Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: A propensity score-matched analysis.

Thrombotic complications occur at high rates in hospitalized patients with COVID-19, yet the impact of intensive antithrombotic therapy on mortality is uncertain. We examined in-hospital mortality with intermediate- compared to prophylactic-dose anticoagulation, and separately with in-hospital aspirin compared to no antiplatelet therapy, in a large, retrospective study of 2785 hospitalized adult COVID-19 patients. In this analysis, we established two separate, nested cohorts of patients (a) who received intermediate- or prophylactic-dose anticoagulation ("anticoagulation cohort", N = 1624), or (b) who were not on home antiplatelet therapy and received either in-hospital aspirin or no antiplatelet therapy ("aspirin cohort", N = 1956). To minimize bias and adjust for confounding factors, we incorporated propensity score matching and multivariable regression utilizing various markers of illness severity and other patient-specific covariates, yielding treatment groups with well-balanced covariates in each cohort. The primary outcome was cumulative incidence of in-hospital death. Among propensity score-matched patients in the anticoagulation cohort (N = 382), in a multivariable regression model, intermediate- compared to prophylactic-dose anticoagulation was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.518 [0.308-0.872]). Among propensity-score matched patients in the aspirin cohort (N = 638), in a multivariable regression model, in-hospital aspirin compared to no antiplatelet therapy was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.522 [0.336-0.812]). In this propensity score-matched, observational study of COVID-19, intermediate-dose anticoagulation and aspirin were each associated with a lower cumulative incidence of in-hospital death.

Abnormalities of Aspiration and Swallowing Function in Survivors of Acute Respiratory Failure.

The mechanisms responsible for aspiration are relatively unknown in patients recovering from acute respiratory failure (ARF) who required mechanical ventilation. Though many conditions may contribute to swallowing dysfunction, alterations in laryngeal structure and swallowing function likely play a role in the development of aspiration. At four university-based tertiary medical centers, we conducted a prospective cohort study of ARF patients who required intensive care and mechanical ventilation for at least 48 h. Within 72 h after extubation, a Fiberoptic Flexible Endoscopic Evaluation of Swallowing (FEES) examination was performed. Univariate and multivariable analyses examined the relationship between laryngeal structure and swallowing function abnormalities. Aspiration was the primary outcome, defined as a Penetration- Aspiration Scale (PAS) score of 6 or greater. Two other salient signs of dysphagia-spillage and residue-were secondary outcomes. A total of 213 patients were included in the final analysis. Aspiration was detected in 70 patients (33%) on at least one bolus. The most commonly aspirated consistency was thin liquids (27%). In univariate analyses, several abnormalities in laryngeal anatomy and structural movement were significantly associated with aspiration, spillage, and residue. In a multivariable analysis, the only variables that remained significant with aspiration were pharyngeal weakness (Odds ratio = 2.57, 95%CI = 1.16-5.84, p = 0.019) and upper airway edema (Odds ratio = 3.24, 95%CI = 1.44-7.66, p = 0.004). These results demonstrated that dysphagia in ARF survivors is multifactorial and characterized by both anatomic and physiologic abnormalities. These findings may have important implications for the development of novel interventions to treat dysphagia in ARF survivors.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT02363686, Aspiration in Acute Respiratory Failure Survivors.

The Association Between Endotracheal Tube Size and Aspiration (During Flexible Endoscopic Evaluation of Swallowing) in Acute Respiratory Failure Survivors.

OBJECTIVES: To determine whether a modifiable risk factor, endotracheal tube size, is associated with the diagnosis of postextubation aspiration in survivors of acute respiratory failure. DESIGN: Prospective cohort study. SETTING: ICUs at four academic tertiary care medical centers. PATIENTS: Two hundred ten patients who were at least 18 years old, admitted to an ICU, and mechanically ventilated with an endotracheal tube for longer than 48 hours were enrolled. INTERVENTIONS: Within 72 hours of extubation, all patients received a flexible endoscopic evaluation of swallowing examination that entailed administration of ice, thin liquid, thick liquid, puree, and cracker boluses. Patient demographics, treatment variables, and hospital outcomes were abstracted from the patient's medical records. Endotracheal tube size was independently selected by the patient's treating physicians. MEASUREMENTS AND MAIN RESULTS: For each flexible endoscopic evaluation of swallowing examination, laryngeal pathology was evaluated, and for each bolus, a Penetration Aspiration Scale score was assigned. Aspiration (Penetration Aspiration Scale score ≥ 6) was further categorized into nonsilent aspiration (Penetration Aspiration Scale score = 6 or 7) and silent aspiration (Penetration Aspiration Scale score = 8). One third of patients (n = 68) aspirated (Penetration Aspiration Scale score ≥ 6) on at least one bolus, 13.6% (n = 29) exhibited silent aspiration, and 23.8% (n = 50) exhibited nonsilent aspiration. In a multivariable analysis, endotracheal tube size (≤ 7.5 vs ≥ 8.0) was significantly associated with patients exhibiting any aspiration (Penetration Aspiration Scale score ≥ 6) (p = 0.016; odds ratio = 2.17; 95% CI 1.14-4.13) and with risk of developing laryngeal granulation tissue (p = 0.02). CONCLUSIONS: Larger endotracheal tube size was associated with increased risk of aspiration and laryngeal granulation tissue. Using smaller endotracheal tubes may reduce the risk of postextubation aspiration.

Relationship Between Laryngeal Sensation, Length of Intubation, and Aspiration in Patients with Acute Respiratory Failure.

Dysphagia is common in hospitalized patients post-extubation and associated with poor outcomes. Laryngeal sensation is critical for airway protection and safe swallowing. However, current understanding of the relationship between laryngeal sensation and aspiration in post-extubation populations is limited. Acute respiratory failure patients requiring intensive care unit admission and mechanical ventilation received a Flexible Endoscopic Evaluation of Swallowing (FEES) within 72 h of extubation. Univariate and multivariable analyses were performed to examine the relationship between laryngeal sensation, length of intubation, and aspiration. Secondary outcomes included pharyngolaryngeal secretions, pneumonia, and diet recommendations. One-hundred and three patients met inclusion criteria. Fifty-one patients demonstrated an absent laryngeal adductor reflex (LAR). Altered laryngeal sensation correlated with the presence of secretions (p = 0.004). There was a significant interaction between the LAR, aspiration, and duration of mechanical ventilation. Altered laryngeal sensation was significantly associated with aspiration on FEES only in patients with a shorter length of intubation (p = 0.008). Patients with altered laryngeal sensation were prescribed significantly more restricted liquid (p = 0.03) and solid (p = 0.001) diets. No relationship was found between laryngeal sensation and pneumonia. There is a high prevalence of laryngeal sensory deficits in mechanically ventilated patients post-extubation. Altered laryngeal sensation was associated with secretions, aspiration, and modified diet recommendations especially in those patients with a shorter length of mechanical ventilation. These results demonstrate that laryngeal sensory abnormalities impact the development of post-extubation dysphagia.

"Deterioration to Door Time": An Exploratory Analysis of Delays in Escalation of Care for Hospitalized Patients.

BACKGROUND: Timely escalation of care for patients experiencing clinical deterioration in the inpatient setting is challenging. Deterioration on a general floor has been associated with an increased risk of death, and the early period of deterioration may represent a time during which admission to the intensive care unit (ICU) improves survival. Previous studies examining the association between delay from onset of clinical deterioration to ICU transfer and mortality are few in number and were conducted more than 10 years ago. OBJECTIVE: We aimed to evaluate the impact of delays in the escalation of care among clinically deteriorating patients in the current era of inpatient medicine. DESIGN AND PARTICIPANTS: This was a retrospective cohort study that analyzed data from 793 patients transferred from non-intensive care unit (ICU) inpatient floors to the medical intensive care unit (MICU), from 2011 to 2013 at an urban, tertiary, academic medical center. MAIN MEASURES: "Deterioration to door time (DTDT)" was defined as the time between onset of clinical deterioration (as evidenced by the presence of one or more vital sign indicators including respiratory rate, systolic blood pressure, and heart rate) and arrival in the MICU. KEY RESULTS: In our sample, 64.6 % had delays in care escalation, defined as greater than 4 h based on previous studies. Mortality was significantly increased beginning at a DTDT of 12.1 h after adjusting for age, gender, and severity of illness. CONCLUSIONS: Delays in the escalation of care for clinically deteriorating hospitalized patients remain frequent in the current era of inpatient medicine, and are associated with increased in-hospital mortality. Development of performance measures for the care of clinically deteriorating inpatients remains essential, and timeliness of care escalation deserves further consideration.

Oral Alimentation in Neonatal and Adult Populations Requiring High-Flow Oxygen via Nasal Cannula.

Use of high-flow oxygen via nasal cannula (HFO2-NC) is increasingly common in intensive care unit (ICU) settings. Despite the critical interface between respiration and swallowing, and the high acuity of patients in ICUs, the impact of HFO2-NC on feeding and swallowing is unknown. The present prospective, single-center, cohort study investigated the impact of HFO2-NC use on oral alimentation in neonatal and adult ICU patients. Oral alimentation status was evaluated in 100 consecutive ICU inpatients (50 neonatal and 50 adult) requiring HFO2-NC. Participant characteristics, respiratory support, successful initiation of oral feeding in neonates, and successful resumption of oral feeding in adults were recorded. Seventeen of 50 (34 %) neonates requiring HFO2-NC were deemed developmentally and medically appropriate by the neonatologist and nursing to begin oral alimentation. All 17 (100 %) were successful with initiation of oral feedings. Thirty-three of 50 (66 %) continued nil per os due to prematurity or medical conditions precluding oral alimentation at time of data collection. Thirty-nine of 50 (78 %) adults requiring HFO2-NC were deemed medically appropriate by the intensivist and nursing to resume oral alimentation (n = 34) or with a functional swallow without aspiration on FEES (n = 5). All 39 (100 %) resumed oral alimentation successfully. Eleven of 50 (22 %) continued nil per os due to severe respiratory issues precluding both swallow testing and oral alimentation at time of data collection. All developmentally and medically appropriate neonatal and adult patients requiring HFO2-NC were successful with either the introduction or resumption of oral alimentation. Patients requiring HFO2-NC who are identified as having feeding or swallowing issues should be referred for swallowing evaluations using the same criteria as patients who do not require HFO2-NC, as it is not the use of HFO2-NC but rather patient-specific determinants of feeding and swallowing readiness and their underlying medical conditions that impact readiness for oral alimentation status.

Protocols and Hospital Mortality in Critically Ill Patients: The United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study.

OBJECTIVE: Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized ICUs have superior patient outcomes compared with less highly protocolized ICUs. DESIGN: Observational study in which participating ICUs completed a general assessment and enrolled new patients 1 day each week. PATIENTS: A total of 6,179 critically ill patients. SETTING: Fifty-nine ICUs in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was the number of ICU protocols; the primary outcome was hospital mortality. A total of 5,809 participants were followed prospectively, and 5,454 patients in 57 ICUs had complete outcome data. The median number of protocols per ICU was 19 (interquartile range, 15-21.5). In single-variable analyses, there were no differences in ICU and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in ICUs with a high versus low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p = 0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between ICUs with high versus low numbers of protocols for lung protective ventilation in acute respiratory distress syndrome (47% vs 52%; p = 0.28) and for spontaneous breathing trials (55% vs 51%; p = 0.27). CONCLUSIONS: Clinical protocols are highly prevalent in U.S. ICUs. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality.

Protocol-Based Care versus Individualized Management of Patients in the Intensive Care Unit.

The delivery of evidence-based care in the high-acuity environment of the intensive care unit can be challenging. In an effort to help turn guidelines and standards of care into consistent and uniform practice, physicians and hospitals turn toward protocol-based medical care. A protocol can help guide a practitioner to make correct interventions, at the right time, and in the proper order when managing a given disease. But to be considered a success, a protocol must meet several standards. A protocol must facilitate consistent practice, guiding the practitioner to deliver care more consistently than without the protocol. A good protocol must also be in alignment with the provider's general practice and beliefs to assure wide adoption and complete penetrance. Finally, the protocol must deliver the most medically correct care-neither simplifying nor overcomplicating health care delivery. In addition to the care the protocol delivers, it must overcome other barriers to gain acceptance. These include concerns about protocol usage among medical trainees, physician concern regarding loss of autonomy, and the ceiling effect protocol-driven care places on expert practitioners, among other concerns. The aim of this article is to critically appraise what it means for a protocol to be considered successful with an aim toward improving protocol design and implementation in the future.

Structure, process, and annual ICU mortality across 69 centers: United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study.

OBJECTIVE: Hospital-level variations in structure and process may affect clinical outcomes in ICUs. We sought to characterize the organizational structure, processes of care, use of protocols, and standardized outcomes in a large sample of U.S. ICUs. DESIGN: We surveyed 69 ICUs about organization, size, volume, staffing, processes of care, use of protocols, and annual ICU mortality. SETTING: ICUs participating in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. SUBJECTS: Sixty-nine intensivists completed the survey. MEASUREMENTS AND MAIN RESULTS: We characterized structure and process variables across ICUs, investigated relationships between these variables and annual ICU mortality, and adjusted for illness severity using Acute Physiology and Chronic Health Evaluation II. Ninety-four ICU directors were invited to participate in the study and 69 ICUs (73%) were enrolled, of which 25 (36%) were medical, 24 (35%) were surgical, and 20 (29%) were of mixed type, and 64 (93%) were located in teaching hospitals with a median number of five trainees per ICU. Average annual ICU mortality was 10.8%, average Acute Physiology and Chronic Health Evaluation II score was 19.3, 58% were closed units, and 41% had a 24-hour in-house intensivist. In multivariable linear regression adjusted for Acute Physiology and Chronic Health Evaluation II and multiple ICU structure and process factors, annual ICU mortality was lower in surgical ICUs than in medical ICUs (5.6% lower [95% CI, 2.4-8.8%]) or mixed ICUs (4.5% lower [95% CI, 0.4-8.7%]). We also found a lower annual ICU mortality among ICUs that had a daily plan of care review (5.8% lower [95% CI, 1.6-10.0%]) and a lower bed-to-nurse ratio (1.8% lower when the ratio decreased from 2:1 to 1.5:1 [95% CI, 0.25-3.4%]). In contrast, 24-hour intensivist coverage (p = 0.89) and closed ICU status (p = 0.16) were not associated with a lower annual ICU mortality. CONCLUSIONS: In a sample of 69 ICUs, a daily plan of care review and a lower bed-to-nurse ratio were both associated with a lower annual ICU mortality. In contrast to 24-hour intensivist staffing, improvement in team communication is a low-cost, process-targeted intervention strategy that may improve clinical outcomes in ICU patients.

Tele-Critical Care Support Outside the Intensive Care Unit.

Tele-intensive care unit (ICU), or Tele Critical Care (TCC), has been in active use for 25 years and has expanded beyond the original model to support critically ill patients beyond the confines of the ICU. Here, the author reviews the role of TCC in supporting rapid response events, critical care in emergency departments, and disaster and pandemic responses. The ability to rapidly expand critical care services has important capacity and care quality implications. Moreover, as TCC infrastructure becomes less expensive, the opportunities to leverage this care modality also have potentially important financial benefits.

A tale of two ligands: angiopoietins, the endothelium, and outcomes.

Angiopoietins signal via the Tie-2 receptor and are essential molecules for vasculogenesis during development and in the adult state play roles in vascular stability as well as inflammation and appear to be involved in the dysregulation of the endothelium in illness. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are, respectively, agonists and competitive partial agonists, which have been found to undergo alterations in individuals with sepsis. In sepsis, Ang-2 levels are elevated and Ang-1 is decreased. In the previous issue of Critical Care, Fiusa and colleagues measure circulating Ang-1 and Ang-2 along with other growth factors in humans with febrile neutropenia. The authors found that an increased Ang-2/Ang-1 ratio, or an elevated Ang-2 level, at the time of an initial fever, is associated with subsequent development of septic shock and death. These findings validate that the Ang-2/Ang-1 balance, which is thought to reflect overall signaling via the Tie-2 receptor, is relevant to outcomes in patients with sepsis. Importantly, the specimens were obtained far in advance of the development of septic shock, suggesting that detectable alterations in this pathway may provide early clues regarding outcomes. This study adds to the evidence that angiopoietins are early markers of endothelial dysfunction in sepsis and provide prognostic information regarding outcomes.

Role of semaphorin 7a signaling in transforming growth factor ß1-induced lung fibrosis and scleroderma-related interstitial lung disease.

OBJECTIVE: Semaphorin 7a regulates transforming growth factor ß1 (TGFß1)-induced fibrosis. This study was undertaken to test the hypothesis that semaphorin 7a exerts its profibrotic effects in part by promoting the tissue accumulation of CD45+ fibrocytes. METHODS: A murine model of pulmonary fibrosis in which an inducible, bioactive form of the human TGFß1 gene is overexpressed in the lung was used. Fibrosis and fibrocytes were evaluated in TGFß1-transgenic mice in which the semaphorin 7a locus had been disrupted. The effect of replacement or deletion of semaphorin 7a on bone marrow-derived cells was ascertained using bone marrow transplantation. The role of the semaphorin 7a receptor ß1 integrin was assessed using neutralizing antibodies. The applicability of these findings to TGFß1-driven fibrosis in humans was examined in patients with scleroderma-related interstitial lung disease (ILD). RESULTS: The appearance of fibrocytes in the lungs of TGFß1-transgenic mice required semaphorin 7a. Replacement of semaphorin 7a on bone marrow-derived cells restored lung fibrosis and fibrocytes. Immunoneutralization of ß1 integrin reduced pulmonary fibrocytes and fibrosis. Peripheral blood mononuclear cells (PBMCs) from patients with scleroderma-related ILD showed increased levels of messenger RNA for semaphorin 7a and its receptors, with semaphorin 7a located on collagen-producing fibrocytes and CD19+ lymphocytes. Peripheral blood fibrocyte outgrowth was enhanced in these patients. Stimulation of normal human PBMCs with recombinant semaphorin 7a enhanced fibrocyte differentiation; these effects were attenuated by ß1 integrin neutralization. CONCLUSION: Our findings indicate that interventions that reduce semaphorin 7a expression or prevent the semaphorin 7a-ß1 integrin interaction may ameliorate TGFß1-driven or fibrocyte-associated autoimmune fibroses.

Lung-Protective Ventilation Over 6 Years at a Large Academic Medical Center: An Evaluation of Trends, Adherence, and Perceptions of Benefit.

The main objective of this study was to evaluate trends in set tidal volumes across all adult ICUs at a large academic medical center over 6 years, with a focus on adherence to lung-protective ventilation (≤ 8-cc/kg ideal body weight). A secondary objective was to survey providers on their perceptions of lung-protective ventilation and barriers to its implementation. DESIGN: Retrospective observational analysis (primary objective) and cross-sectional survey study (secondary objective), both at a single center. PARTICIPANTS: Mechanically ventilated adult patients with a set tidal volume (primary objective) and providers rotating through the Medical and Neurosciences ICUs (secondary objective). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From 2013 to 2018, the average initial set tidal volume (cc/kg ideal body weight) decreased from 8.99 ± 2.19 to 7.45±1.34 (p < 0.001). The cardiothoracic ICU had the largest change in tidal volume from 11.09 ± 1.96 in 2013 to 7.97 ± 1.03 in 2018 (p < 0.001). Although the majority of tidal volumes across all ICUs were between 6.58 and 8.01 (interquartile range) in 2018, 27% of patients were still being ventilated at volumes greater than 8-cc/kg ideal body weight. Most surveyed respondents felt there was benefit to lung-protective ventilation, though many did not routinely calculate the set tidal volume in cc/kg ideal body weight, and most did not feel it was easily calculable with the current electronic medical record system. CONCLUSIONS: Despite a trend toward lower tidal volumes over the years, in 2018, over a quarter of mechanically ventilated adult patients were being ventilated with tidal volumes greater than 8 cc/kg. Survey data indicate that despite respondents acknowledging the benefits of lung-protective ventilation, there are barriers to its optimal implementation. Future modifications of the electronic medical record, including a calculator to set tidal volume in cc/kg and the use of default set tidal volumes, may help facilitate the delivery of and adherence to lung-protective ventilation.

Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: a propensity score-matched analysis.

Background: Thrombotic complications occur at high rates in hospitalized patients with COVID-19, yet the impact of intensive antithrombotic therapy on mortality is uncertain. Research Question: How does in-hospital mortality compare with intermediate- versus prophylactic-dose anticoagulation, and separately with in-hospital aspirin versus no antiplatelet therapy, in treatment of COVID-19? Study Design and Methods: Using data from 2785 hospitalized adult COVID-19 patients, we established two separate, nested cohorts of patients (1) who received intermediate- or prophylactic-dose anticoagulation ("anticoagulation cohort", N = 1624), or (2) who were not on home antiplatelet therapy and received either in-hospital aspirin or no antiplatelet therapy ("aspirin cohort", N = 1956). Propensity score matching utilizing various markers of illness severity and other patient-specific covariates yielded treatment groups with well-balanced covariates in each cohort. The primary outcome was cumulative incidence of in-hospital death. Results: Among propensity score-matched patients in the anticoagulation cohort (N = 382), in a multivariable regression model, intermediate- compared to prophylactic-dose anticoagulation was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.518 [0.308-0.872]). Among propensity-score matched patients in the aspirin cohort (N = 638), in a multivariable regression model, in-hospital aspirin compared to no antiplatelet therapy was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.522 [0.336-0.812]). Interpretation: In this propensity score-matched, observational study of COVID-19, intermediate-dose anticoagulation and aspirin were each associated with a lower cumulative incidence of in-hospital death.

Clinical characteristics and outcomes for 7,995 patients with SARS-CoV-2 infection.

OBJECTIVE: Severe acute respiratory syndrome virus (SARS-CoV-2) has infected millions of people worldwide. Our goal was to identify risk factors associated with admission and disease severity in patients with SARS-CoV-2. DESIGN: This was an observational, retrospective study based on real-world data for 7,995 patients with SARS-CoV-2 from a clinical data repository. SETTING: Yale New Haven Health (YNHH) is a five-hospital academic health system serving a diverse patient population with community and teaching facilities in both urban and suburban areas. POPULATIONS: The study included adult patients who had SARS-CoV-2 testing at YNHH between March 1 and April 30, 2020. MAIN OUTCOME AND PERFORMANCE MEASURES: Primary outcomes were admission and in-hospital mortality for patients with SARS-CoV-2 infection as determined by RT-PCR testing. We also assessed features associated with the need for respiratory support. RESULTS: Of the 28605 patients tested for SARS-CoV-2, 7995 patients (27.9%) had an infection (median age 52.3 years) and 2154 (26.9%) of these had an associated admission (median age 66.2 years). Of admitted patients, 2152 (99.9%) had a discharge disposition at the end of the study period. Of these, 329 (15.3%) required invasive mechanical ventilation and 305 (14.2%) expired. Increased age and male sex were positively associated with admission and in-hospital mortality (median age 80.7 years), while comorbidities had a much weaker association with the risk of admission or mortality. Black race (OR 1.43, 95%CI 1.14-1.78) and Hispanic ethnicity (OR 1.81, 95%CI 1.50-2.18) were identified as risk factors for admission, but, among discharged patients, age-adjusted in-hospital mortality was not significantly different among racial and ethnic groups. CONCLUSIONS: This observational study identified, among people testing positive for SARS-CoV-2 infection, older age and male sex as the most strongly associated risks for admission and in-hospital mortality in patients with SARS-CoV-2 infection. While minority racial and ethnic groups had increased burden of disease and risk of admission, age-adjusted in-hospital mortality for discharged patients was not significantly different among racial and ethnic groups. Ongoing studies will be needed to continue to evaluate these risks, particularly in the setting of evolving treatment guidelines.

Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype.

Profibrotic cells derived from circulating CD14+ monocytes include fibrocytes and alternatively activated macrophages. These cells are associated with interstitial lung disease (ILD) and are implicated in the pathogenesis of systemic sclerosis (SSc); however, the simultaneous presence of profibrotic cells and their associated mediators in the circulation of these patients has not been defined. We hypothesized that monocytes from patients with SSc-related ILD (SSc-ILD) would show profibrotic characteristics when compared with normal controls. We recruited patients with SSc-ILD (n=12) and normal controls (n=27) and quantified circulating collagen-producing cells by flow cytometry for CD45 and pro-collagen I. The in vitro activation potential of CD14+ monocytes in response to lipopolysaccharide was assessed using flow cytometry for CD163, and by ELISA for CCL18 and IL-10 secretion. Profibrotic mediators in plasma were quantified using Luminex-based assays. The concentration of circulating collagen-producing cells was increased in the SSc-ILD patients when compared with controls. These cells were composed of both CD34+ fibrocytes and a population of CD34+CD14+ cells. Cultured CD14+ monocytes from SSc-ILD patients revealed a profibrotic phenotype characterized by expression of CD163 and by enhanced secretion of CCL18 and IL-10 in response to proinflammatory activation. Plasma levels of IL-10, MCP-1, IL-1RA, and TNF levels were significantly elevated in the plasma of the SSc-ILD cohort. Subgroup analysis of the normal controls revealed that unlike the subjects < or =35 years, subjects > or =60 years old showed higher levels of circulating CD34+CD14+ cells, collagen-producing CD14+ monocytes, CD163+ monocytes, IL-4, IL-10, IL-13, MCP-1, and CCL18. These data indicate that the blood of patients with SSc-ILD and of healthy aged controls is enriched for fibrocytes, profibrotic monocytes, and fibrosis-associated mediators. Investigations defining the factors responsible for this peripheral blood profile may provide new insight into SSc-ILD as well as the pathophysiology of aging.

Development of an Accurate Bedside Swallowing Evaluation Decision Tree Algorithm for Detecting Aspiration in Acute Respiratory Failure Survivors.

BACKGROUND: The bedside swallowing evaluation (BSE) is an assessment of swallowing function and airway safety during swallowing. After extubation, the BSE often is used to identify the risk of aspiration in acute respiratory failure (ARF) survivors. RESEARCH QUESTION: We conducted a multicenter prospective study of ARF survivors to determine the accuracy of the BSE and to develop a decision tree algorithm to identify aspiration risk. STUDY DESIGN AND METHODS: Patients extubated after ≥ 48 hours of mechanical ventilation were eligible. Study procedures included the BSE followed by a gold standard evaluation, the flexible endoscopic evaluation of swallowing (FEES). RESULTS: Overall, 213 patients were included in the final analysis. Median time from extubation to BSE was 25 hours (interquartile range, 21-45 hours). The FEES was completed 1 hour after the BSE (interquartile range, 0.5-2 hours). A total of 33% (70/213; 95% CI, 26.6%-39.2%) of patients aspirated on at least one FEES bolus consistency test. Thin liquids were the most commonly aspirated consistency: 27% (54/197; 95% CI, 21%-34%). The BSE detected any aspiration with an accuracy of 52% (95% CI, 45%-58%), a sensitivity of 83% (95% CI, 74%-92%), and negative predictive value (NPV) of 81% (95% CI, 72%-91%). Using recursive partitioning analyses, a five-variable BSE-based decision tree algorithm was developed that improved the detection of aspiration with an accuracy of 81% (95% CI, 75%-87%), sensitivity of 95% (95% CI, 90%-98%), and NPV of 97% (95% CI, 95%-99%). INTERPRETATION: The BSE demonstrates variable accuracy to identify patients at high risk for aspiration. Our decision tree algorithm may enhance the BSE and may be used to identify patients at high risk for aspiration, yet requires further validation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02363686; URL: www.clinicaltrials.gov.