With the continued development of nanomaterials over the past two decades, specialized photonanomedicines (light-activable nanomedicines, PNMs) have evolved to become excitable by alternative energy sources that typically penetrate tissue deeper than visible light. These sources include electromagnetic radiation lying outside the visible near-infrared spectrum, high energy particles, and acoustic waves, amongst others. Various direct activation mechanisms have leveraged unique facets of specialized nanomaterials, such as upconversion, scintillation, and radiosensitization, as well as several others, in order to activate PNMs. Other indirect activation mechanisms have leveraged the effect of the interaction of deeply penetrating energy sources with tissue in order to activate proximal PNMs. These indirect mechanisms include sonoluminescence and Cerenkov radiation. Such direct and indirect deep-tissue activation has been explored extensively in the preclinical setting to facilitate deep-tissue anticancer photodynamic therapy (PDT); however, clinical translation of these approaches is yet to be explored. This review provides a summary of the state of the art in deep-tissue excitation of PNMs and explores the translatability of such excitation mechanisms towards their clinical adoption. A special emphasis is placed on how current clinical instrumentation can be repurposed to achieve deep-tissue PDT with the mechanisms discussed in this review, thereby further expediting the translation of these highly promising strategies.

High-grade gliomas (HGGs; WHO grade III or IV) are the most common and lethal brain malignancy. Patients of Hispanic ethnicity are diagnosed with HGGs earlier than non-Hispanic patients, but they exhibit improved HGG survival following diagnosis. Either environmental or biological factors could explain this survival benefit. We aimed to determine if post-diagnosis advantages would still be present in Hispanic patients with high social vulnerability, an environmental condition predisposing patients to poor oncologic outcomes. HGG outcomes were retrospectively assessed in a cohort of 22 Hispanic patients and 33 non-Hispanic patients treated for HGGs from 2015 to 2020 at a single institution that serves a highly vulnerable region. Compared to non-Hispanic patients, Hispanic patients demonstrated higher social vulnerability index scores (96.8 + 0.7 vs. 76.3 + 4.6; *** p = 0.0002) and a 14-month longer interval between diagnosis and recurrence (19.7 + 5.9 (n = 13) vs. 5.5 + 0.6 months (n = 19); ** p = 0.001). In only those patients with more aggressive IDH-1 wildtype tumors (glioblastoma), Hispanic ethnicity still related to a longer time before recurrence (15.8 + 5.9 months (n = 9); 5.5 + 0.6 months (n = 18); * p = 0.034), and in a multivariate analysis, Hispanic ethnicity predicted time-to-recurrence (* p = 0.027) independent of patient age, functional status, MGMT gene methylation, or treatments received. Therefore, environmental factors, specifically social vulnerability, did not obscure the post-diagnosis benefits associated with Hispanic ethnicity. In future experiments, basic studies should be prioritized which investigate the cellular or genetic mechanisms underlying this ethnicity effect on HGG progression in the hopes of improving care for these devastating malignancies.

Introduction and Importance: Pituitary apoplexy (PA) is a clinical syndrome caused by ischemia or hemorrhage of the pituitary gland, typically in the context of an adenoma. It typically presents with a thunderclap headache and sterile cerebral spinal fluid (CSF). The authors identify a case of PA, which initially presented with the signs and symptoms of viral meningitis. Presentation of Case: A 44-year-old man presented to the emergency department with headache, nuchal rigidity, fever, and delirium. The patient reported a 10-year history of chronic that were partially responsive to acetaminophen. Four days after admission, the patient developed right-sided cranial nerve III, IV, and VI palsies. Labs revealed anemia and hyponatremia. The CSF was leukocytic, lymphocyte-predominant, and had elevated protein. In addition to these results, negative CSF bacterial cultures led the care team to believe this case was viral meningoencephalitis. Routine MRI of the brain at presentation revealed a 3.1×2.5×3.2 (craniocaudal×anterior posterior×transverse) expansile mass centered within the sella turcica. An endocrine workup revealed hypopituitarism. The diagnosis of PA was then made. A microscopic transsphenoidal resection of the sellar mass was performed, and histopathologic analysis confirmed necrotic pituitary adenoma tissue. Following an uncomplicated procedure, the patient recovered fully from his cranial nerve palsies and continues to do well. Discussion: Because life-threatening hypotension from acute adrenal insufficiency can be caused by PA, timely diagnosis is crucial. When a patient presents with meningism, PA should be included in the differential diagnosis. Conclusion: This report illustrates a case of PA presenting with symptoms and a CSF profile classically associated with viral meningitis.

Ectopic pituitary tumors are neoplasms with no connection to the pituitary gland and are commonly deposited in other areas of the anterior skull base. A 32-year-old woman presented with a 3-month history of right-sided facial weakness, sensorineural hearing loss, diplopia, and severe headaches. Physical examination revealed a mid-dilated sluggishly reactive right pupil with slight limitation in all gazes, as well as right-sided orbicularis weakness, lagophthalmos, and decreased facial sensation. A magnetic resonance imaging (MRI) of the head without contrast revealed a 3.7 × 1.8 × 2.6 cm mildly enhancing mass in the right internal acoustic meatus and along the petrous ridge. The case was brought before the institution's tumor board, where concern for higher grade pathology, such as hemangiopericytoma, was discussed. Per patient preference, surgical biopsy of the tumor was performed. Immunohistochemical staining revealed a World Health Organization (WHO) grade II neuroendocrine tumor, with cells staining positive for synaptophysin, chromogranin, and CD56, with a Ki-67 index of 8%. In addition to the ectopic location, this pituitary tumor was noted to be aggressive in nature based on its high Ki-67 index. Surgical excision and radiologic therapy of tumors involving the CPA are appropriate treatments in most cases.

Disparities in neurosurgical care are increasingly recognized, yet how they affect the diagnosis and management of vestibular schwannoma (VS) remains unclear. Differences in tumor size at diagnosis, treatment selection, and outcomes may be influenced by race, insurance status, income, and geography. To date, no comprehensive synthesis has addressed these inequities in patients with sporadic VS. To systematically evaluate the literature for evidence of social determinants of health (SDoH) in the diagnosis, treatment, and outcomes of patients with sporadic vestibular schwannoma. We conducted a PRISMA-guided systematic review of PubMed, Embase, and Web of Science (2000–2024). Included studies examined adult patients with sporadic VS and reported at least one socioeconomic variable. Non-English studies and those involving pediatric patients were excluded. Studies focusing on neurofibromatosis type 2 were excluded. Screening and data extraction were conducted independently by multiple reviewers using Covidence. Outcomes of interest included tumor size, treatment modality (surgery, radiosurgery, observation), hearing preservation, complications, and recurrence. Study quality was assessed using the GRADE framework and evaluated across the domains of risk of bias, inconsistency, indirectness, imprecision, and publication bias. Of 487 records identified, 40 met inclusion criteria. Most were US-based, retrospective studies that utilized national databases for patient recruitment. Race and insurance status were the most frequently reported variables; income and geographic indicators were less commonly assessed. Outcomes described the likelihood of treatment received, including surgery or SRS, complications including morbidity and mortality, length of stay, and discharge disposition including rehab and readmission. Few studies assessed functional status ( n =2), hearing outcomes ( n =2), or quality of life (n=1). In total, 358,843 patients were included across the 40 studies analyzed. This review suggests that disparities in vestibular schwannoma care are multi-factorial, with race and insurance status showing the most consistent associations between management, outcomes, and disparities. As treatment continues to evolve and become more centralized, future work should prioritize multi-institutional studies to incorporate patient-level socioeconomic data and evaluate outcomes beyond management selection.