FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation.

SARS-CoV-2 can cause acute respiratory distress and death in some patients1. Although severe COVID-19 is linked to substantial inflammation, how SARS-CoV-2 triggers inflammation is not clear2. Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D, leading to inflammatory death (pyroptosis) and the release of potent inflammatory mediators3. Here we show that about 6% of blood monocytes of patients with COVID-19 are infected with SARS-CoV-2. Monocyte infection depends on the uptake of antibody-opsonized virus by Fcγ receptors. The plasma of vaccine recipients does not promote antibody-dependent monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in the supernatants of cultures of infected monocytes. Instead, infected cells undergo pyroptosis mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and gasdermin D. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from lung autopsies from patients with COVID-19 have activated inflammasomes. Taken together, these findings suggest that antibody-mediated SARS-CoV-2 uptake by monocytes and macrophages triggers inflammatory cell death that aborts the production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis.

Effects of Low-Level Light Therapy on Resting-State Connectivity Following Moderate Traumatic Brain Injury: Secondary Analyses of a Double-blinded Placebo-controlled Study.

Background Low-level light therapy (LLLT) has been shown to modulate recovery in patients with traumatic brain injury (TBI). However, the impact of LLLT on the functional connectivity of the brain when at rest has not been well studied. Purpose To use functional MRI to assess the effect of LLLT on whole-brain resting-state functional connectivity (RSFC) in patients with moderate TBI at acute (within 1 week), subacute (2-3 weeks), and late-subacute (3 months) recovery phases. Materials and Methods This is a secondary analysis of a prospective single-site double-blinded sham-controlled study conducted in patients presenting to the emergency department with moderate TBI from November 2015 to July 2019. Participants were randomized for LLLT and sham treatment. The primary outcome of the study was to assess structural connectivity, and RSFC was collected as the secondary outcome. MRI was used to measure RSFC in 82 brain regions in participants during the three recovery phases. Healthy individuals who did not receive treatment were imaged at a single time point to provide control values. The Pearson correlation coefficient was estimated to assess the connectivity strength for each brain region pair, and estimates of the differences in Fisher z-transformed correlation coefficients (hereafter, z differences) were compared between recovery phases and treatment groups using a linear mixed-effects regression model. These analyses were repeated for all brain region pairs. False discovery rate (FDR)-adjusted P values were computed to account for multiple comparisons. Quantile mixed-effects models were constructed to quantify the association between the Rivermead Postconcussion Symptoms Questionnaire (RPQ) score, recovery phase, and treatment group. Results RSFC was evaluated in 17 LLLT-treated participants (median age, 50 years [IQR, 25-67 years]; nine female), 21 sham-treated participants (median age, 50 years [IQR, 43-59 years]; 11 female), and 23 healthy control participants (median age, 42 years [IQR, 32-54 years]; 13 male). Seven brain region pairs exhibited a greater change in connectivity in LLLT-treated participants than in sham-treated participants between the acute and subacute phases (range of z differences, 0.37 [95% CI: 0.20, 0.53] to 0.45 [95% CI: 0.24, 0.67]; FDR-adjusted P value range, .010-.047). Thirteen different brain region pairs showed an increase in connectivity in sham-treated participants between the subacute and late-subacute phases (range of z differences, 0.17 [95% CI: 0.09, 0.25] to 0.26 [95% CI: 0.14, 0.39]; FDR-adjusted P value range, .020-.047). There was no evidence of a difference in clinical outcomes between LLLT-treated and sham-treated participants (range of differences in medians, -3.54 [95% CI: -12.65, 5.57] to -0.59 [95% CI: -7.31, 8.49]; P value range, .44-.99), as measured according to RPQ scores. Conclusion Despite the small sample size, the change in RSFC from the acute to subacute phases of recovery was greater in LLLT-treated than sham-treated participants, suggesting that acute-phase LLLT may have an impact on resting-state neuronal circuits in the early recovery phase of moderate TBI. ClinicalTrials.gov Identifier: NCT02233413 © RSNA, 2024 Supplemental material is available for this article.

Accuracy of Patient-Collected Vital Signs.

Introduction: Telehealth has emerged as an important clinical setting for managing acute respiratory tract infections (ARIs), potentially reducing emergency department and urgent care overcrowding, and reducing nosocomial transmission. Many current algorithms for ARI management incorporate information on patient vital signs. However, the accuracy of vital signs collected by patients using readily available home devices and techniques has not been studied. Methods: A cross-sectional sample of patients seen for urgent conditions at a hospital emergency and urgent care center were given instructions and low-cost, readily available devices to collect their vital signs. A trained research coordinator collected a parallel set of vital signs using standard hospital equipment, serving as the gold standard. We analyzed the performance of patient-collected vital signs compared with vital signs collected by a trained research coordinator. Results: A total of 300 patients completed the study. Patient-collected vital signs were highly specific for traditional levels of abnormalities (HR >100 beats per min, RR >24 breaths per min, temperature >100.4 degrees Fahrenheit, oxygen saturation <94 percent); however, sensitivity was poor for elevated heart rate by pulse estimation (25%) and elevated respiratory rate (60%). Heart rate and oxygen saturation by pulse oximeter and oral temperature had higher sensitivity. Conclusions: Vital signs measured and provided by patients are not uniformly accurate, particularly when using manual techniques rather than automated devices. Telehealth algorithms that rely on these values could provide incorrect triage and management advice.

Alveolar, Endothelial, and Organ Injury Marker Dynamics in Severe COVID-19.

Rationale: Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. Objectives: To describe alveolar and endothelial injury dynamics and associations with COVID-19 severity, cardiorenovascular injury, and outcomes. Methods: This single-center observational study enrolled patients with COVID-19 requiring respiratory support at emergency department presentation. More than 40 markers of alveolar (including receptor for advanced glycation endproducts [RAGE]), endothelial (including angiopoietin-2), and cardiorenovascular injury (including renin, kidney injury molecule-1, and troponin-I) were serially compared between invasively and spontaneously ventilated patients using mixed-effects repeated-measures models. Ventilatory ratios were calculated for intubated patients. Associations of biomarkers with modified World Health Organization scale at Day 28 were determined with multivariable proportional-odds regression. Measurements and Main Results: Of 225 patients, 74 (33%) received invasive ventilation at Day 0. RAGE was 1.80-fold higher in invasive ventilation patients at Day 0 (95% confidence interval [CI], 1.50-2.17) versus spontaneous ventilation, but decreased over time in all patients. Changes in alveolar markers did not correlate with changes in endothelial, cardiac, or renal injury markers. In contrast, endothelial markers were similar to lower at Day 0 for invasive ventilation versus spontaneous ventilation, but then increased over time only among intubated patients. In intubated patients, angiopoietin-2 was similar (fold difference, 1.02; 95% CI, 0.89-1.17) to nonintubated patients at Day 0 but 1.80-fold higher (95% CI, 1.56-2.06) at Day 3; cardiorenovascular injury markers showed similar patterns. Endothelial markers were not consistently associated with ventilatory ratios. Endothelial markers were more often significantly associated with 28-day outcomes than alveolar markers. Conclusions: Alveolar injury markers increase early. Endothelial injury markers increase later and are associated with cardiorenovascular injury and 28-day outcome. Alveolar and endothelial injury likely contribute at different times to disease progression in severe COVID-19.

Low concordance between CTPA and echocardiography in identification of right ventricular strain in PERT patients with acute pulmonary embolism.

PURPOSE: Right ventricular strain (RVS) is used to risk stratify patients with acute pulmonary embolism (PE) and influence treatment decisions. Guidelines suggest that either computed tomography pulmonary angiography (CTPA) or transthoracic echocardiography (TTE) can be used to assess RVS. We sought to determine how often CTPA and TTE yield discordant results and to assess the test characteristics of CTPA compared to TTE. METHODS: We analyzed data from a single-center registry of PE cases severe enough to warrant activation of the hospital's Pulmonary Embolism Response Team (PERT). We defined RVS as a right ventricular to left ventricular ratio (RV/LV) ≥ 1 or radiologist's interpretation of RVS on CTPA or as the presence of either RV dilation, hypokinesis, or septal bowing on TTE. RESULTS: We included 554 patients in our analysis, of whom 333 (60%) had concordant RVS findings on CTPA and TTE. Using TTE as the reference standard, CTPA had a sensitivity of 95% (95% CI 92-97%) and a specificity of 4% (95% CI 2-8%) for identifying RVS. CONCLUSIONS: In a selected population of patients with acute PE for which PERT was activated, CTPA is highly sensitive but not specific for the detection of RVS when compared to TTE.

COVID-19 Seroprevalence in ED Health Care Professionals Study: A Cross-Sectional Study.

INTRODUCTION: ED health care professionals are at the frontline of evaluation and management of patients with acute, and often undifferentiated, illness. During the initial phase of the SARS-CoV-2 outbreak, there were concerns that ED health care professionals may have been at increased risk of exposure to SARS-CoV-2 due to difficulty in early identification of patients. This study assessed the seroprevalence of SARS-CoV-2 antibodies among ED health care professionals without confirmed history of COVID-19 infection at a quaternary academic medical center. METHODS: This study used a cross-sectional design. An ED health care professional was deemed eligible if they had worked at least 4 shifts in the adult emergency department from April 1, 2020, through May 31, 2020, were asymptomatic on the day of blood draw, and were not known to have had prior documented COVID-19 infection. The study period was December 17, 2020, to January 27, 2021. Eligible participants completed a questionnaire and had a blood sample drawn. Samples were run on the Roche Cobas Elecsys Anti-SARS-CoV-2 antibody assay. RESULTS: Of 103 health care professionals (16 attending physicians, 4 emergency residents, 16 advanced practice professionals, and 67 full-time emergency nurses), only 3 (2.9%; exact 95% CI, 0.6%-8.3%) were seropositive for SARS-CoV-2 antibodies. DISCUSSION: At this quaternary academic medical center, among those who volunteered to take an antibody test, there was a low seroprevalence of SARS-CoV-2 antibodies among ED clinicians who were asymptomatic at the time of blood draw and not known to have had prior COVID-19 infection.

A pilot clinical trial of a near-infrared laser vaccine adjuvant: safety, tolerability, and cutaneous immune cell trafficking.

Many vaccines require adjuvants to enhance immunogenicity, but there are few safe and effective intradermal (i.d.) adjuvants. Murine studies have validated the potency of laser illumination of skin as an adjuvant for i.d. vaccination with advantages over traditional adjuvants. We report a pilot clinical trial of low-power, continuous-wave, near-infrared laser adjuvant treatment, representing the first human trial of the safety, tolerability, and cutaneous immune cell trafficking changes produced by the laser adjuvant. In this trial we demonstrated a maximum tolerable energy dose of 300 J/cm2 to a spot on the lower back. The irradiated spot was biopsied 4 h later, as was a control spot. Paired biopsies were submitted for histomorphologic and immunohistochemical evaluation in a blinded fashion as well as quantitative PCR analysis for chemokines and cytokines. Similar to prior murine studies, highly significant reductions in CD1a+ Langerhans cells in the dermis and CD11c+ dermal dendritic cells were observed, corresponding to the increased migratory activity of these cells; changes in the epidermis were not significant. There was no evidence of skin damage. The laser adjuvant is a safe, well-tolerated adjuvant for i.d. vaccination in humans and results in significant cutaneous immune cell trafficking.-Gelfand, J. A., Nazarian, R. M., Kashiwagi, S., Brauns, T., Martin, B., Kimizuka, Y., Korek, S., Botvinick, E., Elkins, K., Thomas, L., Locascio, J., Parry, B., Kelly, K. M., Poznansky, M. C. A pilot clinical trial of a near-infrared laser vaccine adjuvant: safety, tolerability, and cutaneous immune cell trafficking.

Correction to: Changes in treatment and outcomes after creation of a pulmonary embolism response team (PERT), a 10-year analysis.

The original version of the article unfortunately contained an error in conflict of interest. This erratum is published with the correct conflict of interest.

Changes in treatment and outcomes after creation of a pulmonary embolism response team (PERT), a 10-year analysis.

Multidisciplinary pulmonary embolism response teams (PERTs) are being implemented to improve care of patients with life-threatening PE. We sought to determine how the creation of PERT affects treatment and outcomes of patients with serious PE. A pre- and post-intervention study was performed using an interrupted time series design, to compare patients with PE before (2006-2012) and after (2012-2016) implementation of PERT at a university hospital. T-tests, Chi square tests and logistic regression were used to compare outcomes, and multivariable regression were used to adjust for differences in PE severity. Two-sided p-value < 0.05 was considered significant. For the interrupted time-series analysis, data was divided into mutually exclusive 6-month time periods (11 pre- and 7 post-PERT). To examine changes in treatment and outcomes associated with PERT, slopes and change points were compared pre- and post-PERT. Two-hundred and twelve pre-PERT and 228 post-PERT patients were analyzed. Patient demographics were generally similar, though pre-PERT, PE were more likely to be low-risk (37% vs. 19%) while post-PERT, PE were more likely to be submassive (32% vs. 49%). More patients underwent catheter directed therapy (1% vs. 14%, p = < 0.0001) or any advanced therapy (19 [9%] vs. 44 [19%], p = 0.002) post PERT. Interrupted time series analysis demonstrated that this increase was sudden and coincident with implementation of PERT, and most noticeable among patients with submassive PE. There were no differences in major bleeding or mortality pre- and post-PERT. While the use of advanced therapies, particularly catheter-directed therapies, increased after creation of PERT, especially among patients with submassive PE, there was no apparent increase in bleeding.

D-dimer levels in VTE patients with distal and proximal clots.

OBJECTIVES: There is growing evidence that venous thromboembolism (VTE) patients with distal clots (distal calf deep vein thrombosis [DVT] and sub-segmental pulmonary embolism [PE]) may not routinely benefit from anticoagulation. We compared the D-dimer levels in VTE patients with distal and proximal clots. METHODS: We conducted a multinational, prospective observational study of low-to-intermediate risk adult patients presenting to the emergency department (ED) with suspected VTE. Patients were classified as distal (calf DVT or sub-segmental PE) or proximal (proximal DVT or non-sub-segmental PE) clot groups and compared with univariate and multivariate analyses. RESULTS: Of 1752 patients with suspected DVT, 1561 (89.1%) had no DVT, 78 (4.4%) had a distal calf DVT, and 113 (6.4%) had a proximal DVT. DVT patients with proximal clots had higher D-dimer levels (3760 vs. 1670 mg/dL) than with distal clots. Sensitivity and negative predictive value (NPV) for proximal DVT at an optimal D-dimer cutoff of 5770 mg/dL were 40.7% and 52.1% respectively. Of 1834 patients with suspected PE, 1726 (94.1%) had no PE, 7 (0.4%) had isolated sub-segmental PE, and 101 (5.5%) had non-sub-segmental PE. PE patients with proximal clots had higher D-dimer levels (4170 vs. 2520 mg/dL) than those with distal clots. Sensitivity and NPV for proximal PE at an optimal D-dimer cutoff of 3499 mg/dL were 57.4% and 10.4% respectively. CONCLUSIONS: VTE patients with proximal clots had higher D-dimer levels than patients with distal clots. However, D-dimer levels cannot be used alone to discriminate between VTE patients with distal or proximal clots.

The Outpatient Treatment of Venous Thromboembolism: Operational Impact and the Role of Novel Anticoagulants.

Pulmonary embolism (PE) and venous thromboembolism (VTE) are common diagnoses in the emergency department (ED), with significant potential morbidity and mortality. As a result, historically nearly all patients with PE have been admitted to the hospital for observation and treatment. In recent years, the ability to rapidly and accurately risk stratify patients with VTE according to their risk of short-term clinical deterioration has supported outpatient treatment, and non-vitamin K antagonist oral anticoagulants (NOACs) have further facilitated this approach. This review details the historical context and operational impact of managing VTE in the outpatient setting, describes a model for outpatient management of VTE, and suggests potential areas of further inquiry.

Comparison between admission natriuretic peptides, NGAL and sST2 testing for the prediction of worsening renal function in patients with acutely decompensated heart failure.

BACKGROUND: In order to predict the occurrence of worsening renal function (WRF) and of WRF plus in-hospital death, 101 emergency department (ED) patients with acute decompensated heart failure (ADHF) were evaluated with testing for amino-terminal pro-B-type natriuretic peptide (NT-proBNP), BNP, sST2, and neutrophil gelatinase associated lipocalin (NGAL). METHODS: In a prospective international study, biomarkers were collected at the time of admission; the occurrence of subsequent in hospital WRF was evaluated. RESULTS: In total 26% of patients developed WRF. Compared to patients without WRF, those with WRF had a longer in-hospital length of stay (LOS) (mean LOS 13.1±13.4 days vs. 4.8±3.7 days, p<0.001) and higher in-hospital mortality [6/26 (23%) vs. 2/75 (2.6%), p<0.001]. Among the biomarkers assessed, baseline NT-proBNP (4846 vs. 3024 pg/mL; p=0.04), BNP (609 vs. 435 pg/mL; p=0.05) and NGAL (234 vs. 174 pg/mL; p=0.05) were each higher in those who developed WRF. In logistic regression, the combination of elevated natriuretic peptide and NGAL were additively predictive for WRF (ORNT-proBNP+NGAL=2.79; ORBNP+NGAL=3.11; both p<0.04). Rates of WRF were considerably higher in patients with elevation of both classes of biomarker. Comparable results were observed in a separate cohort of 162 patients with ADHF from a different center. CONCLUSIONS: In ED patients with ADHF, the combination of NT-proBNP or BNP plus NGAL at presentation may be useful to predict impending WRF (Clinicaltrials.gov NCT#0150153).

Identifying patients with problematic drug use in the emergency department: results of a multisite study.

STUDY OBJECTIVE: Drug-related emergency department (ED) visits have steadily increased, with substance users relying heavily on the ED for medical care. The present study aims to identify clinical correlates of problematic drug use that would facilitate identification of ED patients in need of substance use treatment. METHODS: Using previously validated tests, 15,224 adult ED patients across 6 academic institutions were prescreened for drug use as part of a large randomized prospective trial. Data for 3,240 participants who reported drug use in the past 30 days were included. Self-reported variables related to demographics, substance use, and ED visit were examined to determine their correlative value for problematic drug use. RESULTS: Of the 3,240 patients, 2,084 (64.3%) met criteria for problematic drug use (Drug Abuse Screening Test score ≥ 3). Age greater than or equal to 30 years, tobacco smoking, daily or binge alcohol drinking, daily drug use, primary noncannabis drug use, resource-intense ED triage level, and perceived drug-relatedness of ED visit were highly correlated with problematic drug use. Among primary cannabis users, correlates of problematic drug use were age younger than 30 years, tobacco smoking, binge drinking, daily drug use, and perceived relatedness of the ED visit to drug use. CONCLUSION: Clinical correlates of drug use problems may assist the identification of ED patients who would benefit from comprehensive screening, intervention, and referral to treatment. A clinical decision rule is proposed. The correlation between problematic drug use and resource-intense ED triage levels suggests that ED-based efforts to reduce the unmet need for substance use treatment may help decrease overall health care costs.

Low degree of formal education and musical experience predict degree of music-induced stress reduction in relatives and friends of patients: a single-center, randomized controlled trial.

OBJECTIVE: To determine the factors that may predict music-induced relaxation in friends and family of patients in the emergency department. BACKGROUND: It remains unclear to date which demographic and experiential factors predict the effectiveness of music-induced relaxation. Furthermore, in-hospital stressors for friends and family of patients rather than patients themselves are underresearched and deserve in-depth investigation to improve this group's experience in health care environments. METHODS: A total of 169 relatives and friends of patients in the emergency department-waiting area completed a series of questionnaires, including the Spielberger State-Trait Anxiety Inventory (STAI), the Music Experience Questionnaire (MEQ), and a demographic survey. They were then randomly assigned to either Case Group (1 hour in the waiting area with classical music in the background) or Control Group (1 hour with no music) before completing a second, identical copy of the STAI to measure change from baseline. Data were analyzed for associations between music intervention, change in STAI scores, MEQ scores, and demographic characteristics. RESULTS: Participants who underwent the music intervention experienced a 9.8% decrease in overall mean State Anxiety, whereas those in the Control Group experienced no change over time (P = 0.001). Higher education significantly inversely correlated with the effectiveness of music intervention: participants with no formal education beyond high school showed a greater overall mean decrease in State Anxiety than those with a college education or beyond in response to classical music (P = 0.006). Furthermore, MEQ scores indicated that the Social Uplift scale (a measure of one's tendency to be uplifted in a group-oriented manner by music) was highly predictive of the effectiveness of music intervention. CONCLUSIONS: Music is an effective and inexpensive means of reducing anxiety in friends and family of patients, who are underresearched in medicine. Moreover, low educational attainment and tendency to respond positively to music in a group setting can predict the effectiveness of music-induced relaxation.

Frequent ED users: are most visits for mental health, alcohol, and drug-related complaints?

STUDY OBJECTIVE: To determine whether frequent emergency department (ED) users are more likely to make at least one and a majority of visits for mental health, alcohol, or drug-related complaints compared to non-frequent users. METHODS: We performed a retrospective cohort study exploring frequent ED use and ED diagnosis at a single, academic hospital and included all ED patients between January 1 and December 31, 2010. We compared differences in ED visits with a primary International Classification of Diseases, 9th Revision visit diagnosis of mental health, alcohol or drug-related diagnoses between non-frequent users (<4 visits during previous 12-months) and frequent (repeat [4-7 visits], highly frequent [8-18 visits] and super frequent [≥19 visits]) users in univariate and multivariable analyses. RESULTS: Frequent users (2496/65201 [3.8%] patients) were more likely to make at least one visit associated with mental health, alcohol, or drug-related diagnoses. The proportion of patients with a majority of visits related to any of the three diagnoses increased from 5.8% among non-frequent users (3616/62705) to 9.4% among repeat users (181/1926), 13.1% among highly frequent users (62/473), and 25.8% (25/97 patients) in super frequent users. An increasing proportion of visits with alcohol-related diagnoses was observed among repeat, highly frequent, and super frequent users but was not found for mental health or drug-related complaints. CONCLUSION: Frequent ED users were more likely to make a mental health, alcohol or drug-related visit, but a majority of visits were only noted for those with alcohol-related diagnoses. To address frequent ED use, interventions focusing on managing patients with frequent alcohol-related visits may be necessary.

Evaluation of renal function tests by age and sex to determine emergency department patients' eligibility for cardiac computed tomography.

BACKGROUND: Coronary computed tomography angiography (CCTA) can be used for low-risk chest pain patients, but presents a risk of contrast-induced nephropathy. OBJECTIVE: We compared, by age and sex, the percent of patients who would become ineligible for CCTA based on serum creatinine (SCr) and glomerular filtration rate (GFR) cutoff points. METHODS: All adult patients who presented to the Emergency Department (ED) with chest pain were screened using their first ED SCr as part of the ROMICAT (Rule Out Myocardial Infarction Using Computer Assisted Tomography) study. This was a secondary analysis of the screening logs of that study. The Modification of Diet in Renal Disease formula was applied to calculate estimated GFR and the percent of patients, by age and sex, meeting commonly applied exclusion criteria using selected SCr and GFR cutoff values. This was our primary outcome. RESULTS: Of 2398 patients screened, 384 (16%) were excluded for high-risk features or technical limitations of CCTA, leaving 2014 patients who were studied; 56% were male. For all cutoff points of SCr (≥1.3 mg/dL, ≥1.5 mg/dL, ≥1.8 mg/dL), the percent of males excluded significantly exceeded that of females (p < 0.0001 [28.6% males to 18.5% females]; p < 0.0001 [17.4% males to 11.2% females]; p = 0.0004 [10.1% males to 5.8% females], respectively). Conversely, for two of the three cutoff points of GFR (≤60 mL/min/1.73 m(2) and ≤45 mL/min/1.73 m(2)), the percent of females excluded significantly exceeded that of males (p < 0.0001 [33.6% females to 25.4% males] and p = 0.0015 [17.6% males to 12.5% females], respectively). CONCLUSIONS: The choice of SCr or GFR to screen patients for CCTA selectively excludes either males or females, respectively. Therefore, individual physicians and institutions must understand the impact of both renal function tests and cutoff points when identifying patients who may be eligible for CCTA.