First in Human Phase 1 Clinical Trial of Stereotactic Irradiation to Achieve Lung Volume Reduction (SILVR) in Severe Emphysema.

PURPOSE: Only a subset of patients with severe emphysema qualify for lung volume reduction surgery or endobronchial valves. We previously demonstrated that stereotactic ablative radiation therapy of lung tumors reduces lung volume in treated lobes by creating localized lung fibrosis. We aimed to determine the safety and secondarily explore the efficacy of stereotactic irradiation for lung volume reduction (SILVR) over 18 months after intervention in patients with severe emphysema. METHODS AND MATERIALS: We conducted a single-arm, prospective clinical trial in eligible patients with severe emphysema treated with unilateral stereotactic ablative radiation therapy (45 Gy in 3 fractions) to a target within the most emphysematous region. The primary outcome was safety in terms of incidence of grade ≥3 adverse events, and the secondary outcome was efficacy. RESULTS: Eight patients received the intervention. Median (range) baseline characteristics were age 73 years (63-78); forced expiratory volume in 1 second percent of predicted value (FEV1%) 28.5% (19.0-42.0); diffusing capacity of the lungs for carbon monoxide percent of predicted value 40% (24.0-67.0); and body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index 5.5 (5-9). The incidence of grade ≥3 adverse events was 3 of 8 (37.5%). The relative change in target lobe volume was -23.1% (-1.6 to -41.5) and -26.5% (-20.6 to -40.8) at 6 and 18 months, respectively. The absolute ΔFEV1% was greater in patients with a BODE index ≤5 versus ≥6 (+12.0% vs -2.0%). The mean baseline lung density (in Hounsfield units, reflecting the amount of preserved parenchyma) within the intermediate dose volume (V60BED3) correlated with the absolute change in target lobe volume at 18 months. CONCLUSIONS: SILVR appears to be safe, with a signal for efficacy as a novel therapeutic alternative for patients with severe emphysema. SILVR may be most safe and effective in patients with a lower BODE index and/or less parenchymal destruction.

Pulmonary Vein Sign on Computed Tomography Pulmonary Angiography in Proximal and Distal Chronic Thromboembolic Pulmonary Hypertension With Hemodynamic Correlation.

BACKGROUND: Pulmonary vein sign (PVS) indicates abnormal pulmonary venous flow on computed tomography pulmonary angiography (CTPA) is a frequent finding in proximal chronic thromboembolic pulmonary hypertension (CTEPH). PVS's occurrence in distal CTEPH and correlation to disease severity is unknown. Using right heart catheterization data, we evaluated the relationship between PVS and CTEPH disease distribution and severity. MATERIALS AND METHOD: A total of 93 consecutive CTEPH cases with both CTPA and right heart catheterization were identified in this retrospective multi-institutional study. After excluding 17 cases with suboptimal CTPA, there were 52 proximal and 24 distal CTEPH cases. Blood flow in the major pulmonary veins was graded qualitatively. Subgroup analysis of PVS was performed in 38 proximal CTEPH cases before and after pulmonary endarterectomy. RESULTS: PVS was more frequent in proximal (79%) than distal CTEPH (29%) ( P <0.001). No significant difference was noted in invasive mean pulmonary artery pressure (46±11 and 41±12 mm Hg) or pulmonary vascular resistance (9.4±4.5 and 8.4±4.8 WU) between the 2 groups. In the subgroup analysis, PVS was present in 29/38 patients (76%) before surgery. Postoperatively, 33/38 cases (87%, P <0.001) had normal venous flow (mean pulmonary artery pressure 46±11 and 25; pulmonary vascular resistance 9.2±4.3 and 2.6 WU preop and postop, respectively). CONCLUSION: PVS is a common feature in proximal but infrequent findings in distal CTEPH. PVS does not correlate with hemodynamic severity. PVS resolution was seen in the majority of patients following successful endarterectomy.

Opportunistic Screening for Atrial Fibrillation on Routine Chest Computed Tomography.

PURPOSE: Quantitative biomarkers from chest computed tomography (CT) can facilitate the incidental detection of important diseases. Atrial fibrillation (AFib) substantially increases the risk for comorbid conditions including stroke. This study investigated the relationship between AFib status and left atrial enlargement (LAE) on CT. MATERIALS AND METHODS: A total of 500 consecutive patients who had undergone nongated chest CTs were included, and left atrium maximal axial cross-sectional area (LA-MACSA), left atrium anterior-posterior dimension (LA-AP), and vertebral body cross-sectional area (VB-Area) were measured. Height, weight, age, sex, and diagnosis of AFib were obtained from the medical record. Parametric statistical analyses and receiver operating characteristic curves were performed. Machine learning classifiers were run with clinical risk factors and LA measurements to predict patients with AFib. RESULTS: Eighty-five patients with a diagnosis of AFib were identified. Mean LA-MACSA and LA-AP were significantly larger in patients with AFib than in patients without AFib (28.63 vs. 20.53 cm 2 , P <0.000001; 4.34 vs. 3.5 cm, P <0.000001, respectively), both with area under the curves (AUCs) of 0.73. Multivariable logistic regression analysis including age, sex, and VB-Area with LA-MACSA improved the AUC for predicting AFib (AUC=0.77). An LA-MACSA threshold of 30 cm 2 demonstrated high specificity for AFib diagnosis at 92% and sensitivity of 48%, and LA-AP threshold at 4.5 cm demonstrated 90% specificity and 42% sensitivity. A Bayesian machine learning model using age, sex, height, body surface area, and LA-MACSA predicted AFib with an AUC of 0.743. CONCLUSIONS: LA-MACSA or LA-AP can be rapidly measured from routine chest CT, and when >30 cm 2 and >4.5 cm, respectively, are specific indicators to predict patients at increased risk for AFib.

64Cu-DOTATATE Uptake in a Pulmonary Hamartoma.

ABSTRACT: DOTATATE PET/CT is frequently used to evaluate indeterminant pulmonary nodules suspected to be pulmonary carcinoid. We report an unexpected case of pulmonary hamartoma demonstrating 64Cu-DOTATATE uptake in a 43-year-old woman with a slowly enlarging pulmonary nodule. Histopathological staining showed somatostatin receptor 2 expression on vascular endothelial cells and a proportion of cartilage and smooth muscle cells within the hamartoma.

Prevalence and significance of pulmonary disease on lung ultrasonography in outpatients with SARS-CoV-2 infection.

BACKGROUND: The majority of patients with SARS-CoV-2 infection are diagnosed and managed as outpatients; however, little is known about the burden of pulmonary disease in this setting. Lung ultrasound (LUS) is a convenient tool for detection of COVID-19 pneumonia. Identifying SARS-CoV-2 infected outpatients with pulmonary disease may be important for early risk stratification. OBJECTIVES: To investigate the prevalence, natural history and clinical significance of pulmonary disease in outpatients with SARS-CoV-2. METHODS: SARS-CoV-2 PCR positive outpatients (CV(+)) were assessed with LUS to identify the presence of interstitial pneumonia. Studies were considered positive based on the presence of B-lines, pleural irregularity and consolidations. A subset of patients underwent longitudinal examinations. Correlations between LUS findings and patient symptoms, demographics, comorbidities and clinical outcomes over 8 weeks were evaluated. RESULTS: 102 CV(+) patients underwent LUS with 42 (41%) demonstrating pulmonary involvement. Baseline LUS severity scores correlated with shortness of breath on multivariate analysis. Of the CV(+) patients followed longitudinally, a majority showed improvement or resolution in LUS findings after 1-2 weeks. Only one patient in the CV(+) cohort was briefly hospitalised, and no patient died or required mechanical ventilation. CONCLUSION: We found a high prevalence of LUS findings in outpatients with SARS-CoV-2 infection. Given the pervasiveness of pulmonary disease across a broad spectrum of LUS severity scores and lack of adverse outcomes, our findings suggest that LUS may not be a useful as a risk stratification tool in SARS-CoV-2 in the general outpatient population.

Anatomical variability in the upper tracheobronchial tree: sex-based differences and implications for personalized inhalation therapies.

The morphometry of the large conducting airways is presumed to have a strong effect on the regional deposition of inhaled aerosol particles. Nevertheless, sex-based differences have not been fully quantified and are still largely ignored in designing inhalation therapies. To this end, we retrospectively analyzed high-resolution computed tomography scans for 185 individuals (90 women, 95 men) in the age range of 12-89 yr to determine airway luminal areas, airway lengths, and bifurcation angles. Only subjects free of chronic airway disease were considered. In men, luminal areas of the upper conducting airways were, on average, ∼30%-50% larger when compared with those in women, with the largest differences found in the trachea (289.72 ± 54.25 vs. 193.50 ± 42.37 mm2 for men and women, respectively). The ratio of the largest luminal area in men to the smallest luminal area in women (in any given segment) ranged between 4.5 and 8.6, the largest differences being found in the lobar bronchi. Sex-based differences were minor in the case of bifurcation angles (e.g., average main bifurcation angle: 93.04 ± 9.58° vs. 91.03 ± 9.81° for men and women, respectively), but large intersubject variability was found irrespective of sex (e.g., range of main bifurcation angle: 65.04°-122.01° vs. 69.46°-113.94° for men and women, respectively). Bronchial segments were shorter by ∼5%-20% in women relative to men, the largest differences being located in the upper lobes. False discovery rate analysis revealed statistically significant associations among morphometric measures of the right lung in women (but not in men), suggesting two phenotypes among women that we attribute to the smaller female thoracic volume.NEW & NOTEWORTHY We found significant sex-based morphometric differences in the central airways of healthy men and women that were only mildly attenuated in subsets matched for lung volume. Lumen areas were significantly larger in men (∼30%-50%). Large variability (∼75%-87%) in airway bifurcation angles (60°-122°) was found irrespective of sex. The branching pattern of the right main and right upper bronchi in women (but not in men) follows two phenotypes modulated by lung volume.

Evaluation of integrin αvß6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis.

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvß6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin αvß6.

Single-Lumen Endotracheal Tube and Bronchial Blocker for Airway Management During Tracheobronchoplasty for Tracheobronchomalacia: A Case Report.

We present a case of a 69-year-old man who underwent tracheobronchoplasty for tracheobronchomalacia using a single-lumen endotracheal tube and a Y-shaped bronchial blocker for airway management. Tracheobronchoplasty is performed by sewing mesh to plicate the posterior, membranous wall of the distal trachea and main bronchi through a right posterolateral thoracotomy. The goals of airway management include continuous left-lung ventilation and lung protection from aspiration. Ideally, only conventional airway management tools are used. This case demonstrates that a single-lumen endotracheal tube with a bronchial blocker can be a straightforward strategy for airway management during tracheobronchoplasty.

A Young Woman With a Rapidly Growing Thoracic Tumor.

CASE PRESENTATION: A 38-year-old woman presented with 2 months of dry cough, progressive shortness of breath, central chest pain, nausea, vomiting, and dizziness. She was previously healthy and was not taking any medications. She denied fever, night sweats, or weight loss. She had a two pack-year smoking history and had quit smoking at 27 years of age. She denied drug use and had no recent travel history. Family history was pertinent for ovarian cancer, breast cancer, and colon cancer.

Serial Cardiac FDG-PET for the Diagnosis and Therapeutic Guidance of Patients With Cardiac Sarcoidosis.

BACKGROUND: Cardiac fluorodeoxyglucose positron-emission tomography (FDG-PET) has emerged as a standard imaging modality for the diagnosis of cardiac sarcoidosis (CS); however, there is a scarcity of data on the use of serial FDG-PET to guide immunosuppressive therapy. The aim of this work was to report our experience using serial FDG-PET for the diagnosis and management of patients with CS, focusing on its utility in ongoing immunosuppression management. METHODS AND RESULTS: We studied consecutive patients with CS managed at Stanford University from 2010 to 2017. We evaluated our experience using FDG-PET for diagnosis and guidance of immunosuppressive therapy titration in CS. Among 34 patients diagnosed with CS, 16 (47%), 12 (35%) and 14(41%) presented with heart block, heart failure, and ventricular arrhythmias, respectively. FDG-PET proved beneficial in the initial diagnosis in 21 patients (62%). A total of 128 FDG-PET scans were performed (median 3 per patient). Ninety-four FDG-PET scans (73%) resulted in a change in therapy, with 42FDG-PET scans (33%) instrumental for tapering prednisone. Among patients who were initiated on prednisone, the mean dose of prednisone at 1 year was 9.5mg/d. Over a median follow-up of 2.3years, 48% of patients were successfully weaned from prednisone completely, and 20% were weaned to a maintenance dosage of 5-10mg/d. During the follow-up period, transplant-free survival was 88%. CONCLUSIONS: The use of serial cardiac FDG-PET for the diagnosis and management of CS was critical for guiding immunosuppression management and resulted in low chronic steroid doses and good disease control within 1 year of diagnosis.

Improving Quality of Dynamic Airway Computed Tomography Using an Expiratory Airflow Indicator Device.

PURPOSE: Dynamic computed tomography (CT) of the airways is increasingly used to evaluate patients with suspected expiratory central airway collapse, but current protocols are susceptible to inadequate exhalation caused by variable patient compliance with breathing instructions during the expiratory phase. We developed and tested a low-cost single-use expiratory airflow indicator device that was designed to improve study quality by providing a visual indicator to both patient and operator when adequate expiratory flow was attained. MATERIALS AND METHODS: A total of 56 patients undergoing dynamic airway CT were evaluated, 35 of whom were scanned before introduction of the indicator device (control group), with the rest comprising the intervention group. Lung volumes and tracheal cross-sectional areas on inspiratory/expiratory phases were computed using automated lung segmentation and quantitative software analysis. Inadequate exhalation was defined as absolute volume change of <500 mL during the expiratory phase. RESULTS: Fewer patients in the intervention group demonstrated inadequate exhalation. The average change in volume was higher in the intervention group (P=0.004), whereas the average minimum tracheal cross-sectional area was lower (P=0.01). CONCLUSIONS: The described expiratory airflow indicator device can be used to ensure adequate exhalation during the expiratory phase of dynamic airway CT. A higher frequency of adequate exhalation may improve reliability and sensitivity of dynamic airway CT for diagnosis of expiratory central airway collapse.

Identification of Pulmonary Hypertension Caused by Left-Sided Heart Disease (World Health Organization Group 2) Based on Cardiac Chamber Volumes Derived From Chest CT Imaging.

BACKGROUND: Evaluations of patients with pulmonary hypertension (PH) commonly include chest CT imaging. We hypothesized that cardiac chamber volumes calculated from the same CT scans can yield additional information to distinguish PH related to left-sided heart disease (World Health Organization group 2) from other PH subtypes. METHODS: Patients who had PH confirmed by right heart catheterization and contrast-enhanced chest CT studies were enrolled in this retrospective multicenter study. Cardiac chamber volumes were calculated using automated segmentation software and compared between group 2 and non-group 2 patients with PH. RESULTS: This study included 114 patients with PH, 27 (24%) of whom were classified as group 2 based on their pulmonary capillary wedge pressure. Patients with group 2 PH exhibited significantly larger median left atrial (LA) volumes (118 mL vs 63 mL; P < .001), larger median left ventricular (LV) volumes (90 mL vs 76 mL; P = .02), and smaller median right ventricular (RV) volumes (173 mL vs 210 mL; P = .005) than did non-group 2 patients. On multivariate analysis adjusted for age, sex, and mean pulmonary arterial pressure, group 2 PH was significantly associated with larger median LA and LV volumes (P < .001 and P = .008, respectively) and decreased volume ratios of RA/LA, RV/LV, and RV/LA (P = .001, P = .004, and P < .001, respectively). Enlarged LA volumes demonstrated a high discriminatory ability for group 2 PH (area under the curve, 0.92; 95% CI, 0.870-0.968). CONCLUSIONS: Volumetric analysis of the cardiac chambers from nongated chest CT scans, particularly with findings of an enlarged left atrium, exhibited high discriminatory ability for identifying patients with PH due to left-sided heart disease.

Coccidioidomycosis: Surgical Issues and Implications.

BACKGROUND: Coccidioidomycosis, commonly called "valley fever," "San Joaquin fever," "desert fever," or "desert rheumatism," is a multi-system illness caused by infection with Coccidioides fungi (C. immitis or C. posadasii). This organism is endemic to the desert Southwest regions of the United States and Mexico and to parts of South America. The manifestations of infection occur along a spectrum from asymptomatic to mild self-limited fever to severe disseminated disease. METHODS: Review of the English-language literature. RESULTS: There are five broad indications for surgical intervention in patients with coccidioidomycosis: Tissue diagnosis in patients at risk for co-existing pathology, perforation, bleeding, impingement on critical organs, and failure to resolve with medical management. As part of a multidisciplinary team, surgeons may be responsible for the care of infected patients, particularly those with severe disease. CONCLUSION: This review discusses the history, microbiology, epidemiology, pathology, diagnosis, and treatment of coccidioidomycosis, focusing on situations that may be encountered by surgeons.

Pre-treatment non-target lung FDG-PET uptake predicts symptomatic radiation pneumonitis following Stereotactic Ablative Radiotherapy (SABR).

PURPOSE: To determine if pre-treatment non-target lung FDG-PET uptake predicts for symptomatic radiation pneumonitis (RP) following lung stereotactic ablative radiotherapy (SABR). METHODS: We reviewed a 258 patient database from our institution to identify 28 patients who experienced symptomatic (grade â©¾ 2) RP after SABR, and compared them to 57 controls who did not develop symptomatic RP. We compared clinical, dosimetric and functional imaging characteristics between the 2 cohorts including pre-treatment non-target lung FDG-PET uptake. RESULTS: Median follow-up time was 26.9 months. Patients who experienced symptomatic RP had significantly higher non-target lung FDG-PET uptake as measured by mean SUV (p < 0.0001) than controls. ROC analysis for symptomatic RP revealed area under the curve (AUC) of 0.74, with sensitivity 82.1% and specificity 57.9% with cutoff mean non-target lung SUV > 0.56. Predictive value increased (AUC of 0.82) when mean non-target lung SUV was combined with mean lung dose (MLD). We developed a 0-2 point model using these 2 variables, 1 point each for SUV > 0.56 or MLD > 5.88 Gy equivalent dose in 2 Gy per fraction (EQD2), predictive for symptomatic RP in our cohort with hazard ratio 10.01 for score 2 versus 0 (p < 0.001). CONCLUSIONS: Patients with elevated pre-SABR non-target lung FDG-PET uptake are at increased risk of symptomatic RP after lung SABR. Our predictive model suggests patients with mean non-target lung SUV > 0.56 and MLD > 5.88 Gy EQD2 are at highest risk. Our predictive model should be validated in an external cohort before clinical implementation.