Imaging in Lung Cancer Staging.

Lung cancer remains one of the leading causes of mortality worldwide, as well as in the United States. Clinical staging, primarily with imaging, is integral to stratify patients into groups that determine treatment options and predict survival. The eighth edition of the tumor, node, metastasis (TNM-8) staging system proposed in 2016 by the International Association for the Study of Lung Cancer remains the current standard for lung cancer staging. The system is used for all subtypes of lung cancer, including non-small cell lung cancer, small cell lung cancer, and bronchopulmonary carcinoid tumors.

Pericardial Recesses on Computed Tomography: Implications for the Pulmonologist.

The pericardium comprises a double-walled fibrous-serosal sac that encloses the heart. Reflections of the serosal layer form sinuses and recesses. With advances in multidetector computed tomography (CT) technology, pericardial recesses are frequently detected with thin-section CT. Knowledge of pericardial anatomy on imaging is crucial to avoid misinterpretation of fluid-filled pericardial sinuses and recesses as adenopathy/pericardial metastasis or aortic dissection, which can impact patient management and treatment decisions. The authors offer a comprehensive review of pericardial anatomy and its variations observed on CT, potential pitfalls in image interpretation, and implications for the pulmonologist with respect to unnecessary diagnostic procedures or interventions.

Potential of Ilhéus virus to emerge.

Ilhéus virus (ILHV)(Flaviviridae:Orthoflavivirus) is an arthropod-borne virus (arbovirus) endemic to Central and South America and the Caribbean. First isolated in 1944, most of our knowledge derives from surveillance and seroprevalence studies. These efforts have detected ILHV in a broad range of mosquito and vertebrate species, including humans, but laboratory investigations of pathogenesis and vector competence have been lacking. Here, we develop an immune intact murine model with several ages and routes of administration. Our model closely recapitulates human neuroinvasive disease with ILHV strain- and mouse age-specific virulence, as well as a uniformly lethal Ifnar-/- A129 immunocompromised model. Replication kinetics in several vertebrate and invertebrate cell lines demonstrate that ILHV is capable of replicating to high titers in a wide variety of potential host and vector species. Lastly, vector competence studies provide strong evidence for efficient infection of and potential transmission by Aedes species mosquitoes, despite ILHV's phylogenetically clustering with Culex vectored flaviviruses, suggesting ILHV is poised for emergence in the neotropics.

Imaging evaluation of thymic tumors.

An integral part of managing patients with thymoma and thymic carcinoma is imaging. At diagnosis and staging, imaging helps demonstrate the extent of local invasion and distant metastases which allows the proper stratification of patients for therapy. For decades, the predominant staging system for thymic tumors was the Masaoka-Koga staging system. More recently, however, the International Association for the Study of Lung Cancer, the International Thymic Malignancies Interest Group (ITMIG), the European Society of Thoracic Surgeons, the Chinese Alliance for Research on Thymomas, and the Japanese Association of Research on Thymus partnered together to develop a tumor-node-metastasis (TNM) staging system specifically for thymic tumors based on a retrospective database of nearly 10,000 patients. The TNM 8th edition defines specific criteria for thymic tumors. Imaging also serves to assess treatment response and detect recurrent disease after various treatment modalities. The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is currently used to assess response to treatment. ITMIG recommends certain modifications to RECIST version 1.1, however, in thymic tumors due to unique patterns of spread. While there is often overlap, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) characteristics can help differentiate thymoma and thymic carcinoma, with newer CT and MRI techniques under evaluation showing encouraging potential.

Spectrum of Imaging Patterns of Lung Cancer following Radiation Therapy.

Radiation therapy using conventional or newer high-precision dose techniques, including three-dimensional conformal radiotherapy, intensity-modulated radiation therapy, stereotactic body radiation therapy, four-dimensional conformational radiotherapy, and proton therapy, is an important component of treating patients with lung cancer. Knowledge of the radiation technique used and the expected temporal evolution of radiation-induced lung injury, as well as patient-specific parameters such as previous radiotherapy, concurrent chemoradiotherapy, or immunotherapy, is important in image interpretation. This review discusses factors that affect the development and severity of radiation-induced lung injury and its radiological manifestations, as well as the differences between conventional and high-precision dose radiotherapy techniques.

Lung Cancer Staging: Imaging and Potential Pitfalls.

Lung cancer is the leading cause of cancer deaths in men and women in the United States. Accurate staging is needed to determine prognosis and devise effective treatment plans. The International Association for the Study of Lung Cancer (IASLC) has made multiple revisions to the tumor, node, metastasis (TNM) staging system used by the Union for International Cancer Control and the American Joint Committee on Cancer to stage lung cancer. The eighth edition of this staging system includes modifications to the T classification with cut points of 1 cm increments in tumor size, grouping of lung cancers associated with partial or complete lung atelectasis or pneumonitis, grouping of tumors with involvement of a main bronchus regardless of distance from the carina, and upstaging of diaphragmatic invasion to T4. The N classification describes the spread to regional lymph nodes and no changes were proposed for TNM-8. In the M classification, metastatic disease is divided into intra- versus extrathoracic metastasis, and single versus multiple metastases. In order to optimize patient outcomes, it is important to understand the nuances of the TNM staging system, the strengths and weaknesses of various imaging modalities used in lung cancer staging, and potential pitfalls in image interpretation.

Aedes aegypti Shows Increased Susceptibility to Zika Virus via Both In Vitro and In Vivo Models of Type II Diabetes.

Chronic conditions like type II diabetes (T2DM) have long been known to exacerbate many infectious diseases. For many arboviruses, including Zika virus (ZIKV), severe outcomes, morbidity and mortality usually only occur in patients with such pre-existing conditions. However, the effects of T2DM and other pre-existing conditions on human blood (e.g., hypo/hyperinsulinemia, hyperglycemia and hyperlipidemia) that may impact infectivity of arboviruses for vectors is largely unexplored. We investigated whether the susceptibility of Aedes aegypti mosquitoes was affected when the mosquitoes fed on "diabetic" bloodmeals, such as bloodmeals composed of artificially glycosylated erythrocytes or those from viremic, diabetic mice (LEPRDB/DB). Increasing glycosylation of erythrocytes from hemoglobin A1c (HgbA1c) values of 5.5-5.9 to 6.2 increased the infection rate of a Galveston, Texas strain of Ae. aegypti to ZIKV strain PRVABC59 at a bloodmeal titer of 4.14 log10 FFU/mL from 0.0 to 40.9 and 42.9%, respectively. ZIKV was present in the blood of viremic LEPRDB/DB mice at similar levels as isogenic control C57BL/6J mice (3.3 log10 FFU/mL and 3.6 log10 FFU/mL, respectively. When mice sustained a higher ZIKV viremia of 4.6 log10 FFU/mL, LEPRDB/DB mice infected 36.3% of mosquitoes while control C57BL/6J mice with a viremia of 4.2 log10 FFU/mL infected only 4.1%. Additionally, when highly susceptible Ae. aegypti Rockefeller mosquitoes fed on homozygous LEPRDB/DB, heterozygous LEPRWT/DB, and control C57BL/6J mice with viremias of ≈ 4 log10 FFU/mL, 54%, 15%, and 33% were infected, respectively. In total, these data suggest that the prevalence of T2DM in a population may have a significant impact on ZIKV transmission and indicates the need for further investigation of the impacts of pre-existing metabolic conditions on arbovirus transmission.

Preoperative prediction of unresectability in malignant pleural mesothelioma.

OBJECTIVE: Diffuse chest wall invasion (DCWI) is a common finding in patients undergoing intended resection for malignant pleural mesothelioma. We sought to determine the incidence and preoperative predictors of this finding, and to test our anecdotal impression that contraction of the ipsilateral hemithorax is associated with DCWI. METHODS: This was a single-institution retrospective study of 170 patients undergoing intended macroscopic complete resection for malignant pleural mesothelioma from 2014-2018. A novel metric of thoracic cage volume was calculated by preoperative chest computed tomography. Univariable analyses were performed to determine associations of preoperative variables with DCWI. RESULTS: Macroscopic complete resection was achieved by pleurectomy/decortication in 104 patients (61%) and by extrapleural pneumonectomy in 39 patients (23%). Unresectable disease was discovered at thoracotomy in 27 (16%) of patients; 24 (14%) by DCWI and 3 (2%) by intrathoracic organ invasion. In univariable analysis, decreased ipsilateral thoracic cage volume demonstrated the strongest association with unresectability by DCWI (P = .009) with >5% decrease in thoracic cage volume representing the optimal cutoff (P = .014; area under the curve, 0.67). Other preoperative variables associated with DCWI included preoperative chest pain requiring opioids (P = .028), prior pleurodesis (P = .036), decreased forced vital capacity (P = .023), decreased ipsilateral lung perfusion by ventilation/perfusion lung scan (P = .007), and magnetic resonance imaging findings of chest wall invasion (P = .035). CONCLUSIONS: Preoperative identification of DCWI will avoid unnecessary thoracotomy and accelerate initiation of nonsurgical therapy in malignant pleural mesothelioma. Our data suggest that contraction of thoracic cage volume has merit in predicting malignant pleural mesothelioma unresectability and should be validated in prospective studies.

Loss of diurnal rhythms of blood pressure and heart rate caused by high-fat feeding.

BACKGROUND: Diet-induced obesity using ad libitum high-fat feeding in rabbits causes losses in diurnal rhythms of blood pressure (BP) and heart rate (HR). Because obesity is associated with hypertension, it is difficult to determine independent effects of ad libitum feeding and obesity in altering diurnal rhythms. We studied diurnal rhythms of BP and HR after controlling BP during obesity development using hydralazine. METHODS: New Zealand white rabbits were divided into lean control (LC), lean hydralazine-treated (LH), obese control (OC), and obese hydralazine-treated (OH) groups. Lean animals consumed a maintenance diet, whereas obese animals consumed an ad libitum high-fat diet. Over 12 weeks, BP and HR were monitored from 11:00 to 07:00 using telemetry. Hydralazine treatment consisted of 6 mg/kg/day and 10 to 14 mg/kg/day for LH and OH, respectively. Diurnal rhythms were evaluated using day-night values (day, 11:00 to 16:00 average; night, 02:00 to 07:00 average). RESULTS: Compared with control values, diurnal HR rhythm was abolished on day 1 of high-fat feeding (61.4 +/- 3.6 v 3.1 +/- 4.2 beats/min, respectively; P

Mathematical analysis of the normal anatomy of the aging fovea.

PURPOSE: To mathematically analyze anatomical changes that occur in the normal fovea during aging. METHODS: A total of 2912 spectral-domain optical coherence tomography (SD-OCT) normal foveal scans were analyzed. Subjects were healthy individuals, aged 13 to 97 years, with visual acuity ≥20/40 and without evidence of foveal pathology. Using automated symbolic regression software Eureqa (version 0.98), foveal thickness maps of 390 eyes were analyzed using several measurements: parafoveal retinal thickness at 50 µm consecutive intervals, parafoveal maximum retinal thickness at two points lateral to central foveal depression, distance between two points of maximum retinal thickness, maximal foveal slope at two intervals lateral to central foveal depression, and central length of foveal depression. A unique mathematical equation representing the mathematical analog of foveal anatomy was derived for every decade, between 10 and 100 years. RESULTS: The mathematical regression function for normal fovea followed first order sine curve of level 10 complexity for the second decade of life. The mathematical regression function became more complex with normal aging, up to level 43 complexity (0.085 fit; P < 0.05). Young foveas had higher symmetry (0.92 ± 0.10) along midline, whereas aged foveas had significantly less symmetry (0.76 ± 0.27, P < 0.01) along midline and steeper maximal slopes (29 ± 32°, P < 0.01). CONCLUSIONS: Normal foveal anatomical configuration changes with age. Normal aged foveas are less symmetric along midline with steeper slopes. Differentiating between normal aging and pathologic changes using SD-OCT scans may allow early diagnosis, follow-up, and better management of the aging population.

Cardiovascular function in a rat model of diet-induced obesity.

The obesity-prone/obesity-resistant rat model has been used to study mechanisms responsible for obesity-related abnormalities in renal function and blood pressure, but whether this model exhibits cardiac dysfunction has not been determined. We tested the hypothesis that obesity-prone rats would display cardiovascular abnormalities seen in other diet-induced obese models (ie, hypertension, tachycardia, left ventricular hypertrophy, increased collagen deposition, reduced cardiac contractility, and increased end diastolic pressure). Male Sprague-Dawley rats were fed a control diet or a moderate fat diet containing 32% kcal as fat while hemodynamics were continuously monitored using telemetry. After 12 weeks, obesity-prone rats were significantly heavier and had greater body fat compared with obesity-resistant rats and controls, but daily (20 hours/d) averages and diurnal rhythms of blood pressure and heart rate did not differ among groups. Echocardiographic indices of cardiac structure and function, histological evidence of cardiac collagen, and directly measured heart weights did not differ among groups. Peak left ventricular pressure, end diastolic pressure, +dP/dt, and -dP/dt were also not significantly different among groups. Plasma cholesterol and hepatic cholesterol were significantly higher in obesity-prone rats compared with obesity-resistant rats and controls; hepatic triglycerides were higher in obesity-prone rats compared with controls (P< or =0.05). Leptin was significantly higher in obesity-prone rats compared with controls and across all groups was significantly correlated with body fat (P< or =0.05). These results suggest that 12 weeks of a moderate fat diet in the obesity-prone/obesity-resistant rat model induced lipid and endocrine abnormalities typical of obesity but was not sufficient to cause significant cardiac abnormalities.