James F. Gruden’s research while affiliated with University of North Carolina at Chapel Hill and other places

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Publications (26)


Minute Pulmonary Meningothelial‐Like Nodules: An Incidental Benign Entity in Association With Lung Adenocarcinoma
  • Article

April 2025

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Frederic Askin

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James F. Gruden

We report a case of a 69‐year‐old female smoker who presented with multiple pulmonary micronodules incidentally noted during imaging for aortoiliac occlusive disease. A growing right lower lobe nodule was resected, revealing adenocarcinoma alongside benign minute pulmonary meningothelial‐like nodules (MPMNs). MPMNs, often found incidentally, in association with malignancies, can mimic metastatic disease but are benign and stable. Recognizing MPMNs is essential to prevent misdiagnosis and unnecessary treatment in patients with coexisting malignancies. On chest CT, these nodules are typically peripherally located along the interlobular septa, consistent with their close vascular association around the small pulmonary veins observed in pathology.


Fig. 13.2 Micronodules with pleural and/or fissural involvement. Tiny nodules are present along the pleural and fissural surfaces in a. MIP slabs in the same patient (b) show innumerable, diffusely distributed micronodules along pleural/fissural surfaces in this patient with metastatic thyroid carcinoma. MIP slabs are helpful in the detection of small nodules (see text). Micronodules line the minor and major fissures (arrows) with a patchy distribution in a patient with perilymphatic nodules and sarcoidosis (c). There is minimal nodularity of the peripheral pleural surfaces as well. Sarcoidosis is the prototypical perilymphatic nodular disease [13]. Sagittal reformats are also often helpful in micronodule analysis
Micronodular Lung Disease
  • Chapter
  • Full-text available

February 2025

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14 Reads

Accurate CT evaluation of micronodular lung disease requires accurate nodule localization based on the underlying anatomy of the lungs at the level of both the secondary pulmonary lobule (SPL) and pulmonary interstitium. Identifying each specific micronodule distribution leads to a unique set of differential diagnoses and may prompt specific, focused clinical evaluation.

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Current Imaging of Idiopathic Pulmonary Fibrosis

August 2022

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44 Reads

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4 Citations

Radiologic Clinics of North America

The major role of imaging (CT) in usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) is in the initial diagnosis. We propose several modifications to existing guidelines to help improve the accuracy of this diagnosis and to enhance interobserver agreement. CT detects the common complications and associations that occur with UIP/IPF including acute exacerbation, lung cancer, and dendriform pulmonary ossification and is useful in informing prognosis based on baseline fibrosis severity. Serial CT imaging is a topic of great interest; it may identify disease progression before FVC decline or clinical change.


Management of Incidental Pulmonary Nodules: Influencing Patient Care Through Subspecialized Imaging Review

December 2021

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26 Reads

Current Problems in Diagnostic Radiology

Objective Evaluate whether thoracic radiologist CT-detected incidental pulmonary nodules initially reported by non-thoracic imagers would change management recommendations. Methods The Radiology Consultation Service (RCS) identified 468 CT scans (one per patient) performed through the adult emergency department (ED) from August 2018 through December 2020 that mentioned the presence of a pulmonary nodule. Forty percent (186/468) were read by thoracic radiologists and 60% (282/468) were read by non-thoracic radiologists. The RCS contacted all patients in order to assess risk factors for lung malignancy. Sixty-seven patients were excluded because they were unreachable, declined participation, or were actively followed by a pulmonologist or oncologist. A thoracic radiologist assessed the nodule and follow up recommendations in all remaining cases. Results A total of 215 cases were re-reviewed by thoracic radiologists. The thoracic radiologist disagreed with the initial nodule recommendations in 38% (82/215) of cases and agreed in 62% (133/215) of cases. All discordant cases resulted in a change in management by the thoracic radiologist with approximately one-third (33%, 27/82) decreasing imaging utilization and two-thirds (67%, 55/82) increasing imaging utilization. Nodules were deemed benign and follow up eliminated in 11% (9/82) of discordant cases. Discussion Our study illustrates that nodule review by thoracic radiologists results in a change in management in a large percentage of patients. Continued research is needed to determine whether subspecialty imaging review results in increased or more timely lung cancer detection.


Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial

May 2021

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57 Reads

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274 Citations

The Lancet Oncology

Background Previous phase 2 trials of neoadjuvant anti-PD-1 or anti-PD-L1 monotherapy in patients with early-stage non-small-cell lung cancer have reported major pathological response rates in the range of 15–45%. Evidence suggests that stereotactic body radiotherapy might be a potent immunomodulator in advanced non-small-cell lung cancer (NSCLC). In this trial, we aimed to evaluate the use of stereotactic body radiotherapy in patients with early-stage NSCLC as an immunomodulator to enhance the anti-tumour immune response associated with the anti-PD-L1 antibody durvalumab. Methods We did a single-centre, open-label, randomised, controlled, phase 2 trial, comparing neoadjuvant durvalumab alone with neoadjuvant durvalumab plus stereotactic radiotherapy in patients with early-stage NSCLC, at NewYork-Presbyterian and Weill Cornell Medical Center (New York, NY, USA). We enrolled patients with potentially resectable early-stage NSCLC (clinical stages I–IIIA as per the 7th edition of the American Joint Committee on Cancer) who were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients were randomly assigned (1:1) to either neoadjuvant durvalumab monotherapy or neoadjuvant durvalumab plus stereotactic body radiotherapy (8 Gy × 3 fractions), using permuted blocks with varied sizes and no stratification for clinical or molecular variables. Patients, treating physicians, and all study personnel were unmasked to treatment assignment after all patients were randomly assigned. All patients received two cycles of durvalumab 3 weeks apart at a dose of 1·12 g by intravenous infusion over 60 min. Those in the durvalumab plus radiotherapy group also received three consecutive daily fractions of 8 Gy stereotactic body radiotherapy delivered to the primary tumour immediately before the first cycle of durvalumab. Patients without systemic disease progression proceeded to surgical resection. The primary endpoint was major pathological response in the primary tumour. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrial.gov, NCT02904954, and is ongoing but closed to accrual. Findings Between Jan 25, 2017, and Sept 15, 2020, 96 patients were screened and 60 were enrolled and randomly assigned to either the durvalumab monotherapy group (n=30) or the durvalumab plus radiotherapy group (n=30). 26 (87%) of 30 patients in each group had their tumours surgically resected. Major pathological response was observed in two (6·7% [95% CI 0·8–22·1]) of 30 patients in the durvalumab monotherapy group and 16 (53·3% [34·3–71·7]) of 30 patients in the durvalumab plus radiotherapy group. The difference in the major pathological response rates between both groups was significant (crude odds ratio 16·0 [95% CI 3·2–79·6]; p<0·0001). In the 16 patients in the dual therapy group with a major pathological response, eight (50%) had a complete pathological response. The second cycle of durvalumab was withheld in three (10%) of 30 patients in the dual therapy group due to immune-related adverse events (grade 3 hepatitis, grade 2 pancreatitis, and grade 3 fatigue and thrombocytopaenia). Grade 3–4 adverse events occurred in five (17%) of 30 patients in the durvalumab monotherapy group and six (20%) of 30 patients in the durvalumab plus radiotherapy group. The most frequent grade 3–4 events were hyponatraemia (three [10%] patients in the durvalumab monotherapy group) and hyperlipasaemia (three [10%] patients in the durvalumab plus radiotherapy group). Two patients in each group had serious adverse events (pulmonary embolism [n=1] and stroke [n=1] in the durvalumab monotherapy group, and pancreatitis [n=1] and fatigue [n=1] in the durvalumab plus radiotherapy group). No treatment-related deaths or deaths within 30 days of surgery were reported. Interpretation Neoadjuvant durvalumab combined with stereotactic body radiotherapy is well tolerated, safe, and associated with a high major pathological response rate. This neoadjuvant strategy should be validated in a larger trial. Funding AstraZeneca.


Central paradiaphragmatic middle lobe involvement in nonspecific interstitial pneumonia

February 2021

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21 Reads

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4 Citations

European Radiology

Objectives Nonspecific interstitial pneumonia (NSIP) lacks specific diagnostic guidelines or criteria for imaging diagnosis, and the need for more reliable computed tomography (CT) characterization remains. We hypothesized that central paradiaphragmatic middle lobe (ML) involvement is present in most patients with NSIP. The purpose of this study was to evaluate the prevalence of ML involvement and thus to assess its potential as a unique feature of NSIP.Methods We conducted a retrospective CT-imaging review of 40 patients with biopsy-proven (7/40, 18%) or clinically established (33/40, 82%) NSIP. Three subspecialty-trained thoracic radiologists reviewed CTs for ML involvement both independently and in consensus, and additional CT findings previously described in NSIP independently.ResultsML involvement was present in most cases (70%, 28/40, independent review, 78%, 31/40, consensus reading), with substantial agreement among all three readers (κ = 0.65). Fibrosis was present in almost all cases (93%, 37/40). Subpleural sparing occurred in one-third of patients (30%, 12/40). Homogeneity (48%, 19/40), central bronchiectasis (45%, 18/40), and peripheral bronchiectasis (53%, 21/40) were present in about half of patients. Apart from substantial inter-reader agreement on fibrosis (κ = 0.65), the above-mentioned imaging characteristics had fair to slight universal agreement (κ = 0.07–0.30).Conclusions Central paradiaphragmatic ML ground glass attenuation superimposed on reticulation and traction bronchiectasis occurs in most patients with NSIP, with high interobserver agreement.Key Points• Central paradiaphragmatic middle lobe ground glass attenuation superimposed on reticulation and traction bronchiectasis is common in nonspecific interstitial pneumonia (NSIP).• This finding occurs more frequently than subpleural sparing and has a better interobserver agreement.


Thoracic Manifestations of Rheumatoid Arthritis

January 2021

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42 Reads

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21 Citations

Radiographics

Rheumatoid arthritis (RA) is one of the most common chronic systemic inflammatory diseases and the most common chronic inflammatory arthritis. Classically a progressive symmetric polyarthritis, RA is characterized by inflammation, erosions, bone loss, and joint destruction. Up to half of patients with RA exhibit extra-articular manifestations (EAMs), which may precede articular disease and are more common in patients with seropositive RA (patients with detectable serum levels of rheumatoid factor and/or anticitrullinated peptide antibodies). Cardiovascular and pulmonary EAMs are the largest contributors to morbidity and mortality in RA and may be especially devastating. Imaging has a significant role in diagnosing these EAMs and assessing response to treatment. Although treatment with disease-modifying antirheumatic drugs has redefined the natural history of RA and helped many patients achieve low disease activity, patients are at risk for treatment-related complications, as well as infections. The clinical features of drug-induced lung disease and infection can overlap considerably with those of EAMs, presenting a diagnostic challenge. Radiologists, by recognizing the imaging characteristics and evolution of these various processes, are essential in diagnosing and distinguishing among EAMs, treatment-related complications, and unrelated processes and formulating an appropriate differential diagnosis. Moreover, recognizing these disease processes at imaging and contextualizing imaging findings with clinical information and laboratory and pathologic findings can facilitate definitive diagnosis and proper treatment. The authors review the articular and extra-articular thoracic imaging manifestations of RA, including cardiovascular, respiratory, and pleural diseases, as well as treatment-related complications and common infections. ©RSNA, 2021.


Imaging Utilization and Outcomes in Vulnerable Populations during COVID-19 in New York City

December 2020

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14 Reads

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3 Citations

Radiology Cardiothoracic Imaging

Background: Coronavirus disease 2019 (COVID-19) affects vulnerable populations (VP) adversely. Purpose: To evaluate overall imaging utilization in vulnerable subgroups (elderly, racial/ethnic minorities, socioeconomic status [SES] disadvantage) and determine if a particular subgroup has worse outcomes from COVID-19. Materials/methods: Of 4110 patients who underwent COVID-19 testing from March 3-April 4, 2020 at NewYork-Presbyterian Hospital (NYP) health system, we included 1121 COVID-19 positive adults (mean age 59±18 years, 59% male) from two academic hospitals and evaluated imaging utilization rates and outcomes, including mortality. Results: Of 897 (80%) VP, there were 465 (41%) elderly, 380 (34%) racial/ethnic minorities, and 479 (43%) SES disadvantage patients. Imaging was performed in 88% of patients and mostly portable/bedside studies, with 87% of patients receiving chest radiographs. There were 83% hospital admissions, 25% ICU admissions, 23% intubations, and 13% deaths. Elderly patients had greater imaging utilization, hospitalizations, ICU/intubation requirement, longer hospital stays, and >4-fold increase in mortality compared to non-elderlies (adjusted hazard ratio[aHR] 4.79, p<0.001). Self-reported minorities had fewer ICU admissions (p=0.03) and reduced hazard for mortality (aHR 0.53, p=0.004; complete case analysis: aHR 0.39, p<0.001 excluding "not reported"; sensitivity analysis: aHR 0.61, p=0.005 "not reported" classified as minorities) with similar imaging utilization, compared to non-minorities. SES disadvantage patients had similar imaging utilization and outcomes as compared to their counterparts. Conclusions: In a predominantly hospitalized New York City cohort, elderly patients are at highest mortality risk. Racial/ethnic minorities and SES disadvantage patients fare better or similarly to their counterparts, highlighting the critical role of access to inpatient medical care during the COVID-19 pandemic.


The bullseye sign: A variant of the reverse halo sign in COVID-19 pneumonia

July 2020

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82 Reads

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32 Citations

Clinical Imaging

The predominant pulmonary imaging findings on chest CT in the novel 2019 coronavirus infection (COVID-19) are bilateral ground glass opacities. The reverse halo sign is uncommon. This is a report of the new “bullseye sign,” which is considered a variant of the reverse halo sign and favored to represent a focus of organizing pneumonia. The specificity of this finding is unclear, however its presence should alert radiologists to the possibility of COVID-19 infection.


Citations (20)


... ILA status was shown to be a significant risk factor for radiological ILA progression after surgical resection in patients with lung cancer [88,89]. Evidence has shown that despite the increased use of the term ILA among thoracic-trained radiologists, non-thoracic general radiologists have not begun to use the term [90]. ...

Reference:

Imaging in the diagnosis and management of fibrosing interstitial lung diseases
Practice patterns in reporting interstitial lung abnormality at a tertiary academic medical center
  • Citing Article
  • October 2023

Clinical Imaging

... The ideal interval for performing follow-up HRCT for patients with clinically stable ILD remains uncertain and is often individualized [9,21]. Certain healthcare providers choose to perform imaging studies only in patients with symptomatic worsening or with a decline in pulmonary physiology. ...

Current Imaging of Idiopathic Pulmonary Fibrosis
  • Citing Article
  • August 2022

Radiologic Clinics of North America

... Forest plot of conversion to thoracotomy[1][2][3][4][5][6][7][10][11][12][13][14][15][16][17]. ...

Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial
  • Citing Article
  • May 2021

The Lancet Oncology

... 7 The straight-edge sign occurs when the fibrosis is delineated by a straight interface with the normal orthogonal lung, and when there is no significant superior extension along the lateral chest wall. 8 The histological findings of RA-UIP are similar to those observed in IPF, although prominent lymphocyte aggregation may sometimes be seen in RA-UIP. 5 Around 20% of individuals develop rheumatoid nodules, which are highly specific for RA and more common in men and cigarette smokers. ...

Thoracic Manifestations of Rheumatoid Arthritis
  • Citing Article
  • January 2021

Radiographics

... The details of the study population and design were previously reported. 32 In brief, as shown in Fig. 1, we excluded patients with RT-PCR test results that were negative, indeterminate or invalid (n = 1563), those whose medical records were unavailable for review (n = 1417; 1392 from other NYP Hospitals to which EMR access was inaccessible, 25 restricted healthcare workers), and pediatric cases (n = 9). For this analysis, patients were excluded if they did not have at least one CXR or one chest CT (n = 145). ...

Imaging Utilization and Outcomes in Vulnerable Populations during COVID-19 in New York City
  • Citing Article
  • December 2020

Radiology Cardiothoracic Imaging

... Manual labeling of CT volumes is time-consuming and may increase the workload of clinicians. Additionally, applying deep learning-based segmentation models to data from new unseen sources can result in suboptimal lesion segmentation due to unseen acquisition devices/parameters, variations in patient pathology, or future coronavirus variants resulting in new appearance characteristics or new lesion pathologies [16]. To address this challenge, interactive segmentation methods that can quickly adapt to such changing settings are needed. ...

The bullseye sign: A variant of the reverse halo sign in COVID-19 pneumonia
  • Citing Article
  • July 2020

Clinical Imaging

... The pulmonary CTA is also advantageous to lower slice scanners for follow-up and monitoring, including volumetric quantification, as well as for diagnosing pulmonary embolism, hypertension, and additional pathologies of the chest [8], and can be used in cases in which magnetic resonance imaging is contraindicated or limited due to noncompatible implanted devices like pacemakers and stents or claustrophobia. Pulmonary CT angiography can be diagnosed by studying the complex anatomy and variations in the TOF subtypes such as absent pulmonary valve and pulmonary atresia with major aortopulmonary collateral arteries (MAPCA) [9]. ...

Major Aortopulmonary Collateral Arteries in a Case of Unrepaired Tricuspid and Pulmonary Atresia with Single Ventricle Physiology
  • Citing Article
  • April 2020

Journal of Cardiovascular Computed Tomography

... For example, micronodules in the axial (central) interstitium occur along the airways and arterial branches in the lung and cause "beading" of the bronchovascular bundles. Interlobular septal micronodules cause the septa to appear "beaded," and this can occur even in the absence of pleural and fissural micronodules in some conditions [19][20][21][22][23][24][25][26] (Table 13.1). Every interstitial compartment is not involved in each perilymphatic condition, nor are they affected to a similar degree (Fig. 13.7). ...

How I Do It: An Algorithmic Approach to the Interpretation of Diffuse Lung Disease on Chest CT Imaging
  • Citing Article
  • November 2019

Chest

... The lack of inherent prognostic value of TMB in this large, non-ICI-treated cohort provides a benchmark for future studies, considering the accumulating evidence of the role of neoadjuvant immunotherapy in early-stage NSCLC. [69][70][71] Despite adhering to delivering a statistically robust meta-analysis, certain limitations prevailed. Although two studies in the OS and three studies in the DFS analyses showed a prognostic association of high TMB in early-stage NSCLC, the limited sample sizes (ranging from 55 to 148) in those individual studies portend limited statistical power. ...

P2.04-92 Neoadjuvant Durvalumab With or Without Sub-Ablative Stereotactic Radiotherapy (SBRT) in Patients with Resectable NSCLC (NCT02904954)
  • Citing Article
  • October 2019

Journal of Thoracic Oncology

... The enhancement degree was divided into mild to moderate [net enhanced value ≤ 40 Hounsfield Unit(HU)] and strong (net enhanced value > 40 HU) (16). Lung invasion was considered based on signs: a multilobular tumor convex to the lung with adjacent lung abnormalities, or deep lobulation at the tumor-lung interface (17,18). The pericardiac/ pleural invasion was considered when the space between the tumor and the pericardiac/pleura disappeared, with pericardiac/pleura thickening and/or cavity effusion (17). ...

Multilobulated thymoma with an acute angle: a new predictor of lung invasion
  • Citing Article
  • February 2019

European Radiology