Faculty Bibliography

BACKGROUND:Glioblastoma intramedullary spinal cord metastasis (GISCM) is a rare sequela of high-grade astrocytoma and glioblastoma multiforme (GBM). Discrete intramedullary spinal cord metastases are less common than spinal leptomeningeal spread and may follow a more indolent course. Once identified as GISCM, palliative maximal safe resection of the tumor may be considered to alleviate neurological symptoms. Reports describing the surgical management of these rare lesions, including the use of emerging technologies that may aid in maximal safe resection, are sparse. A further understanding is also required regarding the course of disease and factors contributing to mortality in GISCM. METHODS:We reviewed the intraoperative management and clinical course of three patients treated for GISCM at our institution between 2015 and 2024. We additionally conducted a PRISMA-guided systematic literature review of PubMed Central, MEDLINE, and Bookshelf databases through May 26th, 2025, including original patient reports of GISCM from cranial astrocytoma or GBM. The disease course, management strategies, and causes of mortality in previously reported cases were analyzed. RESULTS:Our institutional cohort had a mean time to spinal metastasis of 26.2 months from diagnosis of cranial disease (range 17.5-40.5 months), with a mean survival of 9.2 months following maximal safe resection of extramedullary components (range 7-12 months). In two cases, intraoperative Stimulated Raman Histology (SRH) was employed to facilitate the rapid identification of metastatic GBM, thereby influencing surgical strategy. In one case, 5-aminolevulinic acid (5-ALA) was used to differentiate between tumor and spinal cord parenchyma, facilitating maximal safe debulking without neurological injury. Literature review identified 38 prior reported cases of GISCM, with a median time to spinal diagnosis of 11.0 months and a median survival of 3.5 months thereafter. The cause of death in the review cohort often involved multiple factors, and when analyzed for contributing factors to death, 38.7% involved cranial progression, 38.7% involved progression of spinal disease, and 29.0% involved medical complications. Gait ataxia at presentation was associated with shorter survival in review patients, potentially reflecting advanced disease with extramedullary cord compression. CONCLUSION/CONCLUSIONS:GISCM represents an entity distinct from leptomeningeal disease and may be managed in conjunction with recurrent cranial disease. Surgical debulking is a technically feasible strategy that can be safely facilitated using tools employed in the management of intracranial GBM, facilitating maximal safe resection without compromising survival.

INTRODUCTION/BACKGROUND:This community-led research study protocol emphasises placing black youth impacted by the legal system, their families and their communities at the forefront of substance use treatment development research and decision-making. The study, the Cultural Adaptation of a Substance Use Treatment (CAST) Project, challenges traditional top-down approaches to treatment creation, advocating for a grassroots model that centres community knowledge, values and active participation. METHODS AND ANALYSIS/METHODS:The CAST project is a US-based mixed-methods study with an exploratory design that examines the impact of racial discrimination on substance use in black youth impacted by the legal system. The study participants are black youth impacted by the legal system (N=15), parents of black youth impacted by the legal system (N=10) and community members who serve black youth (N=10) (total N=35 study participants). Study participants from each group (youth, parents and community members) will participate in three separate focus groups, respectively, to provide feedback on the culturally responsive content needed to best support black youth impacted by the legal system around substance use and mental health. The eight-step Assess, Decision, Adaptation, Production, Topical Expert, Integration, Training, Testing framework will be used as a guide to inform adaptations to the Motivational Enhancement Therapy and Cognitive Behavioural Therapy (MET/CBT12) for black youth impacted by the legal system. Once the cultural adaptation process has been completed, the study will conclude with an open feasibility and accessibility trial of the culturally adapted MET/CBT12 manual. The primary outcomes of this study are the feasibility and acceptability of the culturally adapted manual, measured by treatment attendance and participant feedback. Secondary outcomes include reductions in substance use and discrimination distress, and improvements in mental health symptoms. ETHICS AND DISSEMINATION/BACKGROUND:This study was approved by the Institutional Review Board (IRB) at the University of California, San Francisco (IRB Protocol Number: 23-40126). All study procedures will be conducted in accordance with the ethical standards outlined by the institutional review board. The results from this study will be shared through peer-reviewed publications, academic conferences, community forums and policy briefs to support broader implementation of culturally adapted adolescent substance use interventions that address discrimination-related stress and substance use among black individuals impacted by the legal system. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT06003725.

PURPOSE/OBJECTIVE:Responsive neurostimulation (RNS) is an effective therapeutic option for drug-resistant focal epilepsy, especially when the seizure onset zone lies in an eloquent cortex. However, the safety, tolerability, efficacy, as well as optimal stimulation and detection settings for RNS therapy in the primary motor cortex are poorly understood. METHODS:We performed a multi-center retrospective cohort study to assess the safety and efficacy of treatment with RNS targeting the primary motor cortex in patients with drug-resistant focal motor epilepsy. RESULTS:A total of 20 patients were included in the study. Overall, 79 % of the patients achieved ≥ 50 % seizure reduction at a mean follow-up time of 58.4 months, while 53 % of the patients achieved ≥ 90 % seizure reduction. None of the patients had any complications from the surgical implantation of the RNS device. There were no reported adverse side effects from neurostimulation therapy of the primary motor cortex. CONCLUSION/CONCLUSIONS:For individuals with drug-resistant focal motor epilepsy, treatment with RNS of the primary motor cortex is safe, effective, and well-tolerated.

INTRODUCTION/BACKGROUND:The aim of this work was to investigate the effect of an air layer of different thicknesses on the design of high-permittivity materials (HPM) helmets for ultrahigh field (UHF) magnetic resonance imaging (MRI). METHOD/METHODS:We used a recently proposed analytical formulation of scattering from layered spheres to model an MRI experiment with a variable air layer between a homogenous human head and an HPM helmet. Such model expresses the fields as a superposition of progressive and regressive traveling waves by exploiting the theory of inhomogeneous transmission. Analytical results were compared with numerical simulations, in terms of changes in the radiofrequency (RF) magnetic induction field employing a surface and volume coil, to validate the proposed method. RESULTS:The presence of an air layer, due to differences in head size, results in a slight variation in the optimal permittivity value required to optimize the performance of the helmet, with a maximum relative variation of no more than 12%. This can be explained by the invariance of the impedance at the outer air-HPM interface, due to the high conductivity typical of biological tissues. In both cases, a clear increase in the magnetic induction field is observed, suggesting that the HPM design is robust to the introduction of a small dielectric insulating layer. Also, good agreement was found between the analytical and numerical results suggesting that the model could be employed to optimize the HPM also in real experiments, particularly when canonical geometries, such as cylindrical or spherical shapes, are employed to design the helmet.

We address an ethical challenge in climate change adaptation and global health research. The challenge stems from two pairs of intuitions about justice and responsibility in climate change and health. One pair assigns responsibility for adaptation research to high-income countries given their historical emissions, disproportionate share of resources and capacity to intervene. The other pair assigns responsibility to low- and middle-income countries given their agency, right to self-determination, local authority and legitimacy, and disproportionate burden of climate and health risks. The intuitions create conflicting views: obligation and assistance pull in one direction, and agency and authority pull in another. To resolve the tension, we distinguish two forms of responsibility: (i) adaptation-enabling responsibilities; and (ii) adaptation-enacting responsibilities. The resulting division of labour reflects different forms of justice and aligns with the principle of subsidiarity's core elements, namely: non-abandonment, non-absorption, and cooperation and coordination. We thus propose a framework that ascribes adaptation-enabling responsibilities to high-income countries, including adaptation financing, capacity-building and other forms of support; and adaptation-enacting responsibilities to low- and middle-income countries, including priority-setting in local adaptation research, and creation and implementation of their adaptation plans and policies. Our framework also suggests a third form of responsibility: shared adaptation responsibilities, which are jointly assigned to high-income countries, low- and middle-income countries and agents at multiple levels within them. We conclude that genuine collaboration in adaptation research, where high-income countries enable without dominating and low- and middle-income countries act without being abandoned, will be essential for just and effective adaptation to climate change.

CONTEXT/BACKGROUND:More health systems are establishing outpatient palliative care (PC) programs, increasing demand for ambulatory PC clinicians. However, existing outpatient training during hospice and palliative medicine (HPM) fellowship remains limited and suboptimal. Little is known about the outpatient-specific knowledge and skills PC trainees should acquire for competent outpatient practice. OBJECTIVES/OBJECTIVE:To identify and prioritize outpatient-focused educational topics for HPM fellows and clinicians new to ambulatory practice. METHODS:A cross-sectional survey of United States (U.S.) outpatient PC clinicians (physicians, advanced practice practitioners [APPs]). Using a list of 51 educational topics, respondents selected a maximum of 20 topics they would prioritize as essential to prepare learners for outpatient practice. RESULTS:Of 247 clinicians, 136 (55%) responded, including 115 physicians and 21 APPs from all U.S. regions. Seven of 51 topics were prioritized by more than two-thirds of respondents (n = 92-119, 68%-86%). Four focused on outpatient application of core PC skills (pain management [n = 113, 83%], nonpain symptom management [n = 117, 86%], depression/anxiety [n = 107, 79%], goals of care [n = 92, 68%]). The remaining three covered discrete topics related to pain and opioid management, including best practices for caring for patients with comorbid pain and substance use disorder (n = 104, 76%). CONCLUSION/CONCLUSIONS:This national survey identified foundational outpatient-focused educational topics for HPM learners and suggests that outpatient curricula prioritize deliberate education on the unique application of core PC skills in outpatient settings. This prioritized list provides education leaders a roadmap to enhance existing curricula and informs the development of outpatient educational resources that can be shared across institutions.

PURPOSE/OBJECTIVE:We aimed to determine time trends in incidence, treatment and survival of patients with adrenocortical carcinoma in the Netherlands. METHODS:All 685 adult patients with adrenocortical carcinoma diagnosed between 1993 and 2020 in the Netherlands were included, using the nation-wide prospective Netherlands Cancer Registry. RESULTS:The median age-adjusted incidence rate based on the European Standard Population was 1.62 per million person-years [0.83-2.11] and was stable over time. We saw a gradual increase in stage III on diagnosis (13 to 25%) with a stable proportion of stage IV (40%). The five-year survival remained stable over time for stage I-II at 65% and stage III at 35%, while the survival for stage IV increased from 3% in 1993-1996 to 11% in 2017-2020. Since the Dutch Adrenal Network was founded in 2004, more patients were referred to an expert center (p<0.001), which was associated with increased survival (adjusted HR 0.70, 95%CI[0.57-0.85]). Multivariate cox-regression showed increased survival in all stages when treated with adrenalectomy (adjusted HR 0.53, 95%CI[0.43-0.65]) and mitotane therapy (adjusted HR 0.73, 95%CI[0.55-0.98]). In stage IV disease, adrenalectomy, surgical control of disease, chemotherapy and mitotane therapy were associated with increased survival. However, only 58% of mitotane users reached a therapeutic drug level and 59.5% discontinued treatment prematurely. CONCLUSIONS:The incidence of adrenocortical carcinoma is stable over time. The five-year survival for stage I-III remained stable, while the survival for stage IV increased. Factors associated with increased survival are centralization of care, adrenalectomy, surgical control of disease, chemotherapy and mitotane therapy.

UNLABELLED:Despite the vast promise of abrupt wavefront engineering within subwavelength thickness, most optical metasurfaces are still bound to bulky and rigid substrates. Recently, metasurfaces in suspended membranes (MISMs) have attracted increasing attention due to their unique flexible, conformal properties and their ability to minimize undesired substrate effects. Most importantly, the MISM platform enables metasurface transfer and integration with non-conventional substrates and electronic/photonic devices. By summarizing multiple approaches to create MISMs with a variety of membrane and sacrificial layer materials and configurations, we demonstrate the Omni-Purpose Transfer and Integration of Metasurfaces in Suspended Membranes (OPTIMISM), overcoming the existing limitations on metasurface geometries or materials. It is particularly suitable for metasurface integration on optical fiber tips to form meta-optic probes for broad applications, including biomedical and endoscopic imaging and sensing. Considering the various configurations of membrane dielectric environment in integrated MISM devices, we performed a systematic investigation to demonstrate the strong influence of the surrounding refractive index on ultrathin metasurface design based on both conventional forward design (library search) and inverse design strategy (evolutionary algorithm). Our findings highlight the advantage of the inverse design strategy leveraging meta-atom non-local interactions, and the great potential of the MISM platform for universal and scalable metasurface transfer and integration. SUPPLEMENTARY INFORMATION/UNASSIGNED:The online version contains supplementary material available at 10.1007/s44275-026-00041-y.

BACKGROUND:Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. METHODS:Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. FINDINGS/RESULTS:In 2023, there were an estimated 2·30 million (95% uncertainty interval [UI] 2·01 to 2·61) breast cancer incident cases, 764 000 deaths (672 000 to 854 000), and 24·1 million (21·3 to 27·5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44·2 per 100 000 person-years [31·2 to 58·4]), the age-standardised mortality rate (ASMR) was the highest (24·1 per 100 000 [16·8 to 31·9]). The highest ASIR was in the high-income group (75·7 per 100 000 [67·1 to 84·0]), and the lowest ASMR was in the upper-middle-income group (11·2 per 100 000 [10·2 to 12·3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147·2% (38·1 to 271·7), compared with a 1·2% (-11·5 to 17·2) change in the high-income group. The ASMR decreased in the high-income group, changing by -29·9% (-33·6 to -25·9), but increased by 99·3% (12·5 to 202·9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28·3% (16·6 to 38·9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3·56 million (2·29 to 4·83), with 1·37 million (0·841 to 2·02) deaths. INTERPRETATION/CONCLUSIONS:The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2·5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. FUNDING/BACKGROUND:Gates Foundation, St Jude Children's Research Hospital.