEM (ROTEM [Tem International, GmbH, Munich, Germany]). METHODS: In this retrospective cohort study, children who underwent congenital cardiac surgery in a 12-month period between April 2014 and 2015 were investigated. Children who were receiving antiplatelet or anticoagulant medications in the preoperative period were excluded. Eligible children were categorized by the presence of cyanosis, defined as an oxyhemoglobin concentration ≤85%. Multivariable linear regression analyses were used to determine the relationship between cyanosis and TEM outcomes (primary outcome, fibrinogen/fibrin polymerization [FibTEM] maximal clot firmness [MCF]) adjusting for potential confounding factors. RESULTS: Three hundred forty-five TEM profiles from 320 children were included in the cohort for analysis. Twenty-two percent (76/345) of children had cyanotic CHD. Clot firmness measured using the FibTEM assay was decreased in cyanotic children compared with noncyanotic children, median difference (95% confidence interval) interim [2 (0-3) mm; P = .01], and maximal [2 (1-3) mm; P = .01] clot firmness. The association between cyanosis and fibrinogen/fibrin polymerization clot firmness was not significant (A10, P = .7; MCF, P = .7) after adjusting for confounding factors (hematocrit, platelet count, and sex). There was a significant association between cyanosis and intrinsically activated clot firmness (A10, P = .03; MCF, P = .02), but not other TEM outcomes, after adjusting for confounding factors. CONCLUSIONS: Cyanotic children had decreased clot firmness in the fibrinogen/fibrin polymerization component of the clot compared with noncyanotic children, but the association between cyanosis and clot firmness was accounted for by differences in hematocrit, platelet count, and sex between groups. These findings will help guide the identification and treatment of coagulopathy in this vulnerable population.

What works in genomics education: outcomes of an evidenced-based instructional model for community-based physicians.

PURPOSE: Education of practicing health professionals is likely to be one factor that will speed appropriate integration of genomics into routine clinical practice. Yet many health professionals, including physicians, find it difficult to keep up with the rapid pace of clinical genomic advances and are often uncomfortable using genomic information in practice. METHODS: Having identified the genomics educational needs of physicians in a Silicon Valley-area community hospital, we developed, implemented, and evaluated an educational course entitled Medicine's Future: Genomics for Practicing Doctors. The course structure and approach were based on best practices in adult learning, including interactivity, case-based learning, skill-focused objectives, and sequential monthly modules. RESULTS: Approximately 20-30 physicians attended each module. They demonstrated significant gains in genomics knowledge and confidence in practice skills that were sustained throughout and following the course. Six months following the course, the majority of participants reported that they had changed their practice to incorporate skills learned during the course. CONCLUSION: We believe the adult-learning principles underlying the development and delivery of Medicine's Future were responsible for participants' outcomes. These principles form a model for the development and delivery of other genomics educational programs for health professionals.Genet Med 18 7, 737-745.

Nanobarcoded superparamagnetic iron oxide nanoparticles for nanomedicine: Quantitative studies of cell-nanoparticle interactions by scanning image cytometry.

Oligonucleotide-functionalized nanoparticles (NPs) are promising agents for nanomedicine, but the potential in vitro nanotoxicity that may arise from such conjugates has yet to be evaluated in a dose response manner. Since nanomedicine functions on the single-cell level, measurements of nanotoxicity should also be performed as such. In vitro single-cell nanotoxicity assays based on scanning image cytometry are used to study a specific type of oligo-functionalized NP, "nanobarcoded" superparamagnetic iron oxide NPs (NB-SPIONs). The selected panel of single-cell assays measures well-known modes of nanotoxicity--apoptosis, necrosis, generation of reactive oxygen species (ROS), and cell number. Using these assays, the cytotoxicity of two sizes of NB-SPIONs (10 nm and 30 nm core size) was compared to the parent NP, carboxylated SPIONs (COOH-SPIONs). The results suggest that the conjugated NB confers a biocompatible coating that protects against cytotoxicity at very high SPION doses, but both NB- and COOH-SPIONs of either size generally have low in vitro cytotoxicity at physiologically relevant doses.

A Population-based Study Evaluating the Association between Surgery in Early Life and Child Development at Primary School Entry.

BACKGROUND: It is unclear whether exposure to surgery in early life has long-term adverse effects on child development. The authors aimed to investigate whether surgery in early childhood is associated with adverse effects on child development measured at primary school entry. METHODS: The authors conducted a population-based cohort study in Ontario, Canada, by linking provincial health administrative databases to children's developmental outcomes measured by the Early Development Instrument (EDI). From a cohort of 188,557 children, 28,366 children who underwent surgery before EDI completion (age 5 to 6 yr) were matched to 55,910 unexposed children. The primary outcome was early developmental vulnerability, defined as any domain of the EDI in the lowest tenth percentile of the population. Subgroup analyses were performed based on age at first surgery (less than 2 and greater than or equal to 2 yr) and frequency of surgery. RESULTS: Early developmental vulnerability was increased in the exposed group (7,259/28,366; 25.6%) compared with the unexposed group (13,957/55,910; 25.0%), adjusted odds ratio, 1.05; 95% CI, 1.01 to 1.08. Children aged greater than or equal to 2 yr at the time of first surgery had increased odds of early developmental vulnerability compared with unexposed children (odds ratio, 1.05; 95% CI, 1.01 to 1.10), but children aged less than 2 yr at the time of first exposure were not at increased risk (odds ratio, 1.04; 95% CI, 0.98 to 1.10). There was no increase in odds of early developmental vulnerability with increasing frequency of exposure. CONCLUSIONS: Children who undergo surgery before primary school age are at increased risk of early developmental vulnerability, but the magnitude of the difference between exposed and unexposed children is small.

Effect of surgical safety checklists on pediatric surgical complications in Ontario.

BACKGROUND: In health care, most preventable adverse events occur in the operating room. Surgical safety checklists have become a standard of care for safe operating room practice, but there is conflicting evidence for the effectiveness of checklists to improve perioperative outcomes in some populations. Our objective was to determine whether surgical safety checklists are associated with a reduction in the proportion of children who had perioperative complications. METHODS: We conducted a retrospective cohort study using administrative health care databases housed at the Institute for Clinical Evaluative Sciences to compare the risk of perioperative complications in children undergoing common types of surgery before and after the mandated implementation of surgical safety checklists in 116 acute care hospitals in Ontario. The primary outcome was a composite outcome of 30-day all-cause mortality and perioperative complications. RESULTS: We identified 14 458 and 14 314 surgical procedures in pre- and postchecklist groups, respectively. The proportion of children who had perioperative complications was 4.08% (95% confidence interval [CI] 3.76%-4.40%) before the implementation of the checklist and 4.12% (95% CI 3.80%-4.45%) after implementation. After we adjusted for confounding factors, we found no significant difference in the odds of perioperative complications after the introduction of surgical safety checklists (adjusted odds ratio 1.01, 95% CI 0.90-1.14, p = 0.9). INTERPRETATION: The implementation of surgical safety checklists for pediatric surgery in Ontario was not associated with a reduction in the proportion of children who had perioperative complications. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT02419053.