Principal component analysis of a swine injury model identifies multiple phenotypes in trauma.

BACKGROUND: Trauma is the third leading cause of death in the United States and the primary cause of death for people between the ages of 1 year and 44 years. In addition to tissue damage, trauma may also activate an inflammatory state known as trauma-induced coagulopathy (TIC) that is associated with clotting malfunctions, acidemia, and end-organ dysfunction. Prior work has also demonstrated benefit to acknowledging the type and severity of endothelial injury, coagulation derangements, and systemic inflammation in the management of trauma patients. This study builds upon prior work by combining laboratory, metabolic, and clinical metrics into an analysis of trauma phenotypes, evolution of phenotypes over time after trauma, and significance of trauma phenotype on mortality. METHODS: Seventy 3-month-old female Yorkshire crossbred swine were randomized to injury and resuscitation groups. Principal component analysis (PCA) of longitudinal swine TEG data (Reaction time, Alpha-Angle, Maximum Amplitude, and Clot Lysis at 30 minutes), pH, lactate, and MAP was completed in R at baseline, 1 hour postinjury, 3 hours postinjury, 6 hours postinjury, and 12 hours postinjury. Subjects were compared by principal component factor scores to assess differences in survival, injury severity, and treatment group. RESULTS: Among injured animals, three phenotypes were observed at each time point. Five phenotypes were associated with differences in survival, and of these, four were associated with differences in injury severity. Phenotype alignment was not significantly different by treatment group. CONCLUSION: This application of PCA to a set of coagulation, hemodynamic, and organ perfusion variables has identified multiple evolving phenotypes after trauma. Some of these phenotypes may correlate with injury severity and may have implications for survival. Next steps include validating these findings over greater numbers of subjects and exploring other machine-learning techniques for phenotype identification. LEVEL OF EVIDENCE: Level IV, Therapeutic/Care Management.

Acute respiratory distress syndrome, acute kidney injury, and mortality after trauma are associated with increased circulation of syndecan-1, soluble thrombomodulin, and receptor for advanced glycation end products.

BACKGROUND: Disruption of the vascular endothelium and endothelial glycocalyx (EG) has been described after severe trauma. Plasma has been suggested to restore microvascular integrity by preservation and repair of the EG. We sought to evaluate whether plasma administered in a 1:1:1 ratio was associated with less endothelial marker circulation than a 1:1:2 ratio. METHODS: This is a secondary analysis of the PROPPR trial, which investigated post-traumatic resuscitation with platelets, plasma, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Syndecan-1, soluble thrombomodulin (sTM), and receptor for advanced glycation end products (RAGE) were quantified for each treatment group on admission and at 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours. Patients were excluded if they did not survive longer than 3 hours or had data from fewer than two time points. RESULTS: Three hundred eight patients in the 1:1:1 group and 291 in the 1:1:2 group were analyzed. There were no statistically significant differences in syndecan-1, sTM, or RAGE between treatment groups at any time point ( p > 0.05). Patients who developed acute respiratory distress syndrome, acute kidney injury, and death had significantly elevated biomarker expression at most time points when compared with patients who did not develop these sequelae ( p < 0.05). CONCLUSION: Administration of FFP in a 1:1:1 ratio does not consistently affect circulation of endothelial biomarkers following significant trauma when compared with a 1:1:2 ratio. The development of post-traumatic ARDS, AKI, and death was associated with increased endothelial biomarker circulation. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Improvement of Procedure Documentation Compliance With the Implementation of a Visual Aid.

BACKGROUND: Emergency department (ED) providers face increasing task burdens and requirements related to documentation and paperwork. To decrease the mental task burden for providers, our institution developed an infographic that illustrates which forms are necessary for complete documentation of nonemergent invasive procedures. OBJECTIVES: Our study aims to analyze the effect of a nonelectronic health record-based infographic, paired with direct feedback, on compliance with nonemergent invasive procedure documentation performed in the ED. METHODS: This was a retrospective, observational study of all procedure documentation performed in the ED with a pre-/post-test design. The study included two 8-month study periods, 1 year apart. The preimplementation period used for comparison was January 1, 2019-August 31, 2019, and the postimplementation period was January 1, 2020-August 31, 2020. All invasive procedures that required documentation in addition to a procedure note were included in the study. The primary outcome was the percentage of compliance with documentation requirements. RESULTS: During the pre- and postimplementation study periods, 486 and 405 charts with nonemergent procedures were identified, respectively. In the preimplementation period, 278 (57%) procedures were compliant with all documentation, vs. the postimplementation period, where 287 (71%) procedures were compliant (p < 0.001). CONCLUSION: Implementing an invasive procedure documentation infographic and direct feedback improved overall documentation compliance for nonemergent invasive procedures.

Telemedicine Use by Older Adults in a COVID-19 Epicenter.

BACKGROUND: In early 2020, New York City was the epicenter of the Coronavirus disease 2019 (COVID-19) pandemic in the United States. Older adults were at especially high risk. Telemedicine (TM) was used to shift care from overburdened emergency departments (EDs) to provide health care to a community in lockdown. TM options presented unique challenges to our diverse older adult population, including visual, hearing, cognitive, and language limitations. OBJECTIVE: Our objective was to evaluate the use of TM during the peak of the pandemic in New York City. METHODS: We conducted a retrospective chart review of patients 65 years and older evaluated remotely via TM during our pandemic surge. Chart extraction was performed by six emergency physicians. Outcomes included demographics, technical limitations, rates of ED referral, and 30-day mortality. RESULTS: During the study period, a total of 140 encounters were reviewed. The mean age was 73 years. Overall, 20% of patients in the cohort were emergently referred to the ED. Use of TM by this age cohort increased 20-fold as compared with a similar time frame pre-pandemic. ED referral was highest in those over 75 (45.9% > 75 years). Forty-three percent used family to assist. Thirty-day mortality was 7%. CONCLUSION: TM use by older adults grew substantially at our institution during our initial COVID-19 surge. The same-day emergent referral rate and mortality rate reflect the high acuity represented in this cohort and points to the need for telehealth providers that are trained in triage and emergency medicine with a knowledge of local resource availability.

Factors Affecting Emergency Department Crowding.

Emergency department crowding is a multifactorial issue with causes intrinsic to the emergency department and to the health care system. Understanding that the causes of emergency department crowding span this continuum allows for a more accurate analysis of its effects and a more global consideration of potential solutions. Within the emergency department, boarding of inpatients is the most appreciable effect of hospital-wide crowding, and leads to further emergency department crowding. We explore the concept of emergency department crowding, and its causes, effects, and potential strategies to overcome this problem.

Conscious Proning: An Introduction of a Proning Protocol for Nonintubated, Awake, Hypoxic Emergency Department COVID-19 Patients.

The novel coronavirus, or COVID-19, has rapidly become a global pandemic. A major cause of morbidity and mortality due to COVID-19 has been the worsening hypoxia that, if untreated, can progress to acute respiratory distress syndrome (ARDS) and respiratory failure. Past work has found that intubated patients with ARDS experience physiological benefits to the prone position, because it promotes better matching of pulmonary perfusion to ventilation, improved secretion clearance, and recruitment of dependent areas of the lungs. We created a systemwide multi-institutional (New York-Presbyterian Hospital enterprise) protocol for placing awake, nonintubated, emergency department patients with suspected or confirmed COVID-19 in the prone position. In this piece, we describe the background literature and the approach we have taken at our institution as we care for a high burden of COVID-19 cases with respiratory symptoms.

Correction to: Impact of intensive care unit supportive care on the physiology of Ebola virus disease in a universally lethal non-human primate model.

Please note that four authors (Logan Banadyga, Alixandra Albietz, Brad Pickering, and Gary Wong) have been erroneously omitted from the author list in the published original article [1].

Impact of intensive care unit supportive care on the physiology of Ebola virus disease in a universally lethal non-human primate model.

BACKGROUND: There are currently limited data for the use of specific antiviral therapies for the treatment of Ebola virus disease (EVD). While there is anecdotal evidence that supportive care may be effective, there is a paucity of direct experimental data to demonstrate a role for supportive care in EVD. We studied the impact of ICU-level supportive care interventions including fluid resuscitation, vasoactive medications, blood transfusion, hydrocortisone, and ventilator support on the pathophysiology of EVD in rhesus macaques infected with a universally lethal dose of Ebola virus strain Makona C07. METHODS: Four NHPs were infected with a universally lethal dose Ebola virus strain Makona, in accordance with the gold standard lethal Ebola NHP challenge model. Following infection, the following therapeutic interventions were employed: continuous bedside supportive care, ventilator support, judicious fluid resuscitation, vasoactive medications, blood transfusion, and hydrocortisone as needed to treat cardiovascular compromise. A range of physiological parameters were continuously monitored to gage any response to the interventions. RESULTS: All four NHPs developed EVD and demonstrated a similar clinical course. All animals reached a terminal endpoint, which occurred at an average time of 166.5 ± 14.8 h post-infection. Fluid administration may have temporarily blunted a rise in lactate, but the effect was short lived. Vasoactive medications resulted in short-lived improvements in mean arterial pressure. Blood transfusion and hydrocortisone did not appear to have a significant positive impact on the course of the disease. CONCLUSIONS: The model employed for this study is reflective of an intramuscular infection in humans (e.g., needle stick) and is highly lethal to NHPs. Using this model, we found that the animals developed progressive severe organ dysfunction and profound shock preceding death. While the overall impact of supportive care on the observed pathophysiology was limited, we did observe some time-dependent positive responses. Since this model is highly lethal, it does not reflect the full spectrum of human EVD. Our findings support the need for continued development of animal models that replicate the spectrum of human disease as well as ongoing development of anti-Ebola therapies to complement supportive care.

Effects of eliminating routine use of oral contrast for computed tomography of the abdomen and pelvis: A pilot study.

INTRODUCTION: Computed tomography (CT) of the abdomen and pelvis using only intravenous contrast has been shown to have a high degree of accuracy in evaluating abdominal pain. The aim of this study was to determine the effect on time to completion of study, time to radiologist read, and length of stay in the emergency department (ED) of implementing a protocol that stopped the routine use of oral contrast for CT of the abdomen and pelvis. METHODS: This was a single-center, retrospective cohort study. All patients ≥18 years of age who presented to the ED and required a CT of the abdomen and pelvis during the hours 0700-1500 were included. There were two one-month study periods, before and after implementing a protocol that specified oral contrast should only be used for CT scans of the abdomen and pelvis if body mass index <25 kg/m2 or age < 30 years, or if there was history of inflammatory bowel disease, gastrointestinal surgery, or suspected bowel malignancy. RESULTS: During the pre- and post-implementation periods, there were 93 and 83 patients, respectively, with mean times to CT completion of 158 min and 135 min, representing a reduction of 23 min (15%). The mean lengths of stay in the pre- and post-implementation periods were 365 min and 336 min, a decrease of 29 min (8%). CONCLUSION: A protocol without the routine use of oral contrast for CT of the abdomen and pelvis can result in improved time to completion and ED length of stay.

Bedside echocardiography for undifferentiated hypotension: diagnosis of a right heart thrombus.

A free-floating right heart thrombus is often a harbinger of a massive pulmonary embolism and must be diagnosed and treated rapidly in order to avoid significant adverse sequelae. We present the case of an 84-year-old female who presented with two days of dyspnea and was hypotensive on arrival. Bedside ultrasound was performed by the emergency physician and showed a large, mobile right heart thrombus leading to immediate administration of a thrombolytic. In this case, bedside ultrasound was utilized to help further delineate clinical care in a progressively worsening patient, leading to a potentially lifesaving treatment.

Obesity is associated with lower coronary microvascular density.

BACKGROUND: Obesity is associated with diastolic dysfunction, lower maximal myocardial blood flow, impaired myocardial metabolism and increased risk of heart failure. We examined the association between obesity, left ventricular filling pressure and myocardial structure. METHODS: We performed histological analysis of non-ischemic myocardium from 57 patients (46 men and 11 women) undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation or loop diuretic therapy. RESULTS: Non-obese (body mass index, BMI, ≤ 30 kg/m(2), n=33) and obese patients (BMI >30 kg/m(2), n=24) did not differ with respect to myocardial total, interstitial or perivascular fibrosis, arteriolar dimensions, or cardiomyocyte width. Obese patients had lower capillary length density (1145 ± 239, mean ± SD, vs. 1371 ± 333 mm/mm(3), P=0.007) and higher diffusion radius (16.9 ± 1.5 vs. 15.6 ± 2.0 µm, P=0.012), in comparison with non-obese patients. However, the diffusion radius/cardiomyocyte width ratio of obese patients (0.73 ± 0.11 µm/µm) was not significantly different from that of non-obese patients (0.71 ± 0.11 µm/µm), suggesting that differences in cardiomyocyte width explained in part the differences in capillary length density and diffusion radius between non-obese and obese patients. Increased BMI was associated with increased pulmonary capillary wedge pressure (PCWP, P<0.0001), and lower capillary length density was associated with both increased BMI (P=0.043) and increased PCWP (P=0.016). CONCLUSIONS: Obesity and its accompanying increase in left ventricular filling pressure were associated with lower coronary microvascular density, which may contribute to the lower maximal myocardial blood flow, impaired myocardial metabolism, diastolic dysfunction and higher risk of heart failure in obese individuals.

Types of tolerance seen in autoreactive phosphocholine-specific B cells are dependent on the idiotype of the receptors expressed.

Phosphocholine (PC) is the immunodominant epitope found on the surface of a number of microorganisms, including Streptococcus pneumoniae (SPn), and is thought to play a vital role in the pathogenesis of SPn. B cells expressing M167Hκ24L immunoglobulin receptors specific for PC have been shown to be autoreactive in that they undergo clonal deletion in both X-linked immune-deficient and Rag(-/-) mice. We have now shown that B cells expressing M603Hκ8L PC-specific receptors also delete in Rag(-/-) mice, whereas those expressing T15Hκ22L transgenes do not delete. However, T15Hκ22L B cells are lost in normal heterozygous transgenic mice because they cannot compete with normal B cells. These data indicate that M167Hκ24L and M603Hκ8L PC-specific B cells are recognizing an autoantigen expressed on membranes which causes them to downregulate their receptors and clonally delete, while T15Hκ22L B cells are tolerized by a soluble form of PC-antigen which results in their being trapped in the spleen. Thus, the types of tolerance seen in autoreactive PC-specific B cells are dependent on the idiotype of the receptors expressed.

Reduced microvascular density in non-ischemic myocardium of patients with recent non-ST-segment-elevation myocardial infarction.

BACKGROUND: Myocardial microvascular dysfunction has been implicated in the pathogenesis of myocardial infarction (MI). We tested the hypothesis that patients with MI have lower microvasculature density in myocardium remote from the site of infarction than patients with similar extent of coronary artery disease (CAD) without MI and examined the relationship between myocardial capillary length density and plasma levels of angiogenesis-related biomarkers. METHODS: We analyzed biopsies from non-ischemic left ventricular (LV) myocardium and measured plasma levels of angiogenesis-related biomarkers in patients undergoing coronary artery bypass graft surgery, 57 without previous MI (no-MI) and 27 with recent non-ST-segment-elevation MI (NSTEMI). Comparison was made with biopsies from 31 aortic stenosis (AS) patients and 6 patients with "normal" LV without CAD. RESULTS: Myocardial microvascular density of NSTEMI patients was approximately half the density of no-MI patients, and similar to AS patients. Whereas the reduced microvascular density of AS patients was accounted for by their cardiomyocyte hypertrophy, this was not the case for NSTEMI patients, who had higher diffusion radius/cardiomyocyte width ratio than no-MI, "normal" LV, and AS patients. NSTEMI patients had lower plasma levels of carboxymethyl lysine and low molecular weight fluorophores, higher vascular endothelial growth factor (VEGF) receptor-1/VEGF-A ratio, and higher endostatin and hepatocyte growth factor levels than no-MI patients. CONCLUSIONS: Recent MI was associated with reduced microvasculature density in myocardium remote from the site of infarction and alteration in plasma levels of angiogenesis-related biomarkers.

Diastolic dysfunction of aging is independent of myocardial structure but associated with plasma advanced glycation end-product levels.

BACKGROUND: Heart failure is associated with abnormalities of myocardial structure, and plasma levels of the advanced glycation end-product (AGE) N(ε)-(carboxymethyl)lysine (CML) correlate with the severity and prognosis of heart failure. Aging is associated with diastolic dysfunction and increased risk of heart failure, and we investigated the hypothesis that diastolic dysfunction of aging humans is associated with altered myocardial structure and plasma AGE levels. METHODS: We performed histological analysis of non-ischemic left ventricular myocardial biopsies and measured plasma levels of the AGEs CML and low molecular weight fluorophores (LMWFs) in 26 men undergoing coronary artery bypass graft surgery who had transthoracic echocardiography before surgery. None had previous cardiac surgery, myocardial infarction, atrial fibrillation, or heart failure. RESULTS: The patients were aged 43-78 years and increasing age was associated with echocardiographic indices of diastolic dysfunction, with higher mitral Doppler flow velocity A wave (r = 0.50, P = 0.02), lower mitral E/A wave ratio (r = 0.64, P = 0.001), longer mitral valve deceleration time (r = 0.42, P = 0.03) and lower early diastolic peak velocity of the mitral septal annulus, e' (r = 0.55, P = 0.008). However, neither mitral E/A ratio nor mitral septal e' was correlated with myocardial total, interstitial or perivascular fibrosis (picrosirius red), immunostaining for collagens I and III, CML, and receptor for AGEs (RAGE), cardiomyocyte width, capillary length density, diffusion radius or arteriolar dimensions. Plasma AGE levels were not associated with age. However, plasma CML levels were associated with E/A ratio (r = 0.44, P = 0.04) and e' (r = 0.51, P = 0.02) and LMWF levels were associated with E/A ratio (r = 0.49, P = 0.02). Moreover, the mitral E/A ratio remained correlated with plasma LMWF levels in all patients (P = 0.04) and the mitral septal e' remained correlated with plasma CML levels in non-diabetic patients (P = 0.007) when age was a covariate. CONCLUSIONS: Diastolic dysfunction of aging was independent of myocardial structure but was associated with plasma AGE levels.

Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease.

BACKGROUND: Type 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs) in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE) in men with coronary artery disease. METHODS: We performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction. RESULTS: All three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E'), consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red), or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyl)lysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis. CONCLUSIONS: Impaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the myocardial microvascular structure, or increased myocardial expression of Nε-(carboxymethyl)lysine or RAGE. These findings suggest that the increased myocardial fibrosis and AGE expression, cardiomyocyte hypertrophy, and altered microvasculature structure described in diabetic heart disease were a consequence, rather than an initiating cause, of cardiac dysfunction.

Differences in myocardial structure and coronary microvasculature between men and women with coronary artery disease.

Women younger than 75 years with stable angina or acute coronary syndrome have higher cardiac mortality than similarly aged men, despite less obstructive coronary artery disease. To determine whether the myocardial structure and coronary microvasculature of women differs from that of men, we performed histological analysis of biopsies from nonischemic left ventricular myocardium from 46 men and 11 women undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation, or furosemide therapy. The 2 patient groups had similar clinical characteristics, apart from a lower body surface area (BSA) in women (P = 0.0015). Women had less interstitial fibrosis than men (P = 0.019) but similar perivascular fibrosis. Arteriolar wall area/circumference ratio, a measure of arteriolar wall thickness, was 47% greater in women than men (P = 0.012). Cardiomyocyte width and diffusion radius were positively correlated, and capillary length density was negatively correlated with BSA (P < 0.05). Whereas cardiomyocyte width, capillary length density, diffusion radius, and cardiomyocyte width/BSA ratio were similar for men and women, women had a greater diffusion radius/BSA ratio (P = 0.0038) and a greater diffusion radius/cardiomyocyte width ratio (P = 0.027). Women also had lower vascular endothelial growth factor (VEGF) receptor-1 levels (P = 0.048) and VEGF receptor-1/VEGF-A ratio (P = 0.024) in plasma. We conclude that women with extensive coronary artery disease have greater arteriolar wall thickness and diffusion radius relative to BSA and to cardiomyocyte width than men, which may predispose to myocardial ischemia. Additional studies of larger numbers of women with less extensive coronary artery disease are required to confirm these findings.