Belzutifan Efficacy and Tolerability in Patients with Sporadic Metastatic Clear Cell Renal Cell Carcinoma.

BACKGROUND AND OBJECTIVE: Belzutifan, a hypoxia-inducible factor 2 alpha inhibitor, was approved initially for patients with von Hippel-Lindau disease and more recently for sporadic, metastatic clear cell renal cell carcinoma (ccRCC) based on the results of LITESPARK-005. There is a paucity of data regarding real-world experience with belzutifan in patients with sporadic, metastatic ccRCC. This study aims to describe clinical outcomes with belzutifan in patients with sporadic, metastatic ccRCC. METHODS: A retrospective study of 22 patients who received belzutifan at MD Anderson Cancer Center prior to the Food and Drug Administration approval was conducted. Progression-free survival (PFS) and objective response rate (ORR) were assessed by a blinded radiologist using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. PFS and overall survival (OS) were measured from belzutifan initiation. KEY FINDINGS AND LIMITATIONS: The median follow-up time was 14.9 mo. Most patients had International Metastatic RCC Database Consortium intermediate-risk disease, more than three metastatic sites, and a median of five prior lines of treatment at initiation of belzutifan; all patients received prior immune checkpoint therapy (ICT) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). The median PFS was 8.51 mo (95% confidence interval [CI] 0-18.4) and ORR was 36.4%. The median OS was 14.72 mo (95% CI 7.34-22.10). Of 22 patients, four (18.2%) patients required dose reductions and three (13.6%) patients discontinued belzutifan because of adverse drug events (ADEs). The most common ADEs were anemia (77.3%; 17/22) and hypoxia (36.4%; 8/22). There were no treatment-related deaths. CONCLUSIONS AND CLINICAL IMPLICATIONS: In a heavily pretreated cohort of patients with sporadic, metastatic ccRCC, belzutifan had meaningful clinical activity and was well tolerated. These real-world results add to the results of LITESPARK-005 and support the use of belzutifan after progression on ICT and VEGFR-TKIs. PATIENT SUMMARY: Belzutifan is a new medicine used to treat a type of clear cell kidney cancer that has spread to other parts of the body (metastasized). A study at MD Anderson Cancer Center followed 22 patients who were treated with belzutifan, and found that it worked to control the cancer for almost 9 mo and caused the cancer to shrink in 36% of patients. This study confirms that belzutifan can be effective and safe, even after other treatments have not worked.

Inhaled Nitroglycerin for Pulmonary Edema in Air Medical Services: A Retrospective Pilot Study.

OBJECTIVE: The use of traditional inhaled pulmonary vasodilators, such as nitric oxide, to treat symptomatic pulmonary edema is not practical in the air medical or prehospital environment because of difficulty with administration. A hospital-based critical care air medical transport service initiated a pilot study to investigate the use of inhaled nitroglycerin (iNTG) as an alternative pulmonary vasodilator. METHODS: For this pilot study, iNTG was administered using a jet nebulizer setup and concentrated nitroglycerin, both of which are widely available in acute care settings. In conjunction with medical oversight, transport personnel identified patients with respiratory distress secondary to pulmonary edema. Twenty-two months after initiating the protocol, a retrospective chart review was conducted. Data for patients receiving iNTG were retrospectively abstracted through a medical record search and manual chart review. RESULTS: Twelve patients received iNTG during the pilot study. Basic demographics, medical comorbidities, concurrent medications, laboratory values, and radiographic studies were collected for each patient. Basic statistics were performed to identify any potential trends. CONCLUSION: The administration of iNTG is feasible in an air medical transport setting and may provide a useful adjunct to treating patients with pulmonary edema and respiratory distress. Because iNTG delivery targets the pulmonary vasculature, this may be of particular benefit in patients with a poor hemodynamic profile. Larger randomized controlled or cohort studies are needed to specifically analyze and compare hemodynamics, diagnostics, and patient outcomes.

Ultrasound and Magnetic Resonance Imaging of Agenesis of the Corpus Callosum in Fetuses: Frontal Horns and Cavum Septi Pellucidi Are Clues to Earlier Diagnosis.

OBJECTIVES: We hypothesized that: (1) fetal frontal horn (FH) morphology and their proximity to the cavum septi pellucidi (CSP) can assist in suspecting complete agenesis of the corpus callosum (cACC) and partial agenesis of the corpus callosum (pACC) earlier than known indirect ultrasound (US) findings; (2) FHs assist in differentiating a true CSP from a pseudocavum; and (3) magnetic resonance imaging (MRI) is useful in learning FH morphology and pseudocavum etiology. METHODS: Thirty-two patients with cACC and 9 with pACC were identified on an Institutional Review Board-approved retrospective review. Of the 41 cases, 40 had prenatal US, and 21 had prenatal MRI; 17 had follow-up neonatal US, and 14 had follow-up neonatal MRI. Variables evaluated retrospectively were the presence of a CSP or a pseudocavum, ventricle size and shape, and FH shape (comma, trident, parallel, golf club, enlarged, or fused). Displacement between the inferior edge of the FH and the midline or cavum/pseudocavum was measured. RESULTS: Fetal FHs had an abnormal shape in 77% ≤20 weeks' gestation, 86% ≤24 weeks, and 90% >24 weeks. Frontal horns were laterally displaced greater than 2 mm in 85% ≤20 weeks, 91% ≤24 weeks, and 95% >24 weeks. The CSP was absent in 100% of cACC cases and 78% of pACC cases, and a pseudocavum was present in 88% of cACC cases and 78% of pACC cases across gestation. Magnetic resonance imaging confirmed US pseudocavums to be focal interhemispheric fluid or an elevated/dilated third ventricle. CONCLUSIONS: Frontal horns assist in assessing ACC ≤24 weeks and throughout gestation. Pseudocavums, often simulating CSPs, are common in ACC. Frontal horn lateral displacement and abnormal morphology, recognized by MRI correlations, are helpful in differentiating a pseudocavum from a true CSP. A normal CSP should not be cleared on screening US unless normally shaped FHs are seen directly adjacent to it.

Whole-exome sequencing reveals novel USP9X variant in female fetus with isolated agenesis of the corpus callosum.

Whole-exome sequencing in a female fetus detected a USP9X variant. This X-linked gene was recently associated with intellectual disability and distinct pattern of malformation in females. Isolated agenesis of the corpus callosum has not been reported in association with USP9X. Identifying this variant impacted management of the subsequent pregnancy.

Peer Victimization in Rural Youth and Why it Matters.

Peer victimization is a major public health concern due to its psychological, emotional, and physical short and potentially long-term effects on children. Research conducted with rural youth have shown heightened peer victimization rates compared to urban and suburban locales. Protective factors, such as social support, are underresearched and less emphasized compared to risk factors, particularly in the context of rural youth. This article will review the literature surrounding the constructs of peer victimization in relation to risk and resiliency factors, with a specific focus on rural children.