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Lung microbial and host genomic signatures as predictors of prognosis in early-stage adenocarcinoma

Tsay, Jun-Chieh J; Darawshy, Fares; Wang, Chan; Kwok, Benjamin; Wong, Kendrew K; Wu, Benjamin G; Sulaiman, Imran; Zhou, Hua; Isaacs, Bradley; Kugler, Matthias C; Sanchez, Elizabeth; Bain, Alexander; Li, Yonghua; Schluger, Rosemary; Lukovnikova, Alena; Collazo, Destiny; Kyeremateng, Yaa; Pillai, Ray; Chang, Miao; Li, Qingsheng; Vanguri, Rami S; Becker, Anton S; Moore, William H; Thurston, George; Gordon, Terry; Moreira, Andre L; Goparaju, Chandra M; Sterman, Daniel H; Tsirigos, Aristotelis; Li, Huilin; Segal, Leopoldo N; Pass, Harvey I
BACKGROUND:Risk of early-stage lung adenocarcinoma (LUAD) recurrence after surgical resection is significant, and post-recurrence median survival is approximately two years. Currently there are no commercially available biomarkers that predict recurrence. Here, we investigated whether microbial and host genomic signatures in the lung can predict recurrence. METHODS:In 91 early-stage (Stage IA/IB) LUAD-patients with extensive follow-up, we used 16s rRNA gene sequencing and host RNA-sequencing to map the microbial and host transcriptomic landscape in tumor and adjacent unaffected lung samples. RESULTS:23 out of 91 subjects had tumor recurrence over 5-year period. In tumor samples, LUAD recurrence was associated with enrichment with Dialister, Prevotella, while in unaffected lung, recurrence was associated with enrichment with Sphyngomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with LUAD recurrence were greater in adjacent unaffected lung samples than in the primary tumor. Among microbial-host features in the unaffected lung samples associated with recurrence, enrichment with Stenotrophomonas geniculata and Chryseobacterium were positively correlated with upregulation of IL-2, IL-3, IL-17, EGFR, HIF-1 signaling pathways among the host transcriptome. In tumor samples, enrichment with Veillonellaceae Dialister, Ruminococcacea, Haemophilus Influenza, and Neisseria were positively correlated with upregulation of IL-1, IL-6, IL17, IFN, and Tryptophan metabolism pathways. CONCLUSIONS:Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC=0.83). IMPACT/CONCLUSIONS:This study suggests that LUAD recurrence is associated with distinct pathophysiological mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor.
PMID: 39225784
ISSN: 1538-7755
CID: 5687792

Chest Intensive Care Unit Imaging: Pearls and Pitfalls

Villasana-Gomez, Geraldine; Toussie, Danielle; Kaufman, Brian; Stojanovska, Jadranka; Moore, William H; Azour, Lea; Traube, Leah; Ko, Jane P
Imaging plays a major role in the care of the intensive care unit (ICU) patients. An understanding of the monitoring devices is essential for the interpretation of imaging studies. An awareness of their expected locations aids in identifying complications in a timely manner. This review describes the imaging of ICU monitoring and support catheters, tubes, and pulmonary and cardiac devices, some more commonly encountered and others that have been introduced into clinical patient care more recently. Special focus will be placed on chest radiography and potential pitfalls encountered.
PMID: 38816084
ISSN: 1557-8216
CID: 5663832

Incidental Apical Pleuroparenchymal Scarring on Computed Tomography: Diagnostic Yield, Progression, Morphologic Features and Clinical Significance

Toussie, Danielle; Finkelstein, Mark; Mendoza, Dexter; Concepcion, Jose; Stojanovska, Jadranka; Azour, Lea; Ko, Jane P; Moore, William H; Singh, Ayushi; Sasson, Arielle; Bhattacharji, Priya; Eber, Corey
PURPOSE/OBJECTIVE:Apical pleuroparenchymal scarring (APPS) is commonly seen on chest computed tomography (CT), though the imaging and clinical features, to the best of our knowledge, have never been studied. The purpose was to understand APPS's typical morphologic appearance and associated clinical features. PATIENTS AND METHODS/METHODS:A random generator selected 1000 adult patients from all 21516 chest CTs performed at urban outpatient centers from January 1, 2016 to December 31, 2016. Patients with obscuring apical diseases were excluded to eliminate confounding factors. After exclusions, 780 patients (median age: 64 y; interquartile range: 56 to 72 y; 55% males) were included for analysis. Two radiologists evaluated the lung apices of each CT for the extent of abnormality in the axial plane (mild: <5 mm, moderate: 5 to 10 mm, severe: >10 mm), craniocaudal plane (extension halfway to the aortic arch, more than halfway, vs below the arch), the predominant pattern (nodular vs reticular and symmetry), and progression. Cohen kappa coefficient was used to assess radiologists' agreement in scoring. Ordinal logistic regression was used to determine associations of clinical and imaging variables with APPS. RESULTS:APPS was present on 65% (507/780) of chest CTs (54% mild axial; 80% mild craniocaudal). The predominant pattern was nodular and symmetric. Greater age, female sex, lower body mass index, greater height, and white race were associated with more extensive APPS. APPS was not found to be associated with lung cancer in this cohort. CONCLUSION/CONCLUSIONS:Classifying APPS by the extent of disease in the axial or craniocaudal planes, in addition to the predominant pattern, enabled statistically significant associations to be determined, which may aid in understanding the pathophysiology of apical scarring and potential associated risks.
PMID: 38798201
ISSN: 1536-0237
CID: 5663232

Radiation Therapy for Lung Cancer: Imaging Appearances and Pitfalls

Toussie, Danielle; Ginocchio, Luke A; Cooper, Benjamin T; Azour, Lea; Moore, William H; Villasana-Gomez, Geraldine; Ko, Jane P
Radiation therapy is part of a multimodality treatment approach to lung cancer. The radiologist must be aware of both the expected and the unexpected imaging findings of the post-radiation therapy patient, including the time course for development of post- radiation therapy pneumonitis and fibrosis. In this review, a brief discussion of radiation therapy techniques and indications is presented, followed by an image-heavy differential diagnostic approach. The review focuses on computed tomography imaging examples to help distinguish normal postradiation pneumonitis and fibrosis from alternative complications, such as infection, local recurrence, or radiation-induced malignancy.
PMID: 38816092
ISSN: 1557-8216
CID: 5663852

ACR Appropriateness Criteria® Sepsis

,; Brixey, Anupama G; Fung, Alice; De Leon, Alberto Diaz; Walker, Christopher M; Porter, Kristin K; Khatri, Gaurav; Bang, Tami J; Batra, Kiran; Carter, Brett W; Christensen, Jared D; Cox, Christian W; Davis, Andrew M; Holley, Aaron B; Kandathil, Asha; Little, Brent P; Madan, Rachna; Mehta, Parth; Moore, William H; Shroff, Girish S; Uyeda, Jennifer W; Nikolaidis, Paul; Kamel, Ihab R; Chung, Jonathan H
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. A search for the underlying cause of infection typically includes radiological imaging as part of this investigation. This document focuses on thoracic and abdominopelvic causes of sepsis. In 2017, the global incidence of sepsis was estimated to be 48.9 million cases, with 11 million sepsis-related deaths (accounting for nearly 20% of all global deaths); therefore, understanding which imaging modalities and types of studies are acceptable or not acceptable is imperative. The 5 variants provided include the most commonly encountered scenarios in the setting of sepsis along with recommendations and data for each imaging study. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
PMID: 38823951
ISSN: 1558-349x
CID: 5664182

Pulmonary Cryoablation Outcomes in Octogenarians and Nonagenarians with Primary Lung Cancer

Mabud, Tarub S; Swilling, David; Guichet, Phillip; Zhu, Yuli; Manduca, Sophia; Patel, Bhavin; Azour, Lea; Taslakian, Bedros; Garay, Stuart M; Moore, William
PURPOSE:To characterize the effectiveness, safety, and length of stay (LOS) associated with pulmonary cryoablation for management of primary lung malignancies in patients aged ≥80 years. MATERIALS AND METHODS:A retrospective single-center database was compiled of all consecutive patients aged ≥80 years who underwent percutaneous computed tomography-guided cryoablation using modified triple-freeze protocol (1-3 ablation probes) for Stage IA-IIB primary lung malignancies between March 2017 and March 2020 (n = 19; 53% women; mean age, 85 years ± 3.5; range, 80-94 years). Follow-up imaging was assessed for local recurrence. Adverse events and LOS were recorded from chart review. Kaplan-Meier analysis was performed to assess both overall and local recurrence-free survival. RESULTS:Mean patient follow-up period was 21.6 months ± 10.8, and mean imaging follow-up period was 19.2 months ± 9.6. Overall survival at 3 years was 94% (95% CI, 81%-100%). Local recurrence-free survival was 100% throughout the imaging follow-up period. Intraprocedural pneumothorax occurred in 37% (7 of 19) of patients; pneumothorax risk was significantly associated with increased tumor distance from pleura (odds ratio, 1.2; P = .018). Sixty-three percent (12 of 19) of patients were discharged on the day of the procedure, with a mean LOS of 7.7 hours ± 1.6, whereas 37% of patients required overnight observation (2 of 19) or admission (5 of 19), with a mean LOS of 48.1 hours ± 19.4. Overall LOS for all patients was 22.6 hours ± 22.9. CONCLUSIONS:Percutaneous cryoablation of primary pulmonary malignancies can be performed in select octogenarians and nonagenarians with high 3-year overall and recurrence-free survival. Despite nonnegligible risk of pneumothorax, most patients are discharged on the day of the procedure.
PMID: 37527771
ISSN: 1535-7732
CID: 5708422

The Role of Proton MRI to Evaluate Patient Pathophysiology in Severe Asthma

Moore, William H; Chandarana, Hersh
PMID: 38166342
ISSN: 2638-6135
CID: 5626022

Differentiating Imaging Features of Post-lobectomy Right Middle Lobe Torsion

Tamizuddin, Farah; Ocal, Selin; Toussie, Danielle; Azour, Lea; Wickstrom, Maj; Moore, William H; Kent, Amie; Babb, James; Fansiwala, Kush; Flagg, Eric; Ko, Jane P
PURPOSE/OBJECTIVE:The purpose of this study was to identify differences in imaging features between patients with confirmed right middle lobe (RML) torsion compared to those suspected yet without torsion. MATERIALS AND METHODS/METHODS:This retrospective study entailing a search of radiology reports from April 1, 2014, to April 15, 2021, resulted in 52 patients with suspected yet without lobar torsion and 4 with confirmed torsion, supplemented by 2 additional cases before the search period for a total of 6 confirmed cases. Four thoracic radiologists (1 an adjudicator) evaluated chest radiographs and computed tomography (CT) examinations, and Fisher exact and Mann-Whitney tests were used to identify any significant differences in imaging features (P<0.05). RESULTS:A reversed halo sign was more frequent for all readers (P=0.001) in confirmed RML torsion than patients without torsion (83.3% vs. 0% for 3 readers, one the adjudicator). The CT coronal bronchial angle between RML bronchus and bronchus intermedius was larger (P=0.035) in torsion (121.28 degrees) than nontorsion cases (98.26 degrees). Patients with torsion had a higher percentage of ground-glass opacity in the affected lobe (P=0.031). A convex fissure towards the adjacent lobe on CT (P=0.009) and increased lobe volume on CT (P=0.001) occurred more often in confirmed torsion. CONCLUSION/CONCLUSIONS:A reversed halo sign, larger CT coronal bronchial angle, greater proportion of ground-glass opacity, fissural convexity, and larger lobe volume on CT may aid in early recognition of the rare yet highly significant diagnosis of lobar torsion.
PMID: 37732714
ISSN: 1536-0237
CID: 5614062

Evaluation of Socioeconomic Disparities in Follow-up Completion for Incidental Pulmonary Nodules

Thakore, Nitya L; Russo, Rienna; Hang, Tianchu; Moore, William H; Chen, Yu; Kang, Stella K
OBJECTIVE:To evaluate the association between census-tract level measures of social vulnerability and residential segregation and IPN follow up. METHODS:This retrospective cohort study included patients with IPN ≥6 mm in size or multiple subsolid/ground-glass IPNs <6 mm (with non-optional follow-up recommendations) diagnosed between January 1, 2018 and December 30, 2019 at a large urban tertiary center and followed ≥two years. Geographic sociodemographic context was characterized by 2018 U.S. Centers for Disease Control and Prevention Social Vulnerability Index (SVI) and the Index of Concentration at the Extreme (ICE), categorized in quartiles. Multivariable binomial regression models were utilized with a primary outcome of inappropriate IPN follow up (late or no follow up). Models were also stratified by nodule risk. RESULTS:The study consisted of 2,492 patients (mean age 65.6 years +/- 12.6 years; 1,361 women). Top-quartile SVI patients were more likely to have inappropriate follow up (Risk Ratio [RR]: 1.24, 95% Confidence Interval [95% CI], 1.12-1.36]), compared with the bottom quartile; risk was also elevated in top-quartile SVI subcategories of Socioeconomic Status (RR: 1.23, 95% CI, 1.13-1.34), Minority Status and Language (RR: 1.24, 95% CI, 1.03-1.48), Housing and Transportation (RR: 1.13, 95% CI, 1.02-1.26), and ICE (RR: 1.20, 95% CI, 1.11-1.30). Further, top-quartile ICE was associated with greater risk of inappropriate follow up among high-risk vs. lower-risk IPN (1.33 [1.18-1.50] vs. 1.13 [1.02-1.25]), respectively, P for interaction= 0.017). DISCUSSION/CONCLUSIONS:Local social vulnerability and residential segregation are associated with inappropriate IPN follow up and may inform policy or interventions tailored for neighborhoods.
PMID: 37473854
ISSN: 1558-349x
CID: 5536032

ACR Appropriateness Criteria® Routine Chest Imaging

Bang, Tami J; Chung, Jonathan H; Walker, Christopher M; Brixey, Anupama G; Christensen, Jared D; Faiz, Saadia A; Hanak, Michael; Hobbs, Stephen B; Kandathil, Asha; Little, Brent P; Madan, Rachna; Moore, William H; Richman, Ilana B; Setters, Belinda; Todd, Michael J; Yang, Stephen C; Donnelly, Edwin F
Routine chest imaging has been used to identify unknown or subclinical cardiothoracic abnormalities in the absence of symptoms. Various imaging modalities have been suggested for routine chest imaging. We review the evidence for or against the use of routine chest imaging in different clinical scenarios. This document aims to determine guidelines for the use of routine chest imaging as initial imaging for hospital admission, initial imaging prior to noncardiothoracic surgery, and surveillance imaging for chronic cardiopulmonary disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
PMID: 37236745
ISSN: 1558-349x
CID: 5508732