Lipoid Pneumonia.

Lipoid pneumonia occurs due to the accumulation of lipids within the lung tissue. Autopsy series have reported an incidence of 1.0-2.5% in adult and 8.8% in children. Lipoid pneumonia can be from an exogeneous or an endogenous source. Exogenous lipoid pneumonia is often associated with aspiration of fatty materials, whereas endogenous lipoid pneumonia is associated with an accumulation of lipid-rich debris from destroyed alveolar cells. We describe a 75-year-old man who presented with spiculated lung nodules found incidentally on abdominal CT. Reviews of systems were positive for weight loss, and a history of constipation. A PET/CT revealed spiculated nodules with positive fluorodeoxyglucose (FDG) uptakes. A wedge resection was performed with histopathologic findings consistent with exogenous lipoid pneumonia with granulomatous reaction. We report clinical, radiological, and pathological features of exogenous lipoid pneumonia secondary to chronic aspiration mimicking invasive adenocarcinoma. A high index of suspicion for exogenous lipoid pneumonia should be maintained, especially when evaluating patients with abnormal chest radiographic findings and risk factors for aspirations.

Blood DNA methylation and COVID-19 outcomes.

BACKGROUND: There are no prior reports that compare differentially methylated regions of DNA in blood samples from COVID-19 patients to samples collected before the SARS-CoV-2 pandemic using a shared epigenotyping platform. We performed a genome-wide analysis of circulating blood DNA CpG methylation using the Infinium Human MethylationEPIC BeadChip on 124 blood samples from hospitalized COVID-19-positive and COVID-19-negative patients and compared these data with previously reported data from 39 healthy individuals collected before the pandemic. Prospective outcome measures such as COVID-19-GRAM risk-score and mortality were combined with methylation data. RESULTS: Global mean methylation levels did not differ between COVID-19 patients and healthy pre-pandemic controls. About 75% of acute illness-associated differentially methylated regions were located near gene promoter regions and were hypo-methylated in comparison with healthy pre-pandemic controls. Gene ontology analyses revealed terms associated with the immune response to viral infections and leukocyte activation; and disease ontology analyses revealed a predominance of autoimmune disorders. Among COVID-19-positive patients, worse outcomes were associated with a prevailing hyper-methylated status. Recursive feature elimination identified 77 differentially methylated positions predictive of COVID-19 severity measured by the GRAM-risk score. CONCLUSION: Our data contribute to the awareness that DNA methylation may influence the expression of genes that regulate COVID-19 progression and represent a targetable process in that setting.

Unique inflammatory profile is associated with higher SARS-CoV-2 acute respiratory distress syndrome (ARDS) mortality.

The COVID19 pandemic has caused more than a million of deaths worldwide, primarily due to complications from COVID19-associated acute respiratory distress syndrome (ARDS). Controversy surrounds the circulating cytokine/chemokine profile of COVID19-associated ARDS, with some groups suggesting that it is similar to patients without COVID19 ARDS and others observing substantial differences. Moreover, although a hyperinflammatory phenotype associates with higher mortality in non-COVID19 ARDS, there is little information on the inflammatory landscape's association with mortality in patients with COVID19 ARDS. Even though the circulating leukocytes' transcriptomic signature has been associated with distinct phenotypes and outcomes in critical illness including ARDS, it is unclear whether the mortality-associated inflammatory mediators from patients with COVID19 are transcriptionally regulated in the leukocyte compartment. Here, we conducted a prospective cohort study of 41 mechanically ventilated patients with COVID19 infection using highly calibrated methods to define the levels of plasma cytokines/chemokines and their gene expressions in circulating leukocytes. Plasma IL1RA and IL8 were found positively associated with mortality, whereas RANTES and EGF negatively associated with that outcome. However, the leukocyte gene expression of these proteins had no statistically significant correlation with mortality. These data suggest a unique inflammatory signature associated with severe COVID19.

Large-Scale Multi-omic Analysis of COVID-19 Severity.

We performed RNA-seq and high-resolution mass spectrometry on 128 blood samples from COVID-19-positive and COVID-19-negative patients with diverse disease severities and outcomes. Quantified transcripts, proteins, metabolites, and lipids were associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. We mapped 219 molecular features with high significance to COVID-19 status and severity, many of which were involved in complement activation, dysregulated lipid transport, and neutrophil activation. We identified sets of covarying molecules, e.g., protein gelsolin and metabolite citrate or plasmalogens and apolipoproteins, offering pathophysiological insights and therapeutic suggestions. The observed dysregulation of platelet function, blood coagulation, acute phase response, and endotheliopathy further illuminated the unique COVID-19 phenotype. We present a web-based tool (covid-omics.app) enabling interactive exploration of our compendium and illustrate its utility through a machine learning approach for prediction of COVID-19 severity.

ICU admission body composition: skeletal muscle, bone, and fat effects on mortality and disability at hospital discharge-a prospective, cohort study.

BACKGROUND: Reduced body weight at the time of intensive care unit (ICU) admission is associated with worse survival, and a paradoxical benefit of obesity has been suggested in critical illness. However, no research has addressed the survival effects of disaggregated body constituents of dry weight such as skeletal muscle, fat, and bone density. METHODS: Single-center, prospective observational cohort study of medical ICU (MICU) patients from an academic institution in the USA. Five hundred and seven patients requiring CT scanning of chest or abdomen within the first 24 h of ICU admission were evaluated with erector spinae muscle (ESM) and subcutaneous adipose tissue (SAT) areas and with bone density determinations at the time of ICU admission, which were correlated with clinical outcomes accounting for potential confounders. RESULTS: Larger admission ESM area was associated with decreased odds of 6-month mortality (OR per cm2, 0.96; 95% CI, 0.94-0.97; p < 0.001) and disability at discharge (OR per cm2, 0.98; 95% CI, 0.96-0.99; p = 0.012). Higher bone density was similarly associated with lower odds of mortality (OR per 100 HU, 0.69; 95% CI, 0.49-0.96; p = 0.027) and disability at discharge (OR per 100 HU, 0.52; 95% CI, 0.37-0.74; p < 0.001). SAT area was not significantly associated with these outcomes' measures. Multivariable modeling indicated that ESM area remained significantly associated with 6-month mortality and survival after adjusting for other covariates including preadmission comorbidities, albumin, functional independence before admission, severity scores, age, and exercise capacity. CONCLUSION: In our cohort, ICU admission skeletal muscle mass measured with ESM area and bone density were associated with survival and disability at discharge, although muscle area was the only component that remained significantly associated with survival after multivariable adjustments. SAT had no association with the analyzed outcome measures.

Large-scale Multi-omic Analysis of COVID-19 Severity.

We performed RNA-Seq and high-resolution mass spectrometry on 128 blood samples from COVID-19 positive and negative patients with diverse disease severities. Over 17,000 transcripts, proteins, metabolites, and lipids were quantified and associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. We mapped 219 molecular features with high significance to COVID-19 status and severity, many involved in complement activation, dysregulated lipid transport, and neutrophil activation. We identified sets of covarying molecules, e.g., protein gelsolin and metabolite citrate or plasmalogens and apolipoproteins, offering pathophysiological insights and therapeutic suggestions. The observed dysregulation of platelet function, blood coagulation, acute phase response, and endotheliopathy further illuminated the unique COVID-19 phenotype. We present a web-based tool (covid-omics.app) enabling interactive exploration of our compendium and illustrate its utility through a comparative analysis with published data and a machine learning approach for prediction of COVID-19 severity.

Corticosteroid Administration Is Associated With Improved Outcome in Patients With Severe Acute Respiratory Syndrome Coronavirus 2-Related Acute Respiratory Distress Syndrome.

OBJECTIVES: To compare the clinical outcome of mechanically ventilated patients with severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome, who received corticosteroid with those who did not. DESIGN: Retrospective analysis. SETTING: Intensive care setting. PATIENTS: All adult mechanically ventilated patients, who were admitted to the ICU between March 20, 2020, and May 10, 2020, for severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cohort was divided into two groups based on corticosteroid administration. The primary outcome variable was ventilator-free days at day 28. Secondary outcome variable was ICU-free days at day 30, and hospital-free days at day 30. Consecutive 61 mechanically ventilated patients with severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome were analyzed. Patient in corticosteroid group as compared with noncorticosteroid group have higher 28-day ventilator-free days (mean, 10.2; median, 7 [interquartile range, 0-22.3] vs mean, 4.7; median, 0 [interquartile range, 0-11]; p = 0.01).There was no significant difference noted in secondary outcomes (ICU-free days at day 30 and hospital-free days at day 30). CONCLUSIONS: Among mechanically ventilated severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome patients, corticosteroids use was associated with significant improvement in 28-day ventilator-free days at day 28, but no significant improvement in ICU-free days at day 30, and hospital-free days at day 30.

Unique inflammatory profile is associated with higher SARS-CoV-2 acute respiratory distress syndrome (ARDS) mortality.

The COVID19 pandemic is likely to cause more than a million of deaths worldwide, primarily due to complications from COVID19-associated acute respiratory distress syndrome (ARDS). Controversy surrounds the circulating cytokine/chemokine profile of COVID19-associated ARDS, with some groups suggesting that it is similar to non-COVID19 ARDS patients and others observing substantial differences. Moreover, while a hyperinflammatory phenotype associates with higher mortality in non-COVID19 ARDS, there is little information on the inflammatory landscape's association with mortality in COVID19 ARDS patients. Even though the circulating leukocytes' transcriptomic signature has been associated with distinct phenotypes and outcomes in critical illness including ARDS, it is unclear whether the mortality-associated inflammatory mediators from COVID19 patients are transcriptionally regulated in the leukocyte compartment. Here, we conducted a prospective cohort study of 41 mechanically ventilated patients with COVID19 infection using highly calibrated methods to define the levels of plasma cytokines/chemokines and their gene expressions in circulating leukocytes. Plasma IL1RA and IL8 were found positively associated with mortality while RANTES and EGF negatively associated with that outcome. However, the leukocyte gene expression of these proteins had no statistically significant correlation with mortality. These data suggest a unique inflammatory signature associated with severe COVID19.

Cannabinoid Oil Vaping-Associated Lung Injury and its Radiographic Appearance.

BACKGROUND: Lung injury associated with cannabinoid oil vaping is rapidly becoming a serious public health concern. We describe the clinical and radiographic presentations of 5 patients with lung injury associated with vaping cannabinoid oils seen at a single institution. RESULTS: Of the 5 patients with suspected vaping-associated lung injury seen at our institution, 4 required supplemental oxygen, and all these 4 were admitted to the hospital. Three patients required admission to the intensive care unit. None of the patients required mechanical ventilation. All patients demonstrated a consistent radiologic appearance of diffuse bilateral ground-glass lung opacities that spared the extreme periphery. Three patients underwent bronchoalveolar lavage, which revealed lipid-laden macrophages in 2 of them. All patients were successfully discharged from the hospital. Four received only supportive care, while the fifth required intravenous followed by oral corticosteroids. CONCLUSIONS: We report the clinical and radiographic presentation of 5 patients at our institution with cannabinoid oil vaping-associated lung injury. All patients displayed a consistent chest radiographic pattern of injury. Most responded to supportive care, although one required the addition of corticosteroids. Bronchoalveolar lavage results suggest that this injury may related to a toxic form of lipoid pneumonia.

ICU Admission Muscle and Fat Mass, Survival, and Disability at Discharge: A Prospective Cohort Study.

BACKGROUND: Skeletal muscle dysfunction occurring as a result of ICU admission associates with higher mortality. Although preadmission higher BMI correlates with better outcomes, the impact of baseline muscle and fat mass has not been defined. We therefore investigated the association of skeletal muscle and fat mass at ICU admission with survival and disability at hospital discharge. METHODS: This single-center, prospective, observational cohort study included medical ICU (MICU) patients from an academic institution in the Unites States. A total of 401 patients were evaluated with pectoralis muscle area (PMA) and subcutaneous adipose tissue (SAT) determinations conducted by CT scanning at the time of ICU admission, which were later correlated with clinical outcomes accounting for potential confounders. RESULTS: Larger admission PMA was associated with better outcomes, including higher 6-month survival (OR, 1.03; 95% CI, 1.01-1.04; P < .001), lower hospital mortality (OR, 0.96; 95% CI, 0.93-0.98; P < .001), and more ICU-free days (slope, 0.044 ± 0.019; P = .021). SAT was not significantly associated with any of the measured outcomes. In multivariable analyses, PMA association persisted with 6 months and hospital survival and ICU-free days, whereas SAT remained unassociated with survival or other outcomes. PMA was not associated with regaining of independence at the time of hospital discharge (OR, 0.99; 95% CI, 0.98-1.01; P = .56). CONCLUSIONS: In this study cohort, ICU admission PMA was associated with survival during and following critical illness; it was unable to predict regaining an independent lifestyle following discharge. ICU admission SAT mass was not associated with survival or other measured outcomes.