Acute Respiratory Distress Syndrome: Definition, Diagnosis, and Routine Management.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury characterized by severe hypoxemic respiratory failure, bilateral opacities on chest imaging, and low lung compliance. ARDS is a heterogeneous syndrome that is the common end point of a wide variety of predisposing conditions, with complex pathophysiology and underlying mechanisms. Routine management of ARDS is centered on lung-protective ventilation strategies such as low tidal volume ventilation and targeting low airway pressures to avoid exacerbation of lung injury, as well as a conservative fluid management strategy.

Using vulnerability assessment to characterize coastal protection benefits provided by estuarine habitats of a dynamic intracoastal waterway.

The existence of coastal ecosystems depends on their ability to gain sediment and keep pace with sea level rise. Similar to other coastal areas, Northeast Florida (United States) is experiencing rapid population growth, climate change, and shifting wetland communities. Rising seas and more severe storms, coupled with the intensification of human activities, can modify the biophysical environment, thereby increasing coastal exposure to storm-induced erosion and inundation. Using the Guana Tolomato Matanzas National Estuarine Research Reserve as a case study, we analyzed the distribution of coastal protection services-expressly, wave attenuation and sediment control-provided by estuarine habitats inside a dynamic Intracoastal waterway. We explored six coastal variables that contribute to coastal flooding and erosion-(a) relief, (b) geomorphology, (c) estuarine habitats, (d) wind exposure, (e) boat wake energy, and (f) storm surge potential-to assess physical exposure to coastal hazards. The highest levels of coastal exposure were found in the north and south sections of the Reserve (9% and 14%, respectively) compared to only 4% in the central, with exposure in the south driven by low wetland elevation, high surge potential, and shorelines composed of less stable sandy and muddy substrate. The most vulnerable areas of the central Reserve and main channel of the Intracoastal waterway were exposed to boat wakes from larger vessels frequently traveling at medium speeds (10-20 knots) and had shoreline segments oriented towards the prevailing winds (north-northeast). To guide management for the recently expanded Reserve into vulnerable areas near the City of Saint Augustine, we evaluated six sites of concern where the current distribution of estuarine habitats (mangroves, salt marshes, and oyster beds) likely play the greatest role in natural protection. Spatially explicit outputs also identified potential elevation maintenance strategies such as living shorelines, landform modification, and mangrove establishment for providing coastal risk-reduction and other ecosystem-service co-benefits. Salt marshes and mangroves in two sites of the central section (N-312 and S-312) were found to protect more than a one-quarter of their cross-shore length (27% and 73%, respectively) from transitioning to the highest exposure category. Proposed interventions for mangrove establishment and living shorelines could help maintain elevation in these sites of concern. This work sets the stage for additional research, education, and outreach about where mangroves, salt marshes, and oyster beds are most likely to reduce risk to wetland communities in the region.

Low-dose naltrexone use for the management of post-acute sequelae of COVID-19.

The global prevalence of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) stands at approximately 43 % among individuals who have previously had acute COVID-19. In contrast, in the United States, the National Center for Health Statistics (NCHS) estimates that around 11 % of individuals who have been infected with SARS-CoV-2 go on to experience long COVID. The underlying causes of PASC remains under investigation, and there are no currently established FDA-approved therapies. One of the leading hypotheses for the cause of PASC is the persistent activation of innate immune cells with increase systemic inflammation. Naltrexone is a medication with anti-inflammatory and immunomodulatory properties that has been used in other conditions that overlap with PASC. We performed a retrospective review of a clinical cohort of 59 patients at a single academic center who received low-dose naltrexone (LDN) off-label as a potential therapeutic intervention for PASC. The use of LDN was associated with a fewer number of symptoms, improved clinical symptoms (fatigue, post-exertional malaise, unrefreshing sleep, and abnormal sleep pattern), and a better functional status. This observation warrants testing in rigorous, randomized, placebo-controlled clinical trials.

HIRA: Heart Rate Interval based Rapid Alert score to characterize autonomic dysfunction among patients with sepsis-related acute respiratory failure (ARF).

Objective. To examine whether heart rate interval based rapid alert (HIRA) score derived from a combination model of heart rate variability (HRV) and modified early warning score (MEWS) is a surrogate for the detection of acute respiratory failure (ARF) in critically ill sepsis patients.Approach. Retrospective HRV analysis of sepsis patients admitted to Emory healthcare intensive care unit (ICU) was performed between sepsis-related ARF and sepsis controls without ARF. HRV measures such as time domain, frequency domain, and nonlinear measures were analyzed up to 24 h after patient admission, 1 h before the onset of ARF, and a random event time in the sepsis controls. Statistical significance was computed by the Wilcoxon Rank Sum test. Machine learning algorithms such as eXtreme Gradient Boosting and logistic regression were developed to validate the HIRA score model. The performance of HIRA and early warning score models were evaluated using the area under the receiver operating characteristic (AUROC).Main Results. A total of 89 (ICU) patients with sepsis were included in this retrospective cohort study, of whom 31 (34%) developed sepsis-related ARF and 58 (65%) were sepsis controls without ARF. Time-domain HRV for Electrocardiogram (ECG) Beat-to-Beat RR intervals strongly distinguished ARF patients from controls. HRV measures for nonlinear and frequency domains were significantly altered (p< 0.05) among ARF compared to controls. The HIRA score AUC: 0.93; 95% confidence interval (CI): 0.88-0.98) showed a higher predictive ability to detect ARF when compared to MEWS (AUC: 0.71; 95% CI: 0.50-0.90).Significance. HRV was significantly impaired across patients who developed ARF when compared to controls. The HIRA score uses non-invasively derived HRV and may be used to inform diagnostic and therapeutic decisions regarding the severity of sepsis and earlier identification of the need for mechanical ventilation.

Trend in Clinical Trial Participation During COVID-19: A Secondary Analysis of the I-SPY COVID Clinical Trial.

To analyze the temporal trend in enrollment rates in a COVID-19 platform trial during the first three waves of the pandemic in the United States. DESIGN: Secondary analysis of data from the I-SPY COVID randomized controlled trial (RCT). SETTING: Thirty-one hospitals throughout the United States. PATIENTS: Patients who were approached, either directly or via a legally authorized representative, for consent and enrollment into the I-SPY COVID RCT. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1,338 patients approached for the I-SPY COVID trial from July 30, 2020, to February 17, 2022, the number of patients who enrolled (n = 1,063) versus declined participation (n = 275) was used to calculate monthly enrollment rates. Overall, demographic and baseline clinical characteristics were similar between those who enrolled versus declined. Enrollment rates fluctuated over the course of the COVID-19 pandemic, but there were no significant trends over time (Mann-Kendall test, p = 0.21). Enrollment rates were also comparable between vaccinated and unvaccinated patients. In multivariable logistic regression analysis, age, sex, region of residence, COVID-19 severity of illness, and vaccination status were not significantly associated with the decision to decline consent. CONCLUSIONS: In this secondary analysis of the I-SPY COVID clinical trial, there was no significant association between the enrollment rate and time period or vaccination status among all eligible patients approached for clinical trial participation. Additional studies are needed to better understand whether the COVID-19 pandemic has altered clinical trial participation and to develop strategies for encouraging participation in future COVID-19 and critical care clinical trials.

Serial Measurements of Protein Biomarkers in Sepsis-Induced Acute Respiratory Distress Syndrome.

The role of early, serial measurements of protein biomarkers in sepsis-induced acute respiratory distress syndrome (ARDS) is not clear. OBJECTIVES: To determine the differences in soluble receptor for advanced glycation end-products (sRAGEs), angiopoietin-2, and surfactant protein-D (SP-D) levels and their changes over time between sepsis patients with and without ARDS. DESIGN SETTING AND PARTICIPANTS: Prospective observational cohort study of adult patients admitted to the medical ICU at Grady Memorial Hospital within 72 hours of sepsis diagnosis. MAIN OUTCOMES AND MEASURES: Plasma sRAGE, angiopoietin-2, and SP-D levels were measured for 3 consecutive days after enrollment. The primary outcome was ARDS development, and the secondary outcome of 28-day mortality. The biomarker levels and their changes over time were compared between ARDS and non-ARDS patients and between nonsurvivors and survivors. RESULTS: We enrolled 111 patients, and 21 patients (18.9%) developed ARDS. The three biomarker levels were not significantly different between ARDS and non-ARDS patients on all 3 days of measurement. Nonsurvivors had higher levels of all three biomarkers than did survivors on multiple days. The changes of the biomarker levels over time were not different between the outcome groups. Logistic regression analyses showed association between day 1 SP-D level and mortality (odds ratio, 1.52; 95% CI, 1.03-2.24; p = 0.03), and generalized estimating equation analyses showed association between angiopoietin-2 levels and mortality (estimate 0.0002; se 0.0001; p = 0.04). CONCLUSIONS AND RELEVANCE: Among critically ill patients with sepsis, sRAGE, angiopoietin-2, and SP-D levels were not significantly different between ARDS and non-ARDS patients but were higher in nonsurvivors compared with survivors. The trend toward higher levels of sRAGE and SP-D, but not of angiopoietin-2, in ARDS patients may indicate the importance of epithelial injury in sepsis-induced ARDS. Changes of the biomarker levels over time were not different between the outcome groups.

Comparison of Cyclic and Linear Poly(lactide)s Using Small-Angle Neutron Scattering.

Small-angle neutron scattering (SANS) experiments were conducted on cyclic and linear polymers of racemic and l-lactides (PLA) with the goal of comparing chain configurations, scaling, and effective polymer-solvent interactions of the two topologies in acetone-d 6 and THF-d 8. There are limited reports of SANS results on cyclic polymers due to the lack of substantial development in the field until recently. Now that pure, well-defined cyclic polymers are accessible, unanswered questions about their rheology and physical conformations can be better investigated. Previously reported SANS experiments have used cyclic and linear polystyrene samples; therefore, our work allowed for direct comparison using a contrasting (structurally and sterically) polymer. We compared SANS results of cyclic and linear PLA samples with various microstructures and molecular weights at two different temperatures, allowing for comparison with a wide range of variables. The results followed the trends of previous experiments, but much greater differences in the effective polymer-solvent interaction parameters between cyclic and linear forms of PLA were observed, implying that the small form factor and hydrogen bonding in PLA allowed for much more compact conformations in the cyclic form only. Also, the polymer microstructure was found to influence polymer-solvent interaction parameters substantially. These results illustrate how the difference in polymer-solvent interactions between cyclic and linear polymers can vary greatly depending on the polymer in question and the potential of neutron scattering as a tool for identification and characterization of the cyclic topology.

eARDS: A multi-center validation of an interpretable machine learning algorithm of early onset Acute Respiratory Distress Syndrome (ARDS) among critically ill adults with COVID-19.

We present an interpretable machine learning algorithm called 'eARDS' for predicting ARDS in an ICU population comprising COVID-19 patients, up to 12-hours before satisfying the Berlin clinical criteria. The analysis was conducted on data collected from the Intensive care units (ICU) at Emory Healthcare, Atlanta, GA and University of Tennessee Health Science Center, Memphis, TN and the Cerner® Health Facts Deidentified Database, a multi-site COVID-19 EMR database. The participants in the analysis consisted of adults over 18 years of age. Clinical data from 35,804 patients who developed ARDS and controls were used to generate predictive models that identify risk for ARDS onset up to 12-hours before satisfying the Berlin criteria. We identified salient features from the electronic medical record that predicted respiratory failure among this population. The machine learning algorithm which provided the best performance exhibited AUROC of 0.89 (95% CI = 0.88-0.90), sensitivity of 0.77 (95% CI = 0.75-0.78), specificity 0.85 (95% CI = 085-0.86). Validation performance across two separate health systems (comprising 899 COVID-19 patients) exhibited AUROC of 0.82 (0.81-0.83) and 0.89 (0.87, 0.90). Important features for prediction of ARDS included minimum oxygen saturation (SpO2), standard deviation of the systolic blood pressure (SBP), O2 flow, and maximum respiratory rate over an observational window of 16-hours. Analyzing the performance of the model across various cohorts indicates that the model performed best among a younger age group (18-40) (AUROC = 0.93 [0.92-0.94]), compared to an older age group (80+) (AUROC = 0.81 [0.81-0.82]). The model performance was comparable on both male and female groups, but performed significantly better on the severe ARDS group compared to the mild and moderate groups. The eARDS system demonstrated robust performance for predicting COVID19 patients who developed ARDS at least 12-hours before the Berlin clinical criteria, across two independent health systems.

Synthesis, Properties, and Applications of Bio-Based Cyclic Aliphatic Polyesters.

Cyclic polymers have long been reported in the literature, but their development has often been stunted by synthetic difficulties such as the presence of linear contaminants. Research into the synthesis of these polymers has made great progress in the past decade, and this review covers the synthesis, properties, and applications of cyclic polymers, with an emphasis on bio-based aliphatic polyesters. Synthetic routes to cyclic polymers synthesized from bioderived monomers, alongside mechanistic descriptions for both ring closure and ring expansion polymerization approaches, are reviewed. The review also highlights some of the unique physical properties of cyclic polymers together with potential applications. The findings illustrate the substantial recent developments made in the syntheses of cyclic polymers, as well as the progress which can be made in the commercialization of bio-based polymers through the versatility this topology provides.

Myocardial Viability Imaging using Manganese-Enhanced MRI in the First Hours after Myocardial Infarction.

Early measurements of tissue viability after myocardial infarction (MI) are essential for accurate diagnosis and treatment planning but are challenging to obtain. Here, manganese, a calcium analogue and clinically approved magnetic resonance imaging (MRI) contrast agent, is used as an imaging biomarker of myocardial viability in the first hours after experimental MI. Safe Mn2+ dosing is confirmed by measuring in vitro beating rates, calcium transients, and action potentials in cardiomyocytes, and in vivo heart rates and cardiac contractility in mice. Quantitative T1 mapping-manganese-enhanced MRI (MEMRI) reveals elevated and increasing Mn2+ uptake in viable myocardium remote from the infarct, suggesting MEMRI offers a quantitative biomarker of cardiac inotropy. MEMRI evaluation of infarct size at 1 h, 1 and 14 days after MI quantifies myocardial viability earlier than the current gold-standard technique, late-gadolinium-enhanced MRI. These data, coupled with the re-emergence of clinical Mn2+ -based contrast agents open the possibility of using MEMRI for direct evaluation of myocardial viability early after ischemic onset in patients.

Support for Health Insurance Coverage for Legal Abortion in the United States.

The use of health insurance to cover legal abortion is a controversial issue on which Americans are sharply divided. Currently, there is a lack of research on this issue as data became available only recently. Using data from the newly released General Social Survey in 2018, this study examines who is more or less likely to support health insurance coverage for legal abortion. The results show that the support and opposition were about evenly divided. The findings from the logistic regression analysis reveal that, holding other variables constant, Democrats, liberals, urban residents, the more educated, and the older were more likely to support health insurance coverage for legal abortion while women, Southerners, Christians, the currently married, and those with more children were less likely to favor it, compared to their respective counterparts. Additionally, the effect of education was stronger for liberals than for non-liberals. Race, family income, and full-time work status make no difference in the outcome. The findings have significant implications for research and practices in health insurance coverage for legal abortion.

In COVID-19, adding lopinavir-ritonavir to usual care did not shorten time to clinical improvement.

SOURCE CITATION: Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382:1787-99. 32187464.

Explaining Health Outcomes of Asian Immigrants: Does Ethnicity Matter?

The present study intended to evaluate whether 4 discrete ethnic groups of Asian immigrants could, for empirical reasons, be assigned a set of unique operating factors explaining health outcomes of members. The set comprised several acculturation, social structure, lifestyle, and health-related factors. Our study asked if these factors uniformly explained health outcomes across the 4 groups. We pooled National Health Interview Survey (NHIS) data dating 1999-2015 and developed 2 outcomes: self-rated health and self-reported chronic illness (specifically, diagnosis of cardiovascular disease, prediabetes/diabetes, hypertension, cancer, or stroke). Since data for smaller Asian ethnic groups are not readily available, we confined our analyses to respondents of Chinese, Filipino, Asian Indian, and "other Asian" ethnicity. Descriptive statistics suggested that Asian Indian respondents were least likely to report having 1 of the 5 specified serious illnesses and self-rated their health higher than the other 3 respondent groups. Additionally, while some factors (e.g., body mass index, depression) proved related to the health outcomes across the 4 ethnic groups, we did observe for each group a unique pattern of factors associated with the outcomes. Our results confirmed, furthermore, a moderating role for ethnicity in associations between the outcomes and those operating factors in the set we evaluated. The study results should be of use in tailoring preventive and intervention programs to various ethnic groups of Asian immigrants; clearly, in promoting health, one approach will not fit all.

Risk factors and outcomes of acute respiratory distress syndrome in critically ill patients with cirrhosis.

AIM: Prior randomized controlled trials of acute respiratory distress syndrome (ARDS) excluded critically ill patients with cirrhosis. Data regarding risk factors for ARDS development and outcomes from ARDS in patients with cirrhosis are scarce. We sought to characterize outcomes from ARDS in patients with cirrhosis. METHODS: An observational cohort of patients with cirrhosis admitted to an intensive care unit at a high-volume liver transplant center between 1 January 2012 and 31 December 2014 were reviewed. ARDS cases were identified according to the Berlin definition. Potential risk factors were examined in multivariable logistic regression analysis for ARDS development. Outcomes including in-hospital mortality were compared between ARDS and non-ARDS patients. RESULTS: A total of 559 patients met the inclusion criteria and 45 (8.1%) developed ARDS. Differences between ARDS and non-ARDS patients included sepsis, Model for End-Stage Liver Disease - Sodium score, and Sequential Organ Failure Assessment score. In-hospital mortality was higher in cirrhotic patients with ARDS compared with those without ARDS (82.2% vs. 27.6%, P < 0.001). In multivariable analysis, acute-on-chronic liver failure (OR 8.69, 95% CI 2.28-33.18, P < 0.01) and shock on intensive care unit admission (OR 3.13, 95% CI 1.57-6.24, P = 0.001) were associated with ARDS development, whereas etiology of cirrhosis or alcohol use were not. CONCLUSIONS: Acute-on-chronic liver failure and shock on intensive care unit admission were risk factors for ARDS development, whereas etiology of cirrhosis and alcohol were not. Mortality from ARDS was markedly increased in patients with cirrhosis. Early recognition and treatment for infection might be important for improving the high mortality in this group of patients.

A Computable Phenotype for Acute Respiratory Distress Syndrome Using Natural Language Processing and Machine Learning.

Acute Respiratory Distress Syndrome (ARDS) is a syndrome of respiratory failure that may be identified using text from radiology reports. The objective of this study was to determine whether natural language processing (NLP) with machine learning performs better than a traditional keyword model for ARDS identification. Linguistic pre-processing of reports was performed and text features were inputs to machine learning classifiers tuned using 10-fold cross-validation on 80% of the sample size and tested in the remaining 20%. A cohort of 533 patients was evaluated, with a data corpus of 9,255 radiology reports. The traditional model had an accuracy of 67.3% (95% CI: 58.3-76.3) with a positive predictive value (PPV) of 41.7% (95% CI: 27.7-55.6). The best NLP model had an accuracy of 83.0% (95% CI: 75.9-90.2) with a PPV of 71.4% (95% CI: 52.1-90.8). A computable phenotype for ARDS with NLP may identify more cases than the traditional model.

Family, neighbourhood, and children's health: Trends and racial/ethnic disparities between 2003 and 2007 in the U.S.

The present study examined the race/ethnicity-specific trend of parent-reported health among children aged 17 years and under in the U.S. between 2003 and 2007, and its relationship with family background, neighbourhood support and neighbourhood safety. Data from the 2003 and 2007 National Survey of Children's Health (NSCH) were merged and analysed after taking into account the weighting and the complex sampling design of the data. Trends in children's health and racial/ethnic disparities were identified for this time period. Multivariate models were analysed to examine the association between children's health and their family background variables, neighbourhood support and safety, and other socio-demographic variables. Race/ethnicity-specific stratified models were also performed. Our findings indicated an adverse trend in the parent-reported health among children in the U.S. from 2003 to 2007, and little progress has been made towards reducing the health disparities by race/ethnicity. Racial/ethnic disparities also existed in children's family background and neighbourhood support and safety. Further, the health effects of family background and neighbourhood characteristics differed in magnitudes and directions by race/ethnicity. These findings suggest that different intervention/prevention strategies should be employed in improving childhood health for different racial/ethnic groups.

Immunologic Network and Response to Intramyocardial CD34+ Stem Cell Therapy in Patients With Dilated Cardiomyopathy.

BACKGROUND: Although stem cell therapy (SCT) is emerging as a potential treatment for patients with dilated cardiomyopathy (DCM), clinical response remains variable. Our objective was to determine whether baseline differences in circulating immunologic and nonimmunologic biomarkers may help to identify patients more likely to respond to intramyocardial injection of CD34(+)-based SCT. METHODS AND RESULTS: We enrolled from January 3, 2011 to March 5, 2012 37 patients with longstanding DCM (left ventricular ejection fraction [LVEF] <40%, New York Heart Association functional class III) who underwent peripheral CD34(+) stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) and collection by means of apheresis. CD34(+) cells were labeled with (99m)Tc-hexamethylpropyleneamine oxime to allow assessment of stem cell retention at 18 hours. Response to SCT was predefined as an increase in LVEF of ≥5% at 3 months. The majority (84%) of patients were male with an overall mean LVEF of 27 ± 7% and a median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of 2,774 pg/mL. Nineteen patients (51%) were responders to SCT. There was no significant difference between responders and nonresponders regarding to age, sex, baseline LVEF, NT-proBNP levels, or 6-minute walking distance. With the use of a partial least squares (PLS) predictive model, we identified 9 baseline factors that were associated with both stem cell response and stem cell retention (mechanistic validation). Among the baseline factors positively associated with both clinical response and stem cell retention were G-CSF, SDF-1, LIF, MCP-1, and MCP-3. Among baseline factors negatively associated with both clinical response and retention were IL-12p70, FASL, ICAM-1, and GGT. A decrease in G-CSF at 3-month follow-up was also observed in responders compared with nonresponders (P = .02). CONCLUSIONS: If further validated, baseline immunologic and nonimmunologic biomarkers may help to identify patients with DCM who are more likely to respond to CD34(+)-based SCT.