Bronchoalveolar Lavage Fluid Cytology of Deployed Military Personnel With Chronic Respiratory Symptoms From the STAMPEDE III Study.

INTRODUCTION: Deployed military personnel may be at risk for developing acute and chronic lung disease. Prior studies of this patient population have revealed that unexplained exertional dyspnea is the most common diagnosis despite an extensive evaluation. There is a concern that an occult disorder may be affecting this population. This study evaluated the role for bronchoalveolar lavage (BAL) fluid analysis in the evaluation of chronic deployment-associated dyspnea. MATERIALS AND METHODS: Military personnel who reported chronic respiratory symptoms were evaluated as part of the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures III study. Participants underwent bronchoscopy with BAL as part of a standardized evaluation. RESULTS: A total of 308 patients with a mean age of 38 ± 8.6 years underwent bronchoscopy with BAL. BAL cell-count percentages of macrophages, lymphocytes, neutrophils, and eosinophils were: 76.2 ± 17.0%, 16.3 ± 13.4%, 6.6 ± 8.9%, and 0.9 ± 3.2%, respectively. There was no clear differentiation between groups based on increases in lymphocyte counts (P = .640), although lymphocyte values were more elevated (21.4 ± 12.1%) in the interstitial lung disease category. Neutrophil counts (6.6 ± 8.9%) were elevated compared to the reported normal reference values and were increased in the isolated pulmonary function test abnormality (9.4 ± 11.6%), large airway disorder (10.0 ± 7.5%), miscellaneous (10.9 ± 20.2%), and obstructive lung disease (11.0 ± 15.6%) groups. Eosinophil counts were within normal limits (0.9 ± 3.2%) and showed no differences between groups (P = .545); asthma patients trended higher (1.6 ± 5.7%). BAL counts for the exertional dyspnea group were within normal reference values and showed no differences from the entire cohort. CONCLUSIONS: The addition of BAL cytology did not help differentiate those patients with unexplained dyspnea from other etiologies.

Characterizing the Asthma Phenotype of Military Personnel.

INTRODUCTION: Asthma is the most common diagnosis in military personnel who endorse chronic dyspnea. Service members have unique occupational risk factors, and there is concern that airborne exposures in the deployed environment as well as other occupational exposures may contribute to the development of asthma or exacerbate pre-existing disease. Asthma phenotyping with clinical biomarkers such as serum immunoglobulin E (IgE) levels and eosinophil (EOS) counts is useful in defining treatment strategies for the management of asthma. This study sought to characterize the phenotype of medically separated military personnel with career-limiting asthma to define potential management strategies and guide future research evaluating the unexplained prevalence of asthma in this population. MATERIALS AND METHODS: A retrospective chart review of active duty service members (ADSM) who underwent fitness for duty evaluation via medical evaluation board between 2005 and 2016 and were separated with a minimum 30% conditional disability rating for asthma was performed. Only ADSM who were diagnosed with asthma by a pulmonologist and had spirometry data available were included in the analysis. Demographics, spirometry data, and laboratory data to include IgE levels, radioallergosorbent panels, and EOS counts were analyzed from the DoD electronic medical record. RESULTS: A total of 141 service members were evaluated with a mean age of 42 ± 6.8 years, mean serum EOS count of 300 ± 358 cells/µL, and mean IgE level of 305 ± 363 IU/mL. The patients were further categorized into 4 subgroups based on serum EOS count and IgE level: group A with IgE < 100 IU/mL and EOS < 300 cells/µL (n = 45; 33%), group B with IgE > 100 IU/mL and EOS < 300 cells/µL (n = 44; 32%), group C with IgE < 100 IU/mL and EOS > 300 cells/µL (n = 6; 1%), and group D with IgE > 100 IU/mL, EOS > 300 cells/µL (n = 46; 34%). Among the cohorts, there were no statistically significant differences in demographics, body mass index, spirometry, smoking history, or disability rating. CONCLUSION: The majority of ADSM with a defined asthma history do not have concordant elevations in serum IgE and blood EOS suggestive of a Th2-high phenotype. Asthma in this population is heterogeneous, and phenotyping using clinical biomarkers may be useful to define optimal treatment strategies.

Enterococcus faecium Empyema Following Extracorporeal Membrane Oxygenation for COVID-19 Acute Respiratory Distress Syndrome.

A 33-year-old male with severe COVID-19 required prolonged veno-venous extracorporeal membrane oxygenation (ECMO) support. Following decannulation, he developed an Enterococcus faecium empyema. Tube thoracostomy and broad-spectrum antibiotics were initiated, followed by an unsuccessful attempt at pleural irrigation with saline, given the patient had an increased risk of bleeding due to the concomitant requirement for systemic anticoagulation. Subsequently, intrapleural tissue plasminogen activator (tPA) and recombinant human Dornase alfa (DNase) were safely administered with the resolution of empyema. Enterococcus faecium is an uncommon cause of pleural empyema and, to our knowledge, has not previously been reported to be associated with COVID-19 or ECMO.

Argatroban for Anticoagulation in Patients Requiring Venovenous Extracorporeal Membrane Oxygenation in Coronavirus Disease 2019.

A significant proportion of patients with coronavirus disease 2019 requiring venovenous extracorporeal membrane oxygenation at our institution demonstrated heparin resistance, which in combination with a heparin shortage resulted in the transition to argatroban with or without aspirin as an alternative anticoagulation strategy. The optimal anticoagulation strategy for coronavirus disease 2019 patients requiring venovenous extracorporeal membrane oxygenation is unknown, and therefore, we sought to evaluate the efficacy and safety of argatroban with or without aspirin as an alternative anticoagulation strategy in this patient population. DESIGN: Retrospective cohort. SETTING: Single-center tertiary-care facility in Fort Sam Houston, TX, from 2020 to 2021. PATIENTS: Twenty-four patients who were cannulated for venovenous extracorporeal membrane oxygenation due to respiratory failure secondary to coronavirus disease 2019. INTERVENTIONS: Argatroban, with or without aspirin, was substituted for heparin in coronavirus disease 2019 patients requiring venovenous extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Eighty percent of our coronavirus disease 2019 patients requiring venovenous extracorporeal membrane oxygenation demonstrated heparin resistance, and patients who were initially started on heparin were significantly more likely to require a change to argatroban than vice versa due to difficulty achieving or maintaining therapeutic anticoagulation goals (93.4% vs 11.1%; p < 0.0001). The time to reach the therapeutic anticoagulation goal was significantly longer for patients who were initially started on heparin in comparison with argatroban (24 vs 6 hr; p = 0.0173). Bleeding and thrombotic complications were not significantly different between the two cohorts. CONCLUSIONS: Argatroban, with or without aspirin, is an effective anticoagulation strategy for patients who require venovenous extracorporeal membrane oxygenation support secondary to coronavirus disease 2019. In comparison with heparin, this anticoagulation strategy was not associated with a significant difference in bleeding or thrombotic complications, and was associated with a significantly decreased time to therapeutic anticoagulation goal, likely as a result of high rates of heparin resistance observed in this patient population.

Adoption of coronary artery disease - Reporting and Data System (CAD-RADS™) and observed impact on medical therapy and systolic blood pressure control.

BACKGROUND: CAD-RADS was developed to standardize communication of per-patient maximal stenosis on coronary CT angiography (CCTA) and provide treatment recommendations and may impact primary prevention care and resource utilization. The authors sought to evaluate CAD-RADS adoption on preventive medical therapy and risk factor control amongst a mixed provider population. METHODS: Statins, aspirin (ASA), systolic blood pressure and, when available, lipid panel changes were abstracted for 1796 total patients undergoing CCTA in the 12 months before (non-standard reporting, NSR, cohort) and after adoption of the CAD-RADS reporting template. Only initiation of a medication in a treatment naïve patient, escalation from baseline dose, or transition to a higher potency was considered an escalation/initiation in lipid therapy. RESULTS: The CAD-RADS reporting template was utilized in 83.7% (751/897) of CCTAs after the CAD-RADS adoption period. After adjusting for any coronary artery disease (CAD) on CCTA, statin initiation/escalation was more commonly observed in the CAD-RADS cohort (aOR 1.46; 95%CI 1.12-1.90, p = 0.005), driven by higher rates of new statin initiation (aOR 1.79; 95%CI 1.23-2.58, p = 0.002). This resulted in a higher observed rates of total cholesterol improvement in the CAD-RADS cohort (58% vs 49%, p = 0.016). New ASA initiation was similar between reporting templates after adjustment for CAD on CCTA (aOR 1.40; 95%CI 0.97-2.02, p = 0.069). The ordering provider's specialty (cardiology vs non-cardiology) did not significantly impact the observed differences in initiation/escalation of statins and ASA (pinteraction = NS). CONCLUSIONS: Adoption of CAD-RADS reporting was associated with increased utilization of preventive medications, regardless of ordering provider specialty.

Mycobacterium smegmatis PhoU Proteins Have Overlapping Functions in Phosphate Signaling and Are Essential.

Many bacteria regulate gene expression in response to phosphate availability using a two-component signal transduction system, the activity of which is controlled by interaction with the Pst phosphate specific transporter and a cytoplasmic protein PhoU. Mycobacterium tuberculosis, the causative agent of tuberculosis, requires its phosphate sensing signal transduction system for virulence and antibiotic tolerance, but the molecular mechanisms of phosphate sensing remain poorly characterized. M. smegmatis serves as a model for studying mycobacterial pathogens including M. tuberculosis. M. smegmatis encodes two proteins with similarity to PhoU, but it was unknown if both proteins participated in signal transduction with the phosphate-responsive SenX3-RegX3 two-component system. We constructed phoU single and double deletion mutants and tested expression of genes in the RegX3 regulon. Only the ΔphoU1ΔphoU2 mutant exhibited constitutive activation of all the RegX3-regulated genes examined, suggesting that M. smegmatis PhoU1 and PhoU2 have overlapping functions in inhibiting activity of the SenX3-RegX3 two-component system when phosphate is readily available. The ΔphoU1ΔphoU2 mutant also exhibited decreased tolerance to several anti-tubercular drugs. However, a complex plasmid swapping strategy was required to generate the ΔphoU1ΔphoU2 mutant, suggesting that either phoU1 or phoU2 is essential for in vitro growth of M. smegmatis. Using whole-genome sequencing, we demonstrated that all five of the ΔphoU1ΔphoU2 mutants we isolated had independent suppressor mutations predicted to disrupt the function of the Pst phosphate transporter, suggesting that in the absence of the PhoU proteins phosphate uptake by the Pst system is toxic. Collectively, our data demonstrate that the two M. smegmatis PhoU orthologs have overlapping functions in both controlling SenX3-RegX3 activity in response to phosphate availability and regulating phosphate transport by the Pst system. Our results suggest that M. smegmatis can serve as a tractable model for further characterization of the molecular mechanism of phosphate sensing in mycobacteria and to screen for compounds that would interfere with signal transduction and thereby increase the efficacy of existing anti-tubercular antibiotics.