Lung Ultrasound for Pleural Line Abnormalities, Confluent B-Lines, and Consolidation: Expert Reproducibility and a Method of Standardization.

OBJECTIVES: Discrete B-lines have clear definitions, but confluent B-lines, consolidations, and pleural line abnormalities are less well defined. We proposed definitions for these and determined their reproducibility using COVID-19 patient images obtained with phased array probes. METHODS: Two raters collaborated to refine definitions, analyzing disagreements on 107 derivation scans from 10 patients. Refined definitions were used by those raters and an independent rater on 1260 validation scans from 105 patients. Reliability was evaluated using intraclass correlation coefficients (ICC) or Cohen's kappa. RESULTS: The agreement was excellent between collaborating raters for B-line abnormalities, ICC = 0.97 (95% confidence interval [CI] 0.97-0.98) and pleural line to consolidation abnormalities, ICC = 0.90 (95% CI 0.87-0.92). The independent rater's agreement for B-line abnormalities was excellent, ICC = 0.97 (95% CI 0.96-0.97) and for pleural line to consolidation was good, ICC = 0.88 (95% CI 0.84-0.91). Agreement just on pleural line abnormalities was weak (collaborators, κ = 0.54, 95% CI 0.48-0.60; independent, κ = 0.54, 95% CI 0.49-0.59). CONCLUSION: With proposed definitions or via collaboration, overall agreement on confluent B-lines and pleural line to consolidation abnormalities was robust. Pleural line abnormality agreement itself was persistently weak and caution should be used interpreting pleural line abnormalities with only a phased array probe.

Point-of-Care Lung Ultrasound for COVID-19: Findings and Prognostic Implications From 105 Consecutive Patients.

BACKGROUND: The prognostic value of point-of-care lung ultrasound has not been evaluated in a large cohort of patients with COVID-19 admitted to general medicine ward in the United States. The aim of this study was to describe lung ultrasound findings and their prognostic value in patients with COVID-19 admitted to internal medicine ward. METHOD: This prospective observational study consecutively enrolled 105 hospitalized participants with COVID-19 at 2 tertiary care centers. Ultrasound was performed in 12 lung zones within 24 hours of admission. Findings were assessed relative to 4 outcomes: intensive care unit (ICU) need, need for intensive respiratory support, length of stay, and death. RESULTS: We detected abnormalities in 92% (97/105) of participants. The common findings were confluent B-lines (92%), non-homogenous pleural lines (78%), and consolidations (54%). Large confluent B-lines, consolidations, bilateral involvement, and any abnormality in ≥ 6 areas were associated with a longer hospitalization and need for intensive respiratory support. Large confluent B-lines and bilateral involvement were also associated with ICU stay. A total lung ultrasound score <5 had a negative predictive value of 100% for the need of intensive respiratory support. A higher total lung ultrasound score was associated with ICU need (median total 18 in the ICU group vs. 11 non-ICU, p = 0.004), a hospitalization ≥ 9d (15 vs 10, p = 0.016) and need for intensive respiratory support (18 vs. 8.5, P < 0.001). CONCLUSIONS: Most patients hospitalized with COVID-19 had lung ultrasound abnormalities on admission and a higher lung ultrasound score was associated with worse clinical outcomes except death. A low total lung ultrasound score (<5) had a negative predictive value of 100% for the need of intensive respiratory support. Point-of-care ultrasound can aid in the risk stratification for patients with COVID-19 admitted to general wards.

Hospitalist-Operated Compression Ultrasonography: a Point-of-Care Ultrasound Study (HOCUS-POCUS).

BACKGROUND: Venous thromboembolism includes deep vein thrombosis (DVT) and pulmonary embolism. Compression ultrasonography is the most common way to evaluate DVT and is typically performed by sonographers and interpreted by radiologists. Yet there is evidence that ultrasound examinations can be safely and accurately performed by clinicians at the bedside. OBJECTIVE: To measure the operating characteristics of hospital medicine providers performing point-of-care ultrasound (POCUS) for evaluation of DVT. DESIGN: This is a prospective cohort study enrolling a convenience sample of patients. Hospital medicine providers performed POCUS for DVT and the results were compared with the corresponding formal vascular study (FVS) interpreted by radiologists. PARTICIPANTS: Hospitalized non-ICU patients at four tertiary care hospitals for whom a DVT ultrasound was ordered. MAIN MEASURES: The primary outcomes were the sensitivity, specificity, and predictive values of the POCUS compression ultrasound compared with a FVS. The secondary outcome was the elapsed time between order and the POCUS study compared with the time the FVS was ordered to when the formal radiology report was finalized. KEY RESULTS: One hundred twenty-five limbs from 73 patients were scanned. The prevalence of DVT was 6.4% (8/125). The sensitivity of POCUS for DVT was 100% (95% CI 74-100%) and specificity was 95.8% (95% CI 91-98%) with a positive predictive value of 61.5% (95% CI 35-84%) and a negative predictive value of 100% (95% CI 98-100%). The median time from order to POCUS completion was 5.8 h versus 11.5 h median time from order until the radiology report was finalized (p = 0.001). CONCLUSION: Hospital medicine providers can perform compression-only POCUS for DVT on inpatients with accuracy similar to other specialties and settings, with results available sooner than radiology. The observed prevalence of DVT was lower than expected. POCUS may be reliable in excluding DVT but further study is required to determine how to incorporate a positive POCUS DVT result into clinical practice.

Three-Dimensional Printed Cardiac Models for Focused Cardiac Ultrasound Instruction.

BACKGROUND: Focused cardiac ultrasonography (FCU) is an increasingly integral component of routine medical training and practice. While various instructional methods have been described, few attempts have been made to incorporate a physical 3-dimensional (3D) instructional aid. OBJECTIVE: The aim of this study was to determine if a 3D printed heart model workshop for FCU instruction leads to equivalent structure recognition and scanning ability compared to traditional didactic FCU instruction. INTERVENTION: Twenty first-year medical students with no point-of-care ultrasonography experience were randomly assigned to a traditional lecture (n = 10) or a 3D printed heart model workshop (n = 10). Written examinations at 0 and 3 months as well as image acquisition at 3 months were compared. RESULTS: The median scores from the initial written structure identification in the traditional and 3D heart groups were 74% and 90%, respectively (P = 0.7). The second written exam at 3 months yielded median scores of 56% and 58% in the traditional and 3D heart groups, respectively (P = 0.8). The average scores on the image acquisition practical at 3 months were 3.3 of 5 and 2.7 of 5 (P = 0.1) in the traditional and 3D heart groups, respectively. CONCLUSIONS: Utilizing 3D heart models in an FCU workshop format results in similar skill acquisition and knowledge retention as traditional didactics. The 3D heart models are relatively inexpensive, portable, and reusable, enabling learners to practice repeatedly and at flexible intervals. The reduction in ongoing expenses and the ability to teach large groups may decrease training costs as well as the need for local faculty expertise.

The Ultrasound Hepato-Jugular Reflux: Measuring the Hepato-Jugular Reflux with Ultrasound with Comparison to Invasive Right Heart Catheterization.

BACKGROUND: Ultrasound can overcome barriers to visualizing the internal jugular vein, allowing hepato-jugular reflux and jugular venous pressure measurement. We aimed to determine operating characteristics of the ultrasound hepato-jugular reflux and ultrasound jugular venous pressure predicting right atrial and pulmonary capillary occlusion pressures. METHODS: In a prospective observational cohort at three US academic hospitals the hepato-jugular reflux and jugular venous pressure were measured with ultrasound before right heart catheterization. Receiver operating curves, likelihood ratios, and regression models were utilized to compare the ultrasound hepato-jugular reflux and ultrasound jugular venous pressure to the right atrial and pulmonary capillary occlusion pressures. RESULTS: In 99 adults undergoing right heart catheterization, an ultrasound hepato-jugular reflux had a negative likelihood ratio of 0.4 if 0 cm and a positive likelihood ratio of 4.3 if ≥ 1.5 cm for predicting a pulmonary capillary occlusion pressure ≥ 15 mmHg. Regression modeling predicting pulmonary capillary occlusion pressure was not only improved by including the ultrasound hepato-jugular reflux (P < .001), it was the more impactful predictor compared with the ultrasound jugular venous pressure (adjusted odds ratio 2.6 vs 1.2). The ultrasound hepato-jugular reflux showed substantial agreement (kappa 0.76; 95% confidence interval, 0.30-1.21), with poor agreement for the ultrasound jugular venous pressure (kappa 0.11; 95% confidence interval, -0.37-0.58). CONCLUSION: In patients undergoing right heart catheterization, the ultrasound hepato-jugular reflux is reproducible, has modest impact on the probability of a normal pulmonary capillary occlusion pressure when 0 cm, and more substantial impact on the probability of an elevated pulmonary capillary occlusion pressure when ≥ 1.5 cm.

Lung ultrasound: A comparison of image interpretation accuracy between curvilinear and phased array transducers.

Introduction: Both curvilinear and phased array transducers are commonly used to perform lung ultrasound (LUS). This study seeks to compare LUS interpretation accuracy of images obtained using a curvilinear transducer with those obtained using a phased array transducer. Methods: We invited 166 internists and trainees to interpret 16 LUS images/cineloops of eight patients in an online survey: eight curvilinear and eight phased array, performed on the same lung location. Images depicted normal lung, pneumothorax, pleural irregularities, consolidation/hepatisation, pleural effusions and B-lines. Primary outcome for each participant is the difference in image interpretation accuracy scores between the two transducers. Results: A total of 112 (67%) participants completed the survey. The mean paired accuracy score difference between the curvilinear and phased array images was 3.0% (95% CI: 0.6 to 5.4%, P = 0.015). For novices, scores were higher on curvilinear images (mean difference: 5.4%, 95% CI: 0.9 to 9.9%, P = 0.020). For non-novices, there were no differences between the two transducers (mean difference: 1.4%, 95% CI: -1.1 to 3.9%, P = 0.263). For pleural-based findings, the mean of the paired differences between transducers was higher in the novice group (estimated mean difference-in-differences: 9.5%, 95% CI: 0.6 to 18.4%; P = 0.036). No difference in mean accuracies was noted between novices and non-novices for non-pleural-based pathologies (estimated mean difference-in-differences: 0.6%, 95% CI to 5.4-6.6%; P = 0.837). Conclusions: Lung ultrasound images obtained using the curvilinear transducer are associated with higher interpretation accuracy than the phased array transducer. This is especially true for novices interpreting pleural-based pathologies.

POCUS Finding of Portal Venous Gas: An Unusual Consequence of an Amyloid Dysmotility Related Bezoar.

A 73-year-old male with a recent finding of pericardial effusion and syncope was evaluated with point of care ultrasound for recurrent effusion. A thickened left ventricle and recurrent pericardial effusion were found. Unexpectedly, on scanning the inferior vena cava (IVC), extensive portal venous gas was identified, a finding previously described as a "meteor shower". Subsequent imaging by computed tomography (CT) identified gastric edema and peri-gastric vessel gas as the source of the portal gas, attributed to a large bezoar. The bezoar was later classified as a phytobezoar and the patient was found to have both cardiac and gastrointestinal manifestations of light chain amyloidosis. The gastrointestinal amyloidosis predisposed the patient to bezoar formation owing to associated dysmotility, a rare complication of an unusual manifestation of systemic amyloid.

Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial.

BACKGROUND: Safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear. RESEARCH QUESTION: What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19? STUDY DESIGN AND METHODS: Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on < 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or ICU transfer. Using a Bayesian statistical approach, the posterior probability of superiority within each treatment arm (superiority threshold 95%) was calculated. RESULTS: The trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention-to-treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n = 139 [70 intervention, 69 usual care]), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean, 24.7%; 95% credible interval, 18.6-31.4) receiving usual care and 32 participants (posterior mean, 22.1%; 95% credible interval, 16.6-28.1) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and in 11.9% of participants in the intervention arm. INTERPRETATION: Among nonintubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04344587; URL: www. CLINICALTRIALS: gov.

Empirical comparison of tests for differential expression on time-series microarray experiments.

Methods for identifying differentially expressed genes were compared on time-series microarray data simulated from artificial gene networks. Select methods were further analyzed on existing immune response data of Boldrick et al. (2002, Proc. Natl. Acad. Sci. USA 99, 972-977). Based on the simulations, we recommend the ANOVA variants of Cui and Churchill. Efron and Tibshirani's empirical Bayes Wilcoxon rank sum test is recommended when the background cannot be effectively corrected. Our proposed GSVD-based differential expression method was shown to detect subtle changes. ANOVA combined with GSVD was consistent on background-normalized simulation data. GSVD with empirical Bayes was consistent without background correction. Based on the Boldrick et al. data, ANOVA is best suited to detect changes in temporal data, while GSVD and empirical Bayes effectively detect individual spikes or overall shifts, respectively. For methods tested on simulation data, lowess after background correction improved results. On simulation data without background correction, lowess decreased performance compared to median centering.

Empirical comparison of tests for differential expression on simulated time series microarray experiments.

Methods for identifying differential expression were compared on time series microarray data from artificial gene networks. Identifying differential expression was dependent on normalization and whether the background was removed. Loess after background correction improved results for most methods. On data without background correction median centering improved performance. We recommend Cui and Churchill's ANOVA variants on background subtracted data and Efron and Tibshirani's Empirical Bayes Wilcoxon Rank Sum test when the background cannot be removed.