A 24-Year-Old Man With Dyspnea and a Broken Left Femur.

CASE PRESENTATION: A 24-year-old White man presented with 1-day complaints of progressive shortness of breath and fever. He recently underwent an open reduction and internal fixation of a left midshaft femur fracture from a skiing accident 4 days ago. He denied chest pain, skin rashes, hemoptysis, hematemesis, melena, or surgical site bleeding. On arrival, the patient appeared in mild respiratory distress with a respiratory rate of 23 breaths/min, temperature of 37.8°C, heart rate of 97 beats/min, BP of 95/54 mm Hg, and peripheral saturation of 97% on 6-L/min nasal canula. His initial peripheral saturation on room air was 67%. Physical examination was unremarkable, except for diffuse rhonchi on chest auscultation. Chest radiograph on admission showed alveolar opacities predominantly in bilateral lower lobes. A chest CT angiography revealed no evidence for pulmonary embolism. However, there were findings of diffuse bilateral ground-glass opacities with areas of patchy consolidation and innumerous micronodules in both lungs (Fig 1). Laboratory examination was significant for a drop of hemoglobin by 3 g/dL and hematocrit level by 7% since his hospital discharge 4 days earlier. His renal function and urine analysis were normal. Venous blood gas on admission showed pH of 7.39 and Pco2 of 43 mm Hg. Because of unexplained acute anemia, nonspecific CT chest findings and progressive dyspnea, a bronchoscopy with BAL was performed. Four aliquots of 60 mL saline solution were injected for lavage with fluid return (Fig 2). BAL fluid showed WBC count of 0.411 × 103/mm3, RBC count of 318 × 103/mm3, 100% fresh RBCs, 73% neutrophil, 24% lymphocytes, 1% monocytes, and 2% eosinophils. BAL fluid cytologic condition is shown in Figure 3. A full vasculitis workup by rheumatology was unremarkable. Ophthalmologic and skin examination were unrevealing.

An unusual case of explosive pleuritis without mediastinal shift.

Explosive pleuritis (EP) is an under-reported condition. Although there is no agreed-upon definition, generally, the term EP denotes a dramatic clinical and radiologic progression of pleural space inflammation in the setting of pneumonia. The pleural space inflammation leads to the formation of loculated complex pleural effusion or empyema, and pleural adhesion within a matter of hours, typically in less than 24 hours. Radiologically, these changes are manifested as opacification of the hemithorax with or without contralateral mediastinal shift. Streptococcal pneumonia is the most common cause of EP. Here we present a case and discuss the clinical, microbiologic, radiologic, and treatment aspects of EP. We also scrutinize the medical literature to compare the previously reported cases.

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.

Human Pulmonary Dirofilariasis: A Review for the Clinicians.

Human pulmonary dirofilariasis (HPD) is a rare zoonotic disease caused by Dirofilaria immitis, the nematode responsible for canine cardiopulmonary dirofilariasis (dog heartworm). The incidence of HPD is on the rise throughout the world due to increased awareness and factors affecting the vector (mosquito). Humans are accidental hosts for D. immitis. Most patients are asymptomatic and present with an incidental pulmonary nodule that mimics primary or metastatic pulmonary malignancy. Some patients suffer from pulmonary and systemic symptoms in the acute phase of pneumonitis caused by pulmonary arterial occlusion by the preadult worms resulting in pulmonary infarction and intense inflammation. These patients may have ill-defined pulmonary infiltrate on chest radiology. Pulmonary nodules represent the end result of initial pneumonitis. There are no specific clinical, laboratory, or radiologic findings that differentiate HPD from other causes of a pulmonary nodule. Although serologic tests exist, they are usually not commercially available. The majority of patients are diagnosed by histopathologic identification of the decomposing worm following surgical resection of the lesion.

Incidence and risk factors for secondary pulmonary infections in patients hospitalized with coronavirus disease 2019 pneumonia.

BACKGROUND: Secondary pulmonary infections (SPI) have not been well described in COVID-19 patients. Our study aims to examine the incidence and risk factors of SPI in hospitalized COVID-19 patients with pneumonia. METHODS: This was a retrospective, single-center study of adult COVID-19 patients with radiographic evidence of pneumonia admitted to a regional tertiary care hospital. SPI was defined as microorganisms identified on the respiratory tract with or without concurrent positive blood culture results for the same microorganism obtained at least 48 h after admission. RESULTS: Thirteen out of 244 (5%) had developed SPI during hospitalization. The median of the nadir lymphocyte count during hospitalization was significantly lower in patients with SPI as compared to those without SPI [0.4 K/uL (IQR 0.3-0.5) versus 0.6 K/uL (IQR 0.3-0.9)]. Patients with lower nadir lymphocyte had an increased risk of developing SPI with odds ratio (OR) of 1.21 (95% CI: 1.00 to 1.47, p = 0.04) per 0.1 K/uL decrement in nadir lymphocyte. The baseline median inflammatory markers of CRP [166.4 mg/L vs. 100.0 mg/L, p = 0.01] and d-dimer (18.5 mg/L vs. 1.4 mg/L, p<0.01), and peak procalcitonin (1.4 ng/mL vs. 0.3 ng/mL, p<0.01) and CRP (273.5 mg/L vs. 153.7 mg/L, p<0.01) during hospitalization were significantly higher in SPI group. CONCLUSIONS: The incidence of SPI in hospitalized COVID-19 patients was 5%. Lower nadir median lymphocyte count during hospitalization was associated with an increased OR of developing SPI. The CRP and d-dimer levels on admission, and peak procalcitonin and CRP levels during hospitalization were higher in patients with SPI.

Association between Drainage-Dependent Prolonged Air Leak after Partial Lung Resection and Clinical Outcomes: A Prospective Cohort Study.

Rationale: Prolonged air leak (PAL) after partial lung resection can occur owing to surgical complications or in the presence of residual thoracic space. The former type results in drainage-independent PAL (DIPAL), whereas the latter type results in drainage-dependent PAL (DDPAL). DDPAL is described after thoracentesis in patients with nonexpandable lung, where the thoracostomy tube can be discontinued safely despite an ongoing air leak. This distinction is clinically relevant, as in the presence of DDPAL, tube thoracostomy can be safely discontinued without the need for further interventions. Objectives: To determine the frequency and clinical relevance of DDAPL and DIPAL in patients with PAL after partial lung resection. Methods: We prospectively identified consecutive patients with PAL after partial lung resection. Pleural manometry was performed 3-5 days after surgery. Pleural pressure was measured for 20 minutes after clamping the thoracostomy tube. DDPAL was diagnosed if the end-expiratory pleural pressure remained stable after plateauing in the absence of respiratory symptoms. Results: Of 225 patients who underwent lung resection, we identified 22 (10%) who had PAL. Twenty patients had adequate pleural manometry readings. The majority, 16/20 (80%), had DDPAL and had lower median hospital length of stay than those with DIPAL (6.9 vs. 11 days; P = 0.02). All patients with DIPAL required reexploration surgery, whereas only one patient with DDPAL underwent reexploration surgery. Conclusions: Most PALs after partial lung resection are DDPAL. Patients with DDPAL have lower hospital length of stay and less need for reexploration surgery than those with DIPAL.

A 51-Year-Old Man With a Large Posterior Mediastinal Mass.

CASE PRESENTATION: A 51-year-old White male never-smoker presented with intermittent cough and progressive dyspnea. His symptoms started after an exposure to bat guano while cleaning his attic approximately 9 months earlier. He has received several courses of antibiotic and corticosteroid for these symptoms, with short-term relief.

A 75-Year-Old Woman With Pulmonary Nodules and Dyspnea.

CASE PRESENTATION: A 75-year-old woman was referred to the pulmonary office in January 2020 for cough and progressive worsening of shortness of breath over the years. Her medical history was significant for asthma that was diagnosed approximately 10 years earlier, when she first developed dyspnea. A pre-bronchodilator spirometry at that time showed severe airflow obstruction (Fig 1). The patient was incidentally found to have several noncalcified pulmonary nodules on a chest CT scan in 2015, which was obtained as a part of dyspnea workup. She underwent bronchoscopic evaluation with transbronchial biopsy of the largest nodule (1.6 × 1.2 cm) in the right middle lobe. She was diagnosed with low-grade neuroendocrine tumor (typical carcinoid) and had been under surveillance without any progression in the number of nodules or the size of the existing nodules. She was a lifelong nonsmoker and no family history of asthma. Over the years, she received multiple courses of systemic corticosteroids and different inhalers, without any improvement in her symptoms. The patient was frustrated by the lack of perceived benefit, and she discontinued all respiratory medications. She denied any fever, night sweats, exertional chest pain, or seasonal allergies but reported cough, wheezing, and severe exertional shortness of breath. She was unable to walk more than 20 feet at a time. She had no pets at home and did not travel outside the United States. Her only home medications were multivitamins and low-dose aspirin.

A 67-Year-Old Woman With Progressive Dyspnea and Innumerous Pulmonary Nodules.

CASE PRESENTATION: A 67-year-old woman, who recently immigrated to the United States from Afghanistan, presented to the hospital after sustaining a mechanical fall. She had no significant medical history and was not on any medication routinely. She denied any fever, night sweats, weight loss, shortness of breath, or hemoptysis. The patient had no prior personal history or exposure to TB. Results of a previous purified protein derivative skin test upon immigration were negative.

Pneumothorax in critically ill patients with COVID-19 infection: Incidence, clinical characteristics and outcomes in a case control multicenter study.

BACKGROUND: The clinical features and outcomes of mechanically ventilated patients with COVID-19 infection who develop a pneumothorax has not been rigorously described or compared to those who do not develop a pneumothorax. PURPOSE: To determine the incidence, clinical characteristics, and outcomes of critically ill patients with COVID-19 infection who developed pneumothorax. In addition, we compared the clinical characteristics and outcomes of mechanically ventilated patients who developed a pneumothorax with those who did not develop a pneumothorax. METHODS: This study was a multicenter retrospective analysis of all adult critically ill patients with COVID-19 infection who were admitted to intensive care units in 4 tertiary care centers in the United States. RESULTS: A total of 842 critically ill patients with COVID-19 infection were analyzed, out of which 594 (71%) were mechanically ventilated. The overall incidence of pneumothorax was 85/842 (10%), and 80/594 (13%) in those who were mechanically ventilated. As compared to mechanically ventilated patients in the non-pneumothorax group, mechanically ventilated patients in the pneumothorax group had worse respiratory parameters at the time of intubation (mean PaO2:FiO2 ratio 105 vs 150, P<0.001 and static respiratory system compliance: 30ml/cmH2O vs 39ml/cmH2O, P = 0.01) and significantly higher in-hospital mortality (63% vs 49%, P = 0.04). CONCLUSION: The overall incidence of pneumothorax in mechanically ventilated patients with COVID-19 infection was 13%. Mechanically ventilated patients with COVID-19 infection who developed pneumothorax had worse gas exchange and respiratory mechanics at the time of intubation and had a higher mortality compared to those who did not develop pneumothorax.

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.

The association of ABO blood type with the risk and severity of COVID-19 infection.

BACKGROUND: There is conflicting data in the literature about the association of ABO blood type and susceptibility to COVID-19 infection. Moreover, very few studies have examined the effect of blood type on severity of COVID-19 infection. METHODS: This was a retrospective, single-center analysis of adult patients with COVID-19 infection who were hospitalized between March 8th to July 31st, 2020 at a regional tertiary care hospital. All patients who were hospitalized with a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection and had a documented ABO blood type were enrolled in this analysis. Aims of this study were to examine the prevalence of ABO blood types in patients with COVID-19 infection and to determine the frequency of severe COVID-19 infection among ABO blood types. RESULTS: A total of 227 cases were identified. Our cohort had a mean age of 63.3 years and 60% were males. The most common blood type was O (49%) followed by A (36%), which was similar to the prevalence of ABO blood types in our regional population. Moreover, there was no significant difference in the frequency of severe COVID-19 infection between ABO blood types (O: 50%, A: 53%, B: 56%, AB: 57%; P=0.93), or any additional outcomes including in-hospital mortality rate (P=0.72), need for ICU admission (P=0.66), ICU free days at day 28 (P=0.51), hospital free days at day 28 (P=0.43), or need for acute renal replacement therapy (P=0.09). CONCLUSION: We did not find an increased susceptibility of any blood type to COVID-19 infection, nor was there an increased risk of severe COVID-19 infection in any ABO blood types.

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.

Correlation of Respiratory Physiologic Parameters in Mechanically Ventilated Coronavirus Disease 2019 Patients.

Acute respiratory distress syndrome secondary to severe acute respiratory syndrome coronavirus-2 pneumonia or coronavirus disease 2019-related acute respiratory distress syndrome is the primary cause of mortality in coronavirus disease 2019. Some studies have described the concept of "high and low" elastance coronavirus disease 2019-related acute respiratory distress syndrome and proposed individualized management for the acute respiratory distress syndrome, deviating from low tidal volume ventilation. We report simultaneously measured respiratory parameters (static lung compliance, alveolar dead space ventilation, and shunt fraction) in 14 patients with advanced coronavirus disease 2019-related acute respiratory distress syndrome. The results were consistent with typical acute respiratory distress syndrome and did not support the concept of high-type coronavirus disease 2019-related acute respiratory distress syndrome and low-type coronavirus disease 2019-related acute respiratory distress syndrome.

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.