Novel Approaches with HIF-2α Targeted Therapies in Metastatic Renal Cell Carcinoma.

Germline inactivation of the Von Hippel-Lindau (VHL) tumor suppressor is the defining hallmark in hereditary VHL disease and VHL-associated renal cell carcinoma (RCC). However, somatic VHL mutations are also observed in patients with sporadic RCC. Loss of function VHL mutations result in constitutive activation of hypoxia-inducible factor-2 alpha (HIF-2α), which leads to increased expression of HIF target genes that promote angiogenesis and tumor growth. As of 2023, belzutifan is currently the only approved HIF-2α inhibitor for both VHL-associated and sporadic metastatic RCC (mRCC). However, there is potential for resistance with HIF-2α inhibitors which warrants novel HIF-2α-targeting strategies. In this review, we discuss the potential resistance mechanisms with belzutifan and current clinical trials evaluating novel combinations of belzutifan with other targeted therapies and immune checkpoint inhibitors which may enhance the efficacy of HIF-2α targeting. Lastly, we also discuss newer generation HIF-2α inhibitors that are currently under early investigation and outline future directions and challenges with HIF-2α inhibitors for mRCC.

Scrotal calciphylaxis in a fifty-one-year-old man with end-stage renal disease and prior bacteremia.

Isolated, ischemic scrotal lesions are an uncommon manifestation of systemic calciphylaxis. This highly morbid disease seen in patients with end-stage renal disease and other risk factors for small vessel calcification results in tissue necrosis and ulceration. Scrotal calciphylaxis is uncommon and difficult to diagnose in patients with comorbid conditions that cause isolated genital skin lesions, including prior systemic infections. We describe a 51-year-old male with end-stage renal disease on hemodialysis and recent history of bacteremia who developed isolated penile and scrotal ulceration due to calciphylaxis. The patient died two months after presentation despite multidisciplinary care.

U.S. Emergency Department Telepsychiatry Use in 2019.

Introduction: Although many emergency departments (EDs) receive telehealth services for psychiatry, or telepsychiatry, to manage acute psychiatric emergencies, national research on the usage of ED telepsychiatry is limited. To investigate ED telepsychiatry usage in the pre-COVID-19 era, we surveyed a sample of EDs receiving telepsychiatry in 2019, as a follow-up to a survey targeted to similar EDs in 2017. Methods: All U.S. EDs open in 2019 (n = 5,563) were surveyed to characterize emergency care. A more in-depth second survey on telepsychiatry use (2019 ED Telepsychiatry Survey) was then sent to 235 EDs. Of these EDs, 130 were randomly selected from those that reported telepsychiatry receipt in 2019, and 105 were selected based on their participation in a similar survey in 2017 (2017 ED Telepsychiatry Survey). Results: Of the 235 EDs receiving the 2019 Telepsychiatry Survey, 192 (82%) responded and 172 (90% of responding EDs) confirmed 2019 telepsychiatry receipt. Of these, five were excluded for missing data (analytic samplen = 167). Telepsychiatry was the only form of emergency psychiatric services for 92 (55%) EDs. The most common usage of telepsychiatry was for admission or discharge decisions (82%) and transfer coordination (70%). The most commonly reported telepsychiatry mental health consultants were psychiatrists or other physician-level mental health professionals (74%). Discussion: With telepsychiatry as the only form of psychiatric services for most telepsychiatry-receiving EDs, this innovation fills a critical gap in access to emergency psychiatric care. Further research is needed to investigate the impact of the COVID-19 pandemic on usage of ED telepsychiatry.

Online Calibration of a Linear Micro Tomosynthesis Scanner.

In a linear tomosynthesis scanner designed for imaging histologic samples of several centimeters size at 10 µm resolution, the mechanical instability of the scanning stage (±10 µm) exceeded the resolution of the image system, making it necessary to determine the trajectory of the stage for each scan to avoid blurring and artifacts in the images that would arise from the errors in the geometric information used in 3D reconstruction. We present a method for online calibration by attaching a layer of randomly dispersed micro glass beads or calcium particles to the bottom of the sample stage. The method was based on a parametric representation of the rigid body motion of the sample stage-marker layer assembly. The marker layer was easy to produce and proven effective in the calibration procedure.