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.

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.

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.

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.

Immunostimulatory Tim-1-specific antibody deprograms Tregs and prevents transplant tolerance in mice.

T cell Ig mucin (Tim) molecules modulate CD4(+) T cell responses. In keeping with the view that Tim-1 generates a stimulatory signal for CD4(+) T cell activation, we hypothesized that an agonist Tim-1-specific mAb would intensify the CD4(+) T cell-dependant allograft response. Unexpectedly, we determined that a particular Tim-1-specific mAb exerted reciprocal effects upon the commitment of alloactivated T cells to regulatory and effector phenotypes. Commitment to the Th1 and Th17 phenotypes was fostered, whereas commitment to the Treg phenotype was hindered. Moreover, ligation of Tim-1 in vitro effectively deprogrammed Tregs and thus produced Tregs unable to control T cell responses. Overall, the effects of the agonist Tim-1-specific mAb on the allograft response stemmed from enhanced expansion and survival of T effector cells; a capacity to deprogram natural Tregs; and inhibition of the conversion of naive CD4(+) T cells into Tregs. The reciprocal effects of agonist Tim-1-specific mAbs upon effector T cells and Tregs serve to prevent allogeneic transplant tolerance.

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.

Tim-1 signaling substitutes for conventional signal 1 and requires costimulation to induce T cell proliferation.

Differentiation and clonal expansion of Ag-activated naive T cells play a pivotal role in the adaptive immune response. T cell Ig mucin (Tim) proteins influence the activation and differentiation of T cells. Tim-3 and Tim-2 clearly regulate Th1 and Th2 responses, respectively, but the precise influence of Tim-1 on T cell activation remains to be determined. We now show that Tim-1 stimulation in vivo and in vitro induces polyclonal activation of T cells despite absence of a conventional TCR-dependent signal 1. In this model, Tim-1-induced proliferation is dependent on strong signal 2 costimulation provided by mature dendritic cells. Ligation of Tim-1 upon CD4(+) T cells with an agonist anti-Tim-1 mAb elicits a rise in free cytosolic calcium, calcineurin-dependent nuclear translocation of NF-AT, and transcription of IL-2. Because Tim-4, the Tim-1 ligand, is expressed by mature dendritic cells, we propose that interaction between Tim-1(+) T cells and Tim-4(+) dendritic cells might ensure optimal stimulation of T cells, when TCR-derived signals originating within an inflamed environment are weak or waning.

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.

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.

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].

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.

Regulation of T-cell immunity by T-cell immunoglobulin and mucin domain proteins.

The ability of T helper (TH) precursor cells to differentiate into T effector populations confers the adaptive immune system with a means to protect the host from microbes and react to "foreign" antigenic tissues. T-cell immunoglobulin and mucin domain (TIM) proteins have recently been shown to be novel and critical regulators of T cell subset-driven dependent immune responsiveness. A dichotomy is emerging as to how Tim-3- and Tim-2- related signals respectively impact TH1 and TH2 responses. By comparison, the influence of the Tim-1 pathway seems to be broader and is probably not restricted to a specific type of T helper response. Beyond the mere control of the TH1/TH2 balance, Tim proteins are likely to target other regulatory components of the T cell response. Likewise, it is tempting to speculate that Tim proteins might also modulate the function of other T helper cell subsets such as TH3, TR1 and TH17 cells, among others.

Is there still a role for the classical Cox-Maze III?

BACKGROUND: The incidence of surgery for atrial fibrillation (AF) is rising, paralleled by an increase in the types of lesion sets and energy sources used. These alternate energy sources have simplified the surgery at the expense of increased cost of consumables. The classical Cox-Maze III is the gold standard therapy with a proven efficacy in curing AF. Our complete experience with this procedure is presented. METHODS: All 28 patients undergoing the classical Cox-Maze III procedure at our institution underwent preoperative assessment and were followed prospectively. RESULTS: Twenty-eight patients underwent the Cox-Maze III procedure between January 2001 and May 2003. Their mean age was 65 years (range, 44-80 years). Twenty-five patients had concomitant cardiac procedures. Mean duration of AF was 8.3 years. Permanent AF was present in 82%. Mean follow-up time was 15 +/- 8 months (range, 4-30 months). There were no perioperative or late deaths, or thromboembolic events. Sixty-one per cent had early (<3 months) atrial arrhythmia. Freedom from AF at most recent clinical follow up was 93%. Freedom from late atrial arrhythmia was 82%. Freedom from late AF or atrial flutter by pacemaker interrogation or Holter assessment was 77%. Anti-arrhythmic medication use was reduced. New York Heart Association class improved from an average of 2.8 preoperatively to 1.3 postoperatively. CONCLUSION: The result of the present study shows the safety and efficacy of the classical Cox-Maze III procedure. With the advantage of proven long-term efficacy, demonstrable safety and avoidance of costly technology, the Cox-Maze III should not be discounted as a treatment option in patients because of its perceived complexity.

2 BCR or NOT 2 BCR - receptor dilution: a unique mechanism for preventing the development of holes in the protective B cell repertoire.

The clonal selection theory and the associated corollaries have had a major influence in shaping our thinking about lymphoid cell development as well as how these cells respond to antigenic challenges. Among these concepts are that a single B cell expresses a single receptor with a single antigen specificity. While these hypotheses have proven invaluable in expanding our understanding of immune response, over time numerous observations have been made that suggest that the single cell, single receptor, single specificity model is not absolute. In this manuscript, we review this literature as it pertains to B cells and provide a summary that supports the notion that in certain situations, the over-arching rules by which we consider development and response of immune cells may be compromised. The result of compromising allelic and isotype exclusion is a small but real population of dual receptor expressing B cells. A number of mechanisms that have been proposed for generating these dual expressing B cells are presented and discussed. We also consider the negative implications of dual receptor expression on regulating and controlling autoreactive B cell populations as well as its beneficial contributions to preserving essential receptor specificities and thereby preventing the development of holes in the immune repertoire. Previously, the dual receptor expressing population has received relatively little attention. Improvements in the tools available to examine individual B cell populations have resulted in our identification of and discrimination between novel populations of B cells, including novel dual receptor expressing populations. This combined with continuing increases in our understanding of how the immune repertoire relates to a protective immune response will strengthen and further define this novel aspect of immune cell development.

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.

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.

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.