Robotic bronchoscopy (RB) aims to increase the diagnostic yield of guided bronchoscopy by providing improved navigation, farther reach, and stability during lesion sampling.
We reviewed data on ...consecutive cases in which RB was used to diagnose lung lesions from June 15, 2018, to December 15, 2019, at the University of Chicago Medical Center.
The median lesion size was 20.5 mm. All patients had at least 12 months of follow-up. The overall diagnostic accuracy was 77% (95 of 124). The diagnostic accuracy was 85%, 84%, and 38% for concentric, eccentric, and absent radial endobronchial ultrasound (r-EBUS) views, respectively (P < .001). A positive r-EBUS view and lesions size of 20 to 30 mm had higher odds of achieving a diagnosis on multivariate analysis. The 12-month diagnostic accuracy, sensitivity, specificity, and positive and negative predictive value for malignancy were 77%, 69%, 100%, 100%, and 58%, respectively. Pneumothorax was noted in 1.6% (n = 2) patients with bleeding reported in 3.2% (n = 4). No postprocedure respiratory failure was noted.
The overall diagnostic accuracy using RB for pulmonary lesion sampling in our cohort with 12-month follow-up compared favorably with established guided bronchoscopy technologies. Lesion size ≥20 mm and confirmation by r-EBUS predicted higher accuracy independent of concentric or eccentric r-EBUS patterns.
The relationship between asthma, atopy, and underlying type 2 (T2) airway inflammation is complex. Although the bacterial airway microbiota is known to differ in asthmatic patients, the fungal and ...bacterial markers that discriminate T2-high (eosinophilic) and T2-low (neutrophilic/mixed-inflammation) asthma and atopy are still incompletely identified.
The aim of this study was to demonstrate the fungal microbiota structure of airways in asthmatic patients associated with T2 inflammation, atopy, and key clinical parameters.
We collected endobronchial brush (EB) and bronchoalveolar lavage (BAL) samples from 39 asthmatic patients and 19 healthy subjects followed by 16S gene and internal transcribed spacer–based microbiota sequencing. The microbial sequences were classified into exact sequence variants. The T2 phenotype was defined by using a blood eosinophil count with a threshold of 300 cells/μL.
Fungal diversity was significantly lower in EB samples from patients with T2-high compared with T2-low inflammation; key fungal genera enriched in patients with T2-high inflammation included Trichoderma species, whereas Penicillium species was enriched in patients with atopy. In BAL fluid samples the dominant genera were Cladosporium, Fusarium, Aspergillus, and Alternaria. Using generalized linear models, we identified significant associations between specific fungal exact sequence variants and FEV1, fraction of exhaled nitric oxide values, BAL fluid cell counts, and corticosteroid use. Investigation of interkingdom (bacterial-fungal) co-occurrence patterns revealed different topologies between asthmatic patients and healthy control subjects. Random forest models with fungal classifiers predicted asthma status with 75% accuracy for BAL fluid samples and 80% accuracy for EB samples.
We demonstrate clear differences in bacterial and fungal microbiota in asthma-associated phenotypes. Our study provides additional support for considering microbial signatures in delineating asthma phenotypes.
Display omitted
The single pulmonary nodule evaluation is a complex problem. In particular, attempts to biopsy peripheral nodules with bronchoscopy have been hampered by difficulty navigating to the correct airway ...and then confirming the instruments' proximity to the nodule. Virtual systems in use do not provide real-time feedback of a live image of the nodule in question. Fluoroscopy has traditionally offered limited assistance as often the nodule is not visible and provides no information on airways/pathways to the nodule. We describe the use of LungVision augmented fluoroscopy to aid in real-time navigation assistance to peripheral lung nodules.
The Robotic Endoscopic System (Auris Health, Inc., Redwood City, CA) has the potential to overcome several limitations of contemporary guided-bronchoscopic technologies for the diagnosis of lung ...lesions. Our objective is to report on the initial post-marketing feasibility, safety and diagnostic yield of this technology.
We retrospectively reviewed data on consecutive cases in which robot-assisted bronchoscopy was used to sample lung lesions at four centers in the US (academic and community) from June 15th, 2018 to December 15th, 2018.
One hundred and sixty-seven lesions in 165 patients were included in the analysis, with an average follow-up of 185 ± 55 days. The average size of target lesions was 25.0 ± 15.0 mm. Seventy-one percent were located in the peripheral third of the lung. Pneumothorax and airway bleeding occurred in 3.6 and 2.4% cases, respectively. Navigation was successful in 88.6% of cases. Tissue samples were successfully obtained in 98.8%. The diagnostic yield estimates ranged from 69.1 to 77% assuming the cases of biopsy-proven inflammation without any follow-up information (N = 13) were non-diagnostic and diagnostic, respectively. The yield was 81.5, 71.7 and 26.9% for concentric, eccentric and absent r-EBUS views, respectively. Diagnostic yield was not affected by lesion size, density, lobar location or centrality.
RAB implementation in community and academic centers is safe and feasible, with an initial diagnostic yield of 69.1-77% in patients with lung lesions that require diagnostic bronchoscopy. Comparative trials with the existing bronchoscopic technologies are needed to determine cost-effectiveness of this technology.
Background The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on ...the microbial community composition and structure are not clear. Objectives We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia. Methods DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencing was used to compare the relative abundance of bacterial genera with clinical characteristics. Results Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus , Pseudomonas , and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella , Streptococcus , and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV1 and the proportion of lavage eosinophils. Conclusion The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use.
Atrial fibrillation (AF) that newly occurs during critical illness presents challenges for both short- and long-term management. During critical illness, patients with new-onset AF are clinically ...evaluated for hemodynamic instability owing to the arrhythmia as well as for potentially reversible arrhythmia triggers. Hemodynamically significant AF that persists during critical illness may be treated with heart rate or rhythm control strategies. Recent evidence suggests that patients in whom AF develops during acute illness (eg, sepsis, postoperatively) have high long-term risks for AF recurrence and for AF-associated complications, such as stroke, heart failure, and death. Therefore, we suggest increased efforts to improve communication of AF events between inpatient and outpatient providers and to reassess patients who had experienced new-onset AF during critical illness after they transition to the post-ICU setting. We describe various strategies for the assessment and long-term management of patients with new-onset AF during critical illness.
A 36-year-old woman with rheumatoid arthritis who was receiving systemic immunotherapy died from disseminated histoplasmosis while participating in a gene-therapy trial of a tumor necrosis factor α ...antagonist delivered through an adeno-associated viral vector delivery system and administered by intraarticular injection.
A 36-year-old woman with rheumatoid arthritis who was receiving systemic immunotherapy died from disseminated histoplasmosis while participating in a gene-therapy trial of a tumor necrosis factor α antagonist.
Rheumatoid arthritis is a chronic inflammatory disease that is characterized by autoimmune destruction of multiple joints, causing substantial pain, swelling, and loss of mobility.
1
TNF-α inhibitors have represented a dramatic improvement in the treatment of rheumatoid arthritis; they include the two antibodies infliximab and adalimumab, as well as etanercept, a dimeric fusion protein that combines an immunoglobulin domain with a TNF-receptor domain (TNFR:Fc).
2
,
3
Trials of TNF-α inhibitors delivered with the use of gene-therapy methods in patients with rheumatoid arthritis are increasing in number.
4
The most common vectors used in models of rheumatoid arthritis are viral vectors such as lentivirus, . . .
The one-year and median overall survival (mOS) rates of advanced gastroesophageal adenocarcinomas (GEA) are ∼50% and <12 months, respectively. Baseline spatial and temporal molecular heterogeneity of ...targetable alterations may be a cause of failure of targeted/immunooncologic therapies. This heterogeneity, coupled with infrequent incidence of some biomarkers, has resulted in stalled therapeutic progress. We hypothesized that a personalized treatment strategy, applied at first diagnosis then serially over up to three treatment lines using monoclonal antibodies combined with optimally sequenced chemotherapy, could contend with these hurdles. This was tested using a novel clinical expansion-platform type II design with a survival primary endpoint. Of 68 patients by intention-to-treat, the one-year survival rate was 66% and mOS was 15.7 months, meeting the primary efficacy endpoint (one-sided
= 0.0024). First-line response rate (74%), disease control rate (99%), and median progression-free survival (8.2 months) were superior to historical controls. The PANGEA strategy led to improved outcomes warranting a larger randomized study. SIGNIFICANCE: This study highlights excellent outcomes achieved by individually optimizing chemotherapy, biomarker profiling, and matching of targeted therapies at baseline and over time for GEA. Testing a predefined treatment strategy resulted in improved outcomes versus historical controls. Therapeutic resistance observed in correlative analyses suggests that dual targeted inhibition may be beneficial.
.
Bronchial thermoplasty is an alternative treatment for patients with severe, uncontrolled asthma in which the airway smooth muscle is eliminated using radioablation. Although this emerging therapy ...shows promising outcomes, little is known about its effects on airway inflammation.
We examined the presence of bronchoalveolar lavage cytokines and expression of smooth muscle actin in patients with severe asthma before and in the weeks after bronchial thermoplasty.
Endobronchial biopsies and bronchoalveolar lavage samples from 11 patients with severe asthma were collected from the right lower lobe before and 3 and 6 weeks after initial bronchial thermoplasty. Samples were analyzed for cell proportions and cytokine concentrations in bronchoalveolar lavage and for the presence of α-SMA in endobronchial biopsies.
α-SMA expression was decreased in endobronchial biopsies of 7 of 11 subjects by Week 6. In bronchoalveolar lavage fluid, both transforming growth factor-β1 and regulated upon activation, normal T-cell expressed and secreted (RANTES)/CCL5 were substantially decreased 3 and 6 weeks post bronchial thermoplasty in all patients. The cytokine tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL), which induces apoptosis in several cell types, was increased in concentration both 3 and 6 weeks post bronchial thermoplasty.
Clinical improvement and reduction in α-SMA after bronchial thermoplasty in severe, uncontrolled asthma is associated with substantial changes in key mediators of inflammation. These data confirm the substantial elimination of airway smooth muscle post thermoplasty in the human asthmatic airway and represent the first characterization of significant changes in airway inflammation in the first weeks after thermoplasty.
PDF
