A genetic history of the pre-contact Caribbean.

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago1-3. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work4, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500-1,500 and a maximum of 1,530-8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large5,6. Confirming a small and interconnected Ceramic Age population7, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world1,8.

Evinacumab for Pediatric Patients With Homozygous Familial Hypercholesterolemia.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) levels due to profoundly defective LDL receptor (LDLR) function. Given that severely elevated LDL-C starts in utero, atherosclerosis often presents during childhood or adolescence, creating a largely unmet need for aggressive LDLR-independent lipid-lowering therapies in young patients with HoFH. Here we present the first evaluation of the efficacy and safety of evinacumab, a novel LDLR-independent lipid-lowering therapy, in pediatric patients with HoFH from parts A and B of a 3-part study. METHODS: The phase 3, part B, open-label study treated 14 patients 5 to 11 years of age with genetically proven HoFH (true homozygotes and compound heterozygotes) with LDL-C >130 mg/dL, despite optimized lipid-lowering therapy (including LDLR-independent apheresis and lomitapide), with intravenous evinacumab 15 mg/kg every 4 weeks. RESULTS: Evinacumab treatment rapidly and durably (through week 24) decreased LDL-C with profound reduction in the first week, with a mean (SE) LDL-C reduction of -48.3% (10.4%) from baseline to week 24. ApoB (mean [SE], -41.3% [9.0%]), non-high-density lipoprotein cholesterol (-48.9% [9.8%]), and total cholesterol (-49.1% [8.1%]) were similarly decreased. Treatment-emergent adverse events were reported in 10 (71.4%) patients; however, only 2 (14.3%) reported events that were considered to be treatment-related (nausea and abdominal pain). One serious treatment-emergent adverse event of tonsillitis occurred (n=1), but this was not considered treatment-related. CONCLUSIONS: Evinacumab constitutes a new treatment for pediatric patients with HoFH and inadequately controlled LDL-C despite optimized lipid-lowering therapy, lowering LDL-C levels by nearly half in these extremely high-risk and difficult-to-treat individuals. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04233918.

Effects of Recombinant Human Lecithin Cholesterol Acyltransferase on Lipoprotein Metabolism in Humans.

BACKGROUND: LCAT (lecithin cholesterol acyl transferase) catalyzes the conversion of unesterified, or free cholesterol, to cholesteryl ester, which moves from the surface of HDL (high-density lipoprotein) into the neutral lipid core. As this iterative process continues, nascent lipid-poor HDL is converted to a series of larger, spherical cholesteryl ester-enriched HDL particles that can be cleared by the liver in a process that has been termed reverse cholesterol transport. METHODS: We conducted a randomized, placebocontrolled, crossover study in 5 volunteers with atherosclerotic cardiovascular disease, to examine the effects of an acute increase of recombinant human (rh) LCAT via intravenous administration (300-mg loading dose followed by 150 mg at 48 hours) on the in vivo metabolism of HDL APO (apolipoprotein)A1 and APOA2, and the APOB100-lipoproteins, very low density, intermediate density, and low-density lipoproteins. RESULTS: As expected, recombinant human LCAT treatment significantly increased HDL-cholesterol (34.9 mg/dL; P≤0.001), and this was mostly due to the increase in cholesteryl ester content (33.0 mg/dL; P=0.014). This change did not affect the fractional clearance or production rates of HDL-APOA1 and HDL-APOA2. There were also no significant changes in the metabolism of APOB100-lipoproteins. CONCLUSIONS: Our results suggest that an acute increase in LCAT activity drives greater flux of cholesteryl ester through the reverse cholesterol transport pathway without significantly altering the clearance and production of the main HDL proteins and without affecting the metabolism of APOB100-lipoproteins. Long-term elevations of LCAT might, therefore, have beneficial effects on total body cholesterol balance and atherogenesis.

Evinacumab in homozygous familial hypercholesterolaemia: long-term safety and efficacy.

BACKGROUND AND AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder characterized by severely elevated LDL cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. In the pivotal Phase 3 HoFH trial (NCT03399786), evinacumab significantly decreased LDL-C in patients with HoFH. This study assesses the long-term safety and efficacy of evinacumab in adult and adolescent patients with HoFH. METHODS: In this open-label, single-arm, Phase 3 trial (NCT03409744), patients aged ≥12 years with HoFH who were evinacumab-naïve or had previously received evinacumab in other trials (evinacumab-continue) received intravenous evinacumab 15 mg/kg every 4 weeks with stable lipid-lowering therapy. RESULTS: A total of 116 patients (adults: n = 102; adolescents: n = 14) were enrolled, of whom 57 (49.1%) were female. Patients were treated for a median (range) duration of 104.3 (28.3-196.3) weeks. Overall, treatment-emergent adverse events (TEAEs) and serious TEAEs were reported in 93 (80.2%) and 27 (23.3%) patients, respectively. Two (1.7%) deaths were reported (neither was considered related to evinacumab). Three (2.6%) patients discontinued due to TEAEs (none were considered related to evinacumab). From baseline to Week 24, evinacumab decreased mean LDL-C by 43.6% [mean (standard deviation, SD), 3.4 (3.2) mmol/L] in the overall population; mean LDL-C reduction in adults and adolescents was 41.7% [mean (SD), 3.2 (3.3) mmol/L] and 55.4% [mean (SD), 4.7 (2.5) mmol/L], respectively. CONCLUSIONS: In this large cohort of patients with HoFH, evinacumab was generally well tolerated and markedly decreased LDL-C irrespective of age and sex. Moreover, the efficacy and safety of evinacumab was sustained over the long term.

Pre-Columbian transregional captive rearing of Amazonian parrots in the Atacama Desert.

The feathers of tropical birds were one of the most significant symbols of economic, social, and sacred status in the pre-Columbian Americas. In the Andes, finely produced clothing and textiles containing multicolored feathers of tropical parrots materialized power, prestige, and distinction and were particularly prized by political and religious elites. Here we report 27 complete or partial remains of macaws and amazon parrots from five archaeological sites in the Atacama Desert of northern Chile to improve our understanding of their taxonomic identity, chronology, cultural context, and mechanisms of acquisition. We conducted a multiproxy archaeometric study that included zooarchaeological analysis, isotopic dietary reconstruction, accelerated mass spectrometry radiocarbon dating, and paleogenomic analysis. The results reveal that during the Late Intermediate Period (1100 to 1450 CE), Atacama oasis communities acquired scarlet macaws (Ara macao) and at least five additional translocated parrot species through vast exchange networks that extended more than 500 km toward the eastern Amazonian tropics. Carbon and nitrogen stable isotopes indicate that Atacama aviculturalists sustained these birds on diets rich in marine bird guano-fertilized maize-based foods. The captive rearing of these colorful, exotic, and charismatic birds served to unambiguously signal relational wealth in a context of emergent intercommunity competition.

Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B.

BACKGROUND: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment-elevation myocardial infarction. METHODS: REAL-TIMI 63B (A Randomized, Placebo­controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012. RESULTS: A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range [IQR], 103-221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6-24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3-13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79-16.38; placebo: 10.48%, [IQR, 4.92-16.61], 1-sided P=0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 [95% CI, NA-1.10], 1-sided P=0.30). There was no significant difference in treatment emergent serious adverse events. CONCLUSIONS: Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03578809.

Archaeological Central American maize genomes suggest ancient gene flow from South America.

Maize (Zea mays ssp. mays) domestication began in southwestern Mexico ∼9,000 calendar years before present (cal. BP) and humans dispersed this important grain to South America by at least 7,000 cal. BP as a partial domesticate. South America served as a secondary improvement center where the domestication syndrome became fixed and new lineages emerged in parallel with similar processes in Mesoamerica. Later, Indigenous cultivators carried a second major wave of maize southward from Mesoamerica, but it has been unclear until now whether the deeply divergent maize lineages underwent any subsequent gene flow between these regions. Here we report ancient maize genomes (2,300-1,900 cal. BP) from El Gigante rock shelter, Honduras, that are closely related to ancient and modern maize from South America. Our findings suggest that the second wave of maize brought into South America hybridized with long-established landraces from the first wave, and that some of the resulting newly admixed lineages were then reintroduced to Central America. Direct radiocarbon dates and cob morphological data from the rock shelter suggest that more productive maize varieties developed between 4,300 and 2,500 cal. BP. We hypothesize that the influx of maize from South America into Central America may have been an important source of genetic diversity as maize was becoming a staple grain in Central and Mesoamerica.

Evaluation of independent risk factors associated with surgical site infections from caesarean section.

BACKGROUND: The present study assessed factors associated with the risk of surgical site infections (SSI) after a caesarean section (C-section). METHODS: Data were collected in 1682 women undergoing elective (53.9%) and emergency (46.1%) C-sections between 1st August 2020, and 30th December 2021, at a National Health Service hospital (Surrey, UK). RESULTS: At the time of C-section, the mean age was 33.1 yr (SD ± 5.2). Compared to women with BMI < 30 kg/m2, those with a BMI ≥ 35 kg/m2 had a greater risk of SSI, OR 4.07 (95%CI 2.48-6.69). Women with a history of smoking had a greater risk of SSI than those who had never smoked, OR 1.69 (95%CI 1.05-2.27). Women with a BMI ≥ 30 kg/m2 and had a smoking history or emergency C-section had 3- to tenfold increases for these adverse outcomes. Ethnic minority, diabetes or previous C-section did not associate with any of the outcomes. CONCLUSIONS: High BMI, smoking, and emergency C-section are independent risk factors for SSI from C-section. Women planning conception should avoid excess body weight and smoking. Women with diabetes and from ethnic minority backgrounds did not have increased risks of SSI, indicating a consistent standard of care for all patients.

LEGACY: Phase 2a Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Effects of the Anti-EL (Endothelial Lipase) Antibody MEDI5884 in Patients With Stable Coronary Artery Disease.

OBJECTIVE: Functional HDL (high-density lipoprotein) particles that facilitate cholesterol efflux may be cardioprotective. EL (endothelial lipase) hydrolyzes phospholipids promoting catabolism of HDL and subsequent renal excretion. MEDI5884 is a selective, humanized, monoclonal, EL-neutralizing antibody. We sought to determine the safety, pharmacokinetics, and pharmacodynamic effects of multiple doses of MEDI5884 in patients with stable coronary artery disease. Approach and Results: LEGACY was a phase 2a, double-blind, placebo-controlled, parallel-design trial that randomized 132 patients with stable coronary artery disease receiving high-intensity statin therapy to 3 monthly doses of 1 of 5 dose levels of MEDI5884 (50, 100, 200, 350, or 500 mg SC) or matching placebo. The primary end point was the safety and tolerability of MEDI5884 through the end of the study (day 151). Additional end points included change in HDL cholesterol and cholesterol efflux from baseline to day 91, hepatic uptake of cholesterol at day 91, changes in various other lipid parameters. The incidence of adverse events was similar between the placebo and MEDI5884 groups. In a dose-dependent manner, MEDI5884 increased HDL cholesterol up to 51.4% (P<0.0001) and global cholesterol efflux up to 26.2% ([95% CI, 14.3-38.0] P<0.0001). MEDI5884 increased HDL particle number up to 14.4%. At the highest dose tested, an increase in LDL (low-density lipoprotein) cholesterol up to 28.7% (P<0.0001) and apoB (apolipoprotein B) up to 13.1% (P=0.04) was observed with MEDI5884. However, at the potential target doses for future studies, there was no meaningful increase in LDL cholesterol or apoB. CONCLUSIONS: Inhibition of EL by MEDI5884 increases the quantity and quality of functional HDL in patients with stable coronary artery disease on high-intensity statin therapy without an adverse safety signal at the likely dose to be used. These data support further clinical investigation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03351738.

Multiregion Trauma Center Follow-Up Protocol for Transferred Trauma Patients.

BACKGROUND: Trauma centers routinely utilize the Injury Severity Score for performance improvement. Yet, transferring facilities do not always have access to patients' final Injury Severity Score. OBJECTIVE: The purpose of this project was to develop and implement a multiregion Injury Severity Score follow-up feedback protocol for transferring facilities to receive standardized information on patient treatment and the ability to calculate an accurate follow-up Injury Severity Score of transferred patients. METHODS: This project included 25 Adult and Pediatric Level I, II, and III trauma centers within three regional trauma systems in a Midwestern state. This project included trauma centers that used one of the two different trauma registry software systems as a solution to develop and implement a protocol for follow-up feedback for transferred trauma patients. A template was created to capture data posttransfer to calculate a final Injury Severity Score. RESULTS: The feedback protocol was well received by participating regions. Implementation revealed the impact of variable trauma registry software on the ability to create multi-institution feedback programs. CONCLUSION: Trauma systems can implement similar strategies to ensure transferring trauma centers routinely receive standardized, timely patient feedback.

Archaeogenomic evidence from the southwestern US points to a pre-Hispanic scarlet macaw breeding colony.

Hundreds of scarlet macaw (Ara macao cyanoptera) skeletons have been recovered from archaeological contexts in the southwestern United States and northwestern Mexico (SW/NW). The location of these skeletons, >1,000 km outside their Neotropical endemic range, has suggested a far-reaching pre-Hispanic acquisition network. Clear evidence for scarlet macaw breeding within this network is only known from the settlement of Paquimé in NW dating between 1250 and 1450 CE. Although some scholars have speculated on the probable existence of earlier breeding centers in the SW/NW region, there has been no supporting evidence. In this study, we performed an ancient DNA analysis of scarlet macaws recovered from archaeological sites in Chaco Canyon and the contemporaneous Mimbres area of New Mexico. All samples were directly radiocarbon dated between 900 and 1200 CE. We reconstructed complete or near-complete mitochondrial genome sequences of 14 scarlet macaws from five different sites. We observed remarkably low genetic diversity in this sample, consistent with breeding of a small founder population translocated outside their natural range. Phylogeographic comparisons of our ancient DNA mitogenomes with mitochondrial sequences from macaws collected during the last 200 years from their endemic Neotropical range identified genetic affinity between the ancient macaws and a single rare haplogroup (Haplo6) observed only among wild macaws in Mexico and northern Guatemala. Our results suggest that people at an undiscovered pre-Hispanic settlement dating between 900 and 1200 CE managed a macaw breeding colony outside their endemic range and distributed these symbolically important birds through the SW.

A Critical Pathway for Mass Casualty Incident Preparedness.

BACKGROUND: Rates of mass casualty incidents (MCIs) have been on the rise in the United States, highlighting the need for health care systems to have an emergency response plan. Trauma centers are fundamental during MCIs and serve a crucial leadership role in preparedness for them. OBJECTIVE: The purpose of this study was to describe the design and implementation of simulated MCI drills at an American College of Surgeons verified Level I trauma center in the Midwest. METHODS: A quasi-experimental time-series design was utilized to determine MCI simulation effects on staff performance using an emergency department checklist to measure emergency department throughput time. A multidisciplinary MCI design team developed a checklist for the emergency department, which identified tasks required to complete it. The 16-item checklist, Critical Pathway Management methodology, was used to identify the critical pathway for patient throughput during a surge. Two in situ MCI simulation drills were conducted in the emergency department (October and December 2019), and Critical Pathway Management identified the primary patient throughput rate limiters as notification and inpatient nursing staff presentation. RESULTS: Emergency department throughput decreased from a mean of 15 to 11 min (reduction of 26.7%) between the two time periods after focusing on rate-limiting tasks. CONCLUSION: This quality improvement project demonstrated that the use of institution-specific checklists and Critical Pathway Management to identify critical pathways and potential rate limiters led to patient throughput improvements.

Improving a Mature Palliative Care Program at a Level I Trauma Center.

BACKGROUND: Similar to the significant rise in the geriatric population in the United States, trauma centers have seen an increase in geriatric trauma patients. These patients present with additional challenges such as a higher likelihood of undertriage, mortality, and frailty. In addition, the varying presence of advanced directive documentation increases the importance of early palliative care consultations for geriatric trauma patients. OBJECTIVE: In 2018, a Level I trauma center in the Midwest reviewed the American College of Surgeons Trauma Quality Improvement Program's Palliative Care Best Practice Guideline to identify opportunities for improvement to strengthen the collaboration between the palliative care consult service and trauma program. METHODS: The guideline drove improvements, which included documentation changes (i.e., expansion of palliative care consultation triggers, frailty assessment, advanced directives questions, depression screening, and addition of palliative care consultation section on the performance improvement program form) and training (1-hr lecture on palliative care and 5-hr palliative care simulation training) opportunities. RESULTS: A 3-month manual chart review (March 2019 through May 2019) revealed that by May 2019, 87.2% of admitted geriatric trauma patients received frailty assessments, which surpassed the benchmark (≥85%). In addition, advanced care planning questions (i.e., health care power of attorney, do not resuscitate order, or living will) exceeded the benchmarks set forth by the guideline (≥90%), with all of the questions being asked and documented in 95.7% of those same patient charts by May 2019. CONCLUSION: This quality improvement project has applicability for trauma centers that treat geriatric trauma patients; using the guidelines can drive changes to meet individual institution needs.

Coronary Artery Disease: Analysis of Diagnostic Performance of CT Perfusion and MR Perfusion Imaging in Comparison with Quantitative Coronary Angiography and SPECT-Multicenter Prospective Trial.

Purpose To compare the diagnostic performance of stress myocardial computed tomography (CT) perfusion with that of stress myocardial magnetic resonance (MR) perfusion imaging in the detection of coronary artery disease (CAD). Materials and Methods All patients gave written informed consent prior to inclusion in this institutional review board-approved study. This two-center substudy of the prospective Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) multicenter trial included 92 patients (mean age, 63.1 years ± 8.1 [standard deviation]; 73% male). All patients underwent perfusion CT and perfusion MR imaging with either adenosine or regadenoson stress. The predefined reference standards were combined quantitative coronary angiography (QCA) and single-photon emission CT (SPECT) or QCA alone. Results from coronary CT angiography were not included, and diagnostic performance was evaluated with the Mantel-Haenszel test stratified by disease status. Results The prevalence of CAD was 39% (36 of 92) according to QCA and SPECT and 64% (59 of 92) according to QCA alone. When compared with QCA and SPECT, per-patient diagnostic accuracy of perfusion CT and perfusion MR imaging was 63% (58 of 92) and 75% (69 of 92), respectively (P = .11); sensitivity was 92% (33 of 36) and 83% (30 of 36), respectively (P = .45); and specificity was 45% (25 of 56) and 70% (39 of 56), respectively (P < .01). When compared with QCA alone, diagnostic accuracy of CT perfusion and MR perfusion imaging was 82% (75 of 92) and 74% (68 of 92), respectively (P = .27); sensitivity was 90% (53 of 59) and 69% (41 of 59), respectively (P < .01); and specificity was 67% (22 of 33) and 82% (27 of 33), respectively (P = .27). Conclusion This multicenter study shows that the diagnostic performance of perfusion CT is similar to that of perfusion MR imaging in the detection of CAD. © RSNA, 2017 Online supplemental material is available for this article.

The Role of Negative Affect on Headache-Related Disability Following Traumatic Physical Injury.

OBJECTIVE: Acute postinjury negative affect (NA) may contribute to headache pain following physical injury. Early psychiatric-headache comorbidity conveys increased vulnerability to chronic headache-related disability and impairment. Yet, it is unknown whether NA is involved in the transition to chronic headache related-disability after injury. This prospective observational study examined the role of acute postinjury NA on subacute and chronic headache-related disability above and beyond nonpsychiatric factors. METHODS: Eighty adult survivors of single-incident traumatic physical injury were assessed for negative affect (NA): a composite of depression and anxiety symptoms, and symptoms of posttraumatic stress disorder (PTSS) during the acute 2-week postinjury phase. NA was examined as the primary predictor of subacute (6-week) and chronic (3-month) headache-related disability; secondary analyses examined whether the individual NA components differentially impacted the outcomes. RESULTS: Hierarchical linear regression confirmed NA as a unique predictor of subacute (Cohen's f 2 = 0.130; P = .005) and chronic headache related-disability (Cohen's f 2 = 0.160; P = .004) beyond demographic and injury-related factors (sex, prior headaches, and closed head injury). Upon further analysis, PTSS uniquely predicted greater subacute (Cohen's f 2 = 0.105; P = .012) and chronic headache-related disability (Cohen's f 2 = 0.103; P = .022) above and beyond demographic and injury-related factors, depression, and anxiety. Avoidance was a robust predictor of subacute headache impairment (explaining 15% of the variance) and hyperarousal was a robust predictor of chronic headache impairment (10% of the variance). CONCLUSION: Although NA consistently predicted headache-related disability, PTSS alone was a unique predictor above and beyond nonpsychiatric factors, depression, and anxiety. These results are suggestive that early treatment of acute postinjury PTSS may correlate with reductions in disability and negative physical health sequelae associated with PTSS and chronic headache.

Optimized Time-Resolved Echo Particle Image Velocimetry- Particle Tracking Velocimetry Measurements Elucidate Blood Flow in Patients With Left Ventricular Thrombus.

Contrast ultrasound is a widely used clinical tool to obtain real-time qualitative blood flow assessments in the heart, liver, etc. Echocardiographic particle image velocimetry (echo-PIV) is a technique for obtaining quantitative velocity maps from contrast ultrasound images. However, unlike optical particle image velocimetry (PIV), routine echo images are prone to nonuniform spatiotemporal variations in tracer distribution, making analysis difficult for standard PIV algorithms. This study introduces optimized procedures that integrate image enhancement, PIV, and particle tracking velocimetry (PTV) to obtain reliable time-resolved two-dimensional (2D) velocity distributions. During initial PIV analysis, multiple results are obtained by varying processing parameters. Optimization involving outlier removal and smoothing is used to select the correct vector. These results are used in a multiparameter PTV procedure. To demonstrate their clinical value, the procedures are implemented to obtain velocity and vorticity distributions over multiple cardiac cycles using images acquired from four left ventricular thrombus (LVT) patients. Phase-averaged data elucidate flow structure evolution over the cycle and are used to calculate penetration depth and strength of left ventricular (LV) vortices, as well as apical velocity induced by them. The present data are consistent with previous time-averaged results for the minimum vortex penetration depth associated with LVT occurrence. However, due to decay and fragmentation of LV vortices, as they migrate away from the mitral annulus, in two cases with high penetration, there is still poor washing near the resolved clot throughout the cycle. Hence, direct examination of entire flow evolution may be useful for assessing risk of LVT relapse before prescribing anticoagulants.

Telepresent Focused Assessment With Sonography for Trauma Examination Training Versus Traditional Training for Medical Students: A Simulation-Based Pilot Study.

OBJECTIVES: Telepresent education is becoming an important modality in medical education, as it provides a means for instructors to lead education sessions via videoconferencing technologies. This study aimed to compare the effectiveness of telepresent ultrasound training versus traditional in-person ultrasound training. METHODS: Medical student cohorts were educated by either traditional in-person instruction or telementoring on how to perform a focused assessment with sonography for trauma (FAST) examination. Effectiveness was evaluated by pre- and post-multiple-choice tests (knowledge), confidence surveys, and summative simulation scenarios (hands-on FAST simulation). Formative simulation scenario debriefings were evaluated by each student using the Debriefing Assessment for Simulation in Healthcare student version (DASH-SV). RESULTS: Each method of instruction had significant increases in knowledge, confidence, and hands-on FAST simulation performance (P < .05). The collective increase in knowledge was greater for the in-person group, whereas the improvement in FAST examination performance during simulations was greater for the telementored group. Confidence gains were comparable between the groups. The DASH-SV scores were significantly higher for the in-person group for each criterion; however, both methods were deemed effective via median scoring. CONCLUSIONS: Telepresent education is a viable option for teaching the FAST examination to medical students.

Delayed intracranial hemorrhage in elderly anticoagulated patients sustaining a minor fall.

BACKGROUND: Falls are a common cause of hospitalization, morbidity, and mortality among the elderly in the United States. Evidence-based imaging recommendations for evaluation of delayed intracranial hemorrhage (DICH) are not generally agreed upon. The purpose of this project was to evaluate the incidence of DICH detected by head computer tomography (CT) among an elderly population on pre-injury anticoagulant or antiplatelet (ACAP) therapy. METHODS: Data from a Level 1 Trauma Center trauma registry was used to assess the incidence of DICH in an elderly population of patients (≥65 years) who sustained a minor fall while on pre-injury ACAP medications. Counts and percentages are reported. RESULTS: Data on 1076 elderly trauma patients were downloaded, of which 838 sustained a minor fall and 513 were found to be using a pre-injury ACAP medication. One patient (0.46%) with a DICH was identified out of 218 patients who received a routine repeat head CT. Aspirin and warfarin were the most common pre-injury ACAP medications and 19.27% (42/218) of patients were found to be using multiple ACAP medications. CONCLUSIONS: Universal screening protocols promote immediate-term patient safety, but do so at a great expense with respect to health expenditures and increased radiation exposure. This analysis highlights the need for an effective risk assessment tool for DICH that would reduce the burden of unnecessary screenings while still identifying life-threatening intracranial hemorrhages in affected patients.

Prognostic Value of Combined CT Angiography and Myocardial Perfusion Imaging versus Invasive Coronary Angiography and Nuclear Stress Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events: The CORE320 Multicenter Study.

Purpose To compare the prognostic importance (time to major adverse cardiovascular event [MACE]) of combined computed tomography (CT) angiography and CT myocardial stress perfusion imaging with that of combined invasive coronary angiography (ICA) and stress single photon emission CT myocardial perfusion imaging. Materials and Methods This study was approved by all institutional review boards, and written informed consent was obtained. Between November 2009 and July 2011, 381 participants clinically referred for ICA and aged 45-85 years were enrolled in the Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) prospective multicenter diagnostic study. All images were analyzed in blinded independent core laboratories, and a panel of physicians adjudicated all adverse events. MACE was defined as revascularization (>30 days after index ICA), myocardial infarction, or cardiac death; hospitalization for chest pain or congestive heart failure; or arrhythmia. Late MACE was defined similarly, except for patients who underwent revascularization within the first 182 days after ICA, who were excluded. Comparisons of 2-year survival (time to MACE) used standard Kaplan-Meier curves and restricted mean survival times bootstrapped with 2000 replicates. Results An MACE (49 revascularizations, five myocardial infarctions, one cardiac death, nine hospitalizations for chest pain or congestive heart failure, and one arrhythmia) occurred in 51 of 379 patients (13.5%). The 2-year MACE-free rates for combined CT angiography and CT perfusion findings were 94% negative for coronary artery disease (CAD) versus 82% positive for CAD and were similar to combined ICA and single photon emission CT findings (93% negative for CAD vs 77% positive for CAD, P < .001 for both). Event-free rates for CT angiography and CT perfusion versus ICA and single photon emission CT for either positive or negative results were not significantly different for MACE or late MACE (P > .05 for all). The area under the receiver operating characteristic curve (AUC) for combined CT angiography and CT perfusion (AUC = 68; 95% confidence interval [CI]: 62, 75) was similar (P = .36) to that for combined ICA and single photon emission CT (AUC = 71; 95% CI: 65, 79) in the identification of MACE at 2-year follow-up. Conclusion Combined CT angiography and CT perfusion enables similar prediction of 2-year MACE, late MACE, and event-free survival similar to that enabled by ICA and single photon emission CT. © RSNA, 2017 Online supplemental material is available for this article.

The effect of regadenoson on the integrity of the human blood-brain barrier, a pilot study.

Regadenoson is an FDA approved adenosine receptor agonist which increases blood-brain barrier (BBB) permeability in rodents. Regadenoson is used clinically for pharmacologic cardiac stress testing using SPECT or CT imaging agents that do not cross an intact BBB. This study was conducted to determine if standard doses of regadenoson transiently disrupt the human BBB allowing higher concentrations of systemically administered imaging agents to enter the brain. Patients without known intracranial disease undergoing clinically indicated pharmacologic cardiac stress tests were eligible for this study. They received regadenoson (0.4 mg) followed by brain imaging with either 99mTc-sestamibi for SPECT or visipaque for CT imaging. Pre- and post-regadenoson penetration of imaging agents into brain were quantified [SPECT: radioactive counts, CT: Hounsfield units (HU)] and compared using a matched-pairs t-test. Twelve patients (33% male, median 60 yo) were accrued: 7 SPECT and 5 CT. No significant differences were noted in pre- and post-regadenoson values using mean radionuclide counts (726 vs. 757) or HU (29 vs. 30). While animal studies have demonstrated that regadenoson transiently increases the permeability of the BBB to dextran and temozolomide, we were unable to document changes in the penetration of contrast agents in humans with intact BBB using the FDA approved doses of regadenoson for cardiac evaluation. Further studies are needed exploring alternate regadenoson dosing, schedules, and studies in patients with brain tumors; as transiently disrupting the BBB to improve drug entry into the brain is critical to improving the care of patients with CNS malignancies.