IntroductionAcute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI.MethodsWe performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection.ResultsModerate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method.ConclusionsTwo novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI.Trial registrationClinicalTrials.gov number NCT01209169.

Patients infected with the SARS-CoV-2 virus can present with a wide variety of symptoms including being entirely asymptomatic. Despite having no or minimal symptoms, some patients may have markedly reduced pulse oximetry readings. This has been referred to as "silent" or "apathetic" hypoxia (Ottestad et al., 2020 [1]). We present a case of a 72-year-old male with COVID-19 syndrome who presented to the emergency department with minimal symptoms but low peripheral oxygen saturation readings. The patient deteriorated over the following days and eventually died as a result of overwhelming multi-organ system failure. This case highlights the utility of peripheral oxygen measurements in the evaluation of patients with SARS-CoV-2 infection. Selfmonitoring of pulse oximetry by patients discharged from the emergency department is a potential way to identify patients needing to return for further evaluation.

Objectives: Supine anteroposterior (AP) chest radiographs in patients with blunt trauma have poor sensitivity for the identification of pneumothorax. Ultrasound (US) has been proposed as an alternative screening test for pneumothorax in this population. The authors conducted an evidence-based review of the medical literature to compare sensitivity of bedside US and AP chest radiographs in identifying pneumothorax after blunt trauma.Methods: MEDLINE and EMBASE databases were searched for trials from 1965 through June 2009 using a search strategy derived from the following PICO formulation of our clinical question: patients included adult (18 + years) emergency department (ED) patients in whom pneumothorax was suspected after blunt trauma. The intervention was thoracic ultrasonography for the detection of pneumothorax. The comparator was the supine AP chest radiograph during the initial evaluation of the patient. The outcome was the diagnostic performance of US in identifying the presence of pneumothorax in the study population. The criterion standard for the presence or absence of pneumothorax was computed tomography (CT) of the chest or a rush of air during thoracostomy tube placement (in unstable patients). Prospective, observational trials of emergency physician (EP)-performed thoracic US were included. Trials in which the exams were performed by radiologists or surgeons, or trials that investigated patients suffering penetrating trauma or with spontaneous or iatrogenic pneumothoraces, were excluded. The methodologic quality of the studies was assessed. Qualitative methods were used to summarize the study results. Data analysis consisted of test performance (sensitivity and specificity, with 95% confidence intervals [CIs]) of thoracic US and supine AP chest radiography.Results: Four prospective observational studies were identified, with a total of 606 subjects who met the inclusion and exclusion criteria. The sensitivity and specificity of US for the detection of pneumothorax ranged from 86% to 98% and 97% to 100%, respectively. The sensitivity of supine AP chest radiographs for the detection of pneumothorax ranged from 28% to 75%. The specificity of supine AP chest radiographs was 100% in all included studies.Conclusions: This evidence-based review suggests that bedside thoracic US is a more sensitive screening test than supine AP chest radiography for the detection of pneumothorax in adult patients with blunt chest trauma.

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Background: European data support the use of low high-sensitivity troponin (hs-cTn) measurements or a 0/1-hour (0/1-h) algorithm for myocardial infarction (MI) or to exclude major adverse cardiac events (MACE) among Emergency Department (ED) patients with possible acute coronary syndrome (ACS). However, modest US data exist to validate these strategies. This study evaluated the diagnostic performance of an initial hs-cTnT measure below the limit of quantification (LOQ: 6 ng/L), a 0/1-h algorithm, and their combination with HEART scores for excluding MACE in a multisite US cohort. Methods: A prospective cohort study was conducted at 8 US sites, enrolling adult ED patients with symptoms suggestive of ACS and without ST-elevation on electrocardiogram. Baseline and 1-hour blood samples were collected and hs-cTnT (Roche, Basel Switzerland) measured. Treating providers blinded to hs-cTnT results prospectively calculated HEART scores. MACE (cardiac death, MI, and coronary revascularization) at 30-days was adjudicated. The proportion of patients with initial hs-cTnT measures <LOQ and risk based on a 0/1-h algorithm was determined. The negative predictive value (NPV) was calculated for both strategies when used alone or with a HEART score. Results: Among 1,462 participants with initial hs-cTnT measures, 46.4% (678/1,462) were women and 37.1% (542/1,462) were African American with a mean age of 57.6 (SD±12.9) years. MACE at 30-days occurred in 14.4% (210/1,462). Initial hs-cTnT measures <LOQ occurred in 32.8% (479/1,462), yielding a NPV of 98.3% (95%CI: 96.7-99.3%) for 30-day MACE. A low risk HEART score with an initial hs-cTnT < LOQ occurred in 20.1% (294/1,462) yielding a NPV of 99.0% (95%CI: 97.0-99.8%) for 30-day MACE. A 0/1-h algorithm was complete in 1,430 patients, ruling-out 57.8% (826/1,430) with a NPV of 97.2% (95%CI: 95.9-98.2%) for 30-day MACE. Adding a low HEART score to the 0/1-h algorithm ruled-out 30.8% (441/1430) with a NPV of 98.4% (95%CI: 96.8-99.4%) for 30-day MACE. Conclusions: In a prospective multisite US cohort, an initial hs-cTnT <LOQ combined with a low risk HEART score has 99% NPV for 30-day MACE. The 0/1-h hs-cTnT algorithm did not achieve a NPV > 99% for 30-day MACE when used alone or with a HEART score. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02984436

Objectives Emergency departments (EDs) often serve vulnerable populations who may lack primary care and have suffered disproportionate COVID-19 pandemic effects. Comparing patients having and lacking a regular source of medical care and other ED patient characteristics, we assessed COVID-19 vaccine hesitancy, reasons for not wanting the vaccine, perceived access to vaccine sites and willingness to get the vaccine as part of ED care. Methods Cross sectional survey conducted from 12/10/2020 to 3/7/21 at 15 safety net United States EDs . Primary outcomes were COVID-19 vaccine hesitancy, reasons for vaccine hesitancy, and sites (including EDs) for potential COVID-19 vaccine receipt. Results Of 2575 patients approached, 2301 (89.4%) participated . Of the 18.4% of respondents who lacked a regular source of medical care, 65% used the ED as their usual source of healthcare. The overall rate of vaccine hesitancy was 39%; the range among the 15 sites was 28 to 58%. Respondents who lacked a regular source of medical care were more commonly vaccine hesitant than those who had a regular source of medical care (47 vs 38%, 9% difference, 95% CI 4 – 14%). Other characteristics associated with greater vaccine hesitancy were younger age, female gender, African American race, Latinx ethnicity, and not having received an influenza vaccine in the past five years. Of the 61% COVID-19 vaccine acceptors, 21% stated that they lacked a primary doctor or clinic to receive it; the vast majority (95%) of these respondents would accept the COVID-19 vaccine as part of their care in the ED. Conclusions ED patients who lack a regular source of medical care are particularly hesitant to COVID-19 vaccination. Most COVID-19 vaccine acceptors would accept it as part of their care in the ED. EDs may have pivotal roles in COVID-19 vaccine messaging and delivery to highly vulnerable populations.

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