Clinical Implications and Treatment Strategies for ESR1 Fusions in Hormone Receptor-Positive Metastatic Breast Cancer: A Case Series.

In hormone receptor-positive metastatic breast cancer (HR+ MBC), endocrine resistance is commonly due to genetic alterations of ESR1, the gene encoding estrogen receptor alpha (ERα). While ESR1 point mutations (ESR1-MUT) cause acquired resistance to aromatase inhibition (AI) through constitutive activation, far less is known about the molecular functions and clinical consequences of ESR1 fusions (ESR1-FUS). This case series discusses 4 patients with HR+ MBC with ESR1-FUS in the context of the existing ESR1-FUS literature. We consider therapeutic strategies and raise the hypothesis that CDK4/6 inhibition (CDK4/6i) may be effective against ESR1-FUS with functional ligand-binding domain swaps. These cases highlight the importance of screening for ESR1-FUS in patients with HR+ MBC while continuing investigation of precision treatments for these genomic rearrangements.

Kinematics of the quadrate bone during feeding in mallard ducks.

Avian cranial kinesis, in which mobility of the quadrate, pterygoid and palatine bones contribute to upper bill elevation, is believed to occur in all extant birds. The most widely accepted model for upper bill elevation is that the quadrate rotates rostrally and medially towards the pterygoid, transferring force to the mobile pterygoid-palatine complex, which pushes on the upper bill. Until now, however, it has not been possible to test this hypothesis in vivo because quadrate motions are rapid, three-dimensionally complex and not visible externally. Here we use a new in vivo X-ray motion analysis technique, X-ray reconstruction of moving morphology (XROMM), to create precise (±0.06 mm) 3-D animations of the quadrate, braincase, upper bill and mandible of three mallard ducks, Anas platyrhynchos. We defined a joint coordinate system (JCS) for the quadrato-squamosal joint with the axes aligned to the anatomical planes of the skull. In this coordinate system, the quadrate's 3-D rotations produce an elliptical path of pterygoid process motion, with medial and rostrodorsal then lateral and rostrodorsal motion as the upper bill elevates. As the upper bill depresses, the pterygoid process continues along the ellipsoidal path, with lateral and caudoventral then medial and caudoventral motion. We also found that the mandibular rami bow outwards (streptognathy) during mandibular depression, which may cause the lateral component of quadrate rotation that we observed. Relative to the JCS aligned with the anatomical planes of the skull, a second JCS aligned with quadrato-squamosal joint anatomy did not produce a simpler description of quadrate kinematics.

Longitudinal Urgent Care Psychiatry as a Unique Access Point for Underserved Patients.

OBJECTIVE: The authors sought to determine whether a walk-in psychiatry model with longitudinal follow-up capability could improve access for patients who traditionally miss appointments. METHODS: An urgent care clinic that offers treatment exclusively on a walk-in basis was opened within an adult psychiatry practice to accommodate patients who missed prior scheduled appointments. Electronic health records for patients who received an initial psychiatry evaluation at the practice during a 6-month period (N=355) were reviewed retrospectively to track the clinic's productivity and patient demographic characteristics. RESULTS: Eighty patients (23%) accessed their initial psychiatry encounters through the walk-in clinic. Medicaid recipients (odds ratio [OR]=1.89, 95% confidence interval [CI]=1.10-3.24) and individuals without a college degree (OR=1.86, 95% CI=1.04-3.32) were more likely than patients with other insurance carriers and those with a college degree, respectively, to access care through a walk-in encounter versus a scheduled appointment. CONCLUSIONS: Longitudinal walk-in psychiatry services can feasibly be offered through the longitudinal urgent care psychiatry model. This model may serve as a unique access point for patients from historically underserved groups.