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Fibrotic-like abnormalities are present in 60% of a single-center, longitudinal, multi-ethnic cohort 3-years after severe COVID-19. They are independently associated with male sex, low BMI, shorter telomere length, increased severity of illness, and mechanical ventilation; Black race and asthma are protective. Participants with fibrotic-like abnormalities are more likely to have reduced diffusion capacity and 6-minute walk distance. Fibrotic-like abnormalities persist but modestly improve over time. Transbronchial biopsies show small airways histopathology, consistent with high prevalence of air trapping in expiration, and infrequent interstitial thickening. This study highlights the need for continued monitoring of patients with persistent fibrosis after severe COVID-19.

The transforming growth factor-beta (TGF-β) signaling pathway is a vital regulator of cell proliferation, differentiation, apoptosis, and extracellular matrix production. It functions through canonical SMAD-mediated processes and noncanonical pathways involving MAPK cascades, PI3K/AKT, Rho-like GTPases, and NF-κB signaling. This intricate signaling system is finely tuned by interactions between canonical and noncanonical pathways and plays key roles in both physiologic and pathologic conditions including tissue homeostasis, fibrosis, and cancer progression. TGF-β signaling is known to have paradoxical actions. Under normal physiologic conditions, TGF-β signaling promotes cell quiescence and apoptosis, acting as a tumor suppressor. In contrast, in pathological states such as inflammation and cancer, it triggers processes that facilitate cancer progression and tissue remodeling, thus promoting tumor development and fibrosis. Here, we detail the role that TGF-β plays in cancer and fibrosis and highlight the potential for future theranostics targeting this pathway., (© 2024. The Author(s).)

Both cancer and fibrosis are diseases involving dysregulation of cell signaling pathways resulting in an altered cellular microenvironment which ultimately leads to progression of the condition. The two disease entities share common molecular pathophysiology and recent research has illuminated the how each promotes the other. Multiple imaging techniques have been developed to aid in the early and accurate diagnosis of each disease, and given the commonalities between the pathophysiology of the conditions, advances in imaging one disease have opened new avenues to study the other. Here, we detail the most up-to-date advances in imaging techniques for each disease and how they have crossed over to improve detection and monitoring of the other. We explore techniques in positron emission tomography (PET), magnetic resonance imaging (MRI), second generation harmonic Imaging (SGHI), ultrasound (US), radiomics, and artificial intelligence (AI). A new diagnostic imaging tool in PET/computed tomography (CT) is the use of radiolabeled fibroblast activation protein inhibitor (FAPI). SGHI uses high-frequency sound waves to penetrate deeper into the tissue, providing a more detailed view of the tumor microenvironment. Artificial intelligence with the aid of advanced deep learning (DL) algorithms has been highly effective in training computer systems to diagnose and classify neoplastic lesions in multiple organs. Ultimately, advancing imaging techniques in cancer and fibrosis can lead to significantly more timely and accurate diagnoses of both diseases resulting in better patient outcomes., (© 2024. The Author(s).)

Background and Aims: Early identification of cardiac structural abnormalities indicative of heart failure is crucial to improving patient outcomes. Chest X-rays (CXRs) are routinely conducted on a broad population of patients, presenting an opportunity to build scalable screening tools for structural abnormalities indicative of Stage B or worse heart failure with deep learning methods. In this study, a model was developed to identify severe left ventricular hypertrophy (SLVH) and dilated left ventricle (DLV) using CXRs., Methods: A total of 71 589 unique CXRs from 24 689 different patients completed within 1 year of echocardiograms were identified. Labels for SLVH, DLV, and a composite label indicating the presence of either were extracted from echocardiograms. A deep learning model was developed and evaluated using area under the receiver operating characteristic curve (AUROC). Performance was additionally validated on 8003 CXRs from an external site and compared against visual assessment by 15 board-certified radiologists., Results: The model yielded an AUROC of 0.79 (0.76-0.81) for SLVH, 0.80 (0.77-0.84) for DLV, and 0.80 (0.78-0.83) for the composite label, with similar performance on an external data set. The model outperformed all 15 individual radiologists for predicting the composite label and achieved a sensitivity of 71% vs. 66% against the consensus vote across all radiologists at a fixed specificity of 73%., Conclusions: Deep learning analysis of CXRs can accurately detect the presence of certain structural abnormalities and may be useful in early identification of patients with LV hypertrophy and dilation. As a resource to promote further innovation, 71 589 CXRs with adjoining echocardiographic labels have been made publicly available., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Since its first approval by the FDA in 2017, tremendous progress has been made in chimeric antigen receptor (CAR) T cell therapy, the adoptive transfer of engineered, CAR-expressing T lymphocyte. CAR T cells are all composed of three main elements: an extracellular antigen-binding domain, an intracellular signaling domain responsible for T cell activation, and a hinge that joins these two domains. Continuous improvement has been made in CARs, now in their fifth generation, particularly in the intracellular signaling domain responsible for T cell activation. CAR T cell therapy has revolutionized the treatment of hematologic malignancies. Nonetheless, the use of CAR T cell therapy for solid tumors has not attained comparable levels of success. Here we review the challenges in achieving effective CAR T cell therapy in solid tumors, and emerging CAR T cells that have shown great promise for non-small cell lung cancer (NSCLC). A growing number of clinical trials have been conducted to study the effect of CAR T cell therapy on NSCLC, targeting different types of surface antigens. They include epidermal growth factor receptor (EGFR), mesothelin (MSLN), prostate stem cell antigen (PSCA), and mucin 1 (MUC1). Potential new targets such as erythropoietin-producing hepatocellular carcinoma A2 (EphA2), tissue factor (TF), and protein tyrosine kinase 7 (PTK7) are currently under investigation in clinical trials. The challenges in developing CAR T for NSCLC therapy and other approaches for enhancing CAR T efficacy are discussed. Finally, we provide our perspective on imaging CAR T cell action by reviewing the two main radionuclide-based CAR T cell imaging techniques, the direct labeling of CAR T cells or indirect labeling via a reporter gene.

Objectives: Pulmonary fibrosis is a feared complication of COVID-19. To characterize the risks and outcomes associated with fibrotic-like radiographic abnormalities in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and chronic critical illness., Design: Single-center prospective cohort study., Setting: We examined chest CT scans performed between ICU discharge and 30 days after hospital discharge using established methods to quantify nonfibrotic and fibrotic-like patterns., Patients: Adults hospitalized with COVID-19-related ARDS and chronic critical illness (> 21 d of mechanical ventilation, tracheostomy, and survival to ICU discharge) between March 2020 and May 2020., Interventions: None., Measurements and Main Results: We tested associations of fibrotic-like patterns with clinical characteristics and biomarkers, and with time to mechanical ventilator liberation and 6-month survival, controlling for demographics, comorbidities, and COVID-19 therapies. A total of 141 of 616 adults (23%) with COVID-19-related ARDS developed chronic critical illness, and 64 of 141 (46%) had a chest CT a median (interquartile range) 66 days (42-82 d) after intubation. Fifty-five percent had fibrotic-like patterns characterized by reticulations and/or traction bronchiectasis. In adjusted analyses, interleukin-6 level on the day of intubation was associated with fibrotic-like patterns (odds ratio, 4.40 per quartile change; 95% CI, 1.90-10.1 per quartile change). Other inflammatory biomarkers, Sequential Organ Failure Assessment score, age, tidal volume, driving pressure, and ventilator days were not. Fibrotic-like patterns were not associated with longer time to mechanical ventilator liberation or worse 6-month survival., Conclusions: Approximately half of adults with COVID-19-associated chronic critical illness have fibrotic-like patterns that are associated with higher interleukin-6 levels at intubation. Fibrotic-like patterns are not associated with longer time to liberation from mechanical ventilation or worse 6-month survival., Competing Interests: Dr. Capaccione received funding from Cardinal Health Advisor. Dr. Salvatore received funding from Genetech and Boehringer Ingelheim. Dr. Geleris’ institution received funding from the Department of Defense (DoD) (W81XWH2110217); he received funding from SmarterDx. Dr. Anderson received funding from the National Institutes of Health (NIH) (K23HL150280). Drs. Anderson, Zucker, Cummings, O’Donnell, Wei, and Baldwin received support for article research from the NIH. Dr. Zucker received funding from the NIH (K23AI150378). Dr. Brodie’s institution received funding from LivaNova; he received funding from LivaNova, Medtronic, Cellenkos, Inspira, Xenios, and Abiomed; he disclosed that he has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira, and Cellenkos. Dr. Cummings’ institution received funding from the National Institute of Allergy and Infectious Diseases; he received funding from the NIH (K23AI163364). Dr. McGroder received funding from the NIH (T32HL105323). Drs. Wei and Baldwin disclosed that this work was supported by the DoD (W81XWH2110217). Dr. Garcia’s institution received funding from the DoD (W81XWH2110216), the NIH, the Pulmonary Fibrosis Foundation, and Boehringer Ingelheim; she disclosed that this work was supported by the DoD (W81XWH2110216); disclosed that she consults for Rejuvenation Technologies. Drs. Garcia and Baldwin received support for article research from the DoD. Dr. Baldwin received funding from the NIH (UL1TR001873). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Chimeric antigen receptor (CAR) T cell therapy is a revolutionary form of immunotherapy that has proven to be efficacious in the treatment of many hematologic cancers. CARs are modified T lymphocytes that express an artificial receptor specific to a tumor-associated antigen. These engineered cells are then reintroduced to upregulate the host immune responses and eradicate malignant cells. While the use of CAR T cell therapy is rapidly expanding, little is known about how common side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) present radiographically. Here we provide a comprehensive review of how side effects present in different organ systems and how they can be optimally imaged. Early and accurate recognition of the radiographic presentation of these side effects is critical to the practicing radiologist and their patients so that these side effects can be promptly identified and treated., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kathleen M. Capaccione reports a relationship with Cardinal Health that includes: consulting or advisory. Mary Salvatore reports a relationship with Genentech and Boehringer Ingelheim that includes: consulting or advisory, funding/grants, and speaking and lecture fees., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: Pleuroparenchymal Fibroelastosis (PPFE) is a type of pulmonary fibrosis most commonly occurring at the apices. Patients with PPFE have an increased risk of adverse effects from lung biopsy and in the post-surgical setting. Here, we investigated simple and reproducible measurements on chest CT to evaluate their predictive value in diagnosing PPFE., Methods: We analyzed a cohort of patients with histologically-proven PPFE and compared them to a cohort of patients diagnosed with "biapical scarring" (BAS) on chest CT. We measured plueuroparenchymal thickness using several independent parameters on chest CT. We also assessed other radiologic and clinical characteristics to identify if any were predictive of PPFF., Results: Our analysis demonstrated the average greatest apical thickness with a cut off of 4.5 mm yielded a sensitivity of 94.4% and a specificity of 88.9%, and an area under the curve of 97.2%. Single greatest apical thickness with a cut off of 7.5 mm had a sensitivity of 100% and a specificity of 88.9%, with the area under the curve of 97.8%. Average greatest upper lobe thickness with a cut off of 8.0 mm had a sensitivity of 88.9% and a specificity of 100%, with an area under the curve of 98.2%. Single greatest upper lobe thickness with a cut off of 8.5 yielded both a sensitivity and specificity of 94.4% and an area under the curve of 94.3%., Conclusion: Measurements described above are highly sensitive and specific for the diagnosis of PPFE and warrant investigation with a larger cohort of patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Usual interstitial pneumonia (UIP)/ idiopathic pulmonary fibrosis (IFP) is a relentlessly progressive lung disease with outcomes similar to cancer. We have previously established a radiologic grading system for UIP and demonstrated that it correlates with pulmonary function tests; here we test the hypothesis that it correlates with mortality. Validating a correlation with mortality will demonstrate the utility of this system for monitoring progression over time clinically and in trials of anti-fibrotic agents., Methods: We searched the radiology record system "Catalyst" to identify cases and reviewed each case to confirm the diagnosis. 94 patients met the inclusion criteria for further assessment. Chest CT grade was determined by consensus of two cardiothoracic radiologists. Data was analyzed to identify the interval between chest CT and death. This interval was correlated with CT grade using Spearman correlation analysis., Results: For all cases, chest CT grade and mortality demonstrated a positive correlation of r s  = 0.37732, 2-tailed p = 0.00018. We also employed subgroup analysis; for the subgroup with intervals less than or equal to 100 days, there was a positive correlation, r s  = 0.48339, 2-tailed p = 0.03602; for the subgroup with an interval greater than 100 days between imaging and death there was a positive correlation, r s  = 0.302, 2-tailed p = 0.00846., Conclusion: These data support use of this system for monitoring clinical progression and as a surrogate endpoint for clinical trials. Future work building upon the data presented here will evaluate its utility in clinical trials and develop automated grading., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Women are encouraged to have a yearly mammogram and in addition to screening for breast cancer, the radiologist reports the patient's breast density. High breast density increases a woman's risk of developing breast cancer. The number of chest computed tomography (CT) scans performed each year is increasing. Chest CT scans for lung cancer screening in high-risk patients are the standard of care. Important additional findings can be identified on these exams including coronary artery calcifications, thyroid nodules, and breast density. Our previous research has shown that breast density can be reliably graded on chest CT and is comparable to mammographic grading. However, the inter-reader agreement was higher for chest CT. It is important that thoracic radiologists include the grading of breast density in their chest CT reports. According to mammography literature, this information has proven to be helpful for early detection of breast cancer. Federal legislation recommends notifying both providers and patients about breast density on mammography and so it follows that if we see the same information on chest CT, we should report it so that at the very least the clinician can encourage their patient to have a routine mammogram., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tbcr.amegroups.com/article/view/10.21037/tbcr-23-36/coif). MMS reports grant funding from Boehringer Ingelheim and Genentech, research with Bioclinica, LungLifeAI, AbbVie, and speaking with Peer View and France Foundation. KMC served as an advisor for Cardinal Health Oncology Summits. The other authors have no conflicts of interest to declare., (2023 Translational Breast Cancer Research. All rights reserved.)

One out of eight women will be affected by breast cancer during her lifetime. Imaging plays a key role in breast cancer detection and management, providing physicians with information about tumor location, heterogeneity, and dissemination. In this review, we describe the latest advances in PET/CT imaging of breast cancer, including novel applications of 18 F-FDG PET/CT and the development and testing of new agents for primary and metastatic breast tumor imaging and therapy. Ultimately, these radiopharmaceuticals may guide personalized approaches to optimize treatment based on the patient's specific tumor profile, and may become a new standard of care. In addition, they may enhance the assessment of treatment efficacy and lead to improved outcomes for patients with a breast cancer diagnosis.

Treatment of non-small cell lung cancer (NSCLC) has undergone a paradigm shift. Once a disease with limited potential therapies, treatment options for patients have exploded with the availability of molecular testing to direct management and targeted therapies to treat tumors with specific driver mutations. New in vitro diagnostics allow for the early and non-invasive detection of disease, and emerging in vivo imaging techniques allow for better detection and monitoring. The development of checkpoint inhibitor immunotherapy has arguably been the biggest advance in lung cancer treatment, given that the vast majority of NSCLC tumors can be treated with these therapies. Specific targeted therapies, including those against KRAS, EGFR, RTK, and others have also improved the outcomes for those individuals bearing an actionable mutation. New and emerging therapies, such as bispecific antibodies, CAR T cell therapy, and molecular targeted radiotherapy, offer promise to patients for whom none of the existing therapies have proved effective. In this review, we provide the most up-to-date survey to our knowledge regarding emerging diagnostic and therapeutic strategies for lung cancer to provide clinicians with a comprehensive reference of the options for treatment available now and those which are soon to come.

Purpose: Patients with COVID-19 infection are frequently found to have pulmonary barotrauma. Recent work has identified the Macklin effect as a radiographic sign that often occurs in patients with COVID-19 and may correlate with barotrauma., Methods: We evaluated chest CT scans in COVID-19 positive mechanically ventilated patients for the Macklin effect and any type of pulmonary barotrauma. Patient charts were reviewed to identify demographic and clinical characteristics., Results: The Macklin effect on chest CT scan was identified in a total of 10/75 (13.3%) COVID-19 positive mechanically ventilated patients; 9 developed barotrauma. Patients with the Macklin effect on chest CT scan had a 90% rate of pneumomediastinum (p < 0.001) and a trend toward a higher rate of pneumothorax (60%, p = 0.09). Pneumothorax was most frequently omolateral to the site of the Macklin effect (83.3%)., Conclusion: The Macklin effect may be a strong radiographic biomarker for pulmonary barotrauma, most strongly correlating with pneumomediastinum. Studies in ARDS patients without COVID-19 are needed to validate this sign in a broader population. If validated in a broad population, future critical care treatment algorithms may include the Macklin sign for clinical decision making and prognostication., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Advanced melanoma is one of the deadliest cancers, owing to its invasiveness and its propensity to develop resistance to therapy. Surgery remains the first-line treatment for early-stage tumors but is often not an option for advanced-stage melanoma. Chemotherapy carries a poor prognosis, and despite advances in targeted therapy, the cancer can develop resistance. CAR T-cell therapy has demonstrated great success against hematological cancers, and clinical trials are deploying it against advanced melanoma. Though melanoma remains a challenging disease to treat, radiology will play an increasing role in monitoring both the CAR T-cells and response to therapy. We review the current imaging techniques for advanced melanoma, as well as novel PET tracers and radiomics, in order to guide CAR T-cell therapy and manage potential adverse events.

Background: Pneumonitis has been described as a side effect of immunotherapy as well as traditional chemotherapy. Although immune-related adverse event (IRAE) pneumonitis has been extensively characterized, the relationship between IRAE pneumonitis and pneumonitis secondary to chemotherapy is less clear. Here, we present the first analysis of radiographic features of pneumonitis secondary to immunotherapy compared to chemotherapy., Methods: Using our radiology records system, we searched chest computed tomography (CT) reports for the term "pneumonitis". We evaluated medical records to establish chronicity of pneumonitis occurring after medication administration and excluded cases where radiation therapy appeared to be the cause of pneumonitis. We also obtained information regarding demographic, clinical, and treatment characteristics for comparison., Results: Patients treated with immunotherapy demonstrated more specific features of pneumonitis including consolidation, ground glass opacities, septal thickening, traction bronchiectasis, and pulmonary nodules compared to those treated with chemotherapy. Immunotherapy treatment correlated with the development of pulmonary nodules (p = 0.048), and administration of more than one immunotherapy agent correlated with a greater incidence of development of nodules (p = 0.050). Radiographic features in patients treated with immunotherapy all decreased over time. Conversely, in patients treated with chemotherapy the incidence of ground glass opacities, traction bronchiectasis, pulmonary nodules, and mediastinal/hilar adenopathy increased over time., Conclusions: IRAE-pneumonitis has distinct features and a distinct clinical course compared to pneumonitis secondary to chemotherapy. Importantly, IRAE-pneumonitis features decreased over time, suggesting that careful consideration of the benefit-risk ratio may allow for continuation of immunotherapy in some patients who develop pneumonitis., Competing Interests: Declaration of competing interest Mary M. Salvatore-Speaker and Consultant: Genentech, Boehringer Ingelheim., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Purpose: The COVID-19 pandemic acutely disrupted all facets of healthcare, with future implications that are expected to resonate for many years. We investigated the effect of the pandemic on neuroimaging volume, hypothesizing that all representative studies would experience a reduction in volume, with those typically performed in the inpatient setting (noncontrast enhanced CT head and CTA head/neck) taking longer to recover to pre-pandemic volumes compared to studies typically performed in the outpatient setting (MR brain with and without and MR lumbar spine without)., Materials and Methods: We retrospectively queried our institution's radiology reporting system to collect weekly data for 1 year following the World Health Organization declaration of a pandemic (11 March 2020-9 March 2021) and compared them to imaging volumes from the previous year (11 March 2019-9 March 2020). We subsequently analyzed quarterly data (e.g., first quarter comparison: 3/11/2020-6/9/2020 was compared to 3/11/2019-6/9/2019)., Results: All studies experienced decreased volume during the first quarter of the year following onset of the COVID-19 pandemic, with noncontrast enhanced CT head failing to recover to pre-pandemic volumes. CTA head/neck actually surpassed pre-pandemic volume by the second quarter of the year. MRI brain w/wo and MRI lumbar spine without recovered to baseline volume by the second quarter., Conclusion: Noncontrast enhanced CT head did not recover pre-pandemic imaging volume. CTA head/neck volume initially decreased, however volume increased above pre-pandemic levels during the second quarter; this finding may be attributable to a prothrombotic state in COVID-19 patients.

Cancer immunotherapies are drugs that modulate the body's own immune system as an anticancer strategy. Checkpoint inhibitor immunotherapies interfere with cell surface binding proteins that function to promote self-recognition and tolerance, ultimately leading to upregulation of the immune response. Given the striking success of these agents in early trials in melanoma and lung cancer, they have now been studied in many types of cancer and have become a pillar of anticancer therapy for many tumor types. However, abundant upregulation results in a new class of side effects, known as immune-related adverse events (IRAEs). It is critical for the practicing radiologist to be able to recognize these events to best contribute to care for patients on checkpoint inhibitor immunotherapy. Here, we provide a comprehensive system-based review of immune-related adverse events and associated imaging findings. Further, we detail the best imaging modalities for each as well as describe problem solving modalities. Given that IRAEs can be subclinical before becoming clinically apparent, radiologists may be the first provider to recognize them, providing an opportunity for early treatment. Awareness of IRAEs and how to best image them will prepare radiologists to make a meaningful contribution to patient care as part of the clinical team., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of pulmonary scarring. New treatments slow disease progression and allow pulmonary fibrosis patients to live longer. Persistent pulmonary fibrosis increases a patient's risk of developing lung cancer. Lung cancer in patients with IPF differs from cancers that develop in the non-fibrotic lung. Peripherally located adenocarcinoma is the most frequent cell type in smokers who develop lung cancer, while squamous cell carcinoma is the most frequent in pulmonary fibrosis. Increased fibroblast foci in IPF are associated with more aggressive cancer behaviour and shorter doubling times. Treatment of lung cancer in fibrosis is challenging because of the risk of inducing an exacerbation of fibrosis. In order to improve patient outcomes, modifications of current lung cancer screening guidelines in patients with pulmonary fibrosis will be necessary to avoid delays in treatment. 2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) computed tomography (CT) imaging can help identify cancer earlier and more reliably than CT alone. Increased use of wedge resections, proton therapy and immunotherapy may increase survival by decreasing the risk of exacerbation, but further research will be necessary., Competing Interests: Conflict of interest: M.M. Salvatore reports the following relationships outside the submitted work: speaker and Advisory Board fees received from Genentech and Boehringer Ingelheim; and grant funding received from Boehringer Ingelheim and Genentech. M. Padilla reports the following relationships outside the submitted work: speaker fees received from Genentech; and consultancy fees received from Boehringer Ingelheim. The remaining authors have nothing to disclose., (Copyright ©ERS 2023.)

Background: We report the results of our retrospective analysis of the ability of standard chest CT scans to correctly diagnose cancer in the breast. Methods: Four hundred and fifty-three consecutive women with chest CT scans (contrast and non-contrast) preceding mammograms within one year comprise the study population. All chest CT images were reviewed by an experienced fellowship-trained chest radiologist and mammograms by an experienced fellowship-trained mammographer without the benefit of prior or ancillary studies; only four mammographic views were included for analysis. The size, location, and shape of breast masses were documented; on CT, the average Hounsfield units were measured. On both imaging modalities, the presence of lymphadenopathy, architectural distortion, skin thickening, and microcalcifications were recorded. Ultimately, the interpreting radiologist was asked to decide if a biopsy was indicated, and these recommendations were correlated with the patient’s outcome. Findings: Nineteen of four hundred and fifty-three patients had breast cancer at the time of the mammography. Breast masses were the most common finding on chest CT, leading to the recommendation for biopsy. Hounsfield units were the most important feature for discerning benign from malignant masses. CT sensitivity, specificity, and accuracy of CT for breast cancer detection was 84.21%, 99.3%, and 98.68% compared to 78.95%, 93.78%, and 93.16% for four-view mammography. Chest CT scans with or without contrast had similar outcomes for specificity and accuracy, but sensitivity was slightly less without contrast. Chest CT alone, without the benefit of prior exams and patient recall, correctly diagnosed cancer with a p-value of <0.0001 compared to mammography with the same limitations. Conclusion: Chest CT accurately diagnosed breast cancer with few false positives and negatives and did so without the need for patient recall for additional imaging.

Immunotherapy has dramatically improved outcomes for some cancer patients; however, novel treatments are needed for more patients to achieve a long-lasting response. FAP-targeted molecular radiotherapy has shown efficacy in both preclinical and clinical models and has immunomodulatory effects. Here, we studied if combined immunotherapy and radiotherapy could increase antitumor efficacy in murine models of lung cancer and melanoma and interrogated the mechanisms by which these treatments attenuate tumor growth. Using LLC1 and B16F10 murine models of lung cancer and melanoma, respectively, we tested the efficacy of 177 Lu-FAPI-04 alone and in combination with immunotherapy. Alone, 177 Lu-FAPI-04 significantly reduced tumor growth in both models. In animals with melanoma, combined therapy resulted in tumor regression while lung tumor growth was attenuated, but tumors did not regress. Combined therapy significantly increased caspase-3 and decreased Ki67 compared with immunotherapy alone. Flow cytometry demonstrated that tumor-associated macrophages responded in a tumor-dependent manner which was distinct in animals treated with both therapies compared with either therapy alone. These data demonstrate that 177 Lu-FAPI-04 is an effective anticancer therapy for melanoma and lung cancer which mediates effects at least partially through induction of apoptosis and modulation of the immune response. Translational studies with immunotherapy and 177 Lu-FAPI-04 are needed to demonstrate the clinical efficacy of this combined regimen.

Introduction: Here, we evaluate the effect of the COVID-19 pandemic on utilization of cardiothoracic imaging studies., Methods: We queried our radiology record system to retrospectively identify numbers of specific key cardiothoracic imaging studies for five years prior and during the COVID-19 pandemic. Statistical analysis was performed to evaluate changes in the number of exams in 2020 and 2021 compared to 2019., Results: Five-year retrospective analysis demonstrated progressive increases in nearly all cross-sectional studies. In 2020, daily chest radiograph utilization decreased with an overall number of daily radiographs of 406 (SD = 73.1) compared to 480 per day in 2019 (SD = 82.6) ( p  < 0.0001). Portable radiograph utilization was increased in 2020 averaging 320 (SD = 68.2) films daily in 2020 compared to 266 (SD = 29.1) in 2019 ( p  < 0.0001). Utilization of thoracic CT was decreased during the pandemic, with 21.8 (SD = 12.9) studies daily compared to 52.0 (SD = 21.4) ( p  < 0.0001) studies daily in 2019. Cardiac imaging utilization was also substantially decreased in 2020 compared to 2019, averaging a total of 3.8 (SD = 3.2) versus 10.8 (SD = 6.6) studies daily and 0.88 (SD = 1.7) versus 2.5 (SD = 2.3) studies daily for CT and MRI, respectively. Evaluation of cardiothoracic imaging for the subsequent 18 months after New York's entry to phase I recovery in June 2020 demonstrated that by one year after the emergence of COVID-19 imaging utilization had recovered to prepandemic levels. Cardiac imaging continued to increase throughout the chronic phase of the COVID-19 pandemic, reaching almost twice the prepandemic levels by the end of 2021., Conclusion: COVID-19 has had far-reaching effects on medicine and public health. Here, we demonstrate decreases in all cross-sectional cardiothoracic imaging studies, closely mirroring findings in other fields during the height of the pandemic, which have since rebounded., Competing Interests: The authors are employed by New York Presbyterian-Columbia University Irving Medical Center. Mary M. Salvatore is the speaker and consultant at Genentech, Boehringer Ingelheim and obtained grant funding from Genentech, Boehringer Ingelheim. The remaining authors declare no conflicts of interest., (Copyright © 2022 Kathleen M. Capaccione et al.)

Purpose: To describe the imaging findings of COVID-19 and correlate them with their known pathology observations., Methods: This is an IRB-approved retrospective study performed at Columbia University Irving Medical Center ( IRB # AAAS9652 ) that included symptomatic adult patients (21 years or older) who presented to our emergency room and tested positive for COVID-19 and were either admitted or discharged with at least one chest CT from 11 March 2020 through 1 July 2020. CT scans were ordered by the physicians caring for the patients; our COVID-19 care protocols did not specify the timing for chest CT scans. A scoring system was used to document the extent of pulmonary involvement. The total CT grade was the sum of the individual lobar grades and ranged from 0 (no involvement) to 16 (maximum involvement). The distribution of lung abnormalities was described as peripheral (involving the outer one-third of the lung), central (inner two-thirds of the lung), or both. Additional CT findings, including the presence of pleural fluid, atelectasis, fibrosis, cysts, and pneumothorax, were recorded. Contrast-enhanced CT scans were evaluated for the presence of a pulmonary embolism, while non-contrast chest CT scans were evaluated for hyperdense vessels., Results: 209 patients with 232 CT scans met the inclusion criteria. The average age was 61 years (range 23-97 years), and 56% of the patients were male. The average score reflecting the extent of the disease on the CT was 10.2 (out of a potential grade of 16). Further, 73% of the patients received contrast, which allowed the identification of a pulmonary embolism in 21%. Of those without contrast, 33% had hyperdense vessels, which might suggest a chronic pulmonary embolism. Further, 47% had peripheral opacities and 9% had a Hampton's hump, and 78% of the patients had central consolidation, while 28% had round consolidations. Atelectasis was, overall, infrequent at 5%. Fibrosis was observed in 11% of those studied, with 6% having cysts and 3% pneumothorax., Conclusions: The CT manifestations of COVID-19 can be divided into findings related to endothelial and epithelial injury, as were seen on prior post-mortem reports. Endothelial injury may benefit from treatments to stabilize the endothelium. Epithelial injury is more prone to developing pulmonary fibrotic changes.

Melanoma is a deadly disease that often exhibits relentless progression and can have both early and late metastases. Recent advances in immunotherapy and targeted therapy have dramatically increased patient survival for patients with melanoma. Similar advances in molecular targeted PET imaging can identify molecular pathways that promote disease progression and therefore offer physiological information. Thus, they can be used to assess prognosis, tumor heterogeneity, and identify instances of treatment failure. Numerous agents tested preclinically and clinically demonstrate promising results with high tumor-to-background ratios in both primary and metastatic melanoma tumors. Here, we detail the development and testing of multiple molecular targeted PET-imaging agents, including agents for general oncological imaging and those specifically for PET imaging of melanoma. Of the numerous radiopharmaceuticals evaluated for this purpose, several have made it to clinical trials and showed promising results. Ultimately, these agents may become the standard of care for melanoma imaging if they are able to demonstrate micrometastatic disease and thus provide more accurate information for staging. Furthermore, these agents provide a more accurate way to monitor response to therapy. Patients will be able to receive treatment based on tumor uptake characteristics and may be able to be treated earlier for lesions that with traditional imaging would be subclinical, overall leading to improved outcomes for patients.

Background: The COVID-19 pandemic has resulted in dramatic loss of life worldwide, but as the large number of acutely ill patients subsides, the emerging group of "COVID-19 long-haulers" present a clinical challenge. Studies have shown that many of these patients suffer long-term pulmonary disease related to residual fibrosis. Prior studies have shown that while many patients have non-specific findings of fibrotic-like changes, others develop specific patterns of interstitial lung disease., Case Report: Here, we present the first case of a patient developing pulmonary sarcoidosis one year after critical illness from COVID-19. He developed numerous non-necrotizing and well-formed granulomas in mediastinal lymph nodes and pulmonary nodules, compatible radiographically and pathologically with sarcoid., Conclusions: While the pathophysiology of sarcoid is incompletely understood, inflammation is mediated through the dysregulation of a number of different cytokines (IFNγ, IL-2, IL-12, IL-17, IL-22). This case provides valuable clues for better understanding of the shared pathophysiology of cytokine dysregulation seen in COVID-19 and other interstitial lung diseases such as sarcoidosis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Immunotherapy has become a critical class of anticancer therapy in recent years, functioning by releasing brakes on the immune system that ultimately results in immune cell activation which eliminates cancer cells. Immune related adverse events (IRAEs) are a specific type of adverse event described in patients taking checkpoint inhibitor immunotherapy which results from unrestrained immune activation. Immune related pericardial effusion has been described however has not been comprehensively characterized. Here, we present the most extensive report to date detailing this adverse event., Methods: We queried our medical record system to retrospectively identify patients on checkpoint inhibitor therapy for lung cancer who subsequently developed pericardial effusion. We analyzed the clinical and radiographic characteristics, prior therapies, treatment for the effusion, and outcomes in patients with immune related pericardial effusion and compared them to similar patients with pericardial effusion not attributable to checkpoint inhibitor therapy., Results: Our data demonstrate that most of these pericardial effusions were small and not clinically significant. The majority were successfully treated with steroids or resolved spontaneously. Anti-PD-1 inhibitors were the most common checkpoint inhibitor preceding pericardial effusion, and a significant number of patients who went on to develop IRAE pericardial effusion previously had treatment with carboplatin for their cancer., Conclusions: These data suggest that IRAE pericardial effusion is not a clinically significant adverse event however it sometimes leads to permanent discontinuation of checkpoint inhibitor therapy which is not necessary., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this article, we describe the role of radiology for diagnosis and follow-up of progressive fibrosing interstitial lung disease (PF-ILD). Patients with PF-ILD are at increased risk for early death without treatment. Clinical diagnosis of PF-ILD has been described in the literature. This manuscript reviews the radiographic diagnosis of PF-ILD and the unique CT characteristics associated with specific types of fibrosis. Ultimately, we believe that radiology has the potential to recognize progression early and thus make an important contribution to the multidisciplinary discussion for this important diagnosis., Competing Interests: MS: speaker, advisory board, and grant funding from Genentech and Boehringer Ingelheim. MP: speaker for Vindico Medical education and France Foundation and a consultant for Genentech and Boehringer Ingelheim and Paradigm Medical Communications and has received a research grant from Boehringer Ingelheim. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abu Qubo, Capaccione, Bernstein, Padilla and Salvatore.)

Background: To evaluate the chest CT appearance of patients with a clinicopathologic diagnosis of hypersensitivity pneumonia., Methods: IRB approval was obtained for a retrospective review of patients with a preoperative CT scan, a surgical pathology report from a transbronchial biopsy or wedge resection consistent with hypersensitivity pneumonitis, and a pulmonary consultation, which also supported the diagnosis. The pathology report was evaluated for granulomas, airway-centered fibrosis, microscopic honeycombing, and fibroblast foci. The medical records were reviewed for any known antigen exposure. Patients were separated into two groups; those with and without a known antigen exposure. The CT scans were assessed for distribution of fibrosis: upper lobe or lower lobe predominance, airway-centered versus peripheral distribution, three-density pattern, and honeycombing., Results: 264 pathology reports included the term chronic hypersensitivity pneumonitis (CHP). Thirty-eight of the patients had a pulmonologist who gave the patient a working diagnosis of CHP. The average age of these patients was 64 years, and 21/38 were women. Seventeen of the 38 patients had at least one antigen exposure described in the medical records. All the patients had fibrosis along the airways on chest CT. Both known antigen exposure and no known antigen patients had upper and lower lung-predominant fibrosis. There were more patients with hiatal hernias in the unknown antigen group. Honeycombing was an uncommon finding., Conclusion: Airway-centered fibrosis was present on chest CT in all 38 patients with CHP (100%), with or without known antigen exposure., Competing Interests: Conflict of Interest KM Capaccione MD, PhD, has no conflict of interest. John H.M. Austin, MD, has no conflicts of interest. Anjali Saqi received a research grant from Genentech. Nina Patel MD has no conflicts of interest. Maria Padilla serves as a speaker for the Vindico Medical Education and France Foundation and as a consultant for Genentech and Boehringer Ingelheim and Paradigm Medical Communications. She also received a research grant from Boehringer Ingelheim. Mary Salvatore serves as a speaker for Genentech and Boehringer Ingelheim and as a consultant for Genentech and Boehringer Ingelheim and received a research grant from Boehringer Ingelheim and Genentech., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Chest CT scans are routinely obtained to monitor disease progression in pulmonary fibrosis. However, radiologists do not employ a standardized system for quantitative description of the severity of the disease. Development and validation of a grading system offers potential for enhancing the information that radiologists provide clinicians., Study Design and Methods: Our retrospective review analyzed 100 sequential patients with usual interstitial pneumonitis (UIP) on HRCT scans from 2018 and 2019. A radiologic scoring system evaluated the percent of normal lung on the basis of a 0-5 point scale per lobe (findings for the right middle lobe were included in the right upper lobe score), yielding an overall additive numerical score on a scale of 20 (completely normal lung) to 0 (no normal lung). Two radiologists quantified the percentage of normal lung by consensus agreement. Percent DLCO as well as demographic data were obtained from the medical record. Statistical analysis was performed using Spearman correlation to assess correlation between grade and percent DLCO., Results: 96 patients met the inclusion criteria; average age was 71, 68% were male. Score on CT scan ranged from 18 to 4; average 10.9, SD 3.58. The single-breath diffusing capacity (percent DLCO) ranged from 88% to 17%; mean 44.5%, SD 14.3%. Spearman's correlation for CT score and percent DLCO was 0.622, P < 0.001., Conclusion: This scoring system quantifying the amount of normal lung on chest CT of patients with UIP correlated significantly with percent DLCO (P < 0.001) and appears to offer a promising quantitative measure to assess severity of disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Thrombotic complications of COVID-19 infection have become increasingly apparent as the disease has infected a growing number of individuals. Although less common than upper respiratory symptoms, thrombotic complications are not infrequent and may result in severe and long-term sequelae. Common thrombotic complications include pulmonary embolism, cerebral infarction, or venous thromboembolism; less commonly seen are acute myocardial injury, renal artery thrombosis, and mesenteric ischemia. Several case reports and case series have described acute myocardial injury in patients with COVID-19 characterized by elevations in serum biomarkers., Case Report: Here, we report the first case to our knowledge of a patient with acute coronary syndrome confirmed on catheter angiography and cardiac MRI. This patient was found to additionally have a left ventricular thrombus and ultimately suffered an acute cerebral infarction. Recognition of thrombotic complications in the setting of COVID-19 infection is essential for initiating appropriate therapy., Conclusions: In acute myocardial injury, given the different treatment strategies for myocarditis versus acute myocardial infarction secondary to coronary artery thrombus, imaging can play a key role in clinical decision making for patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Nitrofurantoin is a cause of drug-induced pneumonitis and can result in clinically significant respiratory symptoms manifesting as interstitial lung disease on chest CT, even if the patient has been taking the drug chronically without side-effects https://bit.ly/3v2m29h., Competing Interests: Conflict of interest: K.M. Capaccione has nothing to disclose. Conflict of interest: C.V. Tran has nothing to disclose. Conflict of interest: J.S. Leb has nothing to disclose. Conflict of interest: M.M. Salvatore reports grants and other from Genentech (Speaker and Advisory Board), grants and other from Boehringer Ingelheim (Speaker and Advisory Board), outside the submitted work. Conflict of interest: B. D'souza has nothing to disclose., (Copyright ©ERS 2021.)

Purpose: The purpose of our research is to evaluate the usefulness of chest X-ray for triaging patients with suspected COVID-19 infection., Methods: IRB approval was obtained to allow a retrospective review of adult patients who presented to the Emergency Department with a complaint of fever, cough, dyspnea or hypoxia and had a chest X-ray between 12 March 2020 and 26 March 2020. The initial chest X-ray was graded on a scale of 0-3 with grade 0 representing no alveolar opacities, grade 1: < 1/3 alveolar opacities of the lung, Grade 2: 1/3 to 2/3 lung with alveolar opacities and grade 3: > 2/3 alveolar opacities of the lung. Past medical history of diabetes and hypertension, initial oxygen saturation, COVID-19 testing results, intubation, and outcome were also collected., Results: Four hundred ten patient chest X-rays were reviewed. Oxygen saturation and X-ray grade were both significantly associated with the length of stay in hospital, the hazard ratio (HR) of discharge was 1.05 (95% CI [1.01, 1.09], p = 0.017) and 0.61 (95% CI [0.51, 0.73], p < 0.001), respectively. In addition, oxygen saturation and X-ray grade were significant predictors of intubation (odds ratio (OR) of intubation is 0.88 (95% CI [0.81, 0.96], p = 0.004) and 3.69 (95% CI [2.25, 6.07], p < 0.001)., Conclusions: Initial chest X-ray is a useful tool for triaging those subjects who might have poor outcomes with suspected COVID-19 infection and benefit most from hospitalization.

The human immune system is a complex system which protects against invaders and maintains tissue homeostasis. It is broadly divided into the innate and adaptive branches. Granzyme B is serine protease that plays an important role in both and can serve as a biomarker for cellular activation. Because of this, a granzyme B PET agent (GZP) has recently been developed and has been shown to be able to monitor response to immunotherapy. Here, we evaluated the utility of granzyme B PET imaging to assess the innate immune response. We subcutaneously administered LPS to mice to induce inflammation and performed granzyme B PET imaging after 24 and 120 h. We dissected out tissue in the region of injection and performed granzyme B immunofluorescence (IF) to confirm specificity of the GZP radiotracer. Granzyme B PET imaging demonstrated increased uptake in the region of LPS injection after 24 h, which normalized at 120 h. Granzyme B immunofluorescence showed specific staining in tissue from the 24 h time point compared to the PBS-injected control. These findings support the use of granzyme B PET for imaging innate immunity. In certain clinical contexts, the use of GZP PET imaging may be superior to currently available agents, and we therefore suggest further preclinical studies with the ultimate goal of translation to clinical use.

Objective: To assess the effectiveness of l-cystine dimethyl ester (CDME), an inhibitor of cystine crystal growth, for the treatment of cystine urolithiasis in an Slc3a1 knockout mouse model of cystinuria., Materials and Methods: CDME (200 μg per mouse) or water was delivered by gavage daily for 4 weeks. Higher doses by gavage or in the water supply were administered to assess organ toxicity. Urinary amino acids and cystine stones were analyzed to assess drug efficacy using several analytical methods., Results: Treatment with CDME led to a significant decrease in stone size compared with that of the water group (P = .0002), but the number of stones was greater (P = .005). The change in stone size distribution between the 2 groups was evident by micro computed tomography. Overall, cystine excretion in urine was the same between the 2 groups (P = .23), indicating that CDME did not interfere with cystine metabolism. Scanning electron microscopy analysis of cystine stones from the CDME group demonstrated a change in crystal habit, with numerous small crystals. l-cysteine methyl ester was detected by ultra-performance liquid chromatography-mass spectrometer in stones from the CDME group only, indicating that a CDME metabolite was incorporated into the crystal structure. No pathologic changes were observed at the doses tested., Conclusion: These data demonstrate that CDME promotes formation of small stones but does not prevent stone formation, consistent with the hypothesis that CDME inhibits cystine crystal growth. Combined with the lack of observed adverse effects, our findings support the use of CDME as a viable treatment for cystine urolithiasis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Sox9 has gained increasing importance both functionally and as a prognostic factor in cancer. We demonstrate a functional role for Sox9 in inducing a mesenchymal phenotype in lung ADC. We show that Sox9 mRNA and protein are overexpressed in lung ADC, particularly those with KRAS mutations. Sox9 expression correlated with the Notch target gene Hes1, and numerous other Notch pathway components. We observed that Sox9 is a potent inducer of lung cancer cell motility and invasion, and a negative regulator of E-cadherin, a key protein that is lost during epithelial-mesenchymal transition (EMT). Moreover, we show that Notch1 signaling directly regulates Sox9 expression through a SOX9 promoter binding site, independently of the TGF-β pathway, and that Sox9 participates in Notch-1 induced cell motility, cell invasion, and loss of E-cadherin expression. Together, the results identify a new functional role for a Notch1-Sox9 signaling axis in lung ADC that may explain the correlation of Sox9 with tumor progression, higher tumor grade, and poor lung cancer survival. In addition to Notch and TGF-β, Sox9 also acts downstream of NF-κB, BMP, EGFR, and Wnt/β-catenin signaling. Thus, Sox9 could potentially act as a hub to mediate cross-talk among key oncogenic pathways in lung ADC. Targeting Sox9 expression or transcriptional activity could potentially reduce resistance to targeted therapy for lung ADC caused by pathway redundancy.

The Notch signaling pathway is evolutionarily conserved and responsible for cell fate determination in the developing embryo and mature tissue. At the molecular level, ligand binding activates Notch signaling by liberating the Notch intracellular domain, which then translocates into the nucleus and activates gene transcription. Despite the elegant simplicity of this pathway, which lacks secondary messengers or a signaling cascade, Notch regulates gene expression in a highly context- and cell-type-dependent manner. Notch signaling is frequently dysregulated, most commonly by overactivation, across many cancers and confers a survival advantage on tumors, leading to poorer outcomes for patients. Recent studies demonstrate how Notch signaling increases tumor cell proliferation and provide evidence that active Notch signaling maintains the cancer stem-cell pool, induces epithelial-mesenchymal transition and promotes chemoresistance. These studies imply that pharmacological inhibition of Notch signaling may refine control of cancer therapy and improve patient survival. Gamma secretase inhibitors (GSIs) are drugs that inhibit Notch signaling and may be successful in controlling cancer cell growth in conjunction with standard chemotherapy, but substantial side effects have hampered their widespread use. Recent efforts have been aimed at the development of antibodies against specific Notch receptors and ligands with the hope of limiting side effects while providing the same therapeutic benefit as GSIs. Together, studies characterizing Notch signaling and modulation have offered hope that refined methods targeting Notch may become powerful tools in anticancer therapeutics.

Aim: To analyze the accuracy of short-term bio-impedance as a means of measuring gastric motility., Methods: We evaluated differences in the short-term electrical bio-impedance signal from the gastric region in the following conditions: (1) fasting state, (2) after the administration of metoclopramide (a drug that induces an increase in gastric motility) and (3) after food ingestion in 23 healthy volunteers. We recorded the real component of the electrical impedance signal from the gastric region for 1000 s. We performed a Fast Fourier Transform (FFT) on this data and then compared the signal among the fasting, medicated, and postprandial conditions using the median of the area under the curve, the relative area under the curve and the main peak activity., Results: The median of the area under the curve of the frequency range in the region between 2-8 cycles per minute (cpm) decreased from 4.7 cpm in the fasting condition to 4.0 cpm in the medicated state (t = 3.32, P = 0.004). This concurred with the decrease seen in the relative area under the FFT curve in the region from 4 to 8 cpm from 38.3% to 26.6% (t = 2.81, P = 0.012) and the increase in area in the region from 2 to 4 cpm from 22.4% to 27.7%, respectively (t = -2.5, P = 0.022). Finally the main peak position also decreased in the region from 2 to 8 cpm. Main peak activity in the fasting state was 4.72 cpm and declined to 3.45 cpm in the medicated state (t = 2.47, P = 0.025). There was a decrease from the fasting state to the postprandial state at 3.02 cpm (t = 4.0, P = 0.0013)., Conclusion: Short-term electrical bio-impedance can assess gastric motility changes in individuals experiencing gastric stress by analyzing the area medians and relative areas under the FFT curve.