Clinical Outcomes of Resected Pure Ground-Glass, Heterogeneous Ground-Glass, and Part-Solid Pulmonary Nodules.

BACKGROUND. Increased (but not definitively solid) attenuation within pure ground-glass nodules (pGGNs) may indicate invasive adenocarcinoma and the need for resection rather than surveillance. OBJECTIVE. The purpose of this study was to compare the clinical outcomes among resected pGGNs, heterogeneous ground-glass nodules (GGNs), and part-solid nodules (PSNs). METHODS. This retrospective study included 469 patients (335 female patients and 134 male patients; median age, 68 years [IQR, 62.5-73.5 years]) who, between January 2012 and December 2020, underwent resection of lung adenocarcinoma that appeared as a subsolid nodule on CT. Two radiologists, using lung windows, independently classified each nodule as a pGGN, a heterogeneous GGN, or a PSN, resolving discrepancies through discussion. A heterogeneous GGN was defined as a GGN with internal increased attenuation not quite as dense as that of pulmonary vessels, and a PSN was defined as having an internal solid component with the same attenuation as that of the pulmonary vessels. Outcomes included pathologic diagnosis of invasive adenocarcinoma, 5-year recurrence rates (locoregional or distant), and recurrence-free survival (RFS) and overall survival (OS) over 7 years, as analyzed by Kaplan-Meier and Cox proportional hazards regression analyses, with censoring of patients with incomplete follow-up. RESULTS. Interobserver agreement for nodule type, expressed as a kappa coefficient, was 0.69. Using consensus assessments, 59 nodules were pGGNs, 109 were heterogeneous GGNs, and 301 were PSNs. The frequency of invasive adenocarcinoma was 39.0% in pGGNs, 67.9% in heterogeneous GGNs, and 75.7% in PSNs (for pGGNs vs heterogeneous GGNs, p < .001; for pGGNs vs PSNs, p < .001; and for heterogeneous GGNs vs PSNs, p = .28). The 5-year recurrence rate was 0.0% in patients with pGGNs, 6.3% in those with heterogeneous GGNs, and 10.8% in those with PSNs (for pGGNs vs heterogeneous GGNs, p = .06; for pGGNs vs PSNs, p = .02; and for heterogeneous GGNs vs PSNs, p = .18). At 7 years, RFS was 97.7% in patients with pGGNs, 82.0% in those with heterogeneous GGNs, and 79.4% in those with PSNs (for pGGNs vs heterogeneous GGNs, p = .02; for pGGNs vs PSNs, p = .006; and for heterogeneous GGNs vs PSNs, p = .40); OS was 98.0% in patients with pGGNs, 84.6% in those with heterogeneous GGNs, and 82.9% in those with PSNs (for pGGNs vs heterogeneous GGNs, p = .04; for pGGNs vs PSNs, p = .01; and for heterogeneous GGNs vs PSNs, p = .50). CONCLUSION. Resected pGGNs had excellent clinical outcomes. Heterogeneous GGNs had relatively worse outcomes, more closely resembling outcomes for PSNs. CLINICAL IMPACT. The findings support surveillance for truly homogeneous pGGNs versus resection for GGNs showing internal increased attenuation even if not having a true solid component.

Risk of Malignancy in Incidentally Detected Lung Nodules in Patients Aged Younger Than 35 Years.

BACKGROUND: The risk of malignancy in pulmonary nodules incidentally detected on computed tomography (CT) in patients who are aged younger than 35 years is unclear. OBJECTIVE: The aim of this study was to evaluate the incidence of lung cancer in incidental pulmonary nodules in patients who are 15-34 years old. METHODS: This retrospective study included patients aged 15-34 years who had an incidental pulmonary nodule on chest CT from 2010 to 2018 at our hospital. Patients with prior, current, or suspected malignancy were excluded. A chart review identified patients with diagnosis of malignancy. Incidental pulmonary nodule was deemed benign if stable or resolved on a follow-up CT at least 2 years after initial or if there was a medical visit in our health care network at least 2 years after initial CT without diagnosis of malignancy.Receiver operating characteristic curve analysis was performed with nodule size. Association of categorical variables with lung cancer diagnosis was performed with Fisher exact test, and association of continuous variables was performed with logistic regression. RESULTS: Five thousand three hundred fifty-five chest CTs performed on patients aged 15-34 years between January 2010 and December 2018. After excluding patients without a reported pulmonary nodule and prior or current malignancy, there were a total of 779 patients. Of these, 690 (89%) had clinical or imaging follow-up after initial imaging. Of these, 545 (70% of total patients) patients had imaging or clinical follow-up greater than 2 years after their initial imaging.A malignant diagnosis was established in 2/779 patients (0.3%; 95% confidence interval, 0.1%-0.9%). Nodule size was strongly associated with malignancy ( P = 0.007), with area under the receiver operating characteristic curve of 0.97. There were no malignant nodules that were less than 10 mm in size. Smoking history, number of nodules, and nodule density were not associated with malignancy. CONCLUSIONS: Risk of malignancy for incidentally detected pulmonary nodules in patients aged 15-34 years is extremely small (0.3%). There were no malignant nodules that were less than 10 mm in size. Routine follow-up of subcentimeter pulmonary nodules should be carefully weighed against the risks.

Colour-cued paragraph writing instruction for students with learning disabilities.

Expository paragraph writing is difficult to learn and teach. For many students, particularly those with learning disabilities, it is difficult to manage the multiple, simultaneous complex processes required for success. And for their teachers, writing is the content area in which they feel least prepared to teach. This intervention applied the concept of reverse engineering to instructional design to teach expository paragraph writing using a color-cued graphic organizer. The study evaluated the effects of using a systematic color code to highlight the alignment of where ideas originate in a graphic organizer to their development into a sentence within a well-organized expository paragraph. Using a single case research design, with a pre- and post-intervention assessments, students (n = 5) with dyslexia improved their expository paragraph knowledge and skills. Percentage of non-overlapping data and Tau analyses indicate a large to very large effect of the 2-week intervention. Results, suggestions for further research, and implications for practice are discussed.

Associations of the MUC5B promoter variant with timing of interstitial lung disease and rheumatoid arthritis onset.

OBJECTIVES: To investigate the associations of the common MUC5B promoter variant with timing of RA-associated interstitial lung disease (RA-ILD) and RA onset. METHODS: We identified patients with RA meeting 2010 ACR/EULAR criteria and available genotype information in the Mass General Brigham Biobank, a multihospital biospecimen and clinical data collection research study. We determined RA-ILD presence by reviewing all RA patients who had CT imaging, lung biopsy or autopsy results. We determined the dates of RA and RA-ILD diagnoses by manual records review. We examined the associations of the MUC5B promoter variant (G>T at rs35705950) with RA-ILD, RA-ILD occurring before or within 2 years of RA diagnosis and RA diagnosis at age >55 years. We used multivariable logistic regression to estimate odds ratios (ORs) for each outcome by MUC5B promoter variant status, adjusting for potential confounders including genetic ancestry and smoking. RESULTS: We identified 1005 RA patients with available genotype data for rs35705950 (mean age 45 years, 79% female, 81% European ancestry). The MUC5B promoter variant was present in 155 (15.4%) and was associated with RA-ILD [multivariable OR 3.34 (95% CI 1.97, 5.60)], RA-ILD before or within 2 years of RA diagnosis [OR 4.01 (95% CI 1.78, 8.80)] and RA onset after age 55 years [OR 1.52 (95% CI 1.08, 2.12)]. CONCLUSIONS: The common MUC5B promoter variant was associated with RA-ILD onset earlier in the RA disease course and older age of RA onset. These findings suggest that the MUC5B promoter variant may impact RA-ILD risk early in the RA disease course, particularly in patients with older-onset RA.

Malignant Nodules Detected on Lung Cancer Screening CT: Yield of Short-Term Follow-Up CT in Showing Nodule Growth.

BACKGROUND. Lung-RADS recommends 3-month follow-up for category 4A nodules and downgrading to category 2 of all category 3 or 4 nodules that are unchanged for 3 months or longer, indicating benign behavior. This guidance may be problematic considering the potential for slow-growing cancers in that lack of nodule growth, particularly at short follow-up intervals, may provide false reassurance. OBJECTIVE. The purpose of this study was to evaluate the yield of short-term follow-up CT in showing growth among malignant nodules detected on lung cancer screening CT. METHODS. This retrospective study included 76 patients (53 women, 23 men; median age, 68 years) with a positive lung cancer screening CT result (Lung-RADS category ≥ 3) between June 2015 and May 2021 with a subsequent lung cancer diagnosis and at least one follow-up CT examination at least 3 months before diagnostic or therapeutic intervention. Semiautomated software was used for linear and volumetric nodule measurements. Diameter was defined as the mean of short- and long-axis measurements. For solid nodules, growth was defined as an at least 1.5-mm increase in mean diameter or an at least 25% increase in volume; part-solid nodules, an at least 1.5-mm increase in solid-component mean diameter or an at least 25% increase in volume; and ground-glass nodules, an at least 3-mm increase in mean diameter or development of a new solid component within the nodule. RESULTS. Median time to growth was 13 months by linear and 11 months by volumetric measurement. Frequency of growth at 3 months was 5% by linear and 7% by volumetric measurement. By linear measurement, median time to growth and frequency of growth at 3 months were 13 months and 7% (solid nodules), 18 months and 6% (part-solid nodules), not reached and 0% (ground-glass nodules), not reached and 0% (category 3 nodules), 13 months and 6% (category 4A nodule)s, 6 months and 11% (category 4B nodules), and 12 months and 10% (category 4X nodules). CONCLUSION. Malignant nodules manifest growth slowly on follow-up CT, and 3-month follow-up CT has very low yield. Stability at 3-month follow-up should not instill high confidence in benignancy, and downgrading all such nodules to Lung-RADS category 2 may be problematic. CLINICAL IMPACT. This study highlights the possibility of slow-growing malignancy and associated challenges in application of Lung-RADS to management of unchanged nodules on follow-up imaging.

Cancer Risk in Nodules Detected at Follow-Up Lung Cancer Screening CT.

BACKGROUND. Nodules may have different lung cancer risks when new on follow-up CT versus when present on previously performed CT (i.e., existing nodules). Diameter-based Lung-RADS and volume-based NELSON (Nederlands-Leuvens Longkanker Screenings ONderzoek trial) categories have shown variable performance in nodule risk assessment. OBJECTIVE. The purpose of this study was to assess Lung-RADS and NELSON classifications of nodules detected on follow-up lung cancer screening CT examinations. METHODS. This retrospective study included 185 patients (100 women and 85 men; median age, 66 years) who underwent a lung cancer screening CT examination for which a prior CT examination was available. Stratified random sampling was performed to enrich the sample with suspicious nodules, yielding 50, 45, 47, 30, and 13 nodules with Lung-RADS categories 2, 3, 4A, 4B, and 4X, respectively. Lung-RADS categories were recorded from clinical reports. The linear measurements of the nodules were extracted from clinical reports to generate Lung-RADS categories by use of strict criteria from Lung-RADS version 1.1. Two radiologists used a semiautomated tool to obtain nodule volumes, which were used to generate NELSON categories. Lung cancer risk was assessed. ROC analysis was performed. Percentages and AUCs were weighted on the basis of Lung-RADS category frequencies in the underlying screening cohort. RESULTS. Twenty-nine cancers were diagnosed. The weighted cancer risk was 5% for new nodules, 1% for stable existing nodules, and 44% for growing existing nodules. None of the clinical Lung-RADS category 2 nodules were cancer. With use of strict Lung-RADS version 1.1 criteria, 34 nodules, including seven cancers, were downgraded to category 2. The AUC for cancer was 0.96 for clinical Lung-RADS, 0.81 for strict Lung-RADS, 0.71-0.84 for the NELSON algorithm (two readers), and 0.89 for nodule diameter measurement. Clinical Lung-RADS achieved weighted sensitivity and specificity, respectively, of 100% and 85% for the entire sample, 100% and 41% for new nodules, and 100% and 94% for existing nodules. The optimal diameter threshold was 8 mm for existing nodules versus 6 mm for new nodules. CONCLUSION. Lung-RADS, as applied by radiologists in clinical practice, achieved excellent performance on follow-up screening examinations. Strict Lung-RADS resulted in the downgrading of some cancers to category 2. Volumetric assessments had weaker performance than clinical Lung-RADS. New nodules warrant smaller size thresholds than existing nodules. CLINICAL IMPACT. The findings of the present study provide insight into radiologists' management of nodules detected on follow-up screening examinations.

Radiologic-Pathologic Correlation for Nondiagnostic CT-Guided Lung Biopsies Performed for the Evaluation of Lung Cancer.

OBJECTIVE. For nondiagnostic CT-guided lung biopsies, we tested whether radiologicpathologic correlation could identify patients who may benefit from repeat biopsy. MATERIALS AND METHODS. In this retrospective study, 1525 lung biopsies were performed between July 2013 and June 2017, 243 of which were nondiagnostic. Of these 243 lung biopsies, 98 were performed to evaluate for lung malignancy; 17 were excluded because of insufficient follow-up, leaving a total of 81 cases. The Brock and Herder models were used to calculate risk; in addition, cases were independently blindly reviewed by two thoracic radiologists who assigned a score from 1 (probably benign) to 5 (probably malignant). The final diagnosis was established by pathology results or benignancy was established if the lesion resolved or remained stable for at least 2 years. RESULTS. Of the 81 nondiagnostic lung biopsies, initial pathology results included 33 cases of inflammation, 28 cases of normal lung tissue or insufficient sample, 10 cases of organizing pneumonia, and 10 cases of atypical cells. 42% (34/81) of cases were eventually determined to be malignant (negative predictive value [NPV] of 58%). Pathology results of organizing pneumonia had the lowest rate of malignancy (2/10 = 20%), and pathology results of atypical cells had the highest rate of malignancy (5/10 = 50%, p = 0.51). Within this highly selected cohort, the Brock and Herder models were not predictive of malignancy, with areas under the ROC curve (AUCs) of 0.52 and 0.52, respectively. Evaluation by thoracic radiologists yielded AUCs of 0.85 and 0.77. When radiologist-assigned scores of 1 and 2 were considered as benign, the NPV was 90% and 95%. CONCLUSION. Review of nondiagnostic lung biopsies for radiologic-pathologic concordance by thoracic radiologists can triage patients who may benefit from repeat biopsy.

Multi-professional IAPT CBT training: clinical competence and patient outcomes.

BACKGROUND: There is international interest in the training of psychological therapists to deliver evidence-based treatment for common mental health problems. The UK Improving Access to Psychological Therapies (IAPT) programme, one of the largest training initiatives, relies on competent therapists to successfully deliver cognitive behaviour therapy (CBT) and promote good patient outcome. AIMS: To evaluate an IAPT CBT training course by assessing if trainees' clinical skills improve during training and reach competency standards, and to report patient outcome for submitted training cases. To investigate a possible relationship between trainee competence and patient outcome. To explore professional differences during training. METHOD: CBT trainee (n = 252) competence was assessed via audio recordings of therapy sessions at the beginning, middle and end of training. Patient pre- to post-treatment outcomes were extracted from submitted training cases (n = 1927). Differences in professional background were examined across competence, academic final grade and tutorial support. RESULTS: CBT trainees attained competence by the end of the course with 77% (anxiety recordings) and 72% (depression recordings) improving reliably. Training cases reported pre- to post-treatment effect sizes of 1.08-2.26 across disorders. CBT competence predicted a small variance in clinical outcome for depression cases. Differences in professional background emerged, with clinical psychologists demonstrating greater competence and higher academic grades. Trainees without a core professional background required more additional support to achieve competence. CONCLUSIONS: Part of a new CBT therapist workforce was successfully trained to deliver relatively brief treatment effectively. Trainees without a core profession can be successfully trained to competence, but may need additional support. This has implications for workforce training.

Integration of speech and gesture in aphasia.

BACKGROUND: Information from speech and gesture is often integrated to comprehend a message. This integration process requires the appropriate allocation of cognitive resources to both the gesture and speech modalities. People with aphasia are likely to find integration of gesture and speech difficult. This is due to a reduction in cognitive resources, a difficulty with resource allocation or a combination of the two. Despite it being likely that people who have aphasia will have difficulty with integration, empirical evidence describing this difficulty is limited. Such a difficulty was found in a single case study by Cocks et al. in 2009, and is replicated here with a greater number of participants. AIMS: To determine whether individuals with aphasia have difficulties understanding messages in which they have to integrate speech and gesture. METHODS & PROCEDURES: Thirty-one participants with aphasia (PWA) and 30 control participants watched videos of an actor communicating a message in three different conditions: verbal only, gesture only, and verbal and gesture message combined. The message related to an action in which the name of the action (e.g., 'eat') was provided verbally and the manner of the action (e.g., hands in a position as though eating a burger) was provided gesturally. Participants then selected a picture that 'best matched' the message conveyed from a choice of four pictures which represented a gesture match only (G match), a verbal match only (V match), an integrated verbal-gesture match (Target) and an unrelated foil (UR). To determine the gain that participants obtained from integrating gesture and speech, a measure of multimodal gain (MMG) was calculated. OUTCOMES & RESULTS: The PWA were less able to integrate gesture and speech than the control participants and had significantly lower MMG scores. When the PWA had difficulty integrating, they more frequently selected the verbal match. CONCLUSIONS & IMPLICATIONS: The findings suggest that people with aphasia can have difficulty integrating speech and gesture in order to obtain meaning. Therefore, when encouraging communication partners to use gesture alongside language when communicating with people with aphasia, education regarding the types of gestures that would facilitate understanding is recommended.

Reducing Wait Time for Lung Cancer Diagnosis and Treatment: Impact of a Multidisciplinary, Centralized Referral Program.

BACKGROUND: A multidisciplinary, centralized referral program was established at our institution in 2014 to reduce delays in lung cancer diagnosis and treatment following diagnostic imaging observed with the traditional, primary care provider-led referral process. The main objectives of this retrospective cohort study were to determine if referral to a Thoracic Triage Panel (TTP): 1) expedites lung cancer diagnosis and treatment initiation; and 2) leads to more appropriate specialist consultation. METHODS: Patients with a diagnosis of lung cancer and initial diagnostic imaging between March 1, 2015, and February 29, 2016, at a Memorial University-affiliated tertiary care centre in St John's, Newfoundland, were identified and grouped according to whether they were referred to the TTP or managed through a traditional referral process. Wait times (in days) from first abnormal imaging to biopsy and treatment initiation were recorded. Statistical analysis was performed using the Wilcoxon rank-sum test. RESULTS: A total of 133 patients who met inclusion criteria were identified. Seventy-nine patients were referred to the TTP and 54 were managed by traditional means. There was a statistically significant reduction in median wait times for patients referred to the TTP. Wait time from first abnormal imaging to biopsy decreased from 61.5 to 36.0 days (P < .0001). Wait time from first abnormal imaging to treatment initiation decreased from 118.0 to 80.0 days (P < .001). The percentage of specialist consultations that led to treatment was also greater for patients referred to the TTP. CONCLUSIONS: A collaborative, centralized intake and referral program helps to reduce wait time for diagnosis and treatment of lung cancer.

The impact of diagnostic imaging wait times on the prognosis of lung cancer.

OBJECTIVE: This study was performed to determine whether gaps in patient flow from initial lung imaging to computed tomography (CT) guided lung biopsy in patients with non-small cell lung cancer (NSCLC) was associated with a change in tumour size, stage, and thus prognosis. METHODS: All patients who had a CT-guided lung biopsy in 2009 (phase I) and in 2011 (phase II) with a pathologic diagnosis of primary lung cancer (NSCLC) at Eastern Health, Newfoundland, were identified. Dates of initial abnormal imaging, confirmatory CT (if performed), and CT-guided biopsy were recorded, along with tumour size and resulting T stage at each time point. In 2010, wait times for diagnostic imaging at Eastern Health were reduced. The stage and prognosis of NSCLC in 2009 was compared with 2011. RESULTS: In phase 1, there was a statistically significant increase in tumour size (mean difference, 0.67 cm; P < .0001) and stage (P < .0001) from initial image to biopsy. There was a moderate correlation between the time (in days) between the images and change in size (r = 0.33, P = .008) or stage (r = 0.26, P = .036). In phase II, the median wait time from initial imaging to confirmatory CT was reduced to 7.5 days (from 19 days). At this reduced wait time, there was no statistically significant increase in tumour size (mean difference, 0.02; P > .05) or stage (P > .05) from initial imaging to confirmatory CT. CONCLUSIONS: Delays in patient flow through diagnostic imaging resulted in an increase in tumour size and stage, with a negative impact on prognosis of NSCLC. This information contributed to the hiring of additional CT technologists and extended CT hours to decrease the wait time for diagnostic imaging. With reduced wait times, the prognosis of NSCLC was not adversely impacted as patients navigated through diagnostic imaging.

Interpreting Lung Cancer Screening CTs: Practical Approach to Lung Cancer Screening and Application of Lung-RADS.

Lung cancer screening via low-dose computed tomography (CT) reduces mortality from lung cancer, and eligibility criteria have recently been expanded to include patients aged 50 to 80 with at least 20 pack-years of smoking history. Lung cancer screening CTs should be interepreted with use of Lung Imaging Reporting and Data System (Lung-RADS), a reporting guideline system that accounts for nodule size, density, and growth. The revised version of Lung-RADS includes several important changes, such as expansion of the definition of juxtapleural nodules, discussion of atypical pulmonary cysts, and stepped management for suspicious nodules. By using Lung-RADS, radiologists and clinicians can adopt a uniform approach to nodules detected during CT lung cancer screening and reduce false positives.

Factors Associated With Delay in Lung Cancer Diagnosis and Surgery in a Lung Cancer Screening Program.

PURPOSE: Delays to biopsy and surgery after lung nodule detection can impact survival from lung cancer. The aim of this study was to identify factors associated with delay in a lung cancer screening (LCS) program. MATERIALS AND METHODS: We evaluated patients in an LCS program from May 2015 through October 2021 with a malignant lung nodule classified as lung CT screening reporting and data system (Lung-RADS) 4B/4X. A cutoff of more than 30 days between screening computed tomography (CT) and first tissue sampling and a cutoff of more than 60 days between screening CT and surgery were considered delayed. We evaluated the relationship between delays to first tissue sampling and surgery and patient sex, age, race, smoking status, median income by zip code, language, Lung-RADS category, and site of surgery (academic vs community hospital). RESULTS: A total of 185 lung cancers met the inclusion criteria, of which 150 underwent surgical resection. The median time from LCS CT to first tissue sampling was 42 days, and the median time from CT to surgery was 52 days. 127 (69%) patients experienced a first tissue sampling delay and 60 (40%) had a surgical delay. In multivariable analysis, active smoking status was associated with delay to first tissue sampling (odds ratio: 3.0, CI: 1.4-6.6, P = 0.005). Only performing enhanced diagnostic CT of the chest before surgery was associated with delayed lung cancer surgery (odds ratio: 30, CI: 3.6-252, P = 0.02). There was no statistically significant difference in delays with patients' sex, age, race, language, or Lung-RADS category. CONCLUSION: Delays to first tissue sampling and surgery in a LCS program were associated with current smoking and performing diagnostic CT before surgery.

Comparison of Lung-RADS Version 1.1 and Lung-RADS Version 2022 in Classifying Airway Nodules Detected at Lung Cancer Screening CT.

Purpose To compare the Lung Imaging Reporting and Data System (Lung-RADS) version 1.1 with version 2022 classification of airway nodules detected at lung cancer screening CT examinations. Materials and Methods This retrospective study included all patients who underwent a lung cancer screening CT examination in the authors' health care network between 2015 and 2021 with a reported airway or endobronchial nodule. A fellowship-trained cardiothoracic radiologist reviewed these CT images and characterized the airway nodules by size, location, multiplicity, morphology, dependent portions of airway, internal air, fluid attenuation, distal changes, outcome at follow-up, and final pathologic diagnosis, if malignant. Sensitivity and specificity of Lung-RADS version 1.1 in detecting malignant nodules were compared with those of Lung-RADS version 2022 using the McNemar test. Results A total of 174 patients were included. Of these, 163 (94%) had airway nodules that were deemed benign, while 11 (6%) had malignant nodules. Airway nodules in the trachea and mainstem bronchi were all benign, while lobar and segmental airway nodules had the highest risk for lung cancer (17.2% and 11.1%, respectively). Of the 12 subsegmental airway nodules that were obstructive, three (25%) were malignant and nine (75%) were benign. Nodules with nonobstructive morphologies, dependent portions of airway, internal air, or fluid attenuation were all benign. Only 10 of the 92 (10.9%) patients with positive Lung-RADS by clinical report had cancer. Lung-RADS version 2022 resulted in higher specificity than version 1.1 (82% vs 50%, P < .001), without sacrificing sensitivity (91% for both). Conclusion Compared with the previous version, Lung-RADS version 2022 reduced the number of false-positive screening CT examinations while still identifying malignant airway nodules. Keywords: CT, Lung, Primary Neoplasms, Pulmonary, Lung Cancer Screening, Lung-RADS, Nodule Risk, Airway Nodule, Endobronchial Nodule © RSNA, 2024.

Tissue-resident memory T cells in epicardial adipose tissue comprise transcriptionally distinct subsets that are modulated in atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia and carries an increased risk of stroke and heart failure. Here we investigated how the immune infiltrate of human epicardial adipose tissue (EAT), which directly overlies the myocardium, contributes to AF. Flow cytometry analysis revealed an enrichment of tissue-resident memory T (TRM) cells in patients with AF. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell T cell receptor (TCR) sequencing identified two transcriptionally distinct CD8+ TRM cells that are modulated in AF. Spatial transcriptomic analysis of EAT and atrial tissue identified the border region between the tissues to be a region of intense inflammatory and fibrotic activity, and the addition of TRM populations to atrial cardiomyocytes demonstrated their ability to differentially alter calcium flux as well as activate inflammatory and apoptotic signaling pathways. This study identified EAT as a reservoir of TRM cells that can directly modulate vulnerability to cardiac arrhythmia.

Impact of Sex, Serostatus, and Smoking on Risk for Rheumatoid Arthritis-Associated Interstitial Lung Disease Subtypes.

OBJECTIVE: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) includes multiple subtypes with varying histopathology, prognosis, and potential treatments. Limited research has investigated risk factors for different RA-ILD subtypes. Therefore, we examined demographic, serologic, and lifestyle associations with RA-ILD subtypes. METHODS: We systematically identified RA-ILD cases and RA controls without ILD (RA-noILD) in the Brigham RA Sequential Study and Mass General Brigham Biobank RA cohort. We determined RA-ILD subtype (usual interstitial pneumonia [UIP], nonspecific interstitial pneumonia [NSIP], and other/indeterminate) through chest high-resolution computed tomography imaging pattern. We investigated associations of demographic, lifestyle, and serologic factors with major RA-ILD subtypes using multivariable logistic regression. RESULTS: Among 3,328 patients with RA, we identified 208 RA-ILD cases and 547 RA-noILD controls. RA-UIP was associated with older age (odds ratio [OR] 1.03 per year, 95% confidence interval [95% CI] 1.01-1.05), male sex (OR 2.15, 95% CI 1.33-3.48), and seropositivity (OR 2.08, 95% CI 1.24-3.48), whereas RA-NSIP was significantly associated only with seropositive status (OR 3.21, 95% CI 1.36-7.56). Nonfibrotic ILDs were significantly associated with smoking (OR 2.81, 95% CI 1.52-5.21). Having three RA-ILD risk factors (male, seropositive, smoking) had an OR of 6.89 (95% CI 2.41-19.7) for RA-UIP compared with having no RA-ILD risk factors. CONCLUSION: Older age, seropositivity, and male sex were strongly associated with RA-UIP, whereas RA-related autoantibodies were associated with RA-NSIP. These findings suggest RA-ILD sex differences may be driven by RA-UIP and emphasize the importance of further studies to clarify RA-ILD heterogeneity and optimize screening and treatment approaches.

Volume Doubling Times of Benign and Malignant Nodules in Lung Cancer Screening.

The purpose of this study was to measure the fractions of benign and malignant nodules in lung cancer screening that grow on follow-up, and to measure the volume doubling time (VDT) of those that grow. In this retrospective study, we included nodules from CT lung cancer screening in our healthcare network, for which a follow-up CT performed at least 2 months later showed the nodule to be persistent. The nodules were measured using semiautomated volumetric segmentation software at both timepoints. Growth was defined as an increase in volume by 25%. VDTs were calculated, and the fraction <400 days was recorded. Categorical variables were compared with Fisher's exact test, and continuous variables by the Wilcoxon test. The study included 153 nodules, of which 44 were malignant and 109 benign. Thirty (68%) of malignant nodules and 36 (33%) of benign nodules grew (P < 0.001). For growing nodules, VDT was 318 days for malignant nodules and 389 for benign nodules (P = 0.21). For growing solid nodules, VDT was 204 days for malignant nodules and 386 days for benign nodules (P = 0.01); of these, VDT was <400 days for 12/13 (92%) of malignant nodules and 15/26 (58%) of benign nodules. In conclusion, malignant nodules were more likely to grow, and solid malignant nodules grew faster, than benign nodules. However, there was substantial overlap between benign and malignant nodules. This limits the utility of volume doubling time in determining malignant nodules.

Rate of benign nodule resection in a lung cancer screening program.

PURPOSE: Screening with low dose computed tomography (CT) can reduce lung cancer related death at the expense of unavoidable false positive results. The purpose of this study is to measure the rate of surgery for benign nodules, and evaluate characteristics of those nodules. MATERIALS AND METHODS: In this study, we evaluated patients in the Lung Cancer Screening (LCS) program across a large tertiary healthcare network from 5/2015 through 10/2021 who underwent surgical resection for a lung nodule. We reviewed the pathology reports and subsequent follow-up to establish whether the nodule was benign or malignant. Imaging characteristics of the nodules were evaluated by a radiology fellow, and we recorded Lung-RADS category, nodule status (baseline, stable, new, growing), FDG uptake on PET/CT, and calculated the risk from the Brock model. RESULTS: During this time period, a total of 21,366 LCS CT was performed in 9050 patients, and 260 patients underwent a following surgical resection. Review of the pathology results revealed: 220 lung cancer (85%), 2 other malignancies (1%), and 38 benign findings (15%). Pathology of the benign nodules was as follows: 12 with scarring/fibrosis, 5 with benign neoplasms, 14 with infection/inflammation, and 7 with other diagnoses. Lung-RADS category was as follows: 4 (11%) Lung-RADS 2, 2 (5%) Lung-Rad 3, 11 (29%) Lung-RADS 4A, 13 (34%) Lung-RADS 4B, and 8 (21%) Lung-RADS 4X. The size of the nodules ranged from 4 to 41 mm with a median of 13 mm. 2 (5%) were ground glass, 10 (26%) were part-solid, and 26 (68%) were solid. FDG-PET/CT was performed in 19 out of 38 cases, of which: 2 (11%) had no uptake, 10 (53%) had mild uptake, 3 (16%) had moderate uptake, and 4 (21%) had intense uptake. Risk assessment by Brock calculator revealed that 9 (24) had <5% (very low) risk; 27 (71%) had 5-65% (low-intermediate) risk, and 2 (5%) had >65% (high) risk. CONCLUSION: Surgical resection of benign nodules is unavoidable despite application of Lung-RADS guidelines in a modern screening program, with approximately 15% of surgeries being done for benign lesions.

Reporting and Outcomes of Coronary Calcification on Lung Cancer Screening CT.

RATIONALE AND OBJECTIVES: To evaluate the accuracy and downstream testing and statin prescribing of real-world reporting of coronary calcification on lung cancer screening (LCS) CT. MATERIALS AND METHODS: We retrospectively reviewed LCS CTs from January 2015 to November 2021 for reporting of coronary calcification; reports that denoted coronary calcification as a significant incidental finding ("S" modifier) were also noted. We evaluated calcium scoring accuracy in patients in whom a cardiac or calcium scoring CT was performed within 1 year of the LCS CT. For the first LCS CT in all patients, we evaluated whether a stress test was performed within 6 months and whether a new statin prescription was written within 90 days of the LCS CT. Patients were stratified by atherosclerotic cardiovascular disease (ASCVD) risk group, used in a multivariable regression analysis for new statin prescriptions. RESULTS: Eight thousand nine hundred eighty-seven patients underwent screening. In 117 patients who had a paired cardiac CT, scores were concordant in 65 (56%), and LCS CTs did not mention or underestimated calcifications in 40 (34%). Reporting of coronary artery calcifications led to new statin prescriptions, with OR of 1.8 for calcifications without S modifier and 4.4 for calcifications with S modifier. Reporting of coronary artery calcification with S modifier led to subsequent stress testing in 141/1582 (9%) of patients. CONCLUSION: Coronary calcifications are frequently not mentioned or underestimated at LCS CT. Reporting of coronary calcifications leads to new statin prescriptions, and radiologists should consider reporting these to allow for a risk-benefit discussion with the patient's physician.