Minimally Invasive Treatment Options for Hepatic Uveal Melanoma Metastases.

Uveal melanoma is one of the most common primary intraocular malignancies that accounts for about 85% of all ocular melanomas. The pathophysiology of uveal melanoma is distinct from cutaneous melanoma and has separate tumor profiles. The management of uveal melanoma is largely dependent on the presence of metastases, which confers a poor prognosis with a one-year survival reaching only 15%. Although a better understanding of tumor biology has led to the development of novel pharmacologic agents, there is increasing demand for minimally invasive management of hepatic uveal melanoma metastases. Multiple studies have already summarized the systemic therapeutic options available for metastatic uveal melanoma. This review covers the current research for the most prevalent locoregional treatment options for metastatic uveal melanoma including percutaneous hepatic perfusion, immunoembolization, chemoembolization, thermal ablation, and radioembolization.

Scoping review of disease-modifying effect of drugs in experimental epilepsy.

Objective: Epilepsy affects ~50 million people worldwide causing significant medical, financial, and sociologic concerns for affected patients and their families. To date, treatment of epilepsy is primarily symptomatic management because few effective preventative or disease-modifying interventions exist. However, recent research has identified neurobiological mechanisms of epileptogenesis, providing new pharmacologic targets to investigate. The current scientific evidence remains scattered across multiple studies using different model and experimental designs. The review compiles different models of anti-epileptogenic investigation and highlights specific compounds with potential epileptogenesis-modifying experimental drugs. It provides a platform for standardization of future epilepsy research to allow a more robust compound analysis of compounds with potential for epilepsy prevention. Methods: PubMed, Ovid MEDLINE, and Web of Science were searched from 2007 to 2021. Studies with murine models of epileptogenesis and explicitly detailed experimental procedures were included in the scoping review. In total, 51 articles were selected from 14,983 and then grouped by five core variables: (1) seizure frequency, (2) seizure severity, (3) spontaneous recurrent seizures (SRS), (4) seizure duration, and (5) mossy fiber sprouting (MFS). The variables were differentiated based on experimental models including methods of seizure induction, treatment schedule and timeline of data collection. Data was categorized by the five core variables and analyzed by converting original treatment values to units of percent of its respective control. Results: Discrepancies in current epileptogenesis models significantly complicate inter-study comparison of potential anti-epileptogenic interventions. With our analysis, many compounds showed a potential to reduce epileptogenic characteristics defined by the five core variables. WIN55,212-2, aspirin, rapamycin, 1400W, and LEV + BQ788 were identified compounds with the potential of effective anti-epileptic properties. Significance: Our review highlights the need for consistent methodology in epilepsy research and provides a novel approach for future research. Inconsistent experimental designs hinder study comparison, slowing the progression of treatments for epilepsy. If the research community can optimize and standardize parameters such as methods of seizure induction, administration schedule, sampling time, and aniMal models, more robust meta-analysis and collaborative research would follow. Additionally, some compounds such as rapamycin, WIN 55,212-2, aspirin, 1400W, and LEV + BQ788 showed anti-epileptogenic modulation across multiple variables. We believe they warrant further study both individually and synergistically.

Immunotherapy related pericardial effusion on chest CT.

BACKGROUND: Immunotherapy has become a critical class of anticancer therapy in recent years, functioning by releasing brakes on the immune system that ultimately results in immune cell activation which eliminates cancer cells. Immune related adverse events (IRAEs) are a specific type of adverse event described in patients taking checkpoint inhibitor immunotherapy which results from unrestrained immune activation. Immune related pericardial effusion has been described however has not been comprehensively characterized. Here, we present the most extensive report to date detailing this adverse event. METHODS: We queried our medical record system to retrospectively identify patients on checkpoint inhibitor therapy for lung cancer who subsequently developed pericardial effusion. We analyzed the clinical and radiographic characteristics, prior therapies, treatment for the effusion, and outcomes in patients with immune related pericardial effusion and compared them to similar patients with pericardial effusion not attributable to checkpoint inhibitor therapy. RESULTS: Our data demonstrate that most of these pericardial effusions were small and not clinically significant. The majority were successfully treated with steroids or resolved spontaneously. Anti-PD-1 inhibitors were the most common checkpoint inhibitor preceding pericardial effusion, and a significant number of patients who went on to develop IRAE pericardial effusion previously had treatment with carboplatin for their cancer. CONCLUSIONS: These data suggest that IRAE pericardial effusion is not a clinically significant adverse event however it sometimes leads to permanent discontinuation of checkpoint inhibitor therapy which is not necessary.

A shift in the role of glutamatergic signaling in the nucleus accumbens core with the development of an addicted phenotype.

BACKGROUND: While dopamine signaling in the nucleus accumbens (NAc) plays a well-established role in motivating cocaine use in early nonaddicted stages, recent evidence suggests that other signaling pathways may be critical once addiction has developed. Given the importance of glutamatergic signaling in the NAc for drug seeking and relapse, here we examined its role in motivating cocaine self-administration under conditions known to produce either a nonaddicted or an addicted phenotype. METHODS: Following acquisition, male and female Sprague Dawley rats were given either short access (three fixed-ratio 1 sessions, 20 infusions/day) or extended 24-hour access (10 days; 4 trials/hour; up to 96 infusions/day) to cocaine. Following a 14-day abstinence period, motivation for cocaine was assessed under a progressive-ratio schedule, and once stable, the effects of intra-NAc infusions of the glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate receptor antagonist CNQX (0, .01, .03, .1 µg/side) were determined. As an additional measure for the development of an addicted phenotype, separate groups of rats were screened under an extinction/cue-induced reinstatement procedure following abstinence from short-access versus extended-access self-administration. RESULTS: Motivation for cocaine and levels of extinction and reinstatement responding were markedly higher following extended-access versus short-access self-administration, confirming the development of an addicted phenotype in the extended-access group. CNQX dose-dependently reduced motivation for cocaine in the extended-access group but was without effect in the short-access group. CONCLUSIONS: These results suggest that the role of glutamatergic signaling in the NAc, though not essential for motivating cocaine use in nonaddicted stages, becomes critical once addiction has developed.