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.

Can tablet video-based telehealth assessment of the abdomen safely determine the need for abdominal imaging? A pilot study.

Objective: There is limited evidence on the reliability of video-based physical examinations. We aimed to evaluate the safety of a remote physician-directed abdominal examination using tablet-based video. Methods: This was a prospective observational pilot study of patients >19 years old presenting with abdominal pain to an academic emergency department July 9, 2021-December 21, 2021. In addition to usual care, patients had a tablet video-based telehealth history and examination by an emergency physician who was otherwise not involved in the visit. Both telehealth and in-person clinicians were asked about the patient's need for abdominal imaging (yes/no). Thirty-day chart review searched for subsequent ED visits, hospitalizations, and procedures. Our primary outcome was agreement between telehealth and in-person clinicians on imaging need. Our secondary outcome was potentially missed imaging by the telehealth physicians leading to morbidity or mortality. We used descriptive and bivariate analyses to examine characteristics associated with disagreement on imaging needs. Results: Fifty-six patients were enrolled; the median age was 43 years (interquartile range: 27-59), 31 (55%) were female. The telehealth and in-person clinicians agreed on the need for imaging in 42 (75%) of the patients (95% confidence interval [CI]: 62%-86%), with moderate agreement with Cohen's kappa ((k = 0.41, 95% CI: 0.15-0.67). For study patients who had a procedure within 24 hours of ED arrival (n = 3, 5.4%, 95% CI: 1.1%-14.9%) or within 30 days (n = 7, 12.5%, 95% CI: 5.2%-24.1%), neither telehealth physicians nor in-person clinicians missed timely imaging. Conclusion: In this pilot study, telehealth physicians and in-person clinicians agreed on the need for imaging for the majority of patients with abdominal pain. Importantly, telehealth physicians did not miss the identification of imaging needs for patients requiring urgent or emergent surgery.

SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes.

BACKGROUNDSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive.METHODSWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using a quantitative reverse transcription PCR-based platform. Proteomic data were generated with Proximity Extension Assay using the Olink platform.RESULTSThis study included 300 participants with nucleic acid test-confirmed COVID-19. Plasma SARS-CoV-2 viremia levels at the time of presentation predicted adverse disease outcomes, with an adjusted OR of 10.6 (95% CI 4.4-25.5, P < 0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and 3.9 (95% CI 1.5-10.1, P = 0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, and endothelium/vasculature, and alterations in coagulation pathways.CONCLUSIONThese results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.FUNDINGMark and Lisa Schwartz; the National Institutes of Health (U19AI082630); the American Lung Association; the Executive Committee on Research at Massachusetts General Hospital; the Chan Zuckerberg Initiative; Arthur, Sandra, and Sarah Irving for the David P. Ryan, MD, Endowed Chair in Cancer Research; an EMBO Long-Term Fellowship (ALTF 486-2018); a Cancer Research Institute/Bristol Myers Squibb Fellowship (CRI2993); the Harvard Catalyst/Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH awards UL1TR001102 and UL1TR002541-01); and by the Harvard University Center for AIDS Research (National Institute of Allergy and Infectious Diseases, 5P30AI060354).

SARS-CoV-2 Viremia is Associated with Distinct Proteomic Pathways and Predicts COVID-19 Outcomes.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) plasma viremia has been associated with severe disease and death in coronavirus disease 2019 (COVID-19) in small-scale cohort studies. The mechanisms behind this association remain elusive. METHODS: We evaluated the relationship between SARS-CoV-2 viremia, disease outcome, inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using qRT-PCR based platform. Proteomic data were generated with Proximity Extension Assay (PEA) using the Olink platform. RESULTS: Three hundred participants with nucleic acid test-confirmed COVID-19 were included in this study. Levels of plasma SARS-CoV-2 viremia at the time of presentation predicted adverse disease outcomes, with an adjusted odds ratio (aOR) of 10.6 (95% confidence interval [CI] 4.4, 25.5, P<0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and aOR of 3.9 (95%CI 1.5, 10.1, P=0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, endothelium/vasculature and alterations in coagulation pathways. CONCLUSIONS: These results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.

The diagnosis of respiratory disease in children using a phone-based cough and symptom analysis algorithm: The smartphone recordings of cough sounds 2 (SMARTCOUGH-C 2) trial design.

The diagnosis of acute respiratory diseases in children can be challenging, and no single objective diagnostic test exists for common pediatric respiratory diseases. Previous research has demonstrated that ResAppDx, a cough sound and symptom-based analysis algorithm, can identify common respiratory diseases at the point of care. We present the study protocol for SMARTCOUGH-C 2, a prospective diagnostic accuracy trial of a cough and symptom-based algorithm in a cohort of children presenting with acute respiratory diseases. The objective of the study is to assess the performance characteristics of the ResAppDx algorithm in the diagnosis of common pediatric acute respiratory diseases.

Sex-related differences in D-dimer levels for venous thromboembolism screening.

BACKGROUND: D-dimer is generally considered positive above 0.5 mg/L irrespective of sex. However, women have been shown to be more likely to have a positive D-dimer after controlling for other factors. Thus, differences may exist between males and females for using D-dimer as a marker of venous thromboembolic (VTE) disease. We hypothesized that the accuracy of D-dimer tests may be enhanced by using appropriate cutoff values that reflect sex-related differences in D-dimer levels. METHODS: This research is a secondary analysis of a multicenter, international, prospective, observational study of adult (18+ years) patients suspected of VTE, with low-to-intermediate pretest probability based on Wells criteria ≤ 6 for pulmonary embolism (PE) and ≤ 2 for deep vein thrombosis (DVT). VTE diagnoses were based on computed tomography, ventilation perfusion scanning, or venous ultrasound. D-dimer levels were tested for statistical difference across groups stratified by sex and diagnosis. Multivariable regression was used to investigate sex as a predictor of diagnosis. Sex-specific optimal D-dimer thresholds for PE and DVT were calculated from receiver operating characteristic analyses. A Youden threshold (D-dimer level coinciding with the maximum of sensitivity plus specificity) and a cutoff corresponding to 95% sensitivity were calculated. Statistical difference for cutoffs was tested via 95% confidence intervals from 2,000 bootstrapped samples. RESULTS: We included 3,586 subjects for analysis, of whom 61% were female. Race demographics were 63% White, 27% Black/African American, and 6% Hispanic. In the suspected PE cohort, 6% were diagnosed with PE, while in the suspected DVT cohort, 11% were diagnosed with DVT. D-dimer levels were significantly higher in males than females for the PE-positive group and the DVT-negative group, but males had significantly lower D-dimer levels than females in the PE-negative group. Regression models showed male sex as a significant positive predictor of DVT diagnosis, controlling for D-dimer levels. The Youden thresholds for PE patients were 0.97 (95% CI = 0.64 to 1.79) mg/L and 1.45 (95% CI = 1.36 to 1.95) mg/L for females and males, respectively; 95% sensitivity cutoffs for this group were 0.64 (95% CI = 0.20 to 0.89) and 0.55 (95% CI = 0.29 to 1.61). For DVT, the Youden thresholds were 0.98 (95% CI = 0.84 to 1.56) mg/L for females and 1.25 (95% CI = 0.65 to 3.33) mg/L for males with 95% sensitivity cutoffs of 0.33 (95% CI = 0.2 to 0.61) and 0.32 (95% CI = 0.18 to 0.7), respectively. CONCLUSION: Differences in D-dimer levels between males and females are diagnosis specific; however, there was no significant difference in optimal cutoff values for excluding PE and DVT between the sexes.

Effect of Transcranial Low-Level Light Therapy vs Sham Therapy Among Patients With Moderate Traumatic Brain Injury: A Randomized Clinical Trial.

Importance: Preclinical studies have shown that transcranial near-infrared low-level light therapy (LLLT) administered after traumatic brain injury (TBI) confers a neuroprotective response. Objectives: To assess the feasibility and safety of LLLT administered acutely after a moderate TBI and the neuroreactivity to LLLT through quantitative magnetic resonance imaging metrics and neurocognitive assessment. Design, Setting, and Participants: A randomized, single-center, prospective, double-blind, placebo-controlled parallel-group trial was conducted from November 27, 2015, through July 11, 2019. Participants included 68 men and women with acute, nonpenetrating, moderate TBI who were randomized to LLLT or sham treatment. Analysis of the response-evaluable population was conducted. Interventions: Transcranial LLLT was administered using a custom-built helmet starting within 72 hours after the trauma. Magnetic resonance imaging was performed in the acute (within 72 hours), early subacute (2-3 weeks), and late subacute (approximately 3 months) stages of recovery. Clinical assessments were performed concomitantly and at 6 months via the Rivermead Post-Concussion Questionnaire (RPQ), a 16-item questionnaire with each item assessed on a 5-point scale ranging from 0 (no problem) to 4 (severe problem). Main Outcomes and Measures: The number of participants to successfully and safely complete LLLT without any adverse events within the first 7 days after the therapy was the primary outcome measure. Secondary outcomes were the differential effect of LLLT on MR brain diffusion parameters and RPQ scores compared with the sham group. Results: Of the 68 patients who were randomized (33 to LLLT and 35 to sham therapy), 28 completed at least 1 LLLT session. No adverse events referable to LLLT were reported. Forty-three patients (22 men [51.2%]; mean [SD] age, 50.49 [17.44] years]) completed the study with at least 1 magnetic resonance imaging scan: 19 individuals in the LLLT group and 24 in the sham treatment group. Radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA) showed significant time and treatment interaction at 3-month time point (RD: 0.013; 95% CI, 0.006 to 0.019; P < .001; MD: 0.008; 95% CI, 0.001 to 0.015; P = .03; FA: -0.018; 95% CI, -0.026 to -0.010; P < .001).The LLLT group had lower RPQ scores, but this effect did not reach statistical significance (time effect P = .39, treatment effect P = .61, and time × treatment effect P = .91). Conclusions and Relevance: In this randomized clinical trial, LLLT was feasible in all patients and did not exhibit any adverse events. Light therapy altered multiple diffusion tensor parameters in a statistically significant manner in the late subacute stage. This study provides the first human evidence to date that light therapy engages neural substrates that play a role in the pathophysiologic factors of moderate TBI and also suggests diffusion imaging as the biomarker of therapeutic response. Trial Registration: ClinicalTrials.gov Identifier: NCT02233413.

Thromboembolic Risk of 4-Factor Prothrombin Complex Concentrate versus Fresh Frozen Plasma for Urgent Warfarin Reversal in the Emergency Department.

INTRODUCTION: Warfarin is a potent anticoagulant used for the prevention and treatment of venous and arterial thrombosis. Occasionally, patients require emergent warfarin reversal due to active bleeding, supratherapeutic international normalized ratio, or emergent diagnostic or therapeutic interventions. Various agents can be used for emergent warfarin reversal, including fresh frozen plasma (FFP) and 4-factor prothrombin complex concentrate (4F-PCC). Both FFP and 4F-PCC are generally considered safe; however, both agents contain coagulation factors and have the potential to provoke a thromboembolic event. Although clinical trials have compared the efficacy and safety of FFP and 4F-PCC, data are limited comparing the risk of thromboembolism between the two agents. METHODS: A retrospective chart review was performed at a single, urban, academic medical center comparing the incidence of thromboembolism with FFP or 4F-PCC for warfarin reversal during a three-year period in the emergency department (ED) at Massachusetts General Hospital. Patients were included in the study if they were at least 18 years of age and were on warfarin per electronic health records. Patients were excluded if they had received both FFP and 4F-PCC during the same visit. The primary outcome was the frequency of thromboembolism within 30 days of 4F-PCC or FFP. Secondary outcomes included time to thromboembolic event and in-hospital mortality. RESULTS: Three hundred and thirty-six patients met the inclusion criteria. Thromboembolic events within 30 days of therapy occurred in seven patients (2.7%) in the FFP group and 14 patients (17.7%) in the 4F-PCC group (p=<0.001). Death occurred in 39 patients (15.2%) who received FFP and 18 patients (22.8%) who received 4F-PCC (p=0.115). Since the 4F-PCC group was treated disproportionately for central nervous system (CNS) bleeding, a subgroup analysis was performed including patients requiring reversal due to CNS bleeds that received vitamin K. The primary outcome remained statistically significant, occurring in four patients (4.1%) in the FFP group and nine patients (14.1%) in the 4F-PCC group (p=0.02). CONCLUSION: Our study found a significantly higher risk of thromboembolic events in patients receiving 4F-PCC compared to FFP for urgent warfarin reversal. This difference remained statistically significant when controlled for CNS bleeds and administration of vitamin K.

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.

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.

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.

Secondary cardiac risk stratifying tests after coronary computed tomography angiography in emergency department patients.

BACKGROUND: Several large trials demonstrated that coronary computed tomography angiography (CTA) in a triage strategy could lead to increased secondary cardiac risk stratifying testing (SCRST). Whether this is true for routine clinical care remains unclear. We measured SCRSTs after coronary CTA was implemented in our emergency department (ED) practice by CTA result, and if locally existing management recommendations for a structured post CTA diagnostic strategy were followed. METHODS: This single site retrospective cohort study included all our ED patients who received coronary CTA between October 1, 2012 and September 30, 2016. SCRST's included functional cardiac tests and invasive coronary angiography (ICA), performed during the ED coronary CTA visit or related admission. RESULTS: A total of 1916 subjects were included with a mean age of 52.9 ±â€¯10.8 years. Of their coronary CTAs, 179 were positive (severe stenosis, occlusion or ventricular wall motion abnormalities; 9.3%), 105 intermediate (moderate stenosis; 5.5%), 1611 negative (no to mild obstructive CAD; 84.1%) and 21 non-diagnostic (1.1%). SCRSTs were performed in 237 (overall 12.4%, noninvasive in 5.6%, ICA in 6.7%). After positive coronary CTA, 73.7% of subjects received SCRSTs. For intermediate, negative and non-diagnostic CTAs this was 72.4%, 1.1% and 47.6% respectively. Management conformed to local management recommendations in 96.2% of cases. CONCLUSION: In spite of previous trials, rates of secondary cardiac risk stratifying tests after routine clinical ED coronary CTA are low, especially in patients with negative coronary CTA. Structured management guidelines for post coronary CTA, and adherence to these guidelines, appear essential.

Serial Procalcitonin as a Predictor of Bacteremia and Need for Intensive Care Unit Care in Adults With Pneumonia, Including Those With Highest Severity: A Prospective Cohort Study.

BACKGROUND: Procalcitonin (PCT) is a prohormone that rises in bacterial pneumonia and has promise in reducing antibiotic use. Despite these attributes, there are inconclusive data on its use for clinical prognostication. We hypothesize that serial PCT measurements can predict mortality, intensive care unit (ICU) admission, and bacteremia. METHODS: A prospective cohort study of inpatients diagnosed with pneumonia was performed at a large tertiary care center in Boston, Massachusetts. Procalcitonin was measured on days 1 through 4. The primary endpoint was a composite adverse outcome defined as all-cause mortality, ICU admission, and bacteremia. Regression models were calculated with area under the receiver operating characteristic curve (AUC) as a measure of discrimination. RESULTS: Of 505 patients, 317 patients had a final diagnosis of community-acquired pneumonia (CAP) or healthcare-associated pneumonia (HCAP). Procalcitonin was significantly higher for CAP and HCAP patients meeting the composite primary endpoint, bacteremia, and ICU admission, but not mortality. Incorporation of serial PCT levels into a statistical model including the Pneumonia Severity Index (PSI) improved the prognostic performance of the PSI with respect to the primary composite endpoint (AUC from 0.61 to 0.66), bacteremia (AUC from 0.67 to 0.85), and need for ICU-level care (AUC from 0.58 to 0.64). For patients in the highest risk class PSI >130, PCT was capable of further risk stratification for prediction of adverse outcomes. CONCLUSION: Serial PCT measurement in patients with pneumonia shows promise for predicting adverse clinical outcomes, including in those at highest mortality risk.

Assessment of Right Ventricular Strain by Computed Tomography Versus Echocardiography in Acute Pulmonary Embolism.

BACKGROUND: Right ventricular strain (RVS) identifies patients at risk of hemodynamic deterioration from pulmonary embolism (PE). Our hypothesis was that chest computed tomography (CT) can provide information about RVS analogous to transthoracic echocardiography (TTE) and that RVS on CT is associated with adverse outcomes after PE. METHODS: Consecutive emergency department patients with acute PE were prospectively enrolled and clinical, biomarker, and imaging data were recorded. CTs were overread by two radiologists. We compared diagnoses of RVS on CT (defined as right ventricle:left ventricle ratio ≥ 0.9 or interventricular septal bowing) to echocardiography (defined as right ventricular hypokinesis, right ventricular dilatation, or interventricular septal bowing). We calculated the test characteristics (with 95% confidence interval) of CT and TTE for a composite outcome of severe clinical deterioration, thrombolysis/thrombectomy, or death within 5 days. RESULTS: A total of 298 patients were enrolled; 274 had CT and 118 had formal TTE. Of the 104 patients who had both CT and TTE, the mean (±SD) age was 58 (±17) years; 50 (48%) were female and 88 (85%) were Caucasian. Forty-two (40%) had RVS by TTE and 75 (72%) had RVS by CT. CT and TTE agreed on the presence or absence of RVS in 61 (59%) cases (κ = 0.24). Using TTE as criterion standard, the test characteristics of CT for RVS were as follows: sensitivity = 88%, specificity = 39%, positive predictive value = 49%, and negative predictive value = 83%. Fourteen (13%) patients experienced severe clinical deterioration or required hospital-based intervention within 5 days. This occurred in 30% of patients with RVS on both TTE and CT, 20% of patients with RVS on TTE alone, 3% of patients with RVS on CT alone, and 4% of patients without RVS on either modality. CONCLUSIONS: In acute PE, CT is highly sensitive but only moderately specific for RVS compared to TTE. RVS on both CT and TTE predicts more events than either modality alone. TTE confers additional positive prognostic value compared to CT in predicting post-PE clinical deterioration.

A Multidisciplinary Pulmonary Embolism Response Team: Initial 30-Month Experience With a Novel Approach to Delivery of Care to Patients With Submassive and Massive Pulmonary Embolism.

BACKGROUND: Integrating newly developed tests and treatments for severe pulmonary embolism (PE) into clinical care requires coordinated multispecialty collaboration. To meet this need, we developed a new paradigm: a multidisciplinary Pulmonary Embolism Response Team (PERT). In this report, we provide the first longitudinal analysis of patients treated by a PERT. METHODS: Our PERT includes specialists in cardiovascular medicine and surgery, emergency medicine, hematology, pulmonary/critical care, and radiology, and is organized as a rapid response team. We prospectively captured clinical, therapeutic, and outcome data at PERT activation and during follow-up periods up to 365 days. We analyzed data collectively, and as five mutually exclusive 6-month periods. We performed Fisher exact tests and regression analysis to test for trend. RESULTS: In 30 months, there were 394 unique PERT activations, 314 (80%) for confirmed PE. PERT activations increased by 16% every 6 months. Most confirmed PEs were submassive (n = 143, 46%) or massive (n = 80, 26%). The PERT treated a relatively large proportion of patients with PE and systemic or catheter-directed thrombolysis (n = 35, 11%), though the most common treatment was anticoagulation alone (n = 215, 69%). Hemorrhagic complications were rare overall, especially among patients treated with catheter-directed thrombolysis. The all-cause 30-day mortality of PERT patients with confirmed PE was 12%. CONCLUSIONS: We report our initial 30-month experience with a novel multidisciplinary PERT that rapidly engages multiple specialists to deliver efficient, organized, and evidence-based care to patients with high-risk PE. The PERT paradigm was rapidly adopted and may become a new standard of care for patients with PE.

Chronic widespread pain after motor vehicle collision typically occurs through immediate development and nonrecovery: results of an emergency department-based cohort study.

Motor vehicle collision (MVC) can trigger chronic widespread pain (CWP) development in vulnerable individuals. Whether such CWP typically develops through the evolution of pain from regional to widespread or through the early development of widespread pain with nonrecovery is currently unknown. We evaluated the trajectory of CWP development (American College of Rheumatology criteria) among 948 European-American individuals who presented to the emergency department (ED) for care in the early aftermath of MVC. Pain extent was assessed in the ED and 6 weeks, 6 months, and 1 year after MVC on 100%, 91%, 89%, and 91% of participants, respectively. Individuals who reported prior CWP at the time of ED evaluation (n = 53) were excluded. Trajectory modeling identified a 2-group solution as optimal, with the Bayes Factor value (138) indicating strong model selection. Linear solution plots supported a nonrecovery model. Although the number of body regions with pain in the non-CWP group steadily declined, the number of body regions with pain in the CWP trajectory group (192/895, 22%) remained relatively constant over time. These data support the hypothesis that individuals who develop CWP after MVC develop widespread pain in the early aftermath of MVC, which does not remit.

A comparison of patients diagnosed with pulmonary embolism who are ≥65 years with patients <65 years.

Recent studies have highlighted differences in how older patients respond to high-risk pulmonary embolism (PE) and treatment. However, guidelines for PE risk stratification and treatment are not based on age, and data are lacking for older patients. We characterized the impact of age on clinical features, risk stratification, treatment, and outcomes in a sample of patients with PE in the emergency department. We performed an observational cohort study of 547 consecutive patients with PE in the emergency department from 2005 to 2011 in an urban tertiary hospital. We used bivariate proportions and multivariable logistic regression to compare clinical presentation, risk category, treatment, and outcomes in patients ≥65 years with those <65 years. The mean age was 58 ± 17 years, 276 (50%) were women, and 210 (38%) were ≥65 years. PE was more severe in patients ≥65 years (massive 14% vs 5%, submassive 48% vs 25%, and low risk 38% vs 70%, p <0.0001), with submassive PE being the most common presentation in patients ≥65 years. However, subanalysis removing natriuretic peptides from the definition of submassive PE negated this finding. Treatment with parenteral anticoagulation (88% vs 90%, p = 0.32), thrombolytic therapy (5% vs 4%, p = 0.87), and inferior vena cava filter (4% vs 4%, p = 0.73) were similar among age groups. Patients ≥65 years had higher 30-day mortality (11% vs 3%, p <0.001). In conclusion, patients ≥65 years present with more severe PE and have higher mortality, although treatment patterns were similar to younger patients. Age-specific guideline definitions of submassive PE may better identify high-risk patients.

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).

Usefulness of combining galectin-3 and BIVA assessments in predicting short- and long-term events in patients admitted for acute heart failure.

INTRODUCTION: Acute heart failure (AHF) is associated with a higher risk for the occurrence of rehospitalization and death. Galectin-3 (GAL3) is elevated in AHF patients and is an indicator in predicting short-term mortality. The total body water using bioimpedance vector analysis (BIVA) is able to identify mortality within AHF patients. The aim of this study was to evaluate the short- and long-term predictive value of GAL3, BIVA, and the combination of both in AHF patients in Emergency Department (ED). METHODS: 205 ED patients with AHF were evaluated by testing for B type natriuretic peptide (BNP) and GAL3. The primary endpoint was death and rehospitalization at 30, 60, 90, and 180 days and 12 and 18 months. AHF patients were evaluated at the moment of ED arrival with clinical judgment and GAL3 and BIVA measurement. RESULTS: GAL3 level was significantly higher in patients >71 years old, and with eGFR < 30 cc/min. The area under the curve (AUC) of GAL3 + BIVA, GAL3 and BIVA for death and rehospitalization both when considered in total and when considered serially for the follow-up period showed that the combination has a better prognostic value. Kaplan-Meier survival curve for GAL3 values >17.8 ng/mL shows significant survival difference. At multivariate Cox regression analysis GAL3 is an independent variable to predict death + rehospitalization with a value of 32.24 ng/mL at 30 days (P < 0.005). CONCLUSION: In patients admitted for AHF an early assessment of GAL3 and BIVA seems to be useful in identifying patients at high risk for death and rehospitalization at short and long term. Combining the biomarker and the device could be of great utility since they monitor the severity of two pathophysiological different mechanisms: heart fibrosis and fluid overload.