Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM.

PURPOSE: Pharmacologic ascorbate (P-AscH-) is hypothesized to be an iron (Fe)-dependent tumor-specific adjuvant to chemoradiation in treating glioblastoma (GBM). This study determined the efficacy of combining P-AscH- with radiation and temozolomide in a phase II clinical trial while simultaneously investigating a mechanism-based, noninvasive biomarker in T2* mapping to predict GBM response to P-AscH- in humans. PATIENTS AND METHODS: The single-arm phase II clinical trial (NCT02344355) enrolled 55 subjects, with analysis performed 12 months following the completion of treatment. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method and compared across patient subgroups with log-rank tests. Forty-nine of 55 subjects were evaluated using T2*-based MRI to assess its utility as an Fe-dependent biomarker. RESULTS: Median OS was estimated to be 19.6 months [90% confidence interval (CI), 15.7-26.5 months], a statistically significant increase compared with historic control patients (14.6 months). Subjects with initial T2* relaxation < 50 ms were associated with a significant increase in PFS compared with T2*-high subjects (11.2 months vs. 5.7 months, P < 0.05) and a trend toward increased OS (26.5 months vs. 17.5 months). These results were validated in preclinical in vitro and in vivo model systems. CONCLUSIONS: P-AscH- combined with temozolomide and radiotherapy has the potential to significantly enhance GBM survival. T2*-based MRI assessment of tumor iron content is a prognostic biomarker for GBM clinical outcomes. See related commentary by Nabavizadeh and Bagley, p. 255.

Assessment of a Peer Support Group Intervention for Undocumented Latinx Immigrants With Kidney Failure.

Importance: Most undocumented immigrants with kidney failure rely on emergency dialysis (defined as dialysis after a patient presents as critically ill) and experience significant depression and anxiety and high mortality. Culturally and language-concordant peer support group interventions may be associated with reduced depression and anxiety and may provide emotional support. Objective: To investigate the feasibility and acceptability of a single-group peer support group intervention. Design, setting, and participants: This qualitative and single-group prospective study for undocumented immigrants with kidney failure receiving emergency dialysis was conducted in Denver, Colorado, from December 2017 to July 2018. The 6-month intervention included peer support group meetings in the hospital while participants were hospitalized for emergency dialysis. Data were analyzed from March to June 2022. Main outcomes and measures: To assess feasibility, the recruitment, retention, implementation, and delivery for the intervention were tracked. To measure acceptability, interviews were conducted with participants using a structured format. To assess the value of the peer support group intervention, themes and subthemes were identified from interviews with participants and group meetings. Results: Of 27 undocumented immigrants with kidney failure receiving emergency dialysis, 23 participants (9 females [39.1%] and 14 males [60.9%]; mean [SD] age, 47 [8] years) agreed to participate (recruitment rate, 85.2%). Among them, 5 individuals withdrew and did not attend meetings and 18 participants (retention rate, 78.3%) attended a mean of 6 of 12 meetings (50.0%). From interviews and meetings, 3 themes, with associated subthemes, were identified: camaraderie and emotional support from peers (subthemes: peer support is vital for people newly diagnosed with kidney failure, safe space to build relationships and share hardship with peers, hospital setting for peer support is ideal, solidarity to survive and change policy, and sustainability of the peer support group), solutions to improve care and resilience (subthemes: self-advocacy, self-motivation and optimism, kidney disease education, emotional support from peers caregivers, and faith), and emotional and physical aspects of receiving emergency dialysis (subthemes: psychosocial and physical distress, mixed experiences with language-concordant care, emotional exhaustion from end-of-life conversations, and gratitude for clinicians). Conclusions and relevance: This study found that peer support group intervention achieved feasibility and acceptability. The findings suggest that a peer support group may be a patient-centered strategy to build camaraderie and provide emotional support in kidney failure, especially for socially marginalized uninsured populations who report limited English proficiency.