Digital Commons Network^™

Effective Connectivity In The Default Mode Network After Paediatric Traumatic Brain Injury, Kelly A Vaughn, Dana Demaster, Jeong Hwan Kook, Marina Vannucci, Linda Ewing-Cobbs

Faculty, Staff and Student Publications

Children who experience a traumatic brain injury (TBI) are at elevated risk for a range of negative cognitive and neuropsychological outcomes. Identifying which children are at greatest risk for negative outcomes can be difficult due to the heterogeneity of TBI. To address this barrier, the current study applied a novel method of characterizing brain connectivity networks, Bayesian multi-subject vector autoregressive modelling (BVAR-connect), which used white matter integrity as priors to evaluate effective connectivity-the time-dependent relationship in functional magnetic resonance imaging (fMRI) activity between two brain regions-within the default mode network (DMN). In a prospective longitudinal study, children ages 8-15 years …

Cerebral Infarctions In An Infant With Covid-19 Delta Variant Infection And Disseminated Tuberculosis, Stuart Fraser, Misti Ellsworth, Norma Perez, Hunter Hamilton, Stephen Fletcher, Deborah Brown, Lakshmi Srivaths

Faculty, Staff and Student Publications

No abstract provided.

Renal Disease And The Heart, Hassan N Ibrahim

Faculty, Staff and Student Publications

No abstract provided.

Targeting Etosis By Mir-155 Inhibition Mitigates Mixed Granulocytic Asthmatic Lung Inflammation, Ji Young Kim, Patrick Stevens, Manjula Karpurapu, Hyunwook Lee, Joshua A Englert, Pearlly Yan, Tae Jin Lee, Navjot Pabla, Maciej Pietrzak, Gye Young Park, John W Christman, Sangwoon Chung

Faculty, Staff and Student Publications

Asthma is phenotypically heterogeneous with several distinctive pathological mechanistic pathways. Previous studies indicate that neutrophilic asthma has a poor response to standard asthma treatments comprising inhaled corticosteroids. Therefore, it is important to identify critical factors that contribute to increased numbers of neutrophils in asthma patients whose symptoms are poorly controlled by conventional therapy. Leukocytes release chromatin fibers, referred to as extracellular traps (ETs) consisting of double-stranded (ds) DNA, histones, and granule contents. Excessive components of ETs contribute to the pathophysiology of asthma; however, it is unclear how ETs drive asthma phenotypes and whether they could be a potential therapeutic target. …

Urinary T Cells Are Detected In Patients With Immune Checkpoint Inhibitor-Associated Immune Nephritis That Are Clonotypically Identical To Kidney T Cell Infiltrates, Shailbala Singh, Leticia C Clemente, Edwin R Parra, Amanda Tchakarov, Chao Yang, Yisheng Li, James P Long, Cassian Yee, Jamie S Lin

Faculty, Staff and Student Publications

Acute kidney injury (AKI) occurs in ~20% of patients receiving immune checkpoint inhibitor (ICI) therapy; however, only 2-5% will develop ICI-mediated immune nephritis. Conventional tests are nonspecific in diagnosing disease pathology and invasive procedures (i.e. kidney biopsy) may not be feasible. In other autoimmune renal diseases, urinary immune cells correlated with the pathology or were predictive of disease activity. Corresponding evidence and analysis are absent for ICI-mediated immune nephritis. We report the first investigation analyzing immune cell profiles of matched kidney biopsies and urine of patients with ICI-AKI. We demonstrated the presence of urinary T cells in patients with immune …

Enhancing Mesenchymal Stromal Cell Potency: Inflammatory Licensing Via Mechanotransduction, Max A Skibber, Scott D Olson, Karthik S Prabhakara, Brijesh S Gill, Charles S Cox

Faculty, Staff and Student Publications

Mesenchymal stromal cells (MSC) undergo functional maturation upon their migration from bone marrow and introduction to a site of injury. This inflammatory licensing leads to heightened immune regulation via cell-to-cell interaction and the secretion of immunomodulatory molecules, such as anti-inflammatory mediators and antioxidants. Pro-inflammatory cytokines are a recognized catalyst of inflammatory licensing; however, biomechanical forces, such as fluid shear stress, are a second, distinct class of stimuli that incite functional maturation. Here we show mechanotransduction, achieved by exposing MSC to various grades of wall shear stress (WSS) within a scalable conditioning platform, enhances the immunomodulatory potential of MSC independent of …

Structure Of The Hsp110:Hsc70 Nucleotide Exchange Machine, Yusra Ahmed, Jeremy Miciak, W Pat Taylor, David J Francis

Faculty, Staff and Student Publications

We evaluate the direct and inferential mediation (DIME) model for reading comprehension with a sample of struggling readers in Grades 3 to 5 (N = 364) in the context of a large-scale randomized controlled trial (RCT) investigating two theoretically distinct reading interventions (text processing + foundational skills [n = 117] or text processing only [n = 120]) and a control condition (n = 127). We investigate whether the intervention affects not just reading comprehension levels, but also how variables within the reading system interrelate. This approach allows the focus to shift from intervention as influencing a …

The Value Of Peer Support In Curbing Moral Injury: A Resident’S Perspective, May W Chen, Jennifer K Lee, Gilbert Vezina, Aylin Tekes, Jamie Perin, Ruoying Li, Alexandra O'Kane, Meaghan Mcgowan, Taeun Chang, Charlamaine Parkinson, Colleen Krein, Tareq Al-Shargabi, Frances J Northington, Ken M Brady, An N Massaro, Rathinaswamy B Govindan

Faculty, Staff and Student Publications

Identifying the hemodynamic range that best supports cerebral perfusion using near infrared spectroscopy (NIRS) autoregulation monitoring is a potential physiologic marker for neonatal hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia. However, an optimal autoregulation monitoring algorithm has not been identified for neonatal clinical medicine. We tested whether the hemoglobin volume phase (HVP), hemoglobin volume (HVx), and pressure passivity index (PPI) identify changes in autoregulation that are associated with brain injury on MRI or death. The HVP measures the phase difference between a NIRS metric of cerebral blood volume, the total hemoglobin (THb), and mean arterial blood pressure (MAP) at the frequency …

Immunotherapy Approaches For The Treatment Of Diffuse Midline Gliomas, Joshua D Bernstock, Samantha E Hoffman, Ari D Kappel, Pablo A Valdes, Walid Ibn Essayed, Neil V Klinger, Kyung-Don Kang, Stacie K Totsch, Hannah E Olsen, Charles W Schlappi, Katharina Filipski, Florian A Gessler, Lissa Baird, Mariella G Filbin, Rintaro Hashizume, Oren J Becher, Gregory K Friedman

Faculty, Staff and Student Publications

Diffuse midline gliomas (DMG) are a highly aggressive and universally fatal subgroup of pediatric tumors responsible for the majority of childhood brain tumor deaths. Median overall survival is less than 12 months with a 90% mortality rate at 2 years from diagnosis. Research into the underlying tumor biology and numerous clinical trials have done little to change the invariably poor prognosis. Continued development of novel, efficacious therapeutic options for DMGs remains a critically important area of active investigation. Given that DMGs are not amenable to surgical resection, have only limited response to radiation, and are refractory to traditional chemotherapy, immunotherapy …

Cytokines And Chemokines Profile In Encephalitis Patients: A Meta-Analysis, Alireza Soltani Khaboushan, Mohammad-Taha Pahlevan-Fallahy, Parnian Shobeiri, Antônio L Teixeira, Nima Rezaei

Faculty, Staff and Student Publications

Background: Encephalitis is caused by autoimmune or infectious agents marked by brain inflammation. Investigations have reported altered concentrations of the cytokines in encephalitis. This study was conducted to determine the relationship between encephalitis and alterations of cytokine levels in cerebrospinal fluid (CSF) and serum.

Methods: We found possibly suitable studies by searching PubMed, Embase, Scopus, and Web of Science, systematically from inception to August 2021. 23 articles were included in the meta-analysis. To investigate sources of heterogeneity, subgroup analysis and sensitivity analysis were conducted. The protocol of the study has been registered in PROSPERO with a registration ID of CRD42021289298. …

Associations Between Body Dissatisfaction And Relationship Functioning Among Same-Sex Female Couples: An Actor-Partner Interdependence Model, Cassidy M. Sandoval, Kelly A. Romano, Kristin E. Heron, Charlotte A. Dawson, Tiphanie G. Sutton, Barbara A. Winstead, Robin J. Lewis

Psychology Faculty Publications

Nearly all past research about body dissatisfaction and romantic relationship factors is among heterosexual couples; little is known about these associations in sexual minority couples. The present study aimed to fill gaps in the current literature by using actor-partner interdependence models (APIMs) to examine dyadic patterns of association between body dissatisfaction and different aspects of relationship functioning among same-sex female couples. Participants were 163 same-sex female romantic dyads (326 women) between the ages of 18-35 years who completed measures of body dissatisfaction and relationship factors. Results from significance testing of actor and partner effects indicated higher levels of women's own …

Radiographic Findings And Association With Clinical Severity And Outcomes In Critically Ill Patients With Covid-19, Wei Wu, Pavan K Bhatraju, Natalie Cobb, Neha A Sathe, Kevin I Duan, Kevin P Seitz, Matthew R Thau, Clifford C Sung, Daniel S Hippe, Gautham Reddy, Sudhakar Pipavath

Faculty, Staff and Student Publications

PURPOSE: To describe evolution and severity of radiographic findings and assess association with disease severity and outcomes in critically ill COVID-19 patients.

MATERIALS AND METHODS: This retrospective study included 62 COVID-19 patients admitted to the intensive care unit (ICU). Clinical data was obtained from electronic medical records. A total of 270 chest radiographs were reviewed and qualitatively scored (CXR score) using a severity scale of 0-30. Radiographic findings were correlated with clinical severity and outcome.

RESULTS: The CXR score increases from a median initial score of 10 at hospital presentation to the median peak CXR score of 18 within a …

Alternative Adenosine Receptor Activation: The Netrin-Adora2b Link, Xiaoyi Yuan, Tingting Mills, Marie-Francoise Doursout, Scott E Evans, Marcos F Vidal Melo, Holger K Eltzschig

Faculty, Staff and Student Publications

During hypoxia or inflammation, extracellular adenosine levels are elevated. Studies using pharmacologic approaches or genetic animal models pertinent to extracellular adenosine signaling implicate this pathway in attenuating hypoxia-associated inflammation. There are four distinct adenosine receptors. Of these, it is not surprising that the Adora2b adenosine receptor functions as an endogenous feedback loop to control hypoxia-associated inflammation. First, Adora2b activation requires higher adenosine concentrations compared to other adenosine receptors, similar to those achieved during hypoxic inflammation. Second, Adora2b is transcriptionally induced during hypoxia or inflammation by hypoxia-inducible transcription factor HIF1A. Studies seeking an alternative adenosine receptor activation mechanism have linked netrin-1 …

Online Dermatology Curriculum Experiences Among Us Dermatology Residents And Faculty, Quoc-Bao D Nguyen, Caroline T Starling, Imran T Baig, Misha V Koshelev, Kelly C Nelson

Faculty, Staff and Student Publications

Many dermatology residency programs adapted to the COVID-19 pandemic by transitioning to online teaching methods. This may impact the quality of education and the satisfaction of residents. Dermatology faculty and residents nationwide were surveyed regarding their experiences with the novel online curricula. A total of 65 individuals representing at least 20 ACGME-accredited dermatology programs responded. Many programs implemented a predominantly online curriculum (78%). Most participants reported that both clinical dermatology and dermatopathology were online during the pandemic's peak (90%). Among those who had experienced a live curriculum prior to the pandemic, 49% reported that a virtual curriculum had similar effectiveness, …

Endovascular Treatment And Outcomes For Femoropopliteal In-Stent Restenosis: Insights From The Xlpad Registry, Michael H Vu, Glaiza-Mae Sande-Docor, Yulun Liu, Shirling Tsai, Mitul Patel, Chris Metzger, Mehdi H Shishehbor, Emmanouil S Brilakis, Nicolas W Shammas, Peter Monteleone, Subhash Banerjee

Faculty, Staff and Student Publications

BACKGROUND: There is limited "real-world" evidence examining treatment modalities and outcomes in patients with symptomatic peripheral arterial disease undergoing endovascular treatment of femoropopliteal (FP) in-stent restenosis (ISR).

MATERIALS AND METHODS: We compared outcomes in 2,895 patients from the XLPAD registry (NCT01904851) between 2006 and 2019 treated for FP ISR (

RESULTS: ISR patients were more frequently on antiplatelet (94.5% vs 89.4%,

CONCLUSION: Atherectomy and DCB are more frequently used to treat FP ISR lesions. Patients with FP ISR have more intraprocedural distal embolization, higher repeat revascularization procedures, and lower freedom from MALE at 1 year.

Decontamination Of Geobacillus Stearothermophilus Using The Arca Aerosolized Hydrogen Peroxide Decontamination System, Loren Benjamin Mead, Tanner Mathison, Garry Osborne, Anne Marie Richards

Faculty, Staff and Student Publications

INTRODUCTION: In response to the limited supply of personal protective equipment during the pandemic caused by SARS-CoV-2, recent studies demonstrate that gaseous H2O2 is an effective decontaminant of N95 filtering facepiece respirators to enable reuse of these items in a clinical setting. This paper evaluates the efficacy of the Arca Aerosolized Hydrogen Peroxide Decontamination System (Arca), a novel aerosolized H2O2 decontamination system, using biologic indicator testing.

MATERIALS AND METHODS: The Arca produces and circulates H2O2 aerosol inside of a sealed stainless steel chamber. The Arca's decontamination efficacy was evaluated in 8 decontamination trials with 2 H2O2 concentrations (3% and 12%) …

Evaluation Of Medical Services From The Perspective Of Covid-19 Vaccine Demand Satisfaction In Hangzhou, China, Mingjun Cheng, Yunchen Zhu, Peili Cen, Shan Huang

Faculty, Staff and Student Publications

The outbreak of COVID-19 has had a huge global impact, and it continues to test the resilience of medical services to emergencies worldwide. In the current post-epidemic era, vaccination has become a highly effective strategy to prevent the spread of COVID-19. However, using conventional mathematical models to evaluate the spatial distribution of medical resources, including vaccination, ignore people's behaviors and choices and make simplifications to the real world. In this study, we use an enhanced model based on the Theory of People Behavior (TPB) to perform a macro analysis of the satisfaction ability of medical resources for vaccination in Hangzhou, …

Case Report: Successful Treatment Of Late-Onset Immune Checkpoint Inhibitor-Associated Membranous Nephropathy In A Patient With Advanced Renal Cell Carcinoma, Praveen Ratanasrimetha, Vikas D Reddy, Jaya Kala, Amanda Tchakarov, William F Glass, Pavlos Msaouel, Jamie S Lin

Faculty, Staff and Student Publications

BACKGROUND: Diagnosing immune checkpoint inhibitor (ICI)-associated nephritis can be challenging since it is a rare complication of therapy, associated with a spectrum of immune-mediated pathologies, and can present months after ICI therapy discontinuation (i.e., late-onset). ICIs are increasingly administered in combination with other cancer therapies with associated nephrotoxicity, further obfuscating the diagnosis of ICI-associated nephritis. In this report, we describe the first suspected case of late-onset ICI-associated membranous nephropathy (MN) in a patient with metastatic clear cell renal cell carcinoma (RCC) who had discontinued ICI therapy 6 months prior to presentation. Prompt recognition of the suspected late-onset immune-related adverse event …

Global “Flu-Ization” Of Covid-19: A Perspective From Vietnam, Khoi Quan Nguyen, Le My Anh Nguyen, Andrew W Taylor-Robinson

Faculty, Staff and Student Publications

No abstract provided.

Hispanic Ethnicity And Mortality Among Critically Ill Patients With Covid-19, Ana C Ricardo, Jinsong Chen, Stephanie M Toth-Manikowski, Natalie Meza, Min Joo, Shruti Gupta, Deepa G Lazarous, David E Leaf, James P Lash

Faculty, Staff and Student Publications

BACKGROUND: Hispanic persons living in the United States (U.S.) are at higher risk of infection and death from coronavirus disease 2019 (COVID-19) compared with non-Hispanic persons. Whether this disparity exists among critically ill patients with COVID-19 is unknown.

OBJECTIVE: To evaluate ethnic disparities in mortality among critically ill adults with COVID-19 enrolled in the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID).

METHODS: Multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units (ICU) at 67 U.S. hospitals from March 4 to May 9, 2020. Multilevel logistic regression was used to evaluate …

A T-Cell Engaging Bispecific Antibody With A Tumor-Selective Bivalent Folate Receptor Alpha Binding Arm For The Treatment Of Ovarian Cancer, Brian C Avanzino, Kirthana Prabhakar, Pranjali Dalvi, Sharon Hartstein, Hannes Kehm, Aarti Balasubramani, Andrew A Boudreau, Ben Buelow, Karen Chang, Laura M Davison, Suhasini Iyer, Vidyut Kalwit, Kristin Lewis Wilson, Harbani K Malik-Chaudhry, Will Pierson, Geovanni Pineda, Udaya S Rangaswamy, Sowmya Saiganesh, Ute Schellenberger, Harshad S Ugamraj, Rodolfovan D Yabut, Roland Buelow, Jocelyn Chapman, Nathan D Trinklein, Katherine E Harris

Faculty, Staff and Student Publications

The use of T-cell engagers (TCEs) to treat solid tumors is challenging, and several have been limited by narrow therapeutic windows due to substantial on-target, off-tumor toxicities due to the expression of low levels of target antigens on healthy tissues. Here, we describe TNB-928B, a fully human TCE that has a bivalent binding arm for folate receptor alpha (FRα) to selectively target FRα overexpressing tumor cells while avoiding the lysis of cells with low levels of FRα expression. The bivalent design of the FRα binding arm confers tumor selectivity due to low-affinity but high-avidity binding to high FRα antigen density …

Implementing A Robust Process Improvement Program In The Neonatal Intensive Care Unit To Reduce Harm, Klaus G Nether, Eric J Thomas, Amir Khan, Madelene J Ottosen, Lauren Yager

Faculty, Staff and Student Publications

INTRODUCTION: Preventable harm continues to occur with critically ill neonates despite efforts by hospital neonatal intensive care units (NICUs) to improve processes and reduce harm. Attaining significant and sustainable improvements will require training including leadership support, mentoring, and patient family engagement to improve care processes. This paper describes the implementation of a robust process improvement (RPI) program in the NICU to reduce harm.

METHODS: Leaders, staff, and parents were trained in RPI concepts and tools. Multidisciplinary teams including parent members applied the training and received regular mentorship for their improvement initiatives.

RESULTS: Participants (N = 67) completed pretraining and post-training …

A Message From The Trench: A Day In The Hospital During The Covid-19 Pandemic, Gabriel M Aisenberg

Faculty, Staff and Student Publications

No abstract provided.

Cross-Mentorship: A Unique Lens Into The Realities And Challenges Of Diversity In Surgery., Marina Affi Koprowski, Karen J Dickinson, Crystal N Johnson-Mann, Martha Godfrey, Emilia J Diego, Marie Crandall, Kevin Y. Pei Md, Mhsed

Other Specialties

Mentorship in surgery is a perennial topic of interest, as successful mentoring relationships are associated with improved career satisfaction, academic promotion, research productivity, and overall well-being. While it is true that certain minority groups in surgery find great personal and professional benefit in receiving and providing mentorship among “their own” (ie, a female academic surgeon mentoring a female resident), it is important to recognize that many mentoring relationships, whether intentionally or otherwise, extend across gender, sexuality, generations, race, ethnicity, and other differences. Lived examples of these include an Asian man hailing from the Northeast with no children mentoring a White …

Neuropsychological Outcomes In Individuals With Type 1 And Type 2 Diabetes., Nathaniel M Putnam, Evan L Reynolds, Mousumi Banerjee, Kara Mizokami-Stout, Dana K. Albright Phd, Joyce Lee, Rodica Pop-Busui, Eva L Feldman, Brian C Callaghan

Health Services and Informatics Research

OBJECTIVE: To determine the prevalence of neuropsychological outcomes in individuals with type 1 diabetes compared to individuals with type 2 diabetes or without diabetes, and to evaluate the association of diabetes status and microvascular/macrovascular complications with neuropsychological outcomes.

PATIENTS AND METHODS: We used a nationally representative healthcare claims database of privately insured individuals (1/1/2001-12/31/2018) to identify individuals with type 1 diabetes. Propensity score matching was used as a quasi-randomization technique to match type 1 diabetes individuals to type 2 diabetes individuals and controls. Diabetes status, microvascular/macrovascular complications (retinopathy, neuropathy, nephropathy, stroke, myocardial infarction, peripheral vascular disease, amputations), and neuropsychological outcomes …

Perhaps It Was Too Soon: College Students' Reflections On The Timing Of Their Sexual Debut., Susan Sprecher, Lucia F O'Sullivan, Michelle Drouin, Julie Verette-Lindenbaum, Marion C Willetts

Health Services and Informatics Research

Early sexual debut has been a focus of social scientific research due to its association with adverse circumstances and negative outcomes. However, there has been a recent shift to considering not only chronological age, but also the degree to which the event is viewed to be optimally timed (i.e., the perception that it occurred at the "right time" versus too soon). The purpose of this study was to assess how individual/family background variables and contextual aspects of the experience (including partner and relationship aspects) are associated with both the actual age at sexual debut and the perceived acceptability of the …

The Roles And Contributions Of Certified Transport Registered Nurses In Critical Care Ground Transport Today., Jennifer Esslinger Bsn, Rn, Cfrn, Ctrn, Sue L Parrigin, Amy Grand, Kimberly D Bronow, Jacqueline C Stocking

Nursing Publications, Posters, & Presentations

Registered nurses are core members of critical care ground transport teams because of their education, experience, and scope of practice. Advances in medicine, technology, and equipment, combined with regionalization of specialized care and, most recently, the coronavirus disease 2019 pandemic, necessitate that transport nurses possess specialized knowledge, skills, and abilities. National specialty certification in ground transport nursing via the Certified Transport Registered Nurse (CTRN) offers registered nurses a process to validate their expertise. The most recent transport nursing role delineation study, which was conducted by the Board of Certification for Emergency Nursingin 2019, provided the foundation for the revised CTRN …

Evaluating A Pilot Culturally Sensitive Psychosocial Intervention On Posttraumatic Growth For Chinese American Breast Cancer Survivors, Qiao Chu, Moni Tang, Lingjun Chen, Lucy Young, Alice Loh, Carol Wang, Qian Lu

Faculty, Staff and Student Publications

This study investigated the potential benefit of a pilot culturally sensitive group support intervention, named Joy Luck Academy (JLA), in fostering posttraumatic growth among Chinese American breast cancer survivors. Eighty-six Chinese American breast cancer survivors participated in an eight-week single-arm pre-/post-test trial of an intervention program, which included educational lectures and peer mentor support. The JLA participants were compared with an independent sample of 109 Chinese American breast cancer survivors who went through routine care. Both groups completed baseline and eight-week follow-up assessments of the five facets of posttraumatic growth (meaningful interpersonal relationships, finding new possibilities in life, personal strength, …

Multiagent Chemotherapy And Stereotactic Body Radiation Therapy In Patients With Unresectable Pancreatic Adenocarcinoma: A Prospective Nonrandomized Controlled Trial, Colin S Hill, Lauren Rosati, Hao Wang, Hua-Ling Tsai, Jin He, Amy Hacker-Prietz, Daniel A Laheru, Lei Zheng, Shuchi Sehgal, Vincent Bernard, Dung T Le, Timothy M Pawlik, Matthew J Weiss, Amol K Narang, Joseph M Herman

Faculty, Staff and Student Publications

PURPOSE: In a prospective multicenter study, gemcitabine monotherapy followed by stereotactic body radiation therapy (SBRT) was well tolerated with outcomes comparable to chemoradiation for locally advanced pancreatic cancer (LAPC). Recent trials have reported improved survival with multiagent chemotherapy (MA-CTX) alone. This prospective trial explored whether SBRT could be safely delivered after MA-CTX. Herein, we report the long-term outcomes of adding SBRT after MA-CTX in LAPC patients and evaluate whether genetic profiles of specimens obtained before SBRT influence outcomes.

METHODS AND MATERIALS: This prospective nonrandomized controlled phase 2 trial enrolled 44 LAPC and 4 locally recurrent patients after multidisciplinary evaluation between …

Re-Thinking Therapeutic Development For Cns Metastatic Disease, Chantal Saberian, Michael A Davies

Faculty, Staff and Student Publications

There has been unprecedented progress in the development of systemic therapies for patients with metastatic melanoma over the last decade. There is now tremendous potential and momentum to further and markedly reduce the impact of this disease. However, developing more effective treatments for metastases to the CNS remains a critical challenge for patients with melanoma. Melanoma patients with active CNS metastases have largely been excluded from both early-phase and registration trials for all currently approved targeted and immune therapies for this disease. While this exclusion has generally been justified in clinical research due to concerns about poor prognosis, lack of …