School of Medicine

Coronavirus Disease 2019 (COVID-19) has had an enormous impact on both the medical community as well as society as a whole. Research on the pathogenesis and the treatment of the disease is rapidly emerging, with new observations and hypotheses appearing daily. One aspect that has been receiving increasing attention is the occurrence of both arterial and venous thrombotic complications in patients with COVID-19. We report three cases of thromboembolic complications in patients affected by COVID-19 and discuss clinical features, pathophysiology, and the proposed approaches to management of vascular complications in these patients. Through our discussion, we also urge physicians to be vigilant for any symptoms or signs suggestive of thrombosis in patients with COVID-19.

Introduction: Evaluation recommendations for patients on anticoagulant and antiplatelet (ACAP) therapy that present after mild traumatic brain injury (TBI) are controversial. At our institution, an initial noncontrast head computed tomography (HCT) is performed, with a subsequent HCT performed six hours later to exclude delayed intracranial hemorrhage (ICH). This study was performed to evaluate the yield and advisability of this approach.

Methods: We performed a retrospective review of subjects undergoing evaluation for ICH after mild TBI in patients on ACAP therapy between January of 2012 and April of 2013. We assessed for the frequency of ICH on both the initial noncontrast HCT and on the routine six-hour follow-up HCT. Additionally, chart review was performed to evaluate the clinical implications of ICH, when present, and to interrogate whether pertinent clinical and laboratory data may predict the presence of ICH prior to imaging. We used multivariate generalized linear models to assess whether presenting Glasgow Coma Score (GCS), loss of consciousness (LOC), neurological or physical examination findings, international normalized ratio, prothrombin time, partial thromboplastin time, platelet count, or specific ACAP regimen predicted ICH.

Results: 144 patients satisfied inclusion criteria. Ten patients demonstrated initial HCT positive for ICH, with only one demonstrating delayed ICH on the six-hour follow-up HCT. This patient was discharged without any intervention required or functional impairment. Presenting GCS deviation (p<0.001), LOC (p=0.04), neurological examination findings (p<0.001), clopidogrel (p=0.003), aspirin (p=0.03) or combination regimen (p=0.004) use were more commonly seen in patients with ICH.

Conclusion: Routine six-hour follow-up HCT is likely not indicated in patients on ACAP therapy, as our study suggests clinically significant delayed ICH does not occur. Additionally, presenting GCS deviation, LOC, neurological examination findings, clopidogrel, aspirin or combination regimen use may predict ICH, and, in the absence of these findings, HCT may potentially be forgone altogether. [West J Emerg Med. 2015;16(1):-0.]

ObjectiveTo evaluate quantitative ultrashort echo time (UTE) magnetic resonance imaging (MRI) biomarkers, pore-to-matrix ratio (PMR), and matrix index (MI) for assessing trabecular bone in the proximal femur across aging and osteoporosis-related bone status.Materials and methodsIn this prospective study, 92 female subjects (20–83 years) were classified into four groups based on age and DXA-derived T-scores: Young Normal (n = 19), Old Normal (n = 14), Osteopenia (n = 44), and Osteoporosis (n = 15). All participants underwent 3-T hip MRI using 3D dual-echo proton-density-weighted UTE (PD-UTE) and short TR adiabatic inversion recovery UTE (STAIR-UTE) sequences. Measurements were performed in the femoral head and neck by two readers. Interobserver agreement was assessed via intraclass correlation coefficients (ICC). Group differences were analyzed with the Kruskal–Wallis test and Holm-adjusted post hoc tests. Spearman correlation analysis and receiver operating characteristic (ROC) analysis were performed.ResultsPMR increased and MI decreased with worsening bone status. Significant differences were observed between Young Normal and all older groups (p < 0.001). PMR from the oblique-coronal total femoral head differentiated Old Normal from Osteoporosis (5.35 vs. 8.10; p < 0.05). Both PMR (ρ = −0.406 to −0.211) and MI (ρ = 0.333–0.402) significantly correlated with T-scores (all p < 0.05). The areas under the ROC curve were 0.776 (95% CI, 0.584–0.909) for PMR and 0.738 (95% CI, 0.548–0.886) for MI. Interobserver reproducibility was substantial to almost perfect (ICC: 0.73–0.99).ConclusionPMR and MI demonstrated measurable differences across age and bone status and may provide complementary information on trabecular bone characteristics.Key PointsQuestionCan ultrashort echo time (UTE) MRI biomarkers address the need for radiation-free assessment of age- and osteoporosis-related trabecular bone changes in the proximal femur?FindingsPore-to-matrix ratio (PMR) increased and matrix index (MI) decreased with aging and worsening bone status, and femoral head PMR differentiated osteoporosis from normal bone.Clinical relevanceUTE-MRI-derived PMR and MI may provide radiation-free, complementary information to dual-energy X-ray absorptiometry for assessing trabecular bone changes associated with aging and osteoporosis.Graphical Abstract

PURPOSE: Myelin integrity is increasingly recognized as a potential factor in Alzheimer's disease (AD) pathology, making accurate quantification of myelin essential for elucidating its role in the progression of the disease. This study aims to evaluate the potential of ultrashort echo time magnetization transfer (UTE-MT) imaging for assessing myelin-related alterations in an APP knock-in mouse model of AD (hereafter referred to as APPKI mice). METHOD: Eighteen APPKI mice (∼14 months; 9 females/9 males) and fourteen age-matched wild-type C57BL/6 (WT) (8 females/6 males) were scanned on a 3T Bruker scanner. Two sets of UTE-MT data (TR=80 ms, TE=0.026 ms) were acquired with an MT pulse power of 1500° (θ=1500°) and frequency offset of 2 kHz (Δf = 2 kHz) (MT_on), and with θ=500° and Δf = 50 kHz (MT_off), respectively. UTE-MT ratio (UTE-MTR) maps, calculated as (MT_off - MT_on)/MT_off, were generated for comparing APPKI and WT mice. Luxol Fast Blue (LFB) staining was employed to quantify myelin density in both the APPKI and WT groups by measuring average optical density (AOD) in the corpus callosum (CC) and hippocampus. A fear conditioning paradigm was conducted to assess cognitive function. Students' t-tests were used to compare UTE-MTR and AOD values, as well as freezing behavior between APPKI and WT groups. Furthermore, Pearson's correlation was used to quantify the association between UTE-MTR and AOD measurements. RESULTS: The UTE-MTR values showed a significant reduction in the APPKI group compared to the WT group in both the CC (0.401±0.010 vs. 0.416±0.006, p < 0.0001) and the hippocampus (0.334±0.012 vs. 0.343±0.006, p < 0.05). Histological validation via LFB staining confirmed these findings, revealing a significantly lower AOD in APPKI mice across the same regions (p < 0.05). Pearson correlation analysis demonstrated a positive association between UTE-MTR and AOD in the corpus callosum for the APPKI group (r = 0.8174, P = 0.0132), while no significant correlation was observed in the hippocampus in either group. Additionally, APPKI mice exhibited significant impairments in fear learning, contextual memory recall, and cue memory recall compared with WT controls (p < 0.05), further supporting myelin-related cognitive deficits in this model. CONCLUSION: Our findings suggest that UTE-MTR is a promising tool for detecting myelin-related changes in APPKI mice, with potential to monitor myelin alterations and cognitive deficits associated with AD pathological progression and to evaluate therapeutic efficacy in AD research.

BACKGROUND: Swimming-induced pulmonary edema (SIPE) causes acute respiratory symptoms during strenuous water activities and has been described in military trainees and open-water swimmers. Although SIPE typically presents bilaterally, asymmetric cases may relate to swimmer position. Chest x-ray (CXR) and lung ultrasound (LUS) are used in the clinical evaluation of SIPE, but whether they show similar edema lateralization patterns relative to swimmer position is unclear. RESEARCH QUESTIONS: Is edema laterality in SIPE associated with dependent body position during combat sidestroke (CSS)? When CXR and LUS are obtained during the same SIPE episode, do they show similar edema lateralization patterns? STUDY DESIGN AND METHODS: We retrospectively analyzed 91 SIPE episodes in 82 maritime trainees. Clinical records, CXR, and LUS were reviewed to characterize edema laterality on a five-point ordinal scale. Agreement between CXR and LUS laterality scores was assessed with Cohen's weighted kappa. Associations between imaging laterality and dependent body position during CSS were evaluated using Fisher's exact test, with Cramér's V to quantify effect size. RESULTS: Imaging data were available for 89 episodes with CXR, 49 with LUS, and 47 with both. Pulmonary edema laterality was significantly associated with dependent body position for both modalities (p < 0.001; Cramér's V = 0.41). CXR and LUS showed moderate agreement (κ = 0.58, p < 0.001) using three- and five-point scales, with agreement within ± 1 category in 98% and 81% of paired comparisons, respectively. INTERPRETATION: Among trainees who developed SIPE while performing CSS, edema laterality corresponded with the swimmer's dependent body position. CXR and LUS showed similar lateralization patterns with moderate agreement when obtained during the same SIPE episode. These findings support LUS as a practical tool in field settings for characterizing edema distribution when radiography is unavailable, while CXR remains important for evaluating central abnormalities and alternative pulmonary diagnoses.

Abstract Rationale Swimming-induced pulmonary edema (SIPE) is a condition characterized by acute pulmonary symptoms during strenuous water activities, notably affecting military trainees and open-water swimmers. Unilateral pulmonary edema, often on the dependent side during lateral or side-down positions, suggests gravitational and regional perfusion influences. While chest x-ray (CXR) and lung ultrasound (LUS) are utilized for diagnosis, their comparative effectiveness, particularly in detecting lateralization, remains underexplored. The primary aims of this study are to compare CXR and LUS findings in patients with SIPE, determine whether the dependent side in water while performing combat sidestroke (CSS) correlates with unilateral imaging findings, and explore any differences in detection between these modalities. Addressing these objectives may improve diagnostic precision, deepen understanding of SIPE’s underlying mechanisms, and guide more effective management of affected individuals in aquatic and military training environments. Methods A retrospective review of 82 maritime trainees with SIPE which assessed clinical, radiographic, and ultrasound data to confirm pulmonary edema and its laterality. This review also examines the relationship between side-down positioning during sidestroke and imaging abnormalities. Chest radiographs and lung ultrasounds were scored with a 5-point Likert scale for side predilection. Their concordance was analyzed alongside the influence of body position on chest imaging findings. The two Likert scales were compared for association, agreement, and directionality using Chi squared, Cohen’s Kappa, and Spearman’s rank correlation. Results A significant association was observed between CXR and LUS lateralization scores (χ²=21.45, p<.001), with moderate agreement (κ = 0.57) and a strong positive correlation (ρ = 0.60). When analyzing the full five-point scale, agreement improved (κ = 0.59, ρ = 0.63) (Table 1). A significant association was seen between lung edema lateralization on imaging and body position (p < 0.001). Conclusion This study demonstrates a moderate to strong concordance between chest radiography and lung ultrasound in detecting pulmonary edema lateralization in SIPE patients. Both modalities demonstrate significant correlation between dependent side-down positioning and unilateral edema. The study’s focus on lateralization underscores the importance of positional factors during water activities. Recognizing dependence-related asymmetry in pulmonary edema suggests that positional strategies, such as switching sides during CSS, could help reduce SIPE risk. While LUS is a valuable tool in the evaluation and diagnosis of SIPE, its limitations in identifying or characterizing more centrally located lesions or alternative pathologies should be acknowledged, as these may require complementary imaging modalities for comprehensive assessment. This abstract is funded by: None

Importance: Millions of children worldwide are experiencing prolonged symptoms after SARS-CoV-2 infection, yet social risk factors for developing long COVID are largely unknown. As child health is influenced by the environment in which they live and interact, adverse social determinants of health (SDOH) may contribute to the development of pediatric long COVID. Objective: To identify whether adverse SDOH are associated with increased odds of long COVID in school-aged children and adolescents in the US. Design, Setting, and Participants: This cross-sectional analysis of a multicenter, longitudinal, meta-cohort study encompassed 52 sites (health care and community settings) across the US. School-aged children (6-11 years; n = 903) and adolescents (12-17 years; n = 3681) with SARS-CoV-2 infection history were included. Those with an unknown date of first infection, history of multisystem inflammatory syndrome in children, or symptom surveys with less than 50% of questions completed were excluded. Participants were recruited via health care systems, long COVID clinics, fliers, websites, social media campaigns, radio, health fairs, community-based organizations, community health workers, and existing research cohorts from March 2022 to August 2024, and surveys were completed by caregivers between March 2022 and August 2024. Exposure: Twenty-four individual social determinant of health factors were grouped into 5 Healthy People 2030 domains: economic stability, social and community context, caregiver education access and quality, neighborhood and built environment, and health care access and quality. Latent classes were created within each domain and used in regression models. Main Outcomes and Measures: Presence of long COVID using caregiver-reported, symptom-based, age-specific research indices. Results: The mean (SD) age among 4584 individuals included in this study was 14 (3) years, and 2330 (51%) of participants were male. The number of latent classes varied by domain; the reference group was the class with the least adversity. In unadjusted analyses, most classes in each domain were associated with higher odds of long COVID. After adjusting for many factors, including age group, sex, timing of infection, referral source, and other social determinant of health domains, economic instability characterized by difficulty covering expenses, poverty, receipt of government assistance, and food insecurity were associated with an increased risk of having long COVID (class 2 adjusted odds ratio [aOR], 1.57; 95% CI, 1.18-2.09; class 4 aOR, 2.39; 95% CI, 1.73-3.30); economic instability without food insecurity (class 3) was not (aOR, 0.93; 95% CI, 0.70-1.23). Poorer social and community context (eg, high levels of discrimination and low social support) was also associated with long COVID (aOR, 2.17; 95% CI, 1.77-2.66). Sensitivity analyses stratified by age group and adjusted for race and ethnicity did not alter or attenuate these results. Conclusions and Relevance: In this study, economic instability that included food insecurity and poor social and community context were associated with greater odds of pediatric long COVID. Those with food security, despite experiencing other economic challenges, did not have greater odds of long COVID. Further study is needed to determine if addressing SDOH factors can decrease the rate of pediatric long COVID.

Ultrasound is the standard first-line imaging modality for hepatocellular carcinoma (HCC) screening; however, in certain patient populations, sensitivity is limited, and thus alternative strategies are needed in these patients. This article will provide an overview of MR imaging and computed tomography (CT) for the screening of HCC, with an emphasis on abbreviated MR imaging protocols and recent advancements in CT technology (dual energy and photon-counting CT).

PURPOSE: Ultrashort echo time (UTE) MRI enables direct imaging of cortical bone and quantification of its water compartments via bicomponent T₂* modeling. However, conventional approaches require multiple separate dual-echo scans due to limitations in gradient power. This approach is prone to inter-scan inconsistencies such as motion and signal drift, which degrade fitting accuracy. This study proposes an interleaved dual-echo acquisition sequence that acquires multiple echo time (TE) images in a single scan to improve bicomponent T₂* quantification in cortical bone. METHODS: The proposed UTE sequence utilizes interleaved dual-echo acquisitions with flexible TE spacings. This sequence was tested on five healthy subjects' tibial midshafts and compared to conventional separate dual-echo scans with and without image registration. Bicomponent T₂* modeling was performed, and fitting accuracy was evaluated using normalized-root-mean-squared error (NRMSE). Three subjects were scanned three times to evaluate the scan repeatability. RESULTS: The interleaved method significantly reduced NRMSE (3.2% ± 2.3% vs. 6.2% ± 3.1%, p = 0.0231) and yielded lower and more stable T₂* (T_2s*; 0.50 ± 0.10 ms vs. 0.76 ± 0.13 ms, p < 0.0001) and fraction (F_s; 78.2 ± 5.1 vs. 84.2% ± 7.1%, p = 0.0006) of short T₂ components compared to separate scans without registration. Image registration had a minimal improvement on mapping results for separate scans. Parameter maps from the interleaved scans confirmed more homogeneous distributions of T_2s* and F_s with lower fitting errors. The much lower coefficients of variance of the interleaved scans demonstrated improved repeatability compared with separate scans. CONCLUSION: The proposed interleaved UTE dual-echo sequence improves the robustness of bicomponent T₂* mapping of the cortical bone by reducing inter-scan inconsistencies.