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Purpose To compare non-physician healthcare professional and radiologists' survey responses regarding attitudes and current practices, policies, and procedures related to the follow-up of nonemergent actionable incidental findings (AIF). Materials and Methods The American College of Radiology (ACR) developed a survey with input from a technical expert panel (TEP). Survey items were developed by TEP members, refined by an ACR market research expert, and were examined for face and construct validity. The survey was distributed among ACR membership and various medical professional organizations. Responses from non-physician responders and radiologists were analyzed and compared using descriptive statistics. Results The analysis included 375 responses, 247 from radiologists and 128 from non-physicians. All respondent groups stated that radiology follow-up recommendations are evidence-based. Both respondent groups indicated that there is up to moderate risk associated with AIF follow-up. Both respondent groups similarly favored that the accountability for communicating AIF lies first with the ordering provider, followed by primary care providers, then the patient, and lastly an automated process that is managed by a staff member and/or the radiologist. All respondent groups indicated that tracking processes were more commonly funded by the healthcare system than through the radiology budget. Conclusion There is alignment between non-physicians and radiologists regarding the implementation of tracking systems that assure completion of radiology follow-up recommendations. Building tracking systems represents an opportunity for multi-disciplinary collaboration to address care transition communication and process gaps.

Post-translational modifications alter the biophysical properties of proteins and thereby influence cellular physiology. One emerging manner by which such modifications regulate protein function is through their ability to perturb protein stability. Despite rising interest in this phenomenon, there are few methods that enable global interrogation of the biophysical effects of post-translational modifications on the proteome. Here, we describe an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel. We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. Using this thermal proteomic profiling strategy, we identify a set of 72 proteins displaying O-GlcNAc-dependant thermostability and validate this approach using orthogonal methods targeting specific proteins. These collective observations reveal that the majority of proteins influenced by O-GlcNAc are, surprisingly, destabilized by O-GlcNAc and cluster into distinct macromolecular complexes. These results establish O-GlcNAc as a bi-directional regulator of protein stability and provide a blueprint for exploring the impact of any protein modification on the meltome of, in principle, any organism.

The practice of prescribing β-blockers to lower blood pressure and mitigate perioperative cardiovascular events has been questioned because of reports of an increased risk of stroke. The benefit of β-blocker therapy primarily relies on preventing activation of cardiac β1-adrenergic receptors (ARs). However, we reported that β1ARs also mediate vasodilator responses of rat cerebral arteries (CAs), implying that β-blockers may impair cerebral blood flow under some conditions. Here, we defined the impact of metoprolol (MET), a widely prescribed β1AR-selective antagonist, on adrenergic-elicited diameter responses of rat CAs ex vivo and in vivo. MET (1-10 µmol/l) prevented β1AR-mediated increases in diameter elicited by dobutamine in cannulated rat CAs. The β1AR-mediated dilation elicited by the endogenous adrenergic agonist norepinephrine (NE) was reversed to a sustained constriction by MET. Acute oral administration of MET (30 mg/kg) to rats in doses that attenuated resting heart rate and dobutamine-induced tachycardia also blunted β1AR-mediated dilation of CAs. In the same animals, NE-induced dilation of CAs was reversed to sustained constriction. Administration of MET for 2 weeks in drinking water (2 mg/ml) or subcutaneously (15 mg/kg per day) also resulted in NE-induced constriction of CAs in vivo. Thus, doses of MET that protect the heart from adrenergic stimulation also prevent β1AR-mediated dilation of CAs and favor anomalous adrenergic constriction. Our findings raise the possibility that the increased risk of ischemic stroke in patients on β-blockers relates in part to adrenergic dysregulation of cerebrovascular tone. SIGNIFICANCE STATEMENT: β-Blocker therapy using second-generation, cardioselective β-blockers is associated with an increased risk of stroke, but the responsible mechanisms are unclear. Here, we report that either acute or chronic systemic administration of a cardioselective β-blocker, metoprolol, mitigates adrenergic stimulation of the heart as an intended beneficial action. However, metoprolol concomitantly eliminates vasodilator responses to adrenergic stimuli of rat cerebral arteries in vivo as a potential cause of dysregulated cerebral blood flow predisposing to ischemic stroke.

Care gaps occur when radiology follow-up recommendations are poorly communicated or not completed, resulting in missed or delayed diagnosis potentially leading to worse patient outcomes. This ACR-led initiative assembled a technical expert panel (TEP) to advise development of quality measures intended to improve communication and drive increased completion rates for radiology follow-up recommendations.A multistakeholder TEP was assembled to advise the development of quality measures. The project scope, limited to noncritical actionable incidental findings (AIFs), encourages practices to develop and implement systems ensuring appropriate communication and follow-up to completion.A suite of nine measures were developed: four outcome measures include closing the loop on completion of radiology follow-up recommendations for nonemergent AIFs (with pulmonary nodule and abdominal aortic aneurysm use cases) and overall cancer diagnoses. Five process measures address communication and tracking of AIFs: inclusion of available evidence or guidelines informing the recommendation, communication of AIFs to the practice managing ongoing care, identifying when AIFs have been communicated to the patient, and employing tracking and reminder systems for AIFs.This ACR-led initiative developed a measure set intended to improve patient outcomes by ensuring that AIFs are appropriately communicated and followed up. The intent of these measures is to focus improvement on specific areas in which gaps in communication and AIF follow-up may occur, prompting systems to devote resources that will identify and implement solutions to improve patient care.

B-lines are ultrasound artifacts that can be used to detect a variety of pathologic lung conditions. Computer-aided methods to detect and quantify B-lines may standardize quantification and improve diagnosis by novice users. We sought to test the performance of an automated algorithm for the detection and quantification of B-lines in a handheld ultrasound device (HHUD).Ultrasound images were prospectively collected on adult emergency department patients with dyspnea. Images from the first 124 patients were used for algorithm development. Clips from 80 unique subjects for testing were randomly selected in a predefined proportion of B-lines (0 B-lines, 1-2 B-lines, 3 or more B-lines) and blindly reviewed by five experts using both a manual and reviewer-adjusted process. Intraclass correlation coefficient (ICC) and weighted kappa were used to measure agreement, while an a priori threshold of an ICC (3,k) of 0.75 and precision of 0.3 were used to define adequate performance.ICC between the algorithm and manual count was 0.84 (95% confidence interval [CI] 0.75-0.90), with a precision of 0.15. ICC between the reviewer-adjusted count and the algorithm count was 0.94 (95% CI 0.90-0.96), and the ICC between the manual and reviewer-adjusted counts was 0.94 (95% CI 0.90-0.96). Weighted kappa was 0.72 (95% CI 0.49-0.95), 0.88 (95% CI 0.74-1), and 0.85 (95% CI 0.89-0.96), respectively.This study demonstrates a high correlation between point-of-care ultrasound experts and an automated algorithm to identify and quantify B-lines using an HHUD. Future research may incorporate this HHUD in clinical studies in multiple settings and users of varying experience levels.

Targeted mutagenesis mediated by nucleotide base deaminase–T7 RNA polymerase fusions has recently emerged as a novel and broadly useful strategy to power genetic diversification in the context of in vivo directed evolution campaigns. Here, we expand the utility of this approach by introducing a highly active adenosine deaminase–T7 RNA polymerase fusion protein (eMutaT7A→G), resulting in higher mutation frequencies to enable more rapid directed evolution. We also assess the benefits and potential downsides of using this more active mutator. We go on to show in Escherichia coli that adenosine deaminase-bearing mutators (MutaT7A→G or eMutaT7A→G) can be employed in tandem with a cytidine deaminase-bearing mutator (MutaT7C→T) to introduce all possible transition mutations simultaneously. We illustrate the efficacy of this in vivo mutagenesis approach by exploring mutational routes to antibacterial drug resistance. This work sets the stage for general application of optimized MutaT7 tools able to induce all types of transition mutations during in vivo directed evolution campaigns across diverse organisms.

Software-Defined Radio (SDR) technology has been driven by advances in RF integrated circuits and is generally available up to 40 GHz. State-of-the-art SDRs used with open software frameworks and interfaced to commercially available up/down-converter hardware provide a means for accessing the submm-THz spectrum. This makes it possible to realize measurement systems and communications channels that exploit the flexibility and processing capabilities of SDR backends. This work demonstrates the first use of SDR to implement a 1 THz FM communications channel using commercial off-the-shelf (COTS) SDRs, general RF components, and submillimeter-wave frequency extenders.

Objective To measure prevalence of discordance between electrical activity recorded by electrocardiography (ECG) and myocardial activity visualized by echocardiography (echo) in patients presenting after cardiac arrest and to compare survival outcomes in cohorts defined by ECG and echo. Methods This is a secondary analysis of a previously published prospective study at twenty hospitals. Patients presenting after out-of-hospital arrest were included. The cardiac electrical activity was defined by ECG and contemporaneous myocardial activity was defined by bedside echo. Myocardial activity by echo was classified as myocardial asystole--the absence of myocardial movement, pulseless myocardial activity (PMA)--visible myocardial movement but no pulse, and myocardial fibrillation--visualized fibrillation. Primary outcome was the prevalence of discordance between electrical activity and myocardial activity. Results 793 patients and 1943 pauses in CPR were included. 28.6% of CPR pauses demonstrated a difference in electrical activity (ECG) and myocardial activity (echo), 5.0% with asystole (ECG) and PMA (echo), and 22.1% with PEA (ECG) and myocardial asystole (echo). Twenty-five percent of the 32 pauses in CPR with a shockable rhythm by echo demonstrated a non-shockable rhythm by ECG and were not defibrillated. Survival for patients with PMA (echo) was 29.1% (95%CI-23.9–34.9) compared to those with PEA (ECG) (21.4%, 95%CI–17.7–25.6). Conclusion Patients in cardiac arrest commonly demonstrate different electrical (ECG) and myocardial activity (echo). Further research is needed to better define cardiac activity during cardiac arrest and to explore outcome between groups defined by electrical and myocardial activity.

Background Sepsis is the leading cause of global mortality, and it is frequently attributed to lower respiratory tract infections and subsequent acute respiratory distress syndrome (ARDS). Patients from sub-Saharan Africa (sSA) are underrepresented in existing studies of sepsis, and little is known about ARDS in sSA. Severe respiratory distress (SRD) is a surrogate for ARDS defined by the WHO as O2 saturation 30 breaths/minute and a systolic blood pressure >90 mmHg plus suspected infection in the absence of cardiac failure. In the context of the current COVID-19 pandemic, a better understanding of SRD in sSA is urgently needed. In this study, we aimed to determine the prevalence, clinical characteristics, and in-hospital mortality of adults with SRD in sSA. Methods We analyzed pooled individual-level data from 16 studies of hospitalized patients conducted in 6 countries throughout sSA from 2009 to 2019. We used multiple imputation with chained equations with 10 iterations to impute missing data. We performed multivariable logistic regression to estimate associations between patient vital signs, laboratory studies, SRD, and in-hospital mortality. We characterized factors associated with in-hospital mortality in the subset of patients with SRD. Results The pooled data included 7385 patients with a median age of 37 years, of whom 3584 (49%) were women, 2282 (31%) were living with HIV, 3190 (43%) had a known acute infection, and 946 (13%) had SRD. The mortality for the total population and for patients with SRD was 15% and 22%, respectively. Older age, lower temperature, increased heart rate, increased respiratory rate, decreased oxygen saturation, Glasgow Coma Scale score

Introduction: Thoracic ultrasound is frequently used in the emergency department (ED) to determine the etiology of dyspnea, yet its use is not widespread in the prehospital setting. We sought to investigate the feasibility and diagnostic performance of paramedic acquisition and assessment of thoracic ultrasound images in the prehospital environment, specifically for the detection of B-lines in congestive heart failure (CHF). Methods: This was a prospective observational study of a convenience sample of adult patients with a chief complaint of dyspnea. Paramedics participated in a didactic and hands-on session instructing them how to use a portable ultrasound device. Paramedics assessed patients for the presence of B-lines. Sensitivity and specificity for the presence of bilateral B-lines and any B-lines were calculated based on discharge diagnosis. Clips archived to the ultrasound units were reviewed and paramedic interpretations were compared to expert sonologist interpretations. Results: A total of 63 paramedics completed both didactic and hands-on training, and 22 performed ultrasounds in the field. There were 65 patients with B-line findings recorded and a discharge diagnosis for analysis. The presence of bilateral B-lines for diagnosis of CHF yielded a sensitivity of 80.0% (95% confidence interval [CI], 51.4–94.7%) and specificity of 72.0% (95% CI, 57.3–83.3), while presence of any B-lines was 93.3% sensitive (95% CI, 66.0–99.7%), and 50% specific (95% CI, 35.7–64.2%) for CHF. Paramedics archived 117 ultrasound clips of which 63% were determined to be adequate for interpretation. Comparison of paramedic and expert sonologist interpretation of images showed good inter-rater agreement for detection of any B-lines (k = 0.60; 95% CI, 0.36–0.84). Conclusion: This observational pilot study suggests that prehospital lung ultrasound for B-lines may aid in identifying or excluding CHF as a cause of dyspnea. The presence of bilateral B-lines as determined by paramedics is reasonably sensitive and specific for the diagnosis of CHF and pulmonary edema, while the absence of B lines is likely to exclude significant decompensated heart failure. The study was limited by being a convenience sample and highlighted some of the difficulties related to prehospital research. Larger funded trials will be needed to provide more definitive data.

DNA fragmentation produced by apoptotic DNases (endonucleases) leads to irreversible cell death. Although apoptotic DNases are simultaneously induced following toxic/oxidative cell injury and/or failed DNA repair, the study of DNases in apoptosis has generally been reductionist in approach, focusing on individual DNases rather than their possible cooperativity. Coordinated induction of DNases would require a mechanism of communication; however, mutual DNase induction or activation of DNases by enzymatic or non‐enzymatic mechanisms is not currently recognized. The evidence presented in this review suggests apoptotic DNases operate in a network in which members induce each other through the DNA breaks they produce. With DNA breaks being a common communicator among DNases, it would be logical to propose that DNA breaks from other sources such as oxidative DNA damage or actions of DNA repair endonucleases and DNA topoisomerases may also serve as triggers for a cooperative DNase feedback loop leading to elevated DNA fragmentation and subsequent cell death. Therefore, mutual induction of apoptotic DNases has serious implications for studies focused on activation or inhibition of specific DNases as a strategy for therapeutic intervention aimed at modulation of cell death.

Kidney stones are common, tend to recur, and afflict a young population. Despite evidence and recommendations, adoption of reduced-radiation dose CT (RDCT) for kidney stone CT (KSCT) is slow. We sought to design and test an intervention to improve adoption of RDCT protocols for KSCT using a randomized facility-based intervention.Facilities contributing at least 40 KSCTs to the American College of Radiology dose index registry (DIR) during calendar year 2015 were randomized to intervention or control groups. The Dose Optimization for Stone Evaluation intervention included customized CME modules, personalized consultation, and protocol recommendations for RDCT. Dose length product (DLP) of all KSCTs was recorded at baseline (2015) and compared with 2017, 2018, and 2019. Change in mean DLP was compared between facilities that participated (intervened-on), facilities randomized to intervention that did not participate (intervened-off), and control facilities. Difference-in-difference between intervened-on and control facilities is reported before and after intervention.Of 314 eligible facilities, 155 were randomized to intervention and 159 to control. There were 25 intervened-on facilities, 71 intervened-off facilities, and 96 control facilities. From 2015 to 2017, there was a drop of 110 mGy ∙ cm (a 16% reduction) in the mean DLP in the intervened-on group, which was significantly lower compared with the control group (P.05). The proportion of RDCTs increased for each year in the intervened-on group relative to the other groups for all 3 years (P.01).The Dose Optimization for Stone Evaluation intervention resulted in a significant (P.05) and persistent reduction in mean radiation doses for engaged facilities performing KSCTs.

Study Objectives: Point-of-care ultrasound (POCUS) has become an important tool in the global response to COVID-19, supporting screening, diagnosis and management. Lung features described in COVID-19 include B-lines (ring-down artifacts appearing in the presence of interstitial lung fluid), thickened and irregular pleural line, subpleural consolidations and effusions. Computer-aided interpretation can be incorporated into POCUS platforms to provide objective data and improve interpretations by novices. We sought to test a commercially available B-Lines counting feature previously developed using non-COVID data, on patients suspected of COVID-19. This first step would allow expansion to automated B-line scoring and further lung feature detection, to create an intelligent POCUS system with comprehensive set of lung ultrasound features for COVID-19 pneumonia. Methods: This was a prospective observational study at a single academic medical center. Subjects presenting to the emergency department with shortness of breath and suspected COVID-19 were enrolled. The Philips Lumify TM ultrasound system with sector or linear transducer was used to obtain 6-second clips of 14 lung zones (upper and lower, right and left anterior, lateral and posterior). Right and left anterior upper zone clips were also obtained with a second probe type. Repeat examinations with data collection were performed on days 3, 5, 7 or 12+/- 1 day for admitted patients. All clips with 2 or more B-lines were included (N=80), as well as a random selection of 70 clips with 1 or fewer B-lines. B-line count for inclusion was based on visual rating by two researchers with POCUS training. A POCUS fellowship trained emergency physician visually assessed each clip frame and counted the maximum number of B-lines per clip. This was compared to automatic counts by the commercially available Lumify TM Lung B-lines Quantification software by intraclass correlation coefficient (ICC) and Cohen’s weighted kappa. Results: Of the 899 total clips,150 clips from 30 unique subjects and 44 overall exams were used for analysis, with 100 clips from patients with confirmed COVID by PCR. The average maximum B-line count by algorithm was 1.52 +/- 1.24, and that by expert was 1.60 +/- 1.35 (ns). The ICC between algorithm and expert was 0.87 (95% CI 0.83-0.91), with a weighted kappa of 0.64 (95% CI 0.48-0.81), indicating substantial agreement. Average of maximum B-line counts, ICC and weighted kappa between algorithm and expert were comparable for COVID+ and COVID- subgroups as well as between transducer types. For COVID + subgroup, the average of maximum B-line counts was 1.73 +/- 1.28 for algorithm and 1.78 +/- 1.37 for expert, with weighted kappa 0.67 (95% CI 0.50-0.84), and ICC 0.87 (95% CI 0.83 to 0.91). Conclusion: An automated algorithm developed on non-COVID patients can accurately distinguish and quantify B-lines in clips from patients with COVID-19, with substantial agreement to expert visual rating. [Formula presented]

Severe sepsis is a time critical condition which is known to have a high mortality rate. Evidence suggests that early diagnosis and early administration of antibiotics can reduce morbidity and mortality from sepsis. The prehospital phase of emergency medical care may provide the earliest opportunity for identification of sepsis and delivery of life-saving treatment for patients. We aimed to assess the feasibility of (1) paramedics recognising and screening patients for severe sepsis, collecting blood cultures and administering intravenous antibiotics; and (2) trial methods in order to decide whether a fully-powered trial should be undertaken to determine safety and effectiveness of this intervention. Paramedics were trained in using a sepsis screening tool, aseptic blood culture collection and administration of intravenous antibiotics. If sepsis was suspected, paramedics randomly allocated patients to intervention or usual care using scratchcards. Patients were followed up at 90 days using linked anonymised data to capture length of hospital admission and mortality. We collected self-reported health-related quality of life at 90 days. We pre-specified criteria for deciding whether to progress to a fully-powered trial based on: recruitment of paramedics and patients; delivery of the intervention; retrieval of outcome data; safety; acceptability; and success of anonymised follow-up. Seventy-four of the 104 (71.2%) eligible paramedics agreed to take part and 54 completed their training (51.9%). Of 159 eligible patients, 146 (92%) were recognised as eligible by study paramedics, and 118 were randomised (74% of eligible patients, or 81% of those recognised as eligible). Four patients subsequently dissented to be included in the trial (3%), leaving 114 patients recruited to follow-up. All recruited patients were matched to routine data outcomes in the Secure Anonymised Information Linkage Databank. Ninety of the 114 (79%) recruited patients had sepsis or a likely bacterial infection recorded in ED. There was no evidence of any difference between groups in patient satisfaction, and no adverse reactions reported. There were no statistically significant differences between intervention and control groups in Serious Adverse Events (ICU admissions; deaths). This feasibility study met its pre-determined progression criteria; an application will therefore be prepared and submitted for funding for a fully-powered multi-centre randomised trial.Trial registration: ISRCTN36856873 sought 16th May 2017; https://doi.org/10.1186/ISRCTN36856873

Emergency department patients present with a wide variety of acute undifferentiated complaints. As a result, emergency physicians (EPs) were early adopters of point-of-care ultrasound. For over 30 years EPs have used ultrasound as a pragmatic tool to help answer their clinical questions and offer diagnostic and procedural guidance. The emergency ultrasound (EUS) community has developed significant experience in administrative issues surrounding ultrasound such as equipment selection, training, credentialing, ensuring ongoing quality assurance, and billing and reimbursement. We seek to describe the development of EUS and some of the practical issues in the use and implementation of point-of-care ultrasound that may apply across different specialties.

Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay is a long-established assay used to detect cell death-associated DNA fragmentation (3’-OH DNA termini) by endonucleases. Because these enzymes are particularly active in the kidney, TUNEL is widely used to identify and quantify DNA fragmentation and cell death in cultured kidney cells and animal and human kidneys resulting from toxic or hypoxic injury. The early characterization of TUNEL as an apoptotic assay has led to numerous misinterpretations of the mechanisms of kidney cell injury. Nevertheless, TUNEL is becoming increasingly popular for kidney injury assessment because it can be used universally in cultured and tissue cells and for all mechanisms of cell death. Furthermore, it is sensitive, accurate, quantitative, easily linked to particular cells or tissue compartments, and can be combined with immunohistochemistry to allow reliable identification of cell types or likely mechanisms of cell death. Traditionally, TUNEL analysis has been limited to the presence or absence of a TUNEL signal. However, additional information on the mechanism of cell death can be obtained from the analysis of TUNEL patterns.

In rapidly evolving global situations such as the COVID-19 pandemic, research needs to incorporate the realities of different global contexts. Identifying knowledge gaps and setting research priorities in different global contexts helps to effectively direct resources and scientific efforts towards the most pressing needs, including relevant public health interventions to tackle the direct and indirect impact of the pandemic. Collaborative international research initiatives such as the COVID-19 Clinical Research Coalition are necessary to confront both the current pandemic and prepare for future outbreaks. As evidenced by this Clinical Epidemiology Working Group (WG), the COVID-19 pandemic has emphasized the importance of global communication to optimize evidence-based thinking and collaboration. We present here a list of prioritized research questions in clinical epidemiology that aims to streamline COVID-19 research priority areas for low-resource settings.

Point-of-care ultrasound (POCUS) is frequently used in the emergency department (ED) to aid with the diagnosis and treatment of various diseases. In this chapter, we review the utility and accuracy of POCUS to evaluate both traumatic and non-traumatic abdominal pain; we supplement this review of the literature with technical instructions outlining how to perform the scans at the patient’s bedside. Finally, we provide ultrasound images to aid the reader in conceptualizing the performance of these scans and the normal and pathological variants of the anatomy described. This chapter gives an ED physicians’ perspective on the use of POCUS for the evaluation of common and possibly life-threatening causes of abdominal pain.

Background There are over 395,000 out-of-hospital cardiac arrests (OHCA) annually in the United States with an estimated 70-90% mortality rate and fewer than 10% surviving with a favorable neurologic outcome. Research in animal models and early human studies suggests that REBOA may play a role in augmenting coronary perfusion during OHCA by reducing blood flow to the lower body and re-directing it towards the heart and brain. We describe our initial case and research protocol to investigate the feasibility of REBOA in the emergency department (ED) for OHCA as an adjunct to ACLS. Methods We plan to enroll twenty patients in a single-arm interventional device study utilizing an exception from informed consent over a two-year period. The primary outcome is feasibility, with secondary outcomes assessing for hemodynamic changes pre- and post-aortic occlusion. Results Enrollment began in January 2020 and is ongoing. For the initial patient, an EP obtained ultrasound guided common femoral arterial access under chest compressions, followed by advancement of the REBOA catheter by an interventional radiologist. Immediately after aortic occlusion, investigators noted a substantial improvement in mean arterial pressure (MAP) (37 mmHg to 50 mmHg) and end tidal carbon dioxide (ETCO2) (33 mmHg to 50 mmHg), with transient but non-sustained return of spontaneous circulation (ROSC). Conclusion This is the first research protocol and case report of ED-REBOA initiation involving emergency physicians (EP) for non-traumatic OHCA. We describe our research protocol and initial case of a patient in OHCA who and underwent successful REBOA placement in the ED as an adjunct to ACLS.

Shortness of breath is a major reason that patients present to the emergency department (ED) and point-of-care ultrasound (POCUS) has been shown to aid in diagnosis, particularly through evaluation for artifacts known as B-lines. B-line identification and quantification can be a challenging skill for novice ultrasound users, and experienced users could benefit from a more objective measure of quantification. We sought to develop and test a deep learning (DL) algorithm to quantify the assessment of B-lines in lung ultrasound. We utilized ultrasound clips ( ${n} =400$ ) from an existing database of ED patients to provide training and test sets to develop and test the DL algorithm based on deep convolutional neural networks. Interpretations of the images by algorithm were compared to expert human interpretations on binary and severity (a scale of 0–4) classifications. Our model yielded a sensitivity of 93% (95% confidence interval (CI) 81%–98%) and a specificity of 96% (95% CI 84%–99%) for the presence or absence of B-lines compared to expert read, with a kappa of 0.88 (95% CI 0.79–0.97). Model to expert agreement for severity classification yielded a weighted kappa of 0.65 (95% CI 0.56–074). Overall, the DL algorithm performed well and could be integrated into an ultrasound system in order to help diagnose and track B-line severity. The algorithm is better at distinguishing the presence from the absence of B-lines but can also be successfully used to distinguish between B-line severity. Such methods could decrease variability and provide a standardized method for improved diagnosis and outcome.

The practice of prescribing β-blockers to lower blood pressure and mitigate perioperative cardiovascular events has been questioned because of reports of an increased risk of stroke. The benefit of β-blocker therapy primarily relies on preventing activation of cardiac β1-adrenergic receptors (ARs). However, we reported that β1ARs also mediate vasodilator responses of rat cerebral arteries (CAs), implying that β-blockers may impair cerebral blood flow under some conditions. Here, we defined the impact of metoprolol (MET), a widely prescribed β1AR-selective antagonist, on adrenergic-elicited diameter responses of rat CAs ex vivo and in vivo. MET (1–10 µmol/l) prevented β1AR-mediated increases in diameter elicited by dobutamine in cannulated rat CAs. The β1AR-mediated dilation elicited by the endogenous adrenergic agonist norepinephrine (NE) was reversed to a sustained constriction by MET. Acute oral administration of MET (30 mg/kg) to rats in doses that attenuated resting heart rate and dobutamine-induced tachycardia also blunted β1AR-mediated dilation of CAs. In the same animals, NE-induced dilation of CAs was reversed to sustained constriction. Administration of MET for 2 weeks in drinking water (2 mg/ml) or subcutaneously (15 mg/kg per day) also resulted in NE-induced constriction of CAs in vivo. Thus, doses of MET that protect the heart from adrenergic stimulation also prevent β1AR-mediated dilation of CAs and favor anomalous adrenergic constriction. Our findings raise the possibility that the increased risk of ischemic stroke in patients on β-blockers relates in part to adrenergic dysregulation of cerebrovascular tone. SIGNIFICANCE STATEMENT: β-Blocker therapy using second-generation, cardioselective β-blockers is associated with an increased risk of stroke, but the responsible mechanisms are unclear. Here, we report that either acute or chronic systemic administration of a cardioselective β-blocker, metoprolol, mitigates adrenergic stimulation of the heart as an intended beneficial action. However, metoprolol concomitantly eliminates vasodilator responses to adrenergic stimuli of rat cerebral arteries in vivo as a potential cause of dysregulated cerebral blood flow predisposing to ischemic stroke.

Background Opioids, such as heroin, kill more people worldwide by overdose than any other type of drug, and death rates associated with opioid poisoning in the UK are at record levels (1, 2). Naloxone is an opioid antagonist which can be distributed in ‘kits’ for administration by witnesses in an overdose emergency. This intervention is known as Take Home Naloxone (THN). We know that THN can save lives on an individual level, but there is currently limited evidence about the effectiveness of THN distribution on an aggregate level, in specialist drug service settings or in emergency service settings. Notably, we do not know whether THN kits reduce deaths from opioid overdose in at-risk populations, if there are unforeseen harms associated with THN distribution or if THN is cost-effective. In order to address this research gap, we aim to determine the feasibility of a fully-powered cluster Randomised Controlled Trial (RCT) of THN distribution in emergency settings. Methods We will carry out a feasibility study for a RCT of THN distributed in emergency settings at four sites, clustered by Emergency Department (ED) and catchment area within its associated ambulance service. THN is a peer-administered intervention. At two intervention sites, emergency ambulance paramedics and ED clinical staff will distribute THN to adult patients who are at risk of opioid overdose. At two control sites, practice will carry on as usual. We will develop a method of identifying a population to include in an evaluation, comprising people at risk of fatal opioid overdose, who may potentially receive naloxone included in a THN kit. We will gather anonymised outcomes up to one year following a 12 month ‘live’ trial period for patients at risk of death from opioid poisoning. We expect approximately 100 patients at risk of opioid overdose to be in contact with each service during the one year recruitment period. Our outcomes will include: deaths; emergency admissions; intensive care admissions; and ED attendances. We will collect numbers of eligible patients attended by participating emergency ambulance paramedics and attending ED; THN kits issued; and NHS resource usage. We will determine whether to progress to a fully-powered trial based on pre-specified progression criteria: sign-up of sites (n = 4); staff trained (>= 50%); eligible participants identified (>= 50%); THN provided to eligible participants (>= 50%); people at risk of death from opioid overdose identified for inclusion in follow up (>= 75% of overdose deaths); outcomes retrieved for high risk individuals (>= 75%); and adverse event rate (Discussion This feasibility study is the first randomised, methodologically robust investigation of THN distribution in emergency settings. The study addresses an evidence gap related to the effectiveness of THN distribution in emergency settings. As this study is being carried out in emergency settings, obtaining informed consent on behalf of participants is not feasible. We therefore employ novel methods for identifying participants and capturing follow up data, with effectiveness dependent on the quality of the available routine data.Trial registration ISRCTN13232859 (Registered 16/02/2018)

The COVID‐19 pandemic has spread to 185 countries with over 2.1 million confirmed cases and 145,000 deaths, as per the Johns Hopkins University COVID‐19 dashboard provided at https://coronavirus.jhu.edu/map.html. Imaging modalities such as chest radiography, thoracic and cardiovascular ultrasound, and computed tomography have roles in the diagnosis, prognosis, monitoring, and therapy of COVID‐19. However, the potential benefits of imaging need to be balanced against resource utilization and infectious risk.

A simple and reproducible procedure was developed to measure the volume of liquid microinjected into cells. A calibration curve of droplet fluorescence intensity versus volume was constructed by injecting a fluorescent dextran solution through a 125–150 µm diameter micropipette into an oil-filled culture dish to create a spray of varied-sized droplets. The droplets retained a spherical shape because they were in an oil medium and they settled onto a glass surface coated with a superhydrophobic surface. Fluorescent micrographs of the droplets were obtained and analyzed with Image-J software to quantify the fluorescence intensity and radius of each spherical droplet to produce the calibration curve. Subsequently, Dut-145 human prostate carcinoma cells were microinjected with the same fluorescent dextran solution and fluorescent micrographs of the cells were obtained using the identical exposure conditions used to photograph the droplets. The measured fluorescence intensity of the microinjected cells was entered into the formula for the regression line that was fit to the calibration curve allowing determination of the volume of solution injected into each cell. Thus, a mixture consisting of known concentrations of a test material of test material (macromolecules, drugs, etc.) and a fluorescent dextran, volumetric, tracer can be used to quantify the relationship between the amount of a microinjected material and subsequent effects on cells.

OBJECTIVES An increasing number of medical schools are incorporating point-of-care ultrasound (POCUS) into preclinical and clinical curricula. The ultimate effect of this teaching is unclear, and there has been no distinct link between ultrasound (US) learning and existing standardized student assessments. Additionally, neither optimal timing nor methods of POCUS integration have been established. We aimed to demonstrate the effect of US teaching on standardized objective assessments that already exist within the curriculum and, in doing so, discern a route for POCUS curricular integration. METHODS A longitudinal POCUS pilot curriculum was started in 2013, with the class of 2017. We collected basic science course results, standardized objective structured clinical examination scores, and United States Medical Licensing Examination step 1 scores from both the pilot group (n = 34) and matched control participants (n = 34) from the classes of 2017 and 2018. Scores between POCUS students and controls were analyzed by Student t tests. RESULTS Students participating in the longitudinal POCUS program scored significantly higher on the physical examination portion of their clinical skill objective structured clinical examination assessment than the control group (mean score, 89.2 versus 85.7; P

Laboratory time scale evolution in vivo relies on the generation of large, mutationally diverse gene libraries to rapidly explore biomolecule sequence landscapes. Traditional global mutagenesis methods are problematic because they introduce many off-target mutations that are often lethal and can engender false positives. We report the development and application of the MutaT7 chimera, a potent and highly targeted in vivo mutagenesis agent. MutaT7 utilizes a DNA-damaging cytidine deaminase fused to a processive RNA polymerase to continuously direct mutations to specific, well-defined DNA regions of any relevant length. MutaT7 thus provides a mechanism for in vivo targeted mutagenesis across multi-kb DNA sequences. MutaT7 should prove useful in diverse organisms, opening the door to new types of in vivo evolution experiments.

Background: In secondary care, the urgency of review for transient ischaemic attack (TIA) has relied upon the use of the ABCD2 score, but this tool is not validated for use by emergency ambulance crews. There is a need to evaluate alternative care pathways for patients who might be eligible for direct referral to TIA clinics without prior conveyance to the emergency department (ED). Aim: The aim of this national survey was to describe current service provision across the UK for pre-hospital emergency care of patients with TIA. Methods: The authors approached all UK Ambulance trusts (n=13) by email, asking them to provide details of TIA patient referral pathways. Findings: Twelve ambulance services responded to the survey and nine reported that they had no current pathway; one had discontinued a pathway because of service reconfiguration; and three were currently using one. All pathways used the ABCD2 tool to screen patients and classified patients as low-risk if the ABCD2 score was 3 or below. Non-conveyance exclusion criteria varied. Although compliance with referral pathways was audited in an initial pilot in one service, no other evaluations of the effectiveness of pathways were reported. Conclusion: A minority of UK ambulance services report introducing referral pathways for low-risk TIA patients, avoiding initial assessment in the ED. Safety, effectiveness and acceptability of such pathways have not been evaluated to date.

BackgroundDrug poisoning deaths in England and Wales have increased by 52% since 2011 with over half involving opioids. Deaths are preventable if naloxone is administered in time. Take Home Naloxone (THN) kits have been distributed through drug services; however, uptake is low and effectiveness unproven. The TIME trial tests the feasibility of conducting a full randomised controlled trial of providing THN administration and basic life support training to high-risk opioid-users in emergency care settings.MethodsA multi-site feasibility trial commenced in June 2019 with two hospitals and their surrounding ambulance services (Bristol Royal Infirmary (BRI) with South Western Ambulance NHS Foundation Trust (SWASFT) and Hull Royal Infirmary with Yorkshire Ambulance Service) randomly allocated to intervention arms; and sites in Wrexham and Sheffield allocated as ‘usual care’ controls. SWASFT began recruiting in October 2019 with the aim of recruiting and training 50% (n=111) of paramedics working within the BRI’s catchment area, to supply THN to at least 100 eligible patients during a 12-month period.ResultsThe trial was suspended between 17.03.2020-06.08.2020 and extended to 01.03.2021 (COVID-19). Despite this, 121 SWASFT paramedics undertook TIME training. TIME trained paramedics attended 30% (n=57) of the n=190 opioid-related emergency calls requiring naloxone administration during the study period. A total of n=29 potentially eligible patients were identified before and n=28 after the COVID-19 suspension. Two patients were supplied with THN during each period. During the COVID-19 suspension, twenty-two potentially eligible patients were missed. The majority of eligible patients presented with a reduced consciousness level, preventing recruitment (73%; n=42/48). These patients were transported to hospital for further treatment (n=39) or died on scene following advanced life support (n=3).ConclusionsThe lowered consciousness levels of prehospital emergency ambulance patients who present with opioid poisoning, often prevent the delivery of training required to enable the supply of THN.

Purpose: More than 1 million patients annually seek care in an emergency department for kidney stones but a minority require hospital admission or a urological procedure. We describe predictors of hospital admission or urological intervention.Materials and Methods: This secondary analysis of prospective data included patients with an obstructing ureteral stone that was confirmed by computerized tomography in an emergency department. All patients also underwent point of care limited renal ultrasound. The need for urological intervention at 90 days was assessed by a followup interview. Logistic regression was used to identify predictors of admission and urological intervention, which were further stratified by disposition. Separate regression models with and without computerized tomography findings (point of care limited renal ultrasound only) were compared using c-statistics.Results: Among a cohort of 475 patients with a symptomatic stone on computerized tomography 95 (20%) were admitted and 68 (72%) recei...

Objective Our objective was to determine whether organized or disorganized cardiac activity is associated with increased survival in patients who present in pulseless electrical activity (PEA) treated with either 1) standard advanced cardiac life support (ACLS) medications or 2) other interventions. Methods This was a secondary analysis of a prospective, multi-center observational study utilizing ultrasound in out-of-hospital or inemergency department PEA arrest. Bedside ultrasound was performed as ACLS protocol started and during pulse checks. Only cases with visible cardiac activity on ultrasound were included in the present analysis. Cardiac activity was categorized as disorganized (agonal twitching) or organized (contractions with changes in ventricular dimensions). Patients were categorized as receiving either standard bolus ACLS medications or alternative medications during the resuscitation (continuous adrenergic agents, thrombolytics, others). The primary outcome was survival to hospital admission. The secondary outcome was return of spontaneous circulation (ROSC). Multivariate modeling was performed to assess association between survival to hospital admission in patients with intravenous adrenergic agents and cardiac activity. Results In our cohort of 225 patients in PEA cardiac arrest with cardiac activity on ultrasound, the overall survival rate was higher in patients with organized cardiac activity than with disorganized cardiac activity. PEA cardiac arrest patients with organized cardiac activity treated with standard ACLS interventions demonstrated improved survival to hospital admission compared to those with disorganized activity (37.7% (95%CI 24.8–50.2%) versus 17.9% (95%CI 10.9–28%). PEA cardiac arrest patients with organized cardiac activity who received continuous adrenergic agents during the resuscitation and prior to ROSC demonstrated higher survival to hospital admission 45.5% (95%CI 26.9–65.4%) and ROSC 90.9% (95%CI 71.0–98.7%) compared to those with disorganized cardiac activity who received continuous adrenergic agents during the resuscitation 0% (95%CI 0–23.0%) and 47.1% (95%CI 26–69%). Regression analysis demonstrates an association between increased survival in patients receiving intravenous adrenergic agents and organized cardiac activity. Conclusion Survival in patients following PEA arrest is higher in patients with organized cardiac activity. The initiation of continuous adrenergic agents during PEA was associated with improved survival to hospital admission in patients with organized cardiac activity on bedside ultrasound, but this improvement was not seen in patients in PEA with disorganized cardiac activity. Bedside ultrasound may identify a subset of patients that respond differently to ACLS interventions.

ObjectiveRecent studies have clarified the role of alpha-blockers, such as tamsulosin, for patients diagnosed with ureteral stones

Acute right upper quadrant (RUQ) pain is a common presenting symptom in emergency departments and outpatient medical practices, and is most commonly attributable to biliary and hepatic pathology. Ultrasound should be used as a first-line imaging modality for the diagnosis of gallstones and cholecystitis, as it allows the differentiation of medical and surgical causes of upper abdominal pathology, and in many circumstances is sufficient to guide patient management. Knowledge of strengths and limitations of ultrasound in the evaluation of RUQ is paramount in correct diagnosis. A spectrum of RUQ pathology for which a RUQ ultrasound examination should reasonably be considered as the initial imaging modality of choice will be reviewed.

Background Transplant recipients are at increased risk of bloodstream infection (BSI), which often leads to critical illness. Due to immunosuppression, BSI in these patients may manifest with different pathophysiology compared to non-transplant recipients. We aimed to identify different trends in the pathophysiology of critically ill patients with BSI based on transplant status. Methods We reviewed data from patients admitted to the medical and surgical/trauma intensive care units (ICUs) at the University of Virginia Medical Center from 2011 to 2015. We included both solid organ and hematopoietic stem cell transplant recipients. We performed univariate logistic regression modeling to evaluate trends in different physiological features in both transplant and non-transplant recipients in the 96 hours surrounding a positive blood culture. We then performed multivariate logistic regression modeling to identify features independently associated with a positive blood culture in the next 24 hours in transplant recipients. Results We analyzed 9,954 ICU patient-admissions (including 505 transplant recipients), with a total of 144 patient-years of physiological data, 1.3 million hourly measurements, and 15,577 blood culture instances. Of the 1,068 blood culture instances in transplant recipients, 125 (12%) were positive, compared to 1,051 of 14,509 (7%) blood culture instances in non-transplant recipients. Critically ill transplant recipients with BSI had greater abnormalities in vital signs, oxygen requirement, markers of organ damage, APACHE score, and Charlson Comorbidity Index (CCI) compared to non-transplant recipients (Figure 1). Trends in many of these features also differed based on transplant status. The multivariable logistic regression model of BSI in transplant recipients included, in decreasing strength of association: total bilirubin, systolic blood pressure, fraction of inspired oxygen, number of intravenous lines, and CCI. This model had an AUC of 0.75. Figure 1. Trends in pathophysiological abnormalities in 9,954 critically ill patients with BSI based on transplant status, 2011–2015. Each graph demonstrates the average value of the physiological variable over time relative to the acquisition of a positive blood culture. Blue curves depict trends in transplant recipients, while red curves depict trends in non-transplant recipients. We assessed 108 physiological features and show the 24 features with the greatest change around the time of blood culture. Conclusion Critically ill transplant recipients have a higher prevalence of BSI and different pathophysiological manifestations of BSI compared to non-transplant recipients. This may have implications regarding early detection and treatment of BSI in these patients. Disclosures Randall Moorman, MD, Advanced Medical Predictive Devices, Diagnostics, and Displays (Board Member, Shareholder)

Background: Focused transthoracic echocardiography has been used to determine etiologies of cardiac arrest and evaluate utility of continuing resuscitation after cardiac arrest. Few guidelines exist advising ultrasound timing within the advanced cardiac life support algorithm. Natural timing of echocardiography occurs during the pulse check, when views are unencumbered by stabilization equipment or vigorous movements. However, recent studies suggest that ultrasound performance during pulse checks prolongs the pause duration of cardiopulmonary resuscitation. Transesophageal echocardiography studies have demonstrated benefits in this regard, but there have been no transthoracic echocardiography studies assessing the physical performance of compressions during cardiopulmonary resuscitation. Objective: The purpose of this study was to describe cases where echocardiography performed at the beginning of the cardiac arrest algorithm offers actionable information to cardiopulmonary resuscitation itself without delaying provision of compressions. Conclusion: Providers using focused echocardiography to evaluate cardiac arrest patients should consider initiating scans at the start of compressions to identify the optimal location for compression delivery and to detect inadequate compressions. Subsequent visualization of full left ventricular compression may be seen after a location change, and combined with end tidal carbon dioxide values, gives indication for improved forward circulatory flow. Although it is not possible in all patients, doing so hastens provision of quality compressions that affect hemodynamic parameters without causing prolongations to the pulse check pause. Further research is needed to determine patient outcomes from both out-of-hospital and in-hospital cardiac arrest when cardiopulmonary resuscitation is visually guided by focused echocardiography.

CT is a widely used imaging modality in the diagnosis of urolithiasis but subjects patients to ionizing radiation. Reduced dose protocols have recently gained wide acceptance. Stone density measurements have been used to predict composition and help guide treatment in standard dose CT (sCT) but not in reduced dose CT (RdCT). We aimed to compare density measurements obtained through RdCT