Citations

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, characterized by rapid growth, invasive infiltration into surrounding brain tissue, and resistance to conventional therapies. Despite advancements in surgery, radiotherapy, and chemotherapy, median survival remains approximately 15 months, underscoring the urgent need for innovative treatments. Key considerations informing treatment development include oncogenic genetic and epigenetic alterations that may dually serve as therapeutic targets and facilitate treatment resistance. Various immunotherapeutic strategies have been explored and continue to be refined for their anti-tumor potential. Technical aspects of drug delivery and blood–brain barrier (BBB) penetration have been addressed through novel vehicles and techniques including the incorporation of nanotechnology. Molecular profiling has emerged as an important tool to individualize treatment where applicable, and to identify patient populations with the most drug sensitivity. The goal of this review is to describe the spectrum of potential GBM therapeutic targets, and to provide an overview of key trial outcomes. Altogether, the progress of clinical and preclinical work must be critically evaluated in order to develop therapies for GBM with the strongest therapeutic efficacy.

Background Stroke remains a concern after transcatheter aortic valve replacement (TAVR). Several studies attempted to identify correlates of stroke but there remains a need for better predictors. Objective This study aims to characterize the aortic arch to identify potential correlates of stroke after TAVR using a patient cohort that includes cases with and without stroke. Methods A retrospective analysis was performed on 52 patients who underwent TAVR at Mayo Clinic and Maria Cecilia Hospital. Of these patients, 26 had a stroke after TAVR and 26 did not (control). Anatomical characterization was performed on each patient. Patient-specific 3D digital models of the ascending aorta, aortic arch, and calcium were created for each patient. Geometrical measurements, including cross-sectional areas, volumes, tortuosity, curvature, and length of the model were recorded. Results There was no significant difference in the various area measurements between the two groups, but the aortic arch cross-sectional area ratio (cerebral ostia cross-sectional areas/arch cross-sectional area) was significantly higher in the stroke group. Additionally, there was no significant difference in tortuosity, curvature, aortic volume, and length of the aorta. Aortic valve calcium score, aorta calcium, and aortic arch type (I, II, or III) were not significantly different between the groups. The prevalence of a bovine arch (BA) configuration was significantly higher in the stroke group (46% vs 8% control, p < 0.05). Conclusion Aortic arch cross-sectional area ratio and BA variant were the most significant correlates of stroke after TAVR.

Dermatoneuro syndrome (DNS) is a rare diagnosis of exclusion characterised by fever, altered mental status and seizures in patients with scleromyxoedema. We present a complex case of a patient presenting with a fever, coma, seizures, rigidity and deep T2 fluid-attenuated inversion recovery hyperintensities in the context of both scleromyxoedema and influenza A with extensive, negative infectious workup. This case highlights the shared clinical features of DNS and influenza-associated encephalopathy, the latter being the eventual diagnosis for our patient. We review the DNS literature focusing on presentation, adequacy of investigation, treatment and prognosis. Finally, we provide an initial workup for patients with suspected DNS, including nasopharyngeal influenza PCR.

Abstract Oscillations in the high gamma and ripple frequency ranges are known to coordinate local hippocampal and neocortical neuronal assemblies during memory encoding and recall. Here, we explored spatiotemporal dynamics and the role of global coordination of these fast oscillatory discharges across the sensory and associational cortical areas in distinct phases of memory processing. Individual bursts of high frequency oscillations were detected in intracranial recordings from epilepsy patients remembering word lists for immediate free recall. We found constant coincident bursting across visual and higher order processing areas, peaking before recall and elevated during encoding of words. This global co-bursting was modulated by memory processing, engaged approximately half of the recorded electrode sites, and clustered into a sequence of multiple consecutive bursting discharges. Our results suggest a general role of global coincident high frequency oscillations in organizing large-scale information processing across the brain necessary especially, but not exclusively, for memory functions.

Objective The objective is to provide evidence‐based and expert guidance for the screening, treatment, and management of lupus nephritis. Methods The Core Team developed clinical questions for screening, treatment, and management of lupus nephritis using the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were completed for each PICO question, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of evidence and to formulate recommendations. The Voting Panel achieved a consensus ≥70% on the direction (for or against) and strength (strong or conditional) of each recommendation. Results We present 28 graded recommendations (7 strong, 21 conditional) and 13 ungraded, consensus‐based good practice statements for the screening and management of lupus nephritis. Our recommendations focus on the unifying principle that lupus nephritis therapy is continuous and ongoing, rather than consisting of discrete induction/initial and maintenance/subsequent therapies. Therapy should include pulse glucocorticoids followed by oral glucocorticoid taper and two additional immunosuppressive agents for 3–5 years for those achieving complete renal response. Conclusion This guideline provides direction for clinicians regarding screening and treatment decisions for management of lupus nephritis. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each individual patient.

ImportanceUnderstanding the relationship between patients’ clinical characteristics and outcomes is fundamental to medicine. When critically ill patients die after withdrawal of life-sustaining therapy (WLST), the inability to observe the potential for recovery with continued aggressive care could bias future clinical decisions and research.ObjectiveTo quantify the frequency with which experts consider patients who died after WLST following resuscitated cardiac arrest to have had recovery potential if life-sustaining therapy had been continued.Design, Setting, and ParticipantsThis prospective cohort study included comatose adult patients (aged ≥18 years) treated following resuscitation from cardiac arrest at a single academic medical center between January 1, 2010, and July 31, 2022. Patients with advanced directives limiting critical care or who experienced cardiac arrest of traumatic or neurologic etiology were excluded. An international cohort of experts in post-arrest care based on clinical experience and academic productivity was identified. Experts reviewed the cases between August 24, 2022, and February 11, 2024.ExposurePatients who died after WLST.Main Outcome and MeasuresThree or more experts independently estimated recovery potential for each patient had life-sustaining treatment been continued, using a 7-point numerical ordinal scale. In the primary analysis, which involved the patient cases with death after WLST, a 1% or greater estimated recovery potential was considered to be clinically meaningful. In secondary analyses, thresholds of 5% and 10% estimated recovery probability were explored.ResultsA total of 2391 patients (median [IQR] age, 59 [48-69] years; 1455 men [60.9%]) were included, of whom 714 (29.9%) survived to discharge. Cases of uncertain outcome (1431 patients [59.8%]) in which WLST preceded death were reviewed by 38 experts who rendered 4381 estimates of recovery potential. In 518 cases (36.2%; 95% CI, 33.7%-38.7%), all experts believed that recovery potential was less than 1% if life-sustaining therapies had been continued. In the remaining 913 cases (63.8%; 95% CI, 61.3%-66.3%), at least 1 expert believed that recovery potential was at least 1%. In 227 cases (15.9%; 95% CI, 14.0%-17.9%), all experts agreed that recovery potential was at least 1%, and in 686 cases (47.9%; 95% CI, 45.3%-50.6%), expert estimates differed at this threshold.Conclusions and RelevanceIn this cohort study of comatose patients resuscitated from cardiac arrest, most who died after WLST were considered by experts to have had recovery potential. These findings suggest that novel solutions to avoiding deaths based on biased prognostication or incomplete information are needed.