Objectives: Classification of patients with acute respiratory distress syndrome into hyper- and hypoinflammatory subphenotypes using plasma biomarkers may facilitate more effective targeted therapy. We examined whether established subphenotypes are present not only in patients with acute respiratory distress syndrome but also in patients at risk for acute respiratory distress syndrome (ARFA) and then assessed the prognostic information of baseline subphenotyping on the evolution of host-response biomarkers and clinical outcomes. Design: Prospective, observational cohort study. Setting: Medical ICU at a tertiary academic medical center. Patients: Mechanically ventilated patients with acute respiratory distress syndrome or ARFA. Interventions: None. Measurements and Main Results: We performed longitudinal measurements of 10 plasma biomarkers of host injury and inflammation. We applied unsupervised latent class analysis methods utilizing baseline clinical and biomarker variables and demonstrated that two-class models (hyper- vs hypoinflammatory subphenotypes) offered improved fit compared with one-class models in both patients with acute respiratory distress syndrome and ARFA. Baseline assignment to the hyperinflammatory subphenotype (39/104 [38%] acute respiratory distress syndrome and 30/108 [28%] ARFA patients) was associated with higher severity of illness by Sequential Organ Failure Assessment scores and incidence of acute kidney injury in patients with acute respiratory distress syndrome, as well as higher 30-day mortality and longer duration of mechanical ventilation in ARFA patients (p < 0.0001). Hyperinflammatory patients exhibited persistent elevation of biomarkers of innate immunity for up to 2 weeks postintubation. Conclusions: Our results suggest that two distinct subphenotypes are present not only in patients with established acute respiratory distress syndrome but also in patients at risk for its development. Hyperinflammatory classification at baseline is associated with higher severity of illness, worse clinical outcomes, and trajectories of persistently elevated biomarkers of host injury and inflammation during acute critical illness compared with hypoinflammatory patients. Our findings provide strong rationale for examining treatment effect modifications by subphenotypes in randomized clinical trials to inform precision therapeutic approaches in critical care.

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The role of the gut microbiome in critical illness is being actively investigated, but the optimal sampling methods for sequencing studies of gut microbiota remain unknown. Stool samples are generally considered the reference standard but are not practical to obtain in the intensive care unit (ICU), and thus, rectal swabs are often used. However, the reliability of rectal swabs for gut microbiome profiling has not been established in the ICU setting. In this study, we compared 16S rRNA gene sequencing results between rectal swab and stool samples collected at three time points from mechanically ventilated critically ill adults. Rectal swabs comprised 89% of the samples collected at the baseline time point, but stool samples became more extensively available at later time points. Significant differences in alpha-diversity and beta-diversity between rectal swabs and stool samples were observed, but these differences were primarily due to baseline samples. Higher relative abundances of members of the Actinobacteria phylum (typically skin microbes) were present in rectal swabs than in stool samples (P = 0.05), a difference that was attenuated over time. The progressively increasing similarity of rectal swabs and stool samples likely resulted from increasing levels of stool coating of the rectal vault and direct soiling of the rectal swabs taken at later time points. Therefore, inferences about the role of the gut microbiome in critical illness should be drawn cautiously and should take into account the type and timing of samples analyzed. IMPORTANCE Rectal swabs have been proposed as potential alternatives to stool samples for gut microbiome profiling in outpatients or healthy adults, but their reliability in assessment of critically ill patients has not been defined. Because stool sampling is not practical and often not feasible in the intensive care unit, we performed a detailed comparison of gut microbial sequencing profiles between rectal swabs and stool samples in a longitudinal cohort of critically ill patients. We identified systematic differences in gut microbial profiles between rectal swabs and stool samples and demonstrated that the timing of the rectal swab sampling had a significant impact on sequencing results. Our methodological findings should provide valuable information for the design and interpretation of future investigations of the role of the gut microbiome in critical illness.

Neurologic complications are occurring in coronavirus disease 2019 (COVID-19), and these patients should be monitored for neurologic symptoms. c When evaluating abnormal imaging findings in patients with COVID-19, the presence and specific pattern of deep gray structure involvement can be an important clue to etiology.

Central airway obstruction (CAO) is a dangerous and increasingly common problem. CAO refers to lesions causing narrowing of the trachea or mainstem bronchi and is generally divided into malignant and nonmalignant categories. These 2 entities may be caused by a variety of thoracic and extrathoracic diseases. Imaging is critical during the initial assessment of CAO and may help thoracic physicians focus the differential diagnosis and plan the safest and most appropriate diagnostic and therapeutic interventions. However, direct visualization via flexible or rigid bronchoscopy is often necessary for diagnostic and treatment purposes. A large number of procedures can be performed through bronchoscopy, with the goal of relieving the obstruction and improving patency of the airway. Deciding which procedure to perform is based both upon the type of lesion and whether the lesion is due to a malignant or nonmalignant process. Possible interventions include mechanical debridement, laser therapy, argon plasma coagulation, electrocautery, brachytherapy, and stent placement. Immediate postoperative and follow-up imaging is crucial to monitor for immediate, subacute, and chronic complications as well as disease progression and recurrence.

Patient: Male, 21Final Diagnosis: Bacterial pneumoniaSymptoms: Cough • feverMedication: —Clinical Procedure: —Specialty: Critical Care MedicineObjective:Unusual clinical courseBackground:Severe pneumonia requiring admission to an intensive care unit carries high morbidity and mortality. Evidence-based management includes early administration of empiric antibiotics against plausible bacterial pathogens while awaiting results of microbiologic cultures. However, in over 60% of pneumonia cases, no causative pathogen is identified with conventional diagnostic techniques. In this case report, we demonstrate how direct-from-sample sequencing of bacterial DNA could have identified the multiple culprit pathogens early in the disease course to guide appropriate antibiotic management.Case Report:A previously healthy, 21-year-old man presented with neck pain and fever and rapidly developed acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. He was started on broad-spectrum antibiotics and was found to have septic thrombophlebitis of the left internal jugular vein (Lemierre syndrome), with blood cultures growing Fusobacterium necrophorum. While his antibiotics were narrowed to piperacillin-tazobactam monotherapy, his clinical condition worsened, but repeated efforts to define an additional/alternative respiratory pathogen resulted in negative cultures. He eventually developed bilateral empyemas growing Mycoplasma hominis. Once azithromycin was added to the patient’s regimen, he improved dramatically. Retrospective sequencing of consecutive endotracheal aspirates showed Fusobacterium as the dominant pathogen early in the course, but with significant and increasing Mycoplasma abundance several days prior to clinical detection.Conclusions:Had sequencing information been available to the treating clinicians, the causative pathogens could have been detected earlier, guiding appropriate antibiotic therapy and perhaps preventing his clinical complications. Real-time bacterial DNA sequencing has the potential to shift the diagnostic paradigm in severe pneumonia.

Smoke and tobacco-free policies on hospital campuses have become more prevalent across the U.S. and Europe, de-normalizing smoking and reducing secondhand smoke exposure on hospital grounds. Concerns about the increasing use of electronic cigarettes (e-cigarettes) and the impact of such use on smoke and tobacco-free policies have arisen, but to date, no systematic data describes e-cigarette policies on hospital campuses. The study surveyed all hospitals in North Carolina (n = 121) to assess what proportion of hospitals have developed e-cigarette policies, how policies have been implemented and communicated, and what motivators and barriers have influenced the development of e-cigarette regulations. Seventy-five hospitals (62%) completed the survey. Over 80% of hospitals reported the existence of a policy regulating the use of e-cigarettes on campus and roughly half of the hospitals without a current e-cigarette policy are likely to develop one within the next year. Most e-cigarette policies have been incorporated into existing tobacco-free policies with few reported barriers, though effective communication of e-cigarette policies is lacking. The majority of hospitals strongly agree that e-cigarette use on campus should be prohibited for staff, patients, and visitors. Widespread incorporation of e-cigarette policies into existing hospital smoke and tobacco-free campus policies is feasible but needs communication to staff, patients, and visitors.