International consensus conference recommendations on ultrasound education for undergraduate medical students.

OBJECTIVES: The purpose of this study is to provide expert consensus recommendations to establish a global ultrasound curriculum for undergraduate medical students. METHODS: 64 multi-disciplinary ultrasound experts from 16 countries, 50 multi-disciplinary ultrasound consultants, and 21 medical students and residents contributed to these recommendations. A modified Delphi consensus method was used that included a systematic literature search, evaluation of the quality of literature by the GRADE system, and the RAND appropriateness method for panel judgment and consensus decisions. The process included four in-person international discussion sessions and two rounds of online voting. RESULTS: A total of 332 consensus conference statements in four curricular domains were considered: (1) curricular scope (4 statements), (2) curricular rationale (10 statements), (3) curricular characteristics (14 statements), and (4) curricular content (304 statements). Of these 332 statements, 145 were recommended, 126 were strongly recommended, and 61 were not recommended. Important aspects of an undergraduate ultrasound curriculum identified include curricular integration across the basic and clinical sciences and a competency and entrustable professional activity-based model. The curriculum should form the foundation of a life-long continuum of ultrasound education that prepares students for advanced training and patient care. In addition, the curriculum should complement and support the medical school curriculum as a whole with enhanced understanding of anatomy, physiology, pathophysiological processes and clinical practice without displacing other important undergraduate learning. The content of the curriculum should be appropriate for the medical student level of training, evidence and expert opinion based, and include ongoing collaborative research and development to ensure optimum educational value and patient care. CONCLUSIONS: The international consensus conference has provided the first comprehensive document of recommendations for a basic ultrasound curriculum. The document reflects the opinion of a diverse and representative group of international expert ultrasound practitioners, educators, and learners. These recommendations can standardize undergraduate medical student ultrasound education while serving as a basis for additional research in medical education and the application of ultrasound in clinical practice.

Designing and evaluating a patient decision aid for patients with locally advanced or locally recurrent rectal cancer: a national multicentre mixed methods study protocol.

INTRODUCTION: Approximately 5%-10% of new rectal cancers are locally advanced (locally advanced rectal cancer (LARC)) at presentation with 4%-8% recurring (locally recurrent rectal cancer (LRRC)) after initial treatment. Patients with potentially curable disease have to consider many trade-offs when considering major exenterative surgery. There are no decision tools for these patients and current resources have found to not meet minimum international standards. The overall aim of this study is to produce a validated patient decision aid (PtDA) to assist patients considering radical pelvic exenteration for LARC and LRRC created in line with international minimum standards. METHODS AND ANALYSIS: This study is a national, multicentre mixed methods project and has been designed in keeping with guidance from the International Patient Decision Aids Standard.This study is in four stages. In stage 1, we will develop the PtDA and its content using agile developmental methodology. In stage 2, we will assess the content and face validity of the PtDA using mixed-methods with key stakeholders. In stage 3, we will assess the feasibility and efficacy of the PtDA. In stage 4, we will establish the barriers and facilitators to the use of a PtDA in the outpatient setting. Questionnaires including the QQ-10, EORTC PATSAT-C33, Preparation for Decision-Making Scale and the NoMAD survey will be analysed during the study. Interviews will be analysed using thematic analysis. ETHICS AND DISSEMINATION: Research ethics approval from North of Scotland Research Ethics Service 19/NS/0056 (IRAS 257890) has been granted. Results will be published in open access peer-reviewed journals, presented in conferences and distributed through bowel research UK charity. External endorsement will be sought from the International Patient Decision Standards Collaboration inventory of PtDAs. PROSPERO REGISTRATION NUMBER: CRD42019122933.

Non-invasive fluorescence imaging for tracking immune cells in preclinical models of immunotherapy.

The field of cellular immunotherapy for cancer has experienced exponential growth over the last decade. Several chimeric antigen receptor T cell products have already received FDA approval, which has stimulated growth and enthusiasm for other cellular therapies. Preclinical models are critical steps in the development of these products, and understanding their in vivo trafficking and persistence are critical components of their efficacy and toxicity analogous to volume of distribution and tissue penetration in small molecule therapeutics. Thus, well-established preclinical methodologies for following cells after adoptive transfer are important to understanding immune cell trafficking to, and persistence in, tumors or organs of interest. Here, we describe a quick and reliable method for labeling and in vivo tracking of immune cells adoptively transferred into small animal models by using in vivo fluorescent imaging.

Precision Therapy for Mesothelioma: Feasibility and New Opportunities.

Malignant pleural mesotheliomas (MPMs) are characterised by their wide variation in natural history, ranging from minimally to highly aggressive, associated with both interpatient and intra-tumour genomic heterogeneity. Recent insights into the nature of this genetic variation, the identification of drivers, and the emergence of novel strategies capable of targeting vulnerabilities that result from the inactivation of key tumour suppressors suggest that new approaches to molecularly strategy therapy for mesothelioma may be feasible.

Quantitative characterization of left ventricular function during pulseless electrical activity using echocardiography during out-of-hospital cardiac arrest.

BACKGROUND: Several prospective studies have demonstrated that the echocardiographic detection of any myocardial activity during PEA is strongly associated with higher rates of return of spontaneous circulation (ROSC). We hypothesized that PEA represents a spectrum of disease in which not only the presence of myocardial activity, but more specifically that the degree of left ventricular (LV) function would be a predictor of outcomes. The purpose of this study was to retrospectively assess the association between LV function and outcomes in patients with OHCA. MATERIALS AND METHODS: Using prospectively obtained data from an observational cohort of patients receiving focused echocardiography during cardiopulmonary resuscitation (CPR) in the Emergency Department (ED) setting, we analyzed 312 consecutive subjects with available echocardiography images with initial rhythm of PEA. We used left ventricular systolic fractional shortening (LVFS), a unidimensional echocardiographic parameter to perform the quantification of LV function during PEA. Regression analyses were performed independently to evaluate for relationships between LVFS and a primary outcome of ROSC and secondary outcome of survival to hospital admission. We analyzed LVFS both as a continuous variable and as a categorial variable using the quartiles and the median to perform multiple different comparisons and to illustrate the relationship of LVFS and outcomes of interest. We performed survival analysis using Cox proportional hazards model to evaluate the hazard corresponding to length of resuscitation. RESULTS: We found a positive association between LVFS and the primary outcome of ROSC (OR 1.04, 95%CI 1.01-1.08), but not with the secondary outcome of survival to hospital admission (OR 1.02, 95%CI 0.96-1.08). Given that the relationship was not linear and that we observed a threshold effect in the relationship between LVFS and outcomes, we performed an analysis using quartiles of LVFS. The predicted probability of ROSC was 75% for LVFS between 23.4-96% (fourth quartile) compared to 47% for LVFS between 0-4.7% (first quartile). The hazard of not achieving ROSC was significantly greater for subjects with LVFS below the median (13.1%) compared to the subgroup with LVFS greater than 13.1% (p < 0.05), with the separation of the survival curves occurring at approximately 40 min of resuscitation duration. CONCLUSIONS: Left ventricular function measured by LVFS is positively correlated with higher probability of ROSC and may be associated with higher chances of survival in patients with PEA arrest.

Analysis of an obstetrics point-of-care ultrasound training program for healthcare practitioners in Zanzibar, Tanzania.

BACKGROUND: A point-of-care ultrasound education program in obstetrics was developed to train antenatal healthcare practitioners in rural Zanzibar. The study group consisted of 13 practitioners with different training backgrounds: physicians, clinical officers, and nurse/midwives. Trainees received an intensive 2-week antenatal ultrasound course consisting of lectures and hands-on practice followed by 6 months of direct supervision of hands-on scanning and bedside education in their clinical practice environments. Trainees were given a pre-course written exam, a final exam at course completion, and practical exams at 19 and 27 weeks. Trainees were expected to complete written documentation and record ultrasound images of at least 75 proctored ultrasounds. The objective of this study was prospectively to analyze the success of a longitudinal point-of-care ultrasound training program for antepartum obstetrical care providers in Zanzibar. RESULTS: During the 6-month course, trainees completed 1338 ultrasound exams (average 99 exams per trainee with a range of 42-128 and median of 109). Written exam scores improved from a mean of 33.7% (95% CI 28.6-38.8%) at pre-course assessment to 77.5% (95% CI 71-84%) at course completion (P < 0.0001). Practical exam mean scores improved from 71.2% at course midpoint (95% CI 62.3-80.1%) to 84.7% at course completion (95% Cl 78.5-90.8%) (P < 0.0005). Eight of the 13 trainees completed all training requirements including 75 proctored ultrasound exams. CONCLUSION: Trainees improved significantly on all measures after the training program. 62% of the participants completed all requirements. This relatively low completion rate reflects the challenges of establishing ultrasound capacity in this type of setting. Further study is needed to determine trainees' long-term retention of ultrasound skills and the impact of the program on clinical practice and health outcomes.

Early hemodynamic assessment using NICOM in patients at risk of developing Sepsis immediately after emergency department triage.

BACKGROUND: One factor leading to the high mortality rate seen in sepsis is the subtle, dynamic nature of the disease, which can lead to delayed detection and under-resuscitation. This study investigated whether serial hemodynamic parameters obtained from a non-invasive cardiac output monitor (NICOM) predicts disease severity in patients at risk for sepsis. METHODS: Prospective clinical trial of the NICOM device in a convenience sample of adult ED patients at risk for sepsis who did not have obvious organ dysfunction at the time of triage. Hemodynamic data were collected immediately following triage and 2 hours after initial measurement and compared in two outcome groupings: (1) admitted vs. dehydrated, febrile, hypovolemicdischarged patients; (2) infectious vs. non-infectious sources. Receiver operator characteristic (ROC) curves were calculated to determine whether the NICOM values predict hospital admission better than a serum lactate. RESULTS: 50 patients were enrolled, 32 (64 %) were admitted to the hospital. Mean age was 49.5 (± 16.5) years and 62 % were female. There were no significant associations between changes in hemodynamic variables and patient disposition from the ED or diagnosis of infection. Lactate was significantly higher in admitted patients and those with infection (p = 0.01, p = 0.01 respectively). The area under the ROC [95 % Confidence Intervals] for lactate was 0.83 [0.64-0.92] compared to 0.59 [0.41-0.73] for cardiac output (CO), 0.68 [0.49-0.80] for cardiac index (CI), and 0.63 [0.36-0.80] for heart rate (HR) for predicting hospital admission. CONCLUSIONS: CO and CI, obtained at two separate time points, do not help with early disease severity differentiation of patients at risk for severe sepsis. Although mean HR was higher in those patients who were admitted, a serum lactate still served as a better predictor of patient admission from the ED.

Multi-organ point-of-care ultrasound for COVID-19 (PoCUS4COVID): international expert consensus.

COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.

Effect of Machine Settings on Ultrasound Assessment of B-lines.

OBJECTIVES: B-lines are a lung ultrasound (LUS) artifact that often indicate pathology. Little is known about the optimal ultrasound machine settings to assess B-lines. We compared settings typically used to evaluate B-lines at our institution with adjusted settings based on recent studies. METHODS: In order to determine typical settings for B-line assessment, we retrospectively reviewed LUS images obtained at our institution. We then prospectively performed LUS with both typical and adjusted settings, using curvilinear and phased array probes, in 20 patients presenting to the emergency department with shortness of breath. The prospectively obtained clips were rated for quality and quantity of B-lines by 14 clinicians with experience in LUS, with 1 assigned for typical settings "much greater," 2 for typical settings "slightly greater," 3 for both settings "similar," 4 for adjusted settings "slightly greater," and 5 for adjusted settings "much greater." RESULTS: Mean ratings and 95% confidence intervals significantly exceeded the null value of 3 for both B line quality (curvilinear probe: 4.68, 4.50-4.85; phased array probe: 4.02, 3.70-4.35) and B line quantity (curvilinear probe: 4.16, 3.84-4.49; phased array probe: 3.68, 3.41-3.96). CONCLUSIONS: B-line quality and quantity were rated higher using adjusted settings based on recently published evidence than when using settings that are typically employed in our institution. Our findings suggest that B-line assessment should be performed with focal zone at the level of the pleura, harmonics off, and gain increased in the far field.

CD38 deletion of human primary NK cells eliminates daratumumab-induced fratricide and boosts their effector activity.

Multiple myeloma (MM) is a plasma cell neoplasm that commonly expresses CD38. Daratumumab (DARA), a human monoclonal antibody targeting CD38, has significantly improved the outcome of patients with relapsed or refractory MM, but the response is transient in most cases. Putative mechanisms of suboptimal efficacy of DARA include downregulation of CD38 expression and overexpression of complement inhibitory proteins on MM target cells as well as DARA-induced depletion of CD38high natural killer (NK) cells resulting in crippled antibody-dependent cellular cytotoxicity (ADCC). Here, we tested whether maintaining NK cell function during DARA therapy could maximize DARA-mediated ADCC against MM cells and deepen the response. We used the CRISPR/Cas9 system to delete CD38 (CD38KO) in ex vivo expanded peripheral blood NK cells. These CD38KO NK cells were completely resistant to DARA-induced fratricide, showed superior persistence in immune-deficient mice pretreated with DARA, and enhanced ADCC activity against CD38-expressing MM cell lines and primary MM cells. In addition, transcriptomic and cellular metabolic analysis demonstrated that CD38KO NK cells have unique metabolic reprogramming with higher mitochondrial respiratory capacity. Finally, we evaluated the impact of exposure to all-trans retinoic acid (ATRA) on wild-type NK and CD38KO NK cell function and highlighted potential benefits and drawbacks of combining ATRA with DARA in patients with MM. Taken together, these findings provide proof of concept that adoptive immunotherapy using ex vivo expanded CD38KO NK cells has the potential to boost DARA activity in MM.

Drugs as technologies of the self: Enhancement and transformation in LGBTQ cultures.

The consumption of drugs has long been a mainstay of urban queer cultures and it is well-recognised that complex connections exist between sexual minoritisation and desires to chemically alter bodily experience. Yet despite evidence that rates of consumption are higher among LGBTQ populations, research exploring the gendered and sexual dynamics of these forms of consumption is limited and tends to frame such consumption as a response to stigma, marginalisation and discrimination. Against this dominant explanatory frame, this article explores the diverse experiences of LGBTQ consumers, and in so doing highlights both the pleasures and benefits of consumption, as well as potential risks and harms. Contributing to the growing body of ontopolitically oriented research that treats the materiality of drugs as emergent and contingent, we trace the ontologies of drugs, sexuality and gender that LGBTQ subjects generate through specific practices of consumption. Our analysis draws on qualitative interviews with 42 self-identified LGBTQ people from an Australian study designed to explore how sexual and gender-diverse minorities pursue particular drug effects to enhance or transform their experience of gender and/or sexuality. Our participants' accounts illuminate how drug consumption materialises in relation to sex, desire and play where it enhances pleasure, facilitates transgression and increases endurance. In the context of gender variance, our findings suggest that drug use can transform gendered experience and enable the expression of non-normative gender identities, in the process challenging gender binarism. By considering the productive role of drugs in enacting queer identities, this article treats drugs as 'technologies of the self' (Foucault 1988) and explores how drug consumption, sex and gender shape each other across a range of settings. We conclude by reflecting on the implications of our findings for research and service provision, and suggest ways of engaging LGBTQ consumers in terms that address their diverse priorities and experiences.

Evaluation of out-of-hospital cardiac arrest using transesophageal echocardiography in the emergency department.

BACKGROUND: Transesophageal echocardiography (TEE) has been proposed as a modality to assess patients in the setting of cardiac arrest, both during resuscitation care and following return of spontaneous circulation (ROSC). In this study we aimed to assess the feasibility and clinical impact of TEE during the emergency department (ED) evaluation during out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: We conducted a prospective observational study consisting of a convenience sample of adult patients presenting to the ED of an urban university medical center with non-traumatic OHCA. TEE was performed by emergency physicians following intubation. Images and clinical data were analyzed. TEE was used intra-arrest in order to assist in diagnosis, assess cardiac activity and determine CPR quality by assessing area of maximal compression (AMC), using a 4 view protocol. RESULTS: A total of 33 OHCA patients were enrolled over a one-year period, 21 patients (64%) presented with ongoing CPR and 12 (36%) presented with ROSC. The 4-view protocol was completed in 100% of the cases, with an average time from ED arrival to TEE of 12 min (min 3 max 30 SD 8.16). Fine ventricular fibrillation (VF) was recognized in 4 (12%) cases thought to be in asystole, leading to defibrillation, and 2 cases of pseudo-PEA were identified. Right ventricular (RV) dilation, was seen in 12 (57%) intraarrest cases. Intra-cardiac thrombus was found in one case, leading to thrombolysis. The AMC was identified over the aortic root or LVOT in 53% of cases. TEE was found to have diagnostic, therapeutic or prognostic clinical impact in 32 of the 33 cases (97%). CONCLUSIONS: TEE is feasible and clinically impactful during OHCA management. Resuscitative TEE may allow for characterization of cardiac activity, including identification of pseudo-PEA and fine VF, determination of reversible pathology, and optimization of CPR quality.

Evaluation of Noncommercial Ultrasound Gels for Use in Resource-Limited Settings.

OBJECTIVES: Ultrasound (US) is increasingly used in settings where commercial US gel is unavailable. This study evaluated noncommercial gel recipes compared to commercial gel. METHODS: A search for US gel formulations revealed 6 recipes. Half-strength commercial gel and a modified glucomannan recipe were also tested. Nine gels, including commercial gel, were tested in Liberia and the United States. In each session, 2 physician sonologists evaluated 9 gels on 2 models, obtaining videos from the hepatorenal space with a curvilinear transducer, the cardiac parasternal long view with a phased array transducer, and the left basilic vein with a linear transducer. The sonologists and models, who were blinded to gel identity, made independent quantitative and qualitative gel evaluations comparing the test gel to commercial gel. Two physician sonologists who were blinded to the gel identities and a US operator reviewed the images and rated their quality. An analysis of variance in repeated measures was performed to test for differences in the overall score, real-time quality, and other characteristics. Post hoc pairwise comparisons to commercial gel were performed with a Tukey-Kramer adjustment. Inter- and intra-rater reliability was calculated for the image review. RESULTS: Commercial gel earned a perfect score. Compared to commercial gel, xanthine gum gel scored highest, followed by half-strength commercial gel. Hot concentrated glucomannan and cold glucomannan gel were found to be significantly worse than commercial gel. No significant difference was found between images based on the gel used on the image review. CONCLUSIONS: No significant difference in image quality was found between commercial and noncommercial gels on US image review.

Protocol for faecal microbiota transplantation in ulcerative colitis (FMTUC): a randomised feasibility study.

BACKGROUND: The interaction of the gut microbiota with the human host is implicated in the pathogenesis of inflammatory and immunological diseases including ulcerative colitis (UC). Faecal microbiota transplantation (FMT) as a method of restoring gut microbial diversity is of increasing interest as a therapeutic approach in the management of UC. The current literature lacks consensus about the dose of FMT, route of administration and duration of response. METHODS AND ANALYSIS: This single-blinded randomised trial will explore the feasibility of FMT in 30 treatment-naïve patients with histologically confirmed distal UC limited to the recto-sigmoid region (up to 40 cm from the anal verge). This study aims to estimate the magnitude of treatment response to FMT under controlled conditions. The intervention (FMT) will be administered by rectal retention enema. It will test the feasibility of randomising patients to: (i) single FMT dose, (ii) five daily FMT doses or (iii) control (no FMT dose). All groups will receive standard antibiotic gut decontamination and bowel preparation before FMT. Recruitment will take place over a 24-month period with a 12-week patient follow-up. Trial objectives include evaluation of the magnitude of treatment response to FMT, investigation of the clinical value of metabolic phenotyping for predicting the clinical response to FMT and testing the recruitment rate of donors and patients for a study in FMT. This feasibility trial will enable an estimate of number of patients needed, help determine optimal study conditions and inform the choice of endpoints for a future definitive phase III study. ETHICS AND DISSEMINATION: The trial is approved by the regional ethics committee and is sponsored by Abertawe Bro Morgannwg University's Health Board. Written informed consent from all patients will be obtained. Serious adverse events will be reported to the sponsor. Trial results will be disseminated via peer review publication and shared with trial participants. TRIAL REGISTRATION NUMBER: ISRCTN 58082603; Pre-results.

Erratum: This Article Corrects: "Systemwide Clinical Ultrasound Program Development: An Expert Consensus Model".

[This corrects the article on p. 649 in vol. 19, PMID: 30013699.].

Systemwide Clinical Ultrasound Program Development: An Expert Consensus Model.

Clinical ultrasound (CUS) is integral to the practice of an increasing number of medical specialties. Guidelines are needed to ensure effective CUS utilization across health systems. Such guidelines should address all aspects of CUS within a hospital or health system. These include leadership, training, competency, credentialing, quality assurance and improvement, documentation, archiving, workflow, equipment, and infrastructure issues relating to communication and information technology. To meet this need, a group of CUS subject matter experts, who have been involved in institution- and/or systemwide clinical ultrasound (SWCUS) program development convened. The purpose of this paper was to create a model for SWCUS development and implementation.