Assessment of Cardiac, Vascular, and Pulmonary Pathobiology In Vivo During Acute COVID-19.

Background Acute COVID-19-related myocardial, pulmonary, and vascular pathology and how these relate to each other remain unclear. To our knowledge, no studies have used complementary imaging techniques, including molecular imaging, to elucidate this. We used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID-19. Specifically, we investigated the presence of myocardial inflammation and its association with coronary artery disease, systemic vasculitis, and pneumonitis. Methods and Results Consecutive patients presenting with acute COVID-19 were prospectively recruited during hospital admission in this cross-sectional study. Imaging involved computed tomography coronary angiography (identified coronary disease), cardiac 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/computed tomography (identified vascular, cardiac, and pulmonary inflammatory cell infiltration), and cardiac magnetic resonance (identified myocardial disease) alongside biomarker sampling. Of 33 patients (median age 51 years, 94% men), 24 (73%) had respiratory symptoms, with the remainder having nonspecific viral symptoms. A total of 9 patients (35%, n=9/25) had cardiac magnetic resonance-defined myocarditis. Of these patients, 53% (n=5/8) had myocardial inflammatory cell infiltration. A total of 2 patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with and without myocarditis (8.4 ng/L [interquartile range, IQR: 4.0-55.3] versus 3.5 ng/L [IQR: 2.5-5.5]; P=0.07) or myocardial cell infiltration (4.4 ng/L [IQR: 3.4-8.3] versus 3.5 ng/L [IQR: 2.8-7.2]; P=0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR: 5%-31%) and 11% (IQR: 7%-18%), respectively. Neither were associated with the presence of myocarditis. Conclusions Myocarditis was present in a third patients with acute COVID-19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is nonischemic and not attributable to a vasculitic process. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN12154994.

The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.

BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (ß√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (ß√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (ß√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (ß√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.

A Curriculum Model for Multidisciplinary Training of Midwife Sonographers in a Low Resource Setting.

In many low-resource settings, less than 5% of pregnant women can access ultrasound during pregnancy. Thus, gestational age is often difficult to determine, multiple pregnancies are diagnosed late and foetal and pregnancy-related anomalies can go undetected. A pilot solution was designed beyond the traditional approach of increasing numbers of qualified radiologists, gynaecologists and sonographers. An innovative Human Resource for Health (HRH) task sharing, and maternal child health (MCH) workforce training and capacity building initiative was designed, involving development and testing of a curriculum to train midwife sonographers via a teleradiology innovation platform and a partnership between specialist radiologists, sonographers and midwives. The setting was a tertiary-level private university hospital in Nairobi with implementation in three outreach locations. Direct oversight, support and supervision of specialist radiologists and ultrasonographers effectively addressed issues of quality and safety across the 3-week training period and project implementation. Concepts from sociocultural learning theory informed an initial interactive e-learning module for each midwife at their respective site. Midwives were introduced to ultrasound equipment with a series of didactic and interactive lectures delivered by an expert sonographer at the tertiary hospital teaching site. Lectures were supported by hands-on practical experience, role modelling and mentoring over a four-week period. Assessments included both written examination and practical assessment with an exit examination requiring demonstration of competency in both written and practical format. Final confirmation of scanning accuracy was confirmed with post-delivery verification of results. The pilot was highly successful with an image interpretation accuracy of 99.63% for the midwives. Lessons from this initiative provides guidance in the curriculum development process along with a curriculum outline; pedagogical framework; teaching methods; assessment processes; credentialing; resourcing; and other considerations in scaling up the program. Importantly, the paper details processes for maintaining a high level of quality control and patient safety.

CardiOvaScular Mechanisms In Covid-19: methodology of a prospective observational multimodality imaging study (COSMIC-19 study).

BACKGROUND: 8-28% of patients infected with COVID-19 have evidence of cardiac injury, and this is associated with an adverse prognosis. The cardiovascular mechanisms of injury are poorly understood and speculative. We aim to use multimodality cardiac imaging including cardiac magnetic resonance (CMR) imaging, computed tomography coronary angiography (CTCA) and positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG-PET/CT) to identify the cardiac pathophysiological mechanisms related to COVID-19 infections. METHODS: This is a single-centre exploratory observational study aiming to recruit 50 patients with COVID-19 infection who will undergo cardiac biomarker sampling. Of these, 30 patients will undergo combined CTCA and 18F-FDG-PET/CT, followed by CMR. Prevalence of obstructive and non-obstructive atherosclerotic coronary disease will be assessed using CTCA. CMR will be used to identify and characterise myocardial disease including presence of cardiac dysfunction, myocardial fibrosis, myocardial oedema and myocardial infarction. 18F-FDG-PET/CT will identify vascular and cardiac inflammation. Primary endpoint will be the presence of cardiovascular pathology and the association with troponin levels. DISCUSSION: The results of the study will identify the presence and modality of cardiac injury associated COVID-19 infection, and the utility of multi-modality imaging in diagnosing such injury. This will further inform clinical decision making during the pandemic. TRIAL REGISTRATION: This study has been retrospectively registered at the ISRCTN registry (ID ISRCTN12154994) on 14th August 2020. Accessible at https://www.isrctn.com/ISRCTN12154994.

Medical Student Ultrasound Education, a WFUMB Position Paper, Part II. A consensus statement of ultrasound societies.

Ultrasound is becoming a fundamental first-line diagnostic tool for most medical specialties and an innovative tool to teach anatomy, physiology and pathophysiology to undergraduate and graduate students. However, availability of structured training programs during medical school is lagging behind and many physicians still acquire all their ultrasound skills during postgraduate training.There is wide variation in medical student ultrasound education worldwide. Sharing successful educational strategies from early adopter medical schools and learning from leading education programs should advance the integration of ultrasound into the university medical school curricula. In this overview, we present current approaches and suggestions by ultrasound societies concerning medical student educa-tion throughout the world. Based on these examples, we formulate a consensus statement with suggestions on how to integrate ultrasound teaching into the preclinical and clinical medical curricula.

Medical Student Ultrasound Education: A WFUMB Position Paper, Part I.

The introduction of ultrasound into medical student education is well underway in many locations around the world, but is still in its infancy or has yet to begin in others. Proper incorporation of ultrasound education into medical training requires planning and resources, both capital and human. In this article, we discuss the state of the art of ultrasound in medical education throughout the world, as well as various methodologies utilized to improve student education and to incorporate ultrasound into every facet of training. Experiences from various educational systems and available evidence regarding the impact of ultrasound education are summarized. Representing multiple societies and specialties throughout the world, we discuss established modern as well as novel education structures and different successful approaches.

Difficulties in diagnosis of Riedel's thyroiditis on aspiration cytology: A case report and brief review of the literature.

Riedel's thyroiditis (RT) is a rare disorder characterized by extensive fibrosis extending to the extrathyroidal tissues. An elderly male presented with diffuse moderate thyromegaly and hoarseness of voice for two years. Radiology showed extrathyroidal extension around trachea with compression and deviation suggestive of malignancy. Thyroid was hard and non tender. Ultrasound guided Fine Needle Aspiration (FNA) from multiple foci on both sides using thinner needle yielded moderately cellularity showing follicular cells, lymphoplasmacytic infiltrate, scant colloid and fibrous tissue fragments. Hurthle cells were absent. Adiagnosis of chronic thyroiditis was given with possibility of RT in view of clinical and radiological findings. A core biopsy showed similar picture as cytology. Guided FNA from multiple foci using thinner needle helped to obtain adequate material allowing a confident diagnosis. This case adds to the meagre literature available on the cytologic diagnosis of RT and highlights the diagnostic challenge due to suspicious radiology findings.

Collaborative task-sharing to enhance the Point-Of-Care Ultrasound (POCUS) access among expectant women in Kenya: The role of midwife sonographers.

Unrealized maternal and child health goals continue to challenge Kenya where adverse outcomes remain high and diagnostic services are limited. The acute shortage of doctors and radiographers requires alternate human resources for health (HRH) with the ability to identify risk factors in pregnancy through Point-Of-Care Ultrasound (POCUS). A specialist radiologist and ultrasonography team partnered with midwives to adopt interprofessional task sharing and capacity building. Faculty from the Radiology Department of our hospital designed and implemented the project which was carried out at three outreach health service centres. Designing and implementing a training model to skill midwife sonographers with the capacity to accurately identify risk factors in pregnancy is an effective model to increase POCUS access. A collaborative task sharing model focused on training quality, validation of results, tracking of errors and specialist level clinical supervision yielded a safe and scalable model of HRH capacity building. Programme evaluation, verification of outcomes and dissemination of results were all monitored. The project was a successful HRH task sharing and interprofessional learning initiative involving task sharing a clearly defined suite of sonographer competencies with participating midwives. The programme increased POCUS accessibility at the three outreach clinics with proven outcomes in the early detection and referral of risk factors in pregnancy.

Ethnicity and breast cancer characteristics in Kenya.

PURPOSE: There are no published data from specific regions of sub-Saharan Africa describing the clinical and pathological characteristics and molecular subtypes of invasive breast cancer by ethnic group. The purpose of this study was to investigate these characteristics among the three major ethno-cultural groupings in Kenya. METHODS: The study included women with pathologically confirmed breast cancer diagnosed between March 2012 and May 2015 at 11 hospitals throughout Kenya. Sociodemographic, clinical, and reproductive data were collected by questionnaire, and pathology review and immunohistochemistry were performed centrally. RESULTS: The 846 cases included 661 Bantus (78.1%), 143 Nilotes (16.9%), 19 Cushites (2.3%), and 23 patients of mixed ethnicity (2.7%). In analyses comparing the two major ethnic groups, Bantus were more educated, more overweight, had an older age at first birth, and had a younger age at menopause than Nilotes (p < 0.05 for all comparisons). In analyses restricted to definitive surgery specimens, there were no statistically significant differences in tumor characteristics or molecular subtypes by ethnicity, although the Nilote tumors tended to be larger (OR for ≥ 5 cm vs. < 2 cm: 3.86, 95% CI 0.77, 19.30) and were somewhat more likely to be HER2 enriched (OR for HER2 enriched vs. Luminal A/B: 1.41, 95% CI 0.79, 2.49). CONCLUSION: This case series showed no significant differences in breast cancer tumor characteristics or molecular subtypes, but significant differences in sociodemographic characteristics and reproductive factors, among the three major ethnic groups in Kenya. We suggest further evaluation of ethnic differences in breast cancer throughout the genetically and culturally diverse populations of sub-Saharan Africa.

Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide.

BACKGROUND: Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known. METHODS AND FINDINGS: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (-0.46 cm [95% CI: -0.53, -0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was -0.24 cm (95% CI: -0.34, -0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (-0.38 cm [95% CI: -0.44, -0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature. CONCLUSIONS: Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction.

Training Midwives to Perform Basic Obstetric Point-of-Care Ultrasound in Rural Areas Using a Tablet Platform and Mobile Phone Transmission Technology-A WFUMB COE Project.

Point-of-care ultrasound (POCUS) has become a topical subject and can be applied in a variety of ways with differing outcomes. The cost of all diagnostic procedures including obstetric ultrasound examinations is a major factor in the developing world and POCUS is only useful if it can be equated to good outcomes at a lower cost than a routine obstetric examination. The aim of this study was to assess a number of processes including accuracy of images and reports generated by midwives, performance of a tablet-sized ultrasound scanner, training of midwives to complete ultrasounds, teleradiology solution transmissions of images via internet, review of images by a radiologist, communication between midwife and radiologist, use of this technique to identify high-risk patients and improvement of the education and teleradiology model components. The midwives had no previous experience in ultrasound. They were stationed in rural locations where POCUS was available for the first time. After scanning the patients, an interim report was generated by the midwives and sent electronically together with all images to the main hospital for validation. Unique software was used to send lossless images by mobile phone using a modem. Transmission times were short and quality of images transmitted was excellent. All reports were validated by two experienced radiologists in our department and returned to the centers using the same transmission software. The transmission times, quality of scans, quality of reports and other parameters were recorded and monitored. Analysis showed excellent correlation between provisional and validated reports. Reporting accuracy of scans performed by the midwives was 99.63%. Overall flow turnaround time (from patient presentation to validated report) was initially 35 min but reduced to 25 min. The unique mobile phone transmission was faultless and there was no degradation of image quality. We found excellent correlation between final outcomes of the pregnancies and diagnoses on the basis of reports generated by the midwives. Only 1 discrepancy was found in the midwives' reports. Scan results versus actual outcomes revealed 2 discrepancies in the 20 patients identified as high risk. In conclusion, we found that it is valuable to train midwives in POCUS to use an ultrasound tablet device and transmit images and reports via the internet to radiologists for review of accuracy. This focus on the identification of high-risk patients can be valuable in a remote healthcare facility.

Antenatal Umbilical Coiling Index and Newborn Outcomes: Cohort Study.

OBJECTIVES: We aimed to test the predictive value of antenatal umbilical coiling index (aUCI) among a prospectively recruited cohort of antenatal women. METHODS: Women with singleton pregnancies were recruited at their second-trimester scan. Images of the umbilical cord were used to calculate the aUCI. Pregnancy and birth outcomes were recorded and statistical associations between aUCI and small for gestational age (SGA) using international standard birth weight centiles and preterm birth were investigated (n = 430). RESULTS: aUCI results were consistent with the literature and showed good reproducibility between observers. Abnormal aUCI was not associated with SGA, but there was a statistical association with preterm birth (odds ratio 3.3 (95% confidence interval 1.4-7.7, P = 0.003). The sensitivity, specificity, and positive and negative predictive values for preterm birth were 47.6%, 76.9%, 9.6%, and 96.6%, respectively. CONCLUSIONS: The coiling index is unlikely to be useful in clinical practice as a screening tool for preterm birth owing to limited predictive value. We exclude a statistically or clinically significant association between abnormal coiling and SGA.

Opportunities and Challenges in Realizing Universal Access to Obstetric Ultrasound in Sub-Saharan Africa.

The potential benefits of obstetric ultrasound have yet to be fully realized in sub-Saharan Africa (SSA), despite the region bearing the greatest burden of poor perinatal outcomes. We reviewed the literature for challenges and opportunities of universal access to obstetric ultrasound and explored what is needed to make such access an integral component of maternity care in order to address the massive burden of perinatal morbidity and mortality in SSA. Original peer-reviewed literature was searched in various electronic databases using a 'realist' approach. While the available data were inconclusive, they identify many opportunities for potential future research on the subject within the region that can help build a strong case to justify the provision of universal access to ultrasound as an integral component of comprehensive antenatal care.

Thyroid Ultrasound: State of the Art. Part 2 - Focal Thyroid Lesions.

Accurate differentiation of focal thyroid nodules (FTL) and thyroid abnormalities is pivotal for proper diagnostic and therapeutic work-up. In these two part articles, the role of ultrasound techniques in the characterization of FTL and evaluation of diffuse thyroid diseases is described to expand on the recently published World Federation in Ultrasound and Medicine (WFUMB) thyroid elastography guidelines and review how this guideline fits into a complete thyroid ultrasound exam.

Thyroid Ultrasound: State of the Art Part 1 - Thyroid Ultrasound reporting and Diffuse Thyroid Diseases.

Accurate differentiation of focal thyroid nodules (FTL) and thyroid abnormalities is pivotal for proper diagnostic and therapeutic work-up. In these two part articles, the role of ultrasound techniques in the characterization of FTL and evaluation of diffuse thyroid diseases is described to expand on the recently published World Federation in Ultrasound and Medicine (WFUMB) thyroid elastography guidelines and review how this guideline fits into a complete thyroid ultrasound exam.

Ultrasound shear wave elastography and liver fibrosis: A Prospective Multicenter Study.

AIM: To assess the accuracy of shear wave elastography (SWE) alone and in combination with aminotransferase platelet ratio index (APRI) score in the staging of liver fibrosis. METHODS: A multicenter prospective study was conducted to assess the accuracy of SWE (medians) and APRI to predict biopsy results. The analysis focused on distinguishing the different stages of liver disease, namely, F0 from F1-4, F0-1 from F2-4, F0-2 from F3-4 and F0-3 from F4; F0-F1 from F2-F4 being of primary interest. The area under the receiver operating characteristic (AUROC) curve was computed using logistic regression model. The role of age, gender and steatosis was also assessed. RESULTS: SWE alone accurately distinguished F0-1 from F2-4 with a high probability. The AUROC using SWE alone was 0.91 compared to 0.78 for using the APRI score alone. The APRI score, when used in conjunction with SWE, did not make a significant contribution to the AUROC. SWE and steatosis were the only significant predictors that differentiated F0-1 from F2-4 with an AUROC of 0.944. CONCLUSION: Our study validates the use of SWE in the diagnosis and staging of liver fibrosis. Furthermore, the probability of a correct diagnosis is significantly enhanced with the addition of steatosis as a prognostic factor.

Point of Care Ultrasound: A WFUMB Position Paper.

Over the last decade, the use of portable ultrasound scanners has enhanced the concept of point of care ultrasound (PoC-US), namely, "ultrasound performed at the bedside and interpreted directly by the treating clinician." PoC-US is not a replacement for comprehensive ultrasound, but rather allows physicians immediate access to clinical imaging for rapid and direct solutions. PoC-US has already revolutionized everyday clinical practice, and it is believed that it will dramatically change how ultrasound is applied in daily practice. However, its use and teaching are different from continent to continent and from country to country. This World Federation for Ultrasound in Medicine and Biology position paper discusses the current status and future perspectives of PoC-US. Particular attention is given to the different uses of PoC-US and its clinical significance, including within emergency and critical care medicine, cardiology, anesthesiology, rheumatology, obstetrics, neonatology, gynecology, gastroenterology and many other applications. In the future, PoC-US will be more diverse than ever and be included in medical student training.

WFUMB Guidelines and Recommendations on the Clinical Use of Ultrasound Elastography: Part 4. Thyroid.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has produced guidelines for the use of elastography techniques including basic science, breast and liver. Here we present elastography in thyroid diseases. For each available technique, procedure, reproducibility, results and limitations are analyzed and recommendations are given. Finally, recommendations are given based on the level of evidence of the published literature and on the WFUMB expert group's consensus. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of thyroid diseases.

Mammographic density assessed on paired raw and processed digital images and on paired screen-film and digital images across three mammography systems.

BACKGROUND: Inter-women and intra-women comparisons of mammographic density (MD) are needed in research, clinical and screening applications; however, MD measurements are influenced by mammography modality (screen film/digital) and digital image format (raw/processed). We aimed to examine differences in MD assessed on these image types. METHODS: We obtained 1294 pairs of images saved in both raw and processed formats from Hologic and General Electric (GE) direct digital systems and a Fuji computed radiography (CR) system, and 128 screen-film and processed CR-digital pairs from consecutive screening rounds. Four readers performed Cumulus-based MD measurements (n = 3441), with each image pair read by the same reader. Multi-level models of square-root percent MD were fitted, with a random intercept for woman, to estimate processed-raw MD differences. RESULTS: Breast area did not differ in processed images compared with that in raw images, but the percent MD was higher, due to a larger dense area (median 28.5 and 25.4 cm2 respectively, mean √dense area difference 0.44 cm (95% CI: 0.36, 0.52)). This difference in √dense area was significant for direct digital systems (Hologic 0.50 cm (95% CI: 0.39, 0.61), GE 0.56 cm (95% CI: 0.42, 0.69)) but not for Fuji CR (0.06 cm (95% CI: -0.10, 0.23)). Additionally, within each system, reader-specific differences varied in magnitude and direction (p < 0.001). Conversion equations revealed differences converged to zero with increasing dense area. MD differences between screen-film and processed digital on the subsequent screening round were consistent with expected time-related MD declines. CONCLUSIONS: MD was slightly higher when measured on processed than on raw direct digital mammograms. Comparisons of MD on these image formats should ideally control for this non-constant and reader-specific difference.