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Mediastinal lymph nodes are the most common site of tumor spread in non-small cell lung cancer (NSCLC). We hypothesized that micrometastatic disease could be detected by reverse transcription-polymerase chain reaction (RT-PCR) for expression of human telomerase reverse transcriptase (hTERT) in mediastinal lymph nodes and that a minimally invasive technique (endoscopic ultrasound-guided fine-needle aspiration [EUS-FNA]) is capable of sampling lymph nodes for PCR analysis without surgery. Mediastinal lymph nodes were sampled with EUS-FNA in patients with NSCLC and negative control subjects undergoing EUS for benign disease. Total RNA was harvested from samples, and RT-PCR was performed to detect telomerase gene expression. RNA was available from 87 of 100 lymph node aspirates from 39 patients with NSCLC and from 12 negative control patients. hTERT was expressed in 0 of 14 negative control lymph nodes in 18 of 57 pathologically negative lymph nodes from cancer patients and in 10 of 16 pathologically positive lymph nodes (p < 0.05). Five of 18 (28%) patients with no pathologically evident mediastinal disease expressed telomerase in at least one lymph node. Minimally invasive EUS-FNA with RT-PCR is capable of detecting expression of cancer specific mRNA in lymph nodes. Approximately one-third of pathologically negative mediastinal lymph nodes in NSCLC patients express hTERT mRNA. The clinical significance of this observation is yet to be determined. [ABSTRACT FROM AUTHOR]

This retrospective, single-center study was conducted to assess the response of native idiopathic pulmonary fibrosis (IPF) lungs to a potent cyclosporine-based immunosuppressive regimen in single-lung transplantation recipients. The study included IPF patients who had undergone single-lung transplantation and had chest CT scans before and after transplantation. Five patients underwent single-lung transplantation for IPF between April 1992 and January 2001, and met entry criteria. All patients were placed on an immunosuppressive regimen consisting of prednisone, azathioprine, and cyclosporine. In two of the five patients, ground glass attenuation in the native IPF lung improved post-transplantation. However, fibrotic changes progressed in all five patients. In patients with advanced IPF, a potent cyclosporine-based immunosuppressive regimen is not likely to have an effect on the progression of the disease. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this pilot study was to prospectively evaluate the first integrated positron emission tomography (PET)/dual-energy computed tomography (DECT) system performance in patients with non-small cell lung cancer (NSCLC)., Materials and Methods: In this single-center, prospective trial, consecutive patients with NSCLC referred for a PET study between May 2017 and June 2018 were enrolled. All patients received contrast-enhanced imaging on a clinical PET/DECT system. Data analysis included PET-based standard uptake values (SUVmax) and DECT-based iodine densities of tumor masses, lymph nodes, and distant metastases. Results were analyzed using correlation tests and receiver operating characteristics curves., Results: The study population was composed of 21 patients (median age 62 y, 14 male patients). A moderate positive correlation was found between iodine density values (2.2 mg/mL) and SUVmax (10.5) in tumor masses (ρ=0.53, P<0.01). Iodine density values (2.3 mg/mL) and SUVmax (5.4) of lymph node metastases showed a weak positive correlation (ρ=0.23, P=0.14). In addition, iodine quantification analysis provided no added value in differentiating between pathologic and nonpathologic lymph nodes with an area under the curve (AUC) of 0.55 using PET-based SUVmax as the reference standard. A weak positive correlation was observed between iodine density (2.2 mg/mL) and SUVmax in distant metastases (14.9, ρ=0.23, P=0.52)., Conclusions: The application of an integrated PET/DECT system in lung cancer might provide additional insights in the assessment of tumor masses. However, the added value of iodine density quantification for the evaluation of lymph nodes and distant metastases seems limited., Competing Interests: U.J.S. receives institutional research support and/or honoraria for speaking and consulting from Astellas, Bayer, Bracco, Elucid BioImaging, Guerbet, HeartFlow Inc., and Siemens Healthineers. C.N.D.C. is a consultant for/receives institutional research support from Siemens Healthineers. S.S.M. received speakers’ fees from Siemens Healthineers. The remaining authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Central airway obstruction (CAO) is a dangerous and increasingly common problem. CAO refers to lesions causing narrowing of the trachea or mainstem bronchi and is generally divided into malignant and nonmalignant categories. These 2 entities may be caused by a variety of thoracic and extrathoracic diseases. Imaging is critical during the initial assessment of CAO and may help thoracic physicians focus the differential diagnosis and plan the safest and most appropriate diagnostic and therapeutic interventions. However, direct visualization via flexible or rigid bronchoscopy is often necessary for diagnostic and treatment purposes. A large number of procedures can be performed through bronchoscopy, with the goal of relieving the obstruction and improving patency of the airway. Deciding which procedure to perform is based both upon the type of lesion and whether the lesion is due to a malignant or nonmalignant process. Possible interventions include mechanical debridement, laser therapy, argon plasma coagulation, electrocautery, brachytherapy, and stent placement. Immediate postoperative and follow-up imaging is crucial to monitor for immediate, subacute, and chronic complications as well as disease progression and recurrence.

Patients with cystic fibrosis (CF) often need long-term implanted vascular-access devices for intravenous antibiotics for chronic lower respiratory tract infections. These devices are not without complications, including infection, occlusion, and vascular thrombosis. Such thrombosis can result in superior vena cava (SVC) syndrome due to the position of the catheter proximal to the right atrium. SVC syndrome in CF patients, however, is rarely reported in the literature, suggesting that its incidence is uncommon. We describe three patients with SVC syndrome as a consequence of implanted vascular-access devices.

Objectives: The recurrence of disease after the complete resection of early stage non-small cell lung cancer (NSCLC) indicates that undetected metastases were present at the time of surgery. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is a highly sensitive technique for detecting rare gene transcripts that may indicate the presence of cancer cells, and endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a minimally invasive technique for the nonoperative sampling of mediastinal lymph nodes. The aim of this study was to determine whether these two techniques could enhance the preoperative detection of occult metastases., Methods: Patients with NSCLC were evaluated with chest CT and positron emission tomography scans. Those patients without evidence of metastases (87 patients) underwent EUS-guided FNA. Lymph nodes from levels 2, 4, 5, 7, 8, and 9 were sampled and evaluated by standard cytopathology and real-time RT-PCR. Normal control FNA specimens were obtained from patients without cancer who were undergoing EUS for benign disease (17 control specimens). For each sample, messenger RNA was extracted and real-time RT-PCR was used to quantitate the expression of six lung cancer-associated genes (ie, CEA, CK19, KS1/4, lunx, muc1, and PDEF) relative to the expression of an internal control gene (beta(2)-microglobulin)., Results: Clinical thresholds of marker positivity were set at 100% specificity, as determined by the receiver operating characteristic curve analysis. Of the cytology-positive lymph nodes (27 lymph nodes), the expression of the KS1/4 gene was above its respective clinical threshold in 25 of 27 samples (93%), making this the most sensitive marker for the detection of metastatic NSCLC. At least one of the six lung cancer-associated genes was overexpressed in 18 of 61 cytology-negative patients (30%), of which KS1/4 was overexpressed in 15 of 61 patients (25%)., Conclusions: Based on the high accuracy of EUS-guided FNA/RT-PCR, we predict that some of the patients in the cytology-negative/marker-positive category will have high NSCLC recurrence rates. Among the genes used in our marker panel, KS1/4 appears particularly useful for the detection of overt or occult metastatic disease.

Background: Computed tomography (CT) is the most common method of staging lung cancer. We have previously shown endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) to be highly accurate in staging patients with nonsmall cell lung cancer (NSCLC) who have enlarged mediastinal lymph nodes on CT scan. In this study we report the accuracy and yield of EUS-FNA in staging patients without enlarged mediastinal lymph nodes by CT., Methods: Patients with NSCLC and CT scan showing no enlarged mediastinal lymph nodes (> 1 cm for all nodes except > 1.2 cm for subcarinal) in the mediastinum underwent EUS. Fine needle aspiration was performed on at least one lymph node, if present, in the upper mediastinum, aortopulmonary window, subcarinal, and periesophagus regions. Each specimen was evaluated with on-site cytopathology and confirmed with complete cytopathologic examination., Results: Sixty-nine patients without enlarged mediastinal lymph nodes were evaluated. Endoscopic ultrasound detected malignant mediastinal lymph nodes in 14 of 69 patients as well as other advanced (American Joint Committee on Cancer [AJCC] stage III/IV) in 3 others (1 left adrenal, and 2 with mediastinal invasion of tumor) for a total of 17 of 69 (25%, 95% confidence interval: 16% to 34%) patients. Eleven additional patients were found to have advanced disease by bronchoscopy (2), mediastinoscopy (2), and thoracotomy with mediastinal lymph node dissection (7). The sensitivity of EUS for advanced mediastinal disease was 61% (49% to 75%), and the specificity was 98% (95% to 100%)., Conclusions: Endoscopic ultrasound guided fine needle aspiration can detect advanced mediastinal disease and avoid unnecessary surgical exploration in almost one of four patients who have no evidence of mediastinal disease on CT scan. In addition to previously reported results in patients with enlarged lymph nodes on CT, these data suggest that all potentially operable patients with nonmetastatic NSCLC may benefit from EUS staging.

Interactions between photosynthesis, mitochondrial respiration (mitorespiration), and chlororespiration have been investigated in the green alga Chlamydomonas reinhardtii using flash illumination and a bare platinum electrode. Depending on the physiological status of algae, flash illumination was found to induce either a fast (t(1/2) approximately 300 ms) or slow (t(1/2) approximately 3 s) transient inhibition of oxygen uptake. Based on the effects of the mitorespiratory inhibitors myxothiazol and salicyl hydroxamic acid (SHAM), and of propyl gallate, an inhibitor of the chlororespiratory oxidase, we conclude that the fast transient is due to the flash-induced inhibition of chlororespiration and that the slow transient is due to the flash-induced inhibition of mitorespiration. By measuring blue-green fluorescence changes, related to the redox status of the pyridine nucleotide pool, and chlorophyll fluorescence, related to the redox status of plastoquinones (PQs) in C. reinhardtii wild type and in a photosystem I-deficient mutant, we show that interactions between photosynthesis and chlororespiration are favored when PQ and pyridine nucleotide pools are reduced, whereas interactions between photosynthesis and mitorespiration are favored at more oxidized states. We conclude that the plastid oxidase, similar to the mitochondrial alternative oxidase, becomes significantly engaged when the PQ pool becomes highly reduced, and thereby prevents its over-reduction.

Background: Loss of imprinting (LOI) of the insulin-like growth factor-II (IGF2) gene, an epigenetic alteration associated with expression of the normally silent maternal allele, was observed first in Wilms tumor. Although LOI has subsequently been detected in most adult tumors, the biologic role of LOI in cancer remains obscure. We analyzed the imprinting status of Wilms tumors with respect to pathologic subtype, stage, and patient's age at diagnosis and examined the expression of genes potentially affected by LOI., Methods: Of 60 Wilms tumors examined, 25 were informative for an ApaI polymorphism in the IGF2 gene, allowing analysis of allele-specific gene expression, and could be classified by pathologic subtype. Gene expression was measured quantitatively by real-time polymerase chain reaction, and pathologic analysis was blinded for genetic status. All statistical tests were two-sided., Results: We observed LOI of IGF2 in nine (90%) of 10 Wilms tumors classified as having a pathologic subtype associated with a later stage of renal development and in only one (6.7%) of 15 Wilms tumors with a pathologic subtype associated with an earlier stage of renal development (P< .001). LOI was associated with a 2.2-fold increase (95% confidence interval [CI] = 1.6-fold to 3.1-fold) in IGF2 expression (P< .001). Children whose Wilms tumors displayed LOI of IGF2 were statistically significantly older at diagnosis (median = 65 months; interquartile range [IQR] = 47-83 months) than children whose tumors displayed normal imprinting (median = 24 months; IQR = 13-35 months; P< .001)., Conclusions: These data demonstrate a clear relationship between LOI and altered expression of IGF2 in Wilms tumors and provide a molecular basis for understanding the divergent pathogenesis of this cancer. Analysis of LOI could provide a valuable molecular tool for the classification of Wilms tumor.

Objective: The purpose of this study was to determine how changes in radiographic tube current affect patient dose and image quality in unenhanced chest CT examinations., Subjects and Methods: Ten sets of CT images were obtained from patients undergoing CT-guided chest biopsies. For each patient, six images of the same region were obtained at settings between 40 and 280 mAs. CT data were used to reconstruct tomographic sections with a field of view limited to the normal contralateral lung. Images were printed using lung and mediastinal image display settings. Image quality was determined by asking radiologists to assess the perceived level of mottle in CT images. Five chest radiologists ranked the relative image quality of six images. Patient effective doses were computed for chest CT examinations performed at each milliampere-second setting. Radiologists indicated whether any perceived improvement of image quality at the higher radiation exposures was worth the additional radiation dose., Results: The differences in quality of chest CT images generated at greater than or equal to 160 mAs were negligible. Reducing the radiographic technique factor below 160 mAs resulted in a perceptible reduction in image quality. Differences in CT image quality for radiographic techniques between 120 and 280 mAs were deemed to be insufficient to justify any additional patient exposure. However, the use of 40 mAs results in an inferior image quality that would justify increased patient exposure., Conclusion: Radiographic techniques for unenhanced chest CT examinations can be reduced from 280 to 120 mAs without compromising image quality.

Loss of imprinting (LOI) is the most common molecular abnormality in Wilms' tumor (WT), other embryonal cancers, and most other tumor types. LOI in WT involves activation of the normally silent maternal allele of the insulin-like growth factor-II (IGF2) gene, silencing of the normally active maternal allele of the H19 gene, and aberrant methylation of a differentially methylated region (DMR) upstream of the maternal copy of H19. Recently, the transcription factor CTCF, which binds to the H19 DMR, has been implicated in the maintenance of H19 and IGF2 imprinting. Here, we show that mutations in the CTCF gene or in the H19 DMR do not occur at significant frequency in WT, nor is there transcriptional silencing of CTCF. We also confirm that methylation of the H19 DMR in WT with LOI includes the CTCF core consensus site. However, some WTs with normal imprinting of IGF2 also show aberrant methylation of CTCF binding sites, indicating that methylation of these sites is necessary but not sufficient for LOI in WT.

The KvLQT1 gene encodes a voltage-gated potassium channel. Mutations in KvLQT1 underlie the dominantly transmitted Ward-Romano long QT syndrome, which causes cardiac arrhythmia, and the recessively transmitted Jervell and Lange-Nielsen syndrome, which causes both cardiac arrhythmia and congenital deafness. KvLQT1 is also disrupted by balanced germline chromosomal rearrangements in patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer. Because of the diverse human disorders and organ systems affected by this gene, we developed an animal model by inactivating the murine Kvlqt1. No electrocardiographic abnormalities were observed. However, homozygous mice exhibited complete deafness, as well as circular movement and repetitive falling, suggesting imbalance. Histochemical study revealed severe anatomic disruption of the cochlear and vestibular end organs, suggesting that Kvlqt1 is essential for normal development of the inner ear. Surprisingly, homozygous mice also displayed threefold enlargement by weight of the stomach resulting from mucous neck cell hyperplasia. Finally, there were no features of BWS, suggesting that Kvlqt1 is not responsible for BWS.

In Chlamydomonas reinhardtii mutants deficient in photosystem I because of inactivation of the chloroplast genes psaA or psaB, oxygen evolution from photosystem II occurs at significant rates and is coupled to a stimulation of oxygen uptake. Both activities can be simultaneously monitored by continuous mass spectrometry in the presence of (18)O(2). The light-driven O(2) exchange was shown to involve the plastoquinone pool as an electron carrier, but not cytochrome b(6)f. Photosystem II-dependent O(2) production and O(2) uptake were observed in isolated chloroplast fractions. Photosystem II-dependent oxygen exchange was insensitive to a variety of inhibitors (azide, carbon monoxide, cyanide, antimycin A, and salicylhydroxamic acid) and radical scavengers. It was, however, sensitive to propyl gallate. From inhibitors effects and electronic requirements of the O(2) uptake process, we conclude that an oxidase catalyzing oxidation of plastoquinol and reduction of oxygen to water is present in thylakoid membranes. From the sensitivity of flash-induced O(2) exchange to propyl gallate, we conclude that this oxidase is involved in chlororespiration. Clues to the identity of the protein implied in this process are given by pharmacological and immunological similarities with a protein (IMMUTANS) identified in Arabidopsis chloroplasts.

Four cases of Lemierre syndrome are reported in which metastatic abscesses resulted from septic thrombosis of the internal jugular vein secondary to bacterial pharyngitis. While chest radiographic findings were nonspecific, results of computed tomography (CT) of the thorax in each case were highly suggestive of septic pulmonary emboli. Internal jugular venous thrombosis was demonstrated at ultrasonography and contrast material-enhanced CT.

Myxothiazol and antimycin A are shown to suppress the oxygen transient previously attributed to the flash-induced inhibition of chlororespiration in Chlamydomonas reinhardtii (Peltier et al. 1987, Biochim Biophys Acta 893: 83-90). However, these two compounds do not affect the photosynthetic electron transport chain as inferred by the insensitivity of the CO2-dependent photosynthetic O2 evolution and of the flash-induced electrochromic effect. Chlorophyll fluorescence induction measurements carried out in dark-adapted cells of a mutant of Chlamydomonas lacking photosystem 1, show that myxothiazol and antimycin A significantly increase the redox state of the photosystem 2 acceptors. We conclude from these results that chlororespiration is inhibited by myxothiazol and antimycin A and that the site of inhibition is located on the dark oxidation pathway of the plastoquinone pool. This inhibition is interpreted through the involvement of a myxothiazol and antimycin A sensitive cytochrome in the chlororespiratory chain.