Single Institution Evaluation of Electromagnetic Navigation Bronchoscopy for Diagnosis of Pulmonary Lesions.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) utilizes three-dimensional reconstructions based on computed tomography to guide the biopsy of pulmonary lesions. Various limitations have been described; however, supporting data have been limited by small sample sizes. METHODS: Cases of ENB for evaluation of a pulmonary lesion at a single institution during a 1-year span were reviewed for demographics, lesion location, procedural details, and final tissue diagnosis. ENB was performed by 3 pulmonologists using the Veran platform with rapid on-site evaluation. T test or Mann-Whitney U test compared continuous variables and χ 2 or Fisher exact test compared categorical variables as appropriate. A patient with a negative or inconclusive biopsy was followed for 1 year postprocedure. RESULTS: A total of 107 pulmonary lesions were evaluated. The population studied had a mean age of 67 and a median pulmonary lesion size of 26.0 mm. For malignant lesions, the pathologic diagnostic yield from ENB was 52.1% (37/71). The diagnostic yield of benign lesions was much lower at 16.7% (6/36). The overall procedural complication rate was 8.4% (9/107). Complications were more likely to occur in patients with malignant lesions. The most common complication was pneumothorax, occurring in 5.6% of all biopsies and 7.0% of patients with malignant lesions. CONCLUSION: This study demonstrates significant differences in diagnostic accuracy between lesions found to be malignant versus benign. Our observed complication rate was slightly higher than other groups have reported, with a greater frequency occurring in patients with malignant lesions; however, the rate of pneumothorax was still lower than computed tomography-guided transcutaneous biopsies.

Tracheal stenting by rigid bronchoscopy in right lateral decubitus position in an awake patient.

Rigid bronchoscopy is a common procedure for central airway obstructions (CAO). Many patients with advanced lesions causing CAO have tenuous, positionally dependent respiratory status which requires additional procedural considerations. This case report describes a 57-year-old man with high grade epithelioid angiosarcoma of the right lung and pleura who underwent placement of a tracheal stent by rigid bronchoscopy in the novel procedural conditions of right lateral decubitus, semi-sitting position with dexmedetomidine, midazolam, and propofol for moderate sedation. Dexmedetomidine, which is currently in use for flexible bronchoscopy due to its analgesic, anxiolytic, and antisialogogue properties performed ideally and should be further evaluated for this indication.

Evaluation of the Diagnostic Accuracy and Clinical Utility of Fungal Profile Plus Polymerase Chain Reaction Assay in Pulmonary Infections.

Background: Pulmonary infections due to Aspergillus, Mucorales, and Nocardia have high morbidity and mortality, in part due to diagnostic challenges. Commercially available molecular assays on bronchoalveolar lavage fluid (BALF) may have increased sensitivity over currently available diagnostic options. Our aim was to characterize the diagnostic performance of assays for each of these pathogens in our patient population. Methods: The medical records of patients whose BALF was tested by polymerase chain reaction (PCR) for Aspergillus, Mucorales, and Nocardia between 2019 and 2021 were reviewed in a cross-sectional manner. European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) definitions of "proven," "probable," and "possible" infection were used, including histopathology, serology, and culture. We used (1) "proven" or "probable" infection by EORTC criteria, (2) improvement or stabilization on targeted antimicrobial therapy, and (3) absence of a more likely diagnosis as the reference standard. Results: The Aspergillus PCR assay demonstrated the highest agreement with the diagnostic reference standard, with 31.25% (10/32) sensitivity and 97.17% (206/212) specificity. Positive and negative predictive values were 62.50% (10/16) and 90.35% (206/228), respectively. No Mucorales or Nocardia infections were identified by the diagnostic reference standard, so the sensitivity could not be calculated. The specificity of Mucorales and Nocardia targets was 98.35% and 96.69%, respectively. Conclusions: Our data demonstrated relatively poor clinical sensitivity for all 3 constituent PCR assays in our patient population, suggesting a limited role for this test in the diagnosis of Aspergillus, Mucorales, or Nocardia.

Whole-Genome Analysis of Individual Meiotic Events in Drosophila melanogaster Reveals That Noncrossover Gene Conversions Are Insensitive to Interference and the Centromere Effect.

A century of genetic analysis has revealed that multiple mechanisms control the distribution of meiotic crossover events. In Drosophila melanogaster, two significant positional controls are interference and the strongly polar centromere effect. Here, we assess the factors controlling the distribution of crossovers (COs) and noncrossover gene conversions (NCOs) along all five major chromosome arms in 196 single meiotic divisions to generate a more detailed understanding of these controls on a genome-wide scale. Analyzing the outcomes of single meiotic events allows us to distinguish among different classes of meiotic recombination. In so doing, we identified 291 NCOs spread uniformly among the five major chromosome arms and 541 COs (including 52 double crossovers and one triple crossover). We find that unlike COs, NCOs are insensitive to the centromere effect and do not demonstrate interference. Although the positions of COs appear to be determined predominately by the long-range influences of interference and the centromere effect, each chromosome may display a different pattern of sensitivity to interference, suggesting that interference may not be a uniform global property. In addition, unbiased sequencing of a large number of individuals allows us to describe the formation of de novo copy number variants, the majority of which appear to be mediated by unequal crossing over between transposable elements. This work has multiple implications for our understanding of how meiotic recombination is regulated to ensure proper chromosome segregation and maintain genome stability.

Rare recombination events generate sequence diversity among balancer chromosomes in Drosophila melanogaster.

Multiply inverted balancer chromosomes that suppress exchange with their homologs are an essential part of the Drosophila melanogaster genetic toolkit. Despite their widespread use, the organization of balancer chromosomes has not been characterized at the molecular level, and the degree of sequence variation among copies of balancer chromosomes is unknown. To map inversion breakpoints and study potential diversity in descendants of a structurally identical balancer chromosome, we sequenced a panel of laboratory stocks containing the most widely used X chromosome balancer, First Multiple 7 (FM7). We mapped the locations of FM7 breakpoints to precise euchromatic coordinates and identified the flanking sequence of breakpoints in heterochromatic regions. Analysis of SNP variation revealed megabase-scale blocks of sequence divergence among currently used FM7 stocks. We present evidence that this divergence arose through rare double-crossover events that replaced a female-sterile allele of the singed gene (sn(X2)) on FM7c with a sequence from balanced chromosomes. We propose that although double-crossover events are rare in individual crosses, many FM7c chromosomes in the Bloomington Drosophila Stock Center have lost sn(X2) by this mechanism on a historical timescale. Finally, we characterize the original allele of the Bar gene (B(1)) that is carried on FM7, and validate the hypothesis that the origin and subsequent reversion of the B(1) duplication are mediated by unequal exchange. Our results reject a simple nonrecombining, clonal mode for the laboratory evolution of balancer chromosomes and have implications for how balancer chromosomes should be used in the design and interpretation of genetic experiments in Drosophila.