Open-Label Trial of Amikacin Liposome Inhalation Suspension in Mycobacterium abscessus Lung Disease.

BACKGROUND: Mycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance. RESEARCH QUESTION: Does treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in patients with M abscessus pulmonary disease who are treatment naive or who have treatment-refractory disease? STUDY DESIGN AND METHODS: In an open-label protocol, patients were given ALIS (590 mg) added to background multidrug therapy for 12 months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance. RESULTS: Of 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were female, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%). INTERPRETATION: In a cohort of patients primarily with macrolide-resistant M abscessus, one-half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03038178; URL: www. CLINICALTRIALS: gov.

Pulmonary Vascular Complication Associated With Coronavirus Infection and Role of Lung Resection.

Pulmonary artery pseudoaneurysms are an uncommon diagnosis and have been minimally described in the coronavirus (COVID-19) literature. In our case, a 31-year-old man presented with severe acute hypoxic respiratory failure, stress cardiomyopathy, and combined septic and cardiogenic shock secondary to COVID-19 pneumonia and Streptococcus anginosus bacteremia. The patient had perfusing granulomas eroding into the pulmonary vasculature, causing impending hemothorax. Thoracic surgical procedures for infectious pulmonary artery pseudoaneurysms or perfusing granulomas in patients who have had COVID-19 should be performed selectively and with thoughtful perioperative planning to prevent the life-threatening complications of rupture and bleeding.

ACR Appropriateness Criteria® Chronic Chest Pain-High Probability of Coronary Artery Disease: 2021 Update.

Management of patients with chronic chest pain in the setting of high probability of coronary artery disease (CAD) relies heavily on imaging for determining or excluding presence and severity of myocardial ischemia, hibernation, scarring, and/or the presence, site, and severity of obstructive coronary lesions, as well as course of management and long-term prognosis. In patients with no known ischemic heart disease, imaging is valuable in determining and documenting the presence, extent, and severity of obstructive coronary narrowing and presence of myocardial ischemia. In patients with known ischemic heart disease, imaging findings are important in determining the management of patients with chronic myocardial ischemia and can serve as a decision-making tool for medical therapy, angioplasty, stenting, or surgery. This document summarizes the recent growing body of evidence on various imaging tests and makes recommendations for imaging based on the available data and expert opinion. This document is focused on epicardial CAD and does not discuss the microvascular disease as the cause for CAD. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Functional, transcriptional, and microbial shifts associated with healthy pulmonary aging in rhesus macaques.

Older individuals are at increased risk of developing severe respiratory infections. However, our understanding of the impact of aging on the respiratory tract remains limited as samples from healthy humans are challenging to obtain and results can be confounded by variables such as smoking and diet. Here, we carry out a comprehensive cross-sectional study (n = 34 adult, n = 49 aged) to define the consequences of aging on the lung using the rhesus macaque model. Pulmonary function testing establishes similar age and sex differences as humans. Additionally, we report increased abundance of alveolar and infiltrating macrophages and a concomitant decrease in T cells were in aged animals. scRNAseq reveals shifts from GRZMB to IFN expressing CD8+ T cells in the lungs. These data provide insight into age-related changes in the lungs' functional, microbial, and immunological landscape that explain increased prevalence and severity of respiratory diseases in the elderly.

Primary Aortic Angiosarcoma: A Review of Two Cases Highlighting Unique Imaging and Clinical Characteristics.

Angiosarcomas are rare vascular connective tissue tumors originating from the tunica intima, media, or adventitia and may arise in large vessels. Here two cases of primary angiosarcoma of the aorta are described that highlight initial manifestations and unique complications from diffuse arterial tumor emboli, which led to delayed cancer diagnosis. In patients with aortic lesions, imaging characteristics must be thoughtfully reconciled with clinical scenarios, particularly in patients with no additional evidence of atherosclerosis or vasculitis. Keywords: Oncology, Neoplasms-Primary, MR-Angiography, Aorta © RSNA, 2021.

Mediastinal Mass: An Unusual Location for a Paraganglioma.

A 50-year-old man presented to the hospital for workup of a symptomatic inguinal hernia. At presurgical workup, findings from a contrast material-enhanced CT of the chest, abdomen, and pelvis revealed a large, well-defined and enhancing middle mediastinal mass arising from the right ventricular outflow tract. The mass was ultimately deemed resectable due to preserved fat planes between the mass and other mediastinal structures and the preservation of the right and left coronary arteries. The tumor was diagnosed as a mediastinal paraganglioma at histologic assessment. Keywords: Adults, Angiography, CT-Angiography, MR-Angiography, Cardiac, Neoplasms-Primary ©RSNA, 2021.

Thoracic Endemic Fungi in the United States: Importance of Patient Location.

The digitization of radiographic studies along with high-speed transmission of images has formed the basis of teleradiology, which has become an integral component in the workflow of a contemporary radiology practice. It is with this advent and growing utilization of teleradiology that the significance of the source location of images has gained importance. Specifically, the importance of where the patient resides and what endemic fungi occur in that location cannot be underestimated. In the United States, histoplasmosis, coccidioidomycosis, blastomycosis, and cryptococcosis are caused by endemic fungi occurring in the Ohio and Mississippi river valleys, the Southwest, the Upper Midwest, and the Pacific Northwest, respectively. All of these organisms enter the body through the respiratory system and have the potential to cause significant morbidity and mortality. Patients infected with these fungi are often asymptomatic but may present with acute flulike symptoms such as fever, cough, or dyspnea. Patients may also present with vague chronic symptoms including cough, fever, malaise, and weight loss. Thoracic manifestations at radiography and CT include consolidation, nodules, cavities, lymphadenopathy, and pleural disease. PET may show fluorine 18-fluorodeoxyglucose uptake with active acute or chronic infections, and it is difficult to distinguish infections from malignancy. Imaging findings may be nonspecific and can be confused with other disease processes, including malignancy. The patient demographics, clinical history, and location are clues that may lead to a proper diagnosis of endemic fungal disease. The radiologist should be cognizant of the patient location to provide a correct and timely radiologic diagnosis that helps guide the clinician to initiate appropriate therapy. ©RSNA, 2021.

Transjugular intrahepatic portosystemic shunt creation using intravascular ultrasound guidance.

PURPOSE: To describe the use of intravascular ultrasound (US) guidance for creation of transjugular intrahepatic portosystemic shunts (TIPSs) in humans. MATERIALS AND METHODS: The initial 25 cases of intravascular US-guided TIPS were retrospectively compared versus the last 75 conventional TIPS cases during the same time period at the same institution in terms of the number of needle passes required to establish portal vein (PV) access, fluoroscopy time, and needle pass-related complications. RESULTS: Intravascular US-guided TIPS creation was successful in all cases, and there was no statistically significant difference in number of needle passes, fluoroscopy time, or needle pass-related complications between TIPS techniques. Intravascular US-guided TIPS creation was successful in cases in which conventional TIPS creation had failed as a result of PV thrombosis or distorted anatomy. Intravascular US guidance for TIPS creation was additionally useful in a patient with Budd-Chiari syndrome and in a patient with intrahepatic tumors. CONCLUSIONS: Intravascular US is a safe and reproducible means of real-time image guidance for TIPS creation, equivalent in efficacy to conventional fluoroscopic guidance. Real-time sonographic guidance with intravascular US may prove advantageous for cases in which there is PV thrombus, distorted anatomy, Budd-Chiari syndrome, or hepatic tumors.

Image-guided intensity-modulated radiotherapy for pancreatic carcinoma.

PURPOSE: To present the techniques and preliminary outcomes of ultrasound-based image-guided intensity-modulated radiotherapy (IG-IMRT) for pancreatic cancer. MATERIALS AND METHODS: Retrospective analysis of 41 patients treated between November 2000 and March 2005 with IG-IMRT to mean total doses of 55 Gy (range, 45-64 Gy). We analyzed the clinical feasibility of IG-IMRT, dosimetric parameters, and outcomes, including acute gastrointestinal toxicity (RTOG grading). Survival was assessed for adenocarcinoma (n = 35) and other histologies. RESULTS: Mean daily image-guidance corrective shifts were 4.8 +/- 4.3 mm, 7.5 +/- 7.2 mm, and 4.6 +/- 5.9 mm along the x-, y-, and z-axes, respectively (mean 3D correction vector, 11.7 +/- 8.4 mm). Acute upper gastrointestinal toxicity was grade 0-1 in 22 patients (53.7%), grade 2 in 16 patients (39%), and grade 3 in 3 patients (7.3%). Lower gastrointestinal toxicity was grade 0-1 in 32 patients (78%), grade 2 in 7 patients (17.1%), and grade 4 in 2 patients (4.9%). Treatment was stopped early in 4 patients following administration of 30 to 54 Gy. Median survival for adenocarcinoma histology was 10.3 months (18.6 months in patients alive at analysis; n = 8) with actuarial 1- and 2-year survivals of 38% and 25%, respectively. CONCLUSION: Daily image-guidance during delivery of IMRT for pancreatic carcinoma is clinically feasible. The data presented support the conclusion that safety margin reduction and moderate dose escalation afforded by implementation of these new radiotherapy technologies yields preliminary outcomes at least comparable with published survival data.

Daily ultrasound-based image-guided targeting for radiotherapy of upper abdominal malignancies.

PURPOSE: Development and implementation of a strategy to use a stereotactic ultrasound (US)-based image-guided targeting device (BAT) to align intensity-modulated radiotherapy (IMRT) target volumes accurately in the upper abdomen. Because the outlines of such targets may be poorly visualized by US, we present a method that uses adjacent vascular guidance structures as surrogates for the target position. We assessed the potential for improvement of daily repositioning and the feasibility of daily application. METHODS AND MATERIALS: A total of 62 patients were treated by sequential tomotherapeutic IMRT between October 2000 and June 2003 for cholangiocarcinoma and gallbladder carcinoma (n = 10), hepatocellular carcinoma (n = 10), liver metastases (n = 11), pancreatic carcinoma (n = 20), neuroblastoma (n = 3), and other abdominal and retroperitoneal tumors (n = 8). The target volumes (TVs) and organs at risk were delineated in contrast-enhanced CT data sets. Additionally, vascular guidance structures in close anatomic relation to the TV, or within the TV, were delineated. Throughout the course of IMRT, US BAT images were acquired during daily treatment positioning. In addition to the anatomic structures typically used for US targeting (e.g., the TV and dose-limiting organs at risk), CT contours of guidance structures were superimposed onto the real-time acquired axial and sagittal US images, and target position adjustments, as indicated by the system, were performed accordingly. We report the BAT-derived distribution of shifts in the three principal room axes compared with a skin-mark-based setup, as well as the time required to perform BAT alignment. The capability of the presented method to improve target alignment was assessed in 15 patients by comparing the organ and fiducial position between the respective treatment simulation CT with a control CT study after US targeting in the CT suite. RESULTS: A total of 1,337 BAT alignments were attempted. US images were not useful in 56 setups (4.2%), mainly because of limited visibility due to daily variations in colonic and gastric air. US imaging was facilitated in intrahepatic tumors and asthenic patients. The mean +/- SD shift from the skin mark position was 4.9 +/- 4.35, 6.0 +/- 5.31, and 6.0 +/- 6.7 mm in the x, y, and z direction, respectively. The mean magnitude vector of three-dimensional alignment correction was 11.4 +/- 7.6 mm. The proportion of daily alignments corrected by a magnitude of >10, >15, and >20 mm was 48.9%, 25.1%, and 12.7%, respectively. The magnitude of shifts in the principal directions, as well as the three-dimensional vector of displacement, was statistically significant (test against the zero hypothesis) at p <0.0001. The guidance structures that were the most valuable for identification of the TV position were the branches of the portal vein, hepatic artery, and dilated bile ducts in intrahepatic lesions and the aorta, celiac trunk, superior mesenteric artery, and extrahepatic aspects of the portal vein system in retroperitoneal and extrahepatic lesions. The mean total setup time was 4.6 min. The correlation of BAT targeting with target setup error assessment in the control CT scans in 15 patients revealed setup error reduction in 14 of 15 alignments. The average setup error reduction, assessed as a reduction in the length of setup error three-dimensional magnitude vector, was 54.4% +/- 26.9%, with an observed mean magnitude of residual setup error of 4.6 +/- 3.4 mm. The sole worsening of an initial setup was by a magnitude of <2 mm. US targeting resulted in statistically significant improvements in patient setup (p = 0.03). CONCLUSION: Daily US-guided BAT targeting for patients with upper abdominal tumors was feasible in the vast majority of attempted setups. This method of US-based image-guided tumor targeting has been successfully implemented in clinical routine. The observed improved daily repositioning accuracy might allow for individualized reduction of safety margins and optional dose escalation. Compared with the established application of the BAT device for prostate radiotherapy, in which the target can be directly visualized, the TV in the present study was predominantly positioned relative to guidance vascular structures in close anatomic relation. We perceived an enormous potential in improved and individualized patient positioning for fractionated radiotherapy and also for stereotactic extracranial radiotherapy and radiosurgery, especially for tumors of the liver and pancreas.

Daily stereotactic ultrasound prostate targeting: inter-user variability.

We analyzed the inter-user variability of patient setup for prostate radiotherapy using a stereotactic ultrasound-targeting device. Setup variations in 20 prostate cancer patients were analyzed. Users were a radiation oncologist, a medical physicist, four radiation technologists (RTT) and a radiologist. The radiation oncologist, radiologist, physicist and two RTTs were experienced users of the system (>18 months of experience); two RTTs were users new to the system. Gold standard for this analysis was a control CT acquired immediately following ultrasound targeting. For inter-user variability assessments, the radiation oncologist provided a set of axial and sagittal freeze-frames (standard freeze-frames) for virtual targeting by all users. Additionally each user acquired individual freeze-frames for target alignments. We analyzed the range of virtual setups in each patient along the principal room axes based on standard and individual freeze-frames. The magnitude of residual setup error and percentage of setup change for each user was assessed by control CT/planning CT comparison with individual virtual shifts. A total of 184 alignments were analyzed. The range of virtual shifts between users was 2.7+/-1.4, 3.6+/-1.1, and 4.4+/-1.4 mm (mean+/-SD) in x, y and z-direction for setups based on standard freeze-frames and 3.9+/-2.6, 6.0+/-4.7, and 5.4+/-2.7 mm for setups based on individual freeze-frames. When only virtual shifts of experienced users were analyzed, the mean ranges were reduced by up to 2.4 mm. Average magnitude of initial setup error before ultrasound targeting was 14.3 mm. Average improvement of prostate setup was 63.1+/-23.4% in experienced and 35.14+/-37.7% in inexperienced users, respectively (p<0.0001). Only 5 of 184 (2.7%) virtual alignments would have introduced new larger setup errors (mean 3.2 mm, range 0.2 to 9.5 mm) than the magnitude of the initial setup error. We conclude that ultrasound guided treatment setup for patients treated for prostate cancer can be performed with high inter-user consistency and does lead to improved treatment setup in more than 97% of attempted setups. Experienced use is correlated with a reduced range of setups between users and higher degree of setup improvement when compared with users new to the system