Relationship Between the Mixed Venous-to-Arterial Carbon Dioxide Gradient and Cardiac Index in Acute Pulmonary Embolism.

BACKGROUND: Among patients with acute pulmonary embolism (PE) undergoing mechanical thrombectomy, the cardiac index (CI) is frequently reduced even among those without clinically apparent shock. The purpose of this study was to describe the mixed venous-to-arterial carbon dioxide gradient (CO2 gap), a surrogate of perfusion adequacy, among patients with acute PE undergoing mechanical thrombectomy. METHODS: This was a single-center retrospective study of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization over a 3-year period. RESULTS: Of 107 patients, 97 had simultaneous mixed venous and arterial blood gas measurements available. The CO2 gap was elevated (>6 mmHg) in 51% of the cohort and in 49% of patients with intermediate-risk PE. A reduced CI (≤2.2 L/min/m2) was associated with an increased odds (OR = 7.9; 95% CI 3.49-18.1, p < 0.001) for an elevated CO2 gap. There was an inverse relationship between CI and CO2 gap. For every 1 L/min/m2 decrease in the CI, the CO2 gap increased by 1.3 mmHg (p = 0.001). Among patients with an elevated baseline CO2 gap >6 mmHg, thrombectomy improved CO2 gap, CI, and mixed venous oxygen saturation. When the CO2 gap was dichotomized above and below 6, there was no difference in in-hospital mortality (9% vs. 0%; p = 0.10, HR: 1.24; 95% CI: 0.97-1.60; P = 0.085). CONCLUSIONS: Among patients with acute PE undergoing mechanical thrombectomy, the CO2 gap is abnormal in nearly 50% of patients and inversely related to CI. Further studies should examine the relationship between markers of perfusion and outcomes in this population to refine risk stratification.

Emerging Therapeutic Options for Refractory Pulmonary Sarcoidosis: The Evidence and Proposed Mechanisms of Action.

Sarcoidosis is a systemic disease with heterogenous clinical phenotypes characterized by non-necrotizing granuloma formation in affected organs. Most disease either remits spontaneously or responds to corticosteroids and second-line disease-modifying therapies. These medications are associated with numerous toxicities that can significantly impact patient quality-of-life and often limit their long-term use. Additionally, a minority of patients experience chronic, progressive disease that proves refractory to standard treatments. To date, there are limited data to guide the selection of alternative third-line medications for these patients. This review will outline the pathobiological rationale behind current and emerging therapeutic agents for refractory or drug-intolerant sarcoidosis and summarize the existing clinical evidence in support of their use.

Rationale and design of the SARCoidosis Outcomes in all respiratory Viral Infectious Diseases (SARCOVID) Study.

INTRODUCTION: Respiratory infections are ubiquitous. The COVID-19 pandemic has refocused our attention on how morbid and potentially fatal they can be, and how host factors have an impact on the clinical course and outcomes. Due to a range of vulnerabilities, patients with sarcoidosis may be at higher risk of poor outcomes from respiratory infections. The objective of the SARCoidosis Outcomes in all respiratory Viral Infectious Diseases (SARCOVID) Study is to determine the short-term and long-term impacts of respiratory viral illnesses (COVID-19 and non-COVID-19) in sarcoidosis. METHODS AND ANALYSIS: Up to 20 clinical sites across the USA are participating in the recruitment of 2000 patients for this observational, prospective study. To ensure that the study cohort is representative of the general population with sarcoidosis, participating sites include those dedicated to reaching under-represented minorities or patients from non-urban areas. Baseline data on demographic features, comorbidities, sarcoidosis characteristics and pre-enrolment lung function will be captured at study entry. During this 3-year study, all acute respiratory infectious events (from SARS-CoV-2 and any other respiratory pathogen) will be assessed and recorded at quarterly intervals. The level of required medical care and survival outcomes determine infection severity, and the impact of infection on quality of life measures will be recorded. Post-infection lung function and imaging results will measure the long-term impact on the trajectory of sarcoidosis. Patients will be analysed according to the clinical phenotypes of cardiac and fibrotic pulmonary sarcoidosis. Control groups include non-infected patients with sarcoidosis and patients with non-sarcoidosis interstitial lung disease. ETHICS AND DISSEMINATION: Each site received local institutional review board approval prior to enrolling patients, with the consent process determined by local institution standards. Data will be published in a timely manner (goal <12 months) at the conclusion of the 3-year follow-up period and will be made available upon request.

Respiratory Mechanics and Association With Inflammation in COVID-19-Related ARDS.

BACKGROUND: The novel coronavirus-associated ARDS (COVID-19 ARDS) often requires invasive mechanical ventilation. A spectrum of atypical ARDS with different phenotypes (high vs low static compliance) has been hypothesized in COVID-19. METHODS: We conducted a retrospective analysis to identify respiratory mechanics in COVID-19 ARDS. Berlin definition was used to categorize severity of ARDS. Correlational analysis using t test, chi-square test, ANOVA test, and Pearson correlation was used to identify relationship between subject variables and respiratory mechanics. The primary outcome was duration of mechanical ventilation. Secondary outcomes were correlation between fluid status, C- reactive protein, PEEP, and D-dimer with respiratory and ventilatory parameters. RESULTS: Median age in our cohort was 60.5 y with predominantly male subjects. Up to 53% subjects were classified as severe ARDS (median [Formula: see text] = 86) with predominantly low static compliance (median Cst- 25.5 mL/cm H2O). The overall mortality in our cohort was 61%. The total duration of mechanical ventilation was 35 d in survivors and 14 d in nonsurvivors. High PEEP (r = 0.45, P < .001) and D-dimer > 2,000 ng/dL (P = .009) correlated with significant increase in physiologic dead space without significant correlation with [Formula: see text]. Higher net fluid balance was inversely related to static compliance (r = -0.24, P = .045), and elevation in C- reactive protein was inversely related to [Formula: see text] (r = -0.32, P = .02). CONCLUSIONS: In our cohort of mechanically ventilated COVID-19 ARDS subjects, high PEEP and D-dimer were associated with increase in physiologic dead space without significant effect on oxygenation, raising the question of potential microvascular dysfunction.

Sarcoidosis Epidemiology: Race Matters.

Rather than a single disease entity, sarcoidosis may be a constellation of "sarcoidoses" with a characteristic pattern of organ involvement and clinic course, depending upon the triggering exposure and underlying epidemiologic factors such as race. This review examines the racial disparities inherent to sarcoidosis disease course and mortality and discusses factors that may be responsible for these findings. In the United States, black patients with sarcoidosis experience more severe pulmonary disease, more multiorgan involvement, and an overall worse prognosis with higher rates of hospitalization and mortality. Beyond inherent genotype, ascertainment and access to medical care, physician implicit bias, and patient perceived discrimination likely play a role. Moving forward, epidemiologic concepts can be used to formulate strategies for control, treatment, and even prevention of disease in black Americans at risk for developing life-altering or life-threatening sarcoidosis phenotypes. Identification and rectification of modifiable risk factors such as socioeconomic status, lack of insurance, and financial barriers to care as well as the incorporation of implicit bias training for physician will likely lead to improvement in discordant outcomes.

Clinical Outcomes in Critically Ill Coronavirus Disease 2019 Patients: A Unique New York City Public Hospital Experience.

To explore demographics, comorbidities, transfers, and mortality in critically ill patients with confirmed severe acute respiratory syndrome coronavirus 2. DESIGN: Retrospective cohort study. SETTING: Data were collected from a large tertiary care public hospital ICU that is part of the largest public healthcare network in the United States. PATIENTS: One-hundred thirty-seven adult (≥ 18 yr old) ICU patients admitted between March 10, 2020, and April 7, 2020, with follow-up collected through May 18, 2020. INTERVENTIONS: None. MEASUREMENTS: Demographic, clinical, laboratory, treatment, and outcome data extracted from electronic medical records. MAIN RESULTS: The majority of patients were male (99/137; 72.3%) and older than 50 years old (108/137; 78.9%). The most reported ethnicity and race were Hispanic (61/137; 44.5%) and Black (23/137; 16.7%). One-hundred six of 137 patients had at least one comorbidity (77.4%). One-hundred twenty-one of 137 (78.1%) required mechanical ventilation of whom 30 (24.8%) moved to tracheostomy and 46 of 137 (33.6%) required new onset renal replacement therapy. Eighty-two of 137 patients (59.9%) died after a median of 8 days (interquartile range 5-15 d) in the ICU. Male sex had a trend toward a higher hazard of death (hazard ratio, 2.1 [1.1-4.0]) in the multivariable Cox model. CONCLUSIONS: We report a mortality rate of 59.9% in a predominantly Hispanic and Black patient population. A significant association between comorbidities and mortality was not found in multivariable regression, and further research is needed to study factors that impact mortality in critical coronavirus disease 2019 patients. We also describe how a public hospital developed innovative approaches to safely manage a large volume of interhospital transfers and admitted patients.

Genetic Variants Associated with FDNY WTC-Related Sarcoidosis.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. It may develop in response to an exposure or inflammatory trigger in the background of a genetically primed abnormal immune response. Thus, genetic studies are potentially important to our understanding of the pathogenesis of sarcoidosis. We developed a case-control study which explored the genetic variations between firefighters in the Fire Department of the City of New York (FDNY) with World Trade Center (WTC)-related sarcoidosis and those with WTC exposure, but without sarcoidosis. The loci of fifty-one candidate genes related to granuloma formation, inflammation, immune response, and/or sarcoidosis were sequenced at high density in enhancer/promoter, exonic, and 5' untranslated regions. Seventeen allele variants of human leukocyte antigen (HLA) and non-HLA genes were found to be associated with sarcoidosis, and all were within chromosomes 1 and 6. Our results also suggest an association between extrathoracic involvement and allele variants of HLA and non-HLA genes found not only on chromosomes 1 and 6, but also on chromosomes 16 and 17. We found similarities between genetic variants with WTC-related sarcoidosis and those reported previously in sporadic sarcoidosis cases within the general population. In addition, we identified several allele variants never previously reported in association with sarcoidosis. If confirmed in larger studies with known environmental exposures, these novel findings may provide insight into the gene-environment interactions key to the development of sarcoidosis.

Clinical Evaluation of Sarcoidosis in Community Members with World Trade Center Dust Exposure.

Background: Sarcoidosis is a granulomatous disease involving intrathoracic and extrathoracic organs. Genetic and environmental factors, such as exposure to World-Trade Center (WTC) dust after 9/11, may play a role in clinical presentation. Characterization of sarcoidosis in community members with exposure to the WTC dust can provide further insight into the relationship between environmental exposure and sarcoidosis. Methods: Patients with documented sarcoidosis were identified in the WTC Environmental Health Center (EHC), a treatment program for community members. Demographic and clinical data were collected from standardized questionnaires and chart review. Organ involvement was assessed with a standard instrument. Results: Among patients in the WTC EHC, 87 were identified with sarcoidosis after 9/11. Sarcoidosis cases were more likely African-American, local workers, and had more respiratory symptoms, compared with non-sarcoidosis WTC EHC patients. Many (46%) had ≥ Scadding stage 3 on chest imaging, and had reduced lung function measures. Extrathoracic involvement was identified in 33/87 (38%) with a diversity of organs involved. Conclusions: WTC-exposed sarcoidosis in community members is often characterized by severe pulmonary disease and a high rate of diverse extrathoracic involvement. Further analysis is required to characterize the course of disease progression or resolution.

Clinical Course of Sarcoidosis in World Trade Center-Exposed Firefighters.

BACKGROUND: Sarcoidosis is believed to represent a genetically primed, abnormal immune response to an antigen exposure or inflammatory trigger, with both genetic and environmental factors playing a role in disease onset and phenotypic expression. In a population of firefighters with post-World Trade Center (WTC) 9/11/2001 (9/11) sarcoidosis, we have a unique opportunity to describe the clinical course of incident sarcoidosis during the 15 years postexposure and, on average, 8 years following diagnosis. METHODS: Among the WTC-exposed cohort, 74 firefighters with post-9/11 sarcoidosis were identified through medical records review. A total of 59 were enrolled in follow-up studies. For each participant, the World Association of Sarcoidosis and Other Granulomatous Diseases organ assessment tool was used to categorize the sarcoidosis involvement of each organ system at time of diagnosis and at follow-up. RESULTS: The incidence of sarcoidosis post-9/11 was 25 per 100,000. Radiographic resolution of intrathoracic involvement occurred in 24 (45%) subjects. Lung function for nearly all subjects was within normal limits. Extrathoracic involvement increased, most prominently joints (15%) and cardiac (16%) involvement. There was no evidence of calcium dysmetabolism. Few subjects had ocular (5%) or skin (2%) involvement, and none had beryllium sensitization. Most (76%) subjects did not receive any treatment. CONCLUSIONS: Extrathoracic disease was more prevalent in WTC-related sarcoidosis than reported for patients with sarcoidosis without WTC exposure or for other exposure-related granulomatous diseases (beryllium disease and hypersensitivity pneumonitis). Cardiac involvement would have been missed if evaluation stopped after ECG, 48-h recordings, and echocardiogram. Our results also support the need for advanced cardiac screening in asymptomatic patients with strenuous, stressful, public safety occupations, given the potential fatality of a missed diagnosis.

Airway Disease in Rescue/Recovery Workers: Recent Findings from the World Trade Center Collapse.

PURPOSE OF REVIEW: Our goal is to summarize the airway disease literature since September 11, 2001 (9/11), focusing on studies published since 2011 in World Trade Center-exposed rescue/recovery workers. RECENT FINDINGS: Since 2011, studies have confirmed relationships between initial World Trade Center exposure intensity, severity of symptoms, airway disease diagnoses, and biomarkers of disease progression. Studies continue to document ongoing morbidity in rescue/recovery workers over 10 years after 9/11. Future research should further identify correlates of symptom persistence and new airway disease diagnoses. The unique characteristics of the airway diseases in this population warrant ongoing monitoring and treatment.