Percutaneous image-guided sternal biopsy: a cross-institutional retrospective review of diagnostic yield and safety in 50 cases.

OBJECTIVE: Image-guided sternal biopsy may be technically daunting given the immediately subjacent critical structures. There is a paucity of literature describing technique, safety, and efficacy. This study aims to quantify the diagnostic yield and safety of image-guided sternal biopsies. Secondary aims include (1) describing the preferred approach/technique and (2) identifying imaging features and disease entities associated with higher and lower diagnostic yields. MATERIALS AND METHODS: A retrospective review of 50 image-guided sternal biopsies performed at two quaternary care centers from 2000 to 2019 was performed. Recorded lesion-related variables included as follows: location, density, extraosseous extension, and size. Recorded variables from electronic medical records included as follows: patient demographics, histologic or microbiological diagnosis, and complications. Recorded technique-related variables included as follows: needle obliquity, type, and gauge; biopsy core number and length; and modality. RESULTS: Of the 50 biopsies, 88.0% resulted in a definitive histologic diagnosis. Six biopsies were non-diagnostic. The majority of biopsies were performed under computed tomography (88.0%), followed by ultrasound (12.0%). Tumor was the most common biopsy indication (90.0%), followed by infection (10.0%). Of the diagnostic biopsies indicated for tumor, 88.9% were malignant. Seventy-four percent of the lesions were predominantly lytic. Fifty percent of lesions had extraosseous extension. Lesion locations were as follows: manubrium (48.0%), sternal body (48.0%), and sternomanubrial joint (4.0%). No minor or major, acute, or delayed procedure-related complications were encountered. CONCLUSION: Image-guided sternal biopsy is an efficacious and safe method of obtaining a definitive histologic diagnosis regardless of lesion-specific features or location.

Subunit interfaces contribute differently to activation and allosteric modulation of neuronal nicotinic acetylcholine receptors.

Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed in the nervous system and are implicated in many normal and pathological processes. The structural determinants of allostery in nAChRs are not well understood. One class of nAChR allosteric modulators, including the small molecule morantel (Mor), acts from a site that is structurally homologous to the canonical agonist site but exists in the ß(+)/α(-) subunit interface. We hypothesized that all nAChR subunits move with respect to each other during channel activation and allosteric modulation. We therefore studied five pairs of residues predicted to span the interfaces of α3ß2 receptors, one at the agonist interface and four at the modulator interface. Substituting cysteines in these positions, we used disulfide trapping to perturb receptor function. The pair α3Y168-ß2D190, involving the C loop region of the ß2 subunit, mediates modulation and agonist activation, because evoked currents were reduced up to 50% following oxidation (H2O2) treatment. The pair α3S125-ß2Q39, below the canonical site, is also involved in channel activation, in accord with previous studies of the muscle-type receptor; however, the pair is differentially sensitive to ACh activation and Mor modulation (currents decreased 60% and 80%, respectively). The pairs α3Q37-ß2A127 and α3E173-ß2R46, both in the non-canonical interface, showed increased currents following oxidation, suggesting that subunit movements are not symmetrical. Together, our results from disulfide trapping and further mutation analysis indicate that subunit interface movement is important for allosteric modulation of nAChRs, but that the two types of interfaces contribute unequally to receptor activation.