Quantitative CT Characteristics of Cluster Phenotypes in the Severe Asthma Research Program Cohorts.

Background Clustering key clinical characteristics of participants in the Severe Asthma Research Program (SARP), a large, multicenter prospective observational study of patients with asthma and healthy controls, has led to the identification of novel asthma phenotypes. Purpose To determine whether quantitative CT (qCT) could help distinguish between clinical asthma phenotypes. Materials and Methods A retrospective cross-sectional analysis was conducted with the use of qCT images (maximal bronchodilation at total lung capacity [TLC], or inspiration, and functional residual capacity [FRC], or expiration) from the cluster phenotypes of SARP participants (cluster 1: minimal disease; cluster 2: mild, reversible; cluster 3: obese asthma; cluster 4: severe, reversible; cluster 5: severe, irreversible) enrolled between September 2001 and December 2015. Airway morphometry was performed along standard paths (RB1, RB4, RB10, LB1, and LB10). Corresponding voxels from TLC and FRC images were mapped with use of deformable image registration to characterize disease probability maps (DPMs) of functional small airway disease (fSAD), voxel-level volume changes (Jacobian), and isotropy (anisotropic deformation index [ADI]). The association between cluster assignment and qCT measures was evaluated using linear mixed models. Results A total of 455 participants were evaluated with cluster assignments and CT (mean age ± SD, 42.1 years ± 14.7; 270 women). Airway morphometry had limited ability to help discern between clusters. DPM fSAD was highest in cluster 5 (cluster 1 in SARP III: 19.0% ± 20.6; cluster 2: 18.9% ± 13.3; cluster 3: 24.9% ± 13.1; cluster 4: 24.1% ± 8.4; cluster 5: 38.8% ± 14.4; P < .001). Lower whole-lung Jacobian and ADI values were associated with greater cluster severity. Compared to cluster 1, cluster 5 lung expansion was 31% smaller (Jacobian in SARP III cohort: 2.31 ± 0.6 vs 1.61 ± 0.3, respectively, P < .001) and 34% more isotropic (ADI in SARP III cohort: 0.40 ± 0.1 vs 0.61 ± 0.2, P < .001). Within-lung Jacobian and ADI SDs decreased as severity worsened (Jacobian SD in SARP III cohort: 0.90 ± 0.4 for cluster 1; 0.79 ± 0.3 for cluster 2; 0.62 ± 0.2 for cluster 3; 0.63 ± 0.2 for cluster 4; and 0.41 ± 0.2 for cluster 5; P < .001). Conclusion Quantitative CT assessments of the degree and intraindividual regional variability of lung expansion distinguished between well-established clinical phenotypes among participants with asthma from the Severe Asthma Research Program study. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Verschakelen in this issue.

Quantitative CT metrics are associated with longitudinal lung function decline and future asthma exacerbations: Results from SARP-3.

BACKGROUND: Currently, there is limited knowledge regarding which imaging assessments of asthma are associated with accelerated longitudinal decline in lung function. OBJECTIVES: We aimed to assess whether quantitative computed tomography (qCT) metrics are associated with longitudinal decline in lung function and morbidity in asthma. METHODS: We analyzed 205 qCT scans of adult patients with asthma and calculated baseline markers of airway remodeling, lung density, and pointwise regional change in lung volume (Jacobian measures) for each participant. Using multivariable regression models, we then assessed the association of qCT measurements with the outcomes of future change in lung function, future exacerbation rate, and changes in validated measurements of morbidity. RESULTS: Greater baseline wall area percent (ß = -0.15 [95% CI = -0.26 to -0.05]; P < .01), hyperinflation percent (ß = -0.25 [95% CI = -0.41 to -0.09]; P < .01), and Jacobian gradient measurements (cranial-caudal ß = 10.64 [95% CI = 3.79-17.49]; P < .01; posterior-anterior ß = -9.14, [95% CI = -15.49 to -2.78]; P < .01) were associated with more severe future lung function decline. Additionally, greater wall area percent (rate ratio = 1.06 [95% CI = 1.01-1.10]; P = .02) and air trapping percent (rate ratio =1.01 [95% CI = 1.00-1.02]; P = .03), as well as lower decline in the Jacobian determinant mean (rate ratio = 0.58 [95% CI = 0.41-0.82]; P < .01) and Jacobian determinant standard deviation (rate ratio = 0.52 [95% CI = 0.32-0.85]; P = .01), were associated with a greater rate of future exacerbations. However, imaging metrics were not associated with clinically meaningful changes in scores on validated asthma morbidity questionnaires. CONCLUSIONS: Baseline qCT measures of more severe airway remodeling, more small airway disease and hyperinflation, and less pointwise regional change in lung volumes were associated with future lung function decline and asthma exacerbations.

Use of Quantitative CT Imaging to Identify Bronchial Thermoplasty Responders.

BACKGROUND: Bronchial thermoplasty (BT) is a treatment for patients with poorly controlled, severe asthma. However, predictors of treatment response to BT are defined poorly. RESEARCH QUESTION: Do baseline radiographic and clinical characteristics exist that predict response to BT? STUDY DESIGN AND METHODS: We conducted a longitudinal prospective cohort study of participants with severe asthma receiving BT across eight academic medical centers. Participants received three separate BT treatments and were monitored at 3-month intervals for 1 year after BT. Similar to prior studies, a positive response to BT was defined as either improvement in Asthma Control Test results of ≥ 3 or Asthma Quality of Life Questionnaire of ≥ 0.5. Regression analyses were used to evaluate the association between pretreatment clinical and quantitative CT scan measures with subsequent BT response. RESULTS: From 2006 through 2017, 88 participants received BT, with 70 participants (79.5%) identified as responders by Asthma Control Test or Asthma Quality of Life Questionnaire criteria. Responders were less likely to undergo an asthma-related ICU admission in the prior year (3% vs 25%; P = .01). On baseline quantitative CT imaging, BT responders showed less air trapping percentage (OR, 0.90; 95% CI, 0.82-0.99; P = .03), a greater Jacobian determinant (OR, 1.49; 95% CI, 1.05-2.11), greater SD of the Jacobian determinant (OR, 1.84; 95% CI, 1.04-3.26), and greater anisotropic deformation index (OR, 3.06; 95% CI, 1.06-8.86). INTERPRETATION: To our knowledge, this is the largest study to evaluate baseline quantitative CT imaging and clinical characteristics associated with BT response. Our results show that preservation of normal lung expansion, indicated by less air trapping, a greater magnitude of isotropic expansion, and greater within-lung spatial variation on quantitative CT imaging, were predictors of future BT response. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01185275; URL: www. CLINICALTRIALS: gov.

Reconstruction of massive oncologic defects following extremity amputation: a 10-year experience.

BACKGROUND: Oncologic defects resulting from extremity amputations are often extensive and require substantial soft tissue for reconstruction. METHODS: A review of all patients, who underwent an external hemipelvectomy, forequarter amputation, or hindquarter amputation from 2001 to 2010 at the MD Anderson Cancer Center, was performed. RESULTS: A total of 50 patients were identified; of them, 21 underwent external hemipelvectomy, 22 had forequarter amputation, and 7 had hindquarter amputation. The mean defect size was 644 cm; defects were repaired using fillet flaps (n = 22, 44%), free flaps (n = 4, 8%), or local/regional flaps (n = 24, 48%). Of the fillet flaps, 16 were free flaps and the remaining were pedicled flaps. In all, 29 patients (58%) received preoperative radiation therapy, and 26 patients (52%) received preoperative chemotherapy. Two patients (4%) received postoperative radiation therapy, and 1 patient (2%) received postoperative chemotherapy. Three patients received both pre- and postoperative radiation therapy, and 10 patients were treated with both pre- and postoperative chemotherapy. Patients undergoing free flap reconstruction had significantly fewer complications compared with patients reconstructed using other modalities (2/20 vs. 13/30; P = 0.003). The majority of patients achieved excellent postoperative function, with 73% of upper extremity patients functioning independently and 57% of lower extremity amputees ambulating. CONCLUSIONS: Reconstruction for extensive defects following oncologic extremity amputation is often optimally done using free tissue transfer, particularly by salvaging "spare parts" from the amputated limb for a free fillet flap.

Interleukin-6 Trajectory and Secondary Infections in Mechanically Ventilated Patients With Coronavirus Disease 2019 Acute Respiratory Distress Syndrome Treated With Interleukin-6 Receptor Blocker.

To describe the infectious complications and interleukin-6 trajectories in mechanically ventilated patients with coronavirus disease 2019. DESIGN: Retrospective cohort study. SETTING: ICUs at Washington University-Barnes Jewish Hospital in St. Louis, MO. PARTICIPANTS: All consecutive patients admitted to the medical ICU and requiring mechanical ventilation from March 12, 2020, to April 21, 2020, were included. INTERVENTIONS: Tocilizumab, an interleukin-6 receptor blocker, was prescribed at the discretion of the treating physicians to patients with a clinical picture compatible with cytokine release syndrome. MEASUREMENTS: All the patients were followed to death or hospital discharge. Demographic and laboratory data were collected retrospectively from the electronic medical record. Interleukin-6 levels were measured at days 0, 3, 7, 14, and 21. Infections were divided into culture positive and culture negative (clinically suspected and treated). The main outcomes were infectious complications and interleukin-6 levels at different points in time. RESULTS: Forty-three patients with respiratory failure secondary to coronavirus disease 2019 were on mechanical ventilation during the study period. Twenty-seven (68%) were male, and 31 (72.1%) were African-American. Median Charlson score was 2 (interquartile range, 0-4). Median Pao2/Fio2 was 171.5 (122-221) on the day of mechanical ventilation initiation, and 13 patients (30.2%) required vasopressors. C-reactive protein was 142.7 (97.7-213.7), d-dimer 1,621 (559-13,434), and Acute Physiology and Chronic Health Evaluation-II 11 (9-15). Interleukin-6 levels at admission were 61 pg/mL (interquartile range, 28.6-439 pg/mL). Patients treated with tocilizumab had higher levels of interleukin-6 at each measurement (days 0, 3, 7, 14, and 21) compared with patients receiving standard of care. Both groups reached peak interleukin-6 levels at day 7. Administration of tocilizumab was associated with a trend toward increased risk of infection. CONCLUSIONS: Interleukin-6 levels peak at day 7 in patients with severe coronavirus disease 2019 pneumonia requiring mechanical ventilation and follows a similar trajectory in patients with coronavirus disease 2019 pneumonia requiring mechanical ventilation irrespective of treatment with interleukin-6R blockers. Interleukin-6 levels continued to rise in nonsurvivors, in comparison with survivors, where the rise in interleukin-6 levels was followed by a decline.

Real-time automated clinical deterioration alerts predict thirty-day hospital readmission.

INTRODUCTION: Clinical deterioration alerts (CDAs) are increasingly employed to identify deteriorating patients. METHODS: We performed a retrospective study to determine whether CDAs predict 30-day readmission. Patients admitted to 8 general medicine units were assessed for all-cause 30-day readmission. RESULTS: Among 3015 patients, 567 (18.8%) were readmitted within 30 days. Patients triggering a CDA (n = 1141; 34.4%) were more likely to have a 30-day readmission (23.6% vs 15.9%; P < 0.001). Logistic regression identified triggering of a CDA to be independently associated with 30-day readmission (odds ratio [OR]: 1.40; 95% confidence interval [CI]: 1.26-1.55; P = 0.001). Other predictors were: an emergency department visit in the previous 6 months (OR: 1.23; 95% CI:, 1.20-1.26; P < 0.001), increasing age (OR: 1.01; 95% CI: 1.01-1.02; P = 0.003), presence of connective tissue disease (OR: 1.63; 95% CI: 1.34-1.98; P = 0.012), diabetes mellitus with end-organ complications (OR: 1.23; 95% CI: 1.13-1.33; P = 0.010), chronic renal disease (OR: 1.16; 95% CI: 1.08-1.24; P = 0.034), cirrhosis (OR: 1.25; 95% CI: 1.17-1.33; P < 0.001), and metastatic cancer (OR: 1.12; 95% CI: 1.08-1.17; P = 0.002). Addition of the CDA to the other predictors added only modest incremental value for the prediction of hospital readmission. CONCLUSIONS: Readily identifiable clinical variables can be identified that predict 30-day readmission. It may be important to include these variables in existing prediction tools if pay for performance and across-institution comparisons are to be "fair" to institutions that care for more seriously ill patients. Journal of Hospital Medicine 2016;11:768-772. © 2016 Society of Hospital Medicine.