Unique transcriptional signatures correlate with behavioral and psychological symptom domains in Alzheimer's disease.

Despite the significant burden, cost, and worse prognosis of Alzheimer's disease (AD) with behavioral and psychological symptoms of dementia (BPSD), little is known about the molecular causes of these symptoms. Using antemortem assessments of BPSD in AD, we demonstrate that individual BPSD can be grouped into 4 domain factors in our cohort: affective, apathy, agitation, and psychosis. Then, we performed a transcriptome-wide analysis for each domain utilizing bulk RNA-seq of post-mortem anterior cingulate cortex (ACC) tissues. Though all 4 domains are associated with a predominantly downregulated pattern of hundreds of differentially expressed genes (DEGs), most DEGs are unique to each domain, with only 22 DEGs being common to all BPSD domains, including TIMP1. Weighted gene co-expression network analysis (WGCNA) yielded multiple transcriptional modules that were shared between BPSD domains or unique to each domain, and NetDecoder was used to analyze context-dependent information flow through the biological network. For the agitation domain, we found that all DEGs and a highly associated transcriptional module were functionally enriched for ECM-related genes including TIMP1, TAGLN, and FLNA. Another unique transcriptional module also associated with the agitation domain was enriched with genes involved in post-synaptic signaling, including DRD1, PDE1B, CAMK4, and GABRA4. By comparing context-dependent changes in DEGs between cases and control networks, ESR1 and PARK2 were implicated as two high-impact genes associated with agitation that mediated significant information flow through the biological network. Overall, our work establishes unique targets for future study of the biological mechanisms of BPSD and resultant drug development.

Clinical features of neurotoxicity after CD19 CAR T-cell therapy in mantle cell lymphoma.

ABSTRACT: CD19 chimeric antigen receptor (CAR) T-cell therapy has proven highly effective for treating relapsed/refractory mantle cell lymphoma (MCL). However, immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant concern. This study aimed to evaluate the clinical, radiological, and laboratory correlatives associated with ICANS development after CD19 CAR T-cell therapy in patients with MCL. All patients (N = 26) who received standard-of-care brexucabtagene autoleucel until July 2022 at our institution were evaluated. Laboratory and radiographic correlatives including brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) were evaluated to determine the clinical impact of ICANS. Seventeen (65%) patients experienced ICANS after treatment, with a median onset on day 6. Ten (38%) patients experienced severe (grade ≥3) ICANS. All patients with ICANS had antecedent cytokine release syndrome (CRS), but no correlation was observed between ICANS severity and CRS grade. Overall, 92% of EEGs revealed interictal changes; no patients experienced frank seizures because of ICANS. In total, 86% of patients with severe ICANS with postinfusion brain MRIs demonstrated acute neuroimaging findings not seen on pretreatment MRI. Severe ICANS was also associated with higher rates of cytopenia, coagulopathy, increased cumulative steroid exposure, and prolonged hospitalization. However, severe ICANS did not affect treatment outcomes of patients with MCL. Severe ICANS is frequently associated with a range of postinfusion brain MRI changes and abnormal EEG findings. Longer hospitalization was observed in patients with severe ICANS, especially those with abnormal acute MRI or EEG findings, but there was no discernible impact on overall treatment response and survival.

Behavioral and Molecular Characterization of Prenatal Stress Effects on the C57BL/6J Genetic Background for the Study of Autism Spectrum Disorder.

Stress-inducing events during pregnancy are associated with aberrant neurodevelopment resulting in adverse psychiatric outcomes, including autism spectrum disorder (ASD). While numerous preclinical models for the study of ASD are frequently generated using C57BL/6J mice, few studies have investigated the effects of prenatal stress on this genetic background. In the current manuscript, we stressed C57BL/6 dams during gestation and examined numerous behavioral and molecular endophenotypes in the adult male and female offspring to characterize the resultant phenotype as compared with offspring born from nonstressed (NS) dams. Adult mice born from prenatal restraint stressed (PRS) dams demonstrated reduced sociability and reciprocal social interaction along with increased marble burying behaviors relative to mice born from nonstressed control dams. Differential expression of genes related to excitatory and inhibitory neurotransmission was evaluated in the medial prefrontal cortex, amygdala, hippocampus, nucleus accumbens and caudate putamen via qRT-PCR. The male PRS mouse behavioral phenotype coincided with aberrant expression of glutamate and GABA marker genes (e.g., Grin1, Grin2b, Gls, Gat1, Reln) in neural substrates of social behavior. Rescue of the male PRS sociability deficit by a known antipsychotic with epigenetic properties (i.e., clozapine (5 mg/kg) + 18 hr washout) indicated possible epigenetic regulation of genes that govern sociability. Clozapine treatment increased the expression levels of genes involved in DNA methylation, histone methylation, and histone acetylation in the nucleus accumbens. Identification of etiology-specific mechanisms underlying clinically relevant behavioral phenotypes may ultimately provide novel therapeutic interventions for the treatment of psychiatric disorders including ASD.

Distinguishing features of depression in dementia from primary psychiatric disease.

Depression is a common and devastating neuropsychiatric symptom in the elderly and in patients with dementia. In particular, nearly 80% of patients with Alzheimer's Disease dementia experience depression during disease development and progression. However, it is unknown whether the depression in patients with dementia shares the same molecular mechanisms as depression presenting as primary psychiatric disease or occurs and persists through alternative mechanisms. In this review, we discuss how the clinical presentation and treatment differ between depression in dementia and as a primary psychiatric disease, with a focus on major depressive disorder. Then, we hypothesize several molecular mechanisms that may be unique to depression in dementia such as neuropathological changes, inflammation, and vascular events. Finally, we discuss existing issues and future directions for investigation and treatment of depression in dementia.

Characterization of apathy-like behaviors in the 5xFAD mouse model of Alzheimer's disease.

Most patients with Alzheimer's disease (AD) develop neuropsychiatric symptoms (NPS) alongside cognitive decline, and apathy is one of the most common symptoms. Few preclinical studies have investigated the biological substrates underlying NPS in AD. In this study, we used a cross-sectional design to characterize apathy-like behaviors and assess memory in 5xFAD and wildtype control mice at 6, 12, and 16 months of age. Nest building, burrowing, and marble burying were used to test representative behaviors of apathy, and a composite score of apathy-like behavior was generated from these assays. Soluble Aß42 and plaques were quantified in the prefrontal cortex and hippocampus of the 5xFAD mice with the highest and lowest composite scores using ELISA and histology. Results suggest that 5xFAD mice develop significant apathy-like behaviors starting at 6 months of age that worsen with aging and are positively correlated with soluble Aß42 and plaques in the prefrontal cortex and hippocampus. Our findings highlight the utility of studying NPS in mouse models of AD to uncover important relationships with underlying neuropathology.

Seeking the Amygdala: Novel Use of Diffusion Tensor Imaging to Delineate the Basolateral Amygdala.

The amygdaloid complex, including the basolateral nucleus (BLA), contributes crucially to emotional and cognitive brain functions, and is a major target of research in both humans and rodents. However, delineating structural amygdala plasticity in both normal and disease-related contexts using neuroimaging has been hampered by the difficulty of unequivocally identifying the boundaries of the BLA. This challenge is a result of the poor contrast between BLA and the surrounding gray matter, including other amygdala nuclei. Here, we describe a novel diffusion tensor imaging (DTI) approach to enhance contrast, enabling the optimal identification of BLA in the rodent brain from magnetic resonance (MR) images. We employed this methodology together with a slice-shifting approach to accurately measure BLA volumes. We then validated the results by direct comparison to both histological and cellular-identity (parvalbumin)-based conventional techniques for defining BLA in the same brains used for MRI. We also confirmed BLA connectivity targets using DTI-based tractography. The novel approach enables the accurate and reliable delineation of BLA. Because this nucleus is involved in and changed by developmental, degenerative and adaptive processes, the instruments provided here should be highly useful to a broad range of neuroimaging studies. Finally, the principles used here are readily applicable to numerous brain regions and across species.

Unique Transcriptional Signatures Correlate with Behavioral and Psychological Symptom Domains in Alzheimer's Disease.

Despite the significant burden, cost, and worse prognosis of Alzheimer's disease (AD) with behavioral and psychological symptoms of dementia (BPSD), little is known about the molecular causes of these symptoms. Using antemortem assessments of BPSD in AD, we demonstrate that individual BPSD can be grouped into 4 domain factors in our sample: affective, apathy, agitation, and psychosis. Then, we performed a transcriptome-wide analysis for each domain utilizing bulk RNA-seq of post-mortem anterior cingulate cortex (ACC) tissue. Though all 4 domains are associated with a predominantly downregulated pattern of hundreds of differentially expressed genes (DEGs), most DEGs are unique to each domain, with only 22 DEGs being common to all BPSD domains, including TIMP1. Weighted gene co-expression network analysis (WGCNA) yielded multiple transcriptional modules that were shared between BPSD domains or unique to each domain, and NetDecoder was used to analyze context-dependent information flow through the biological network. For the agitation domain, we found that all DEGs and a highly correlated transcriptional module were functionally enriched for ECM-related genes including TIMP1, TAGLN, and FLNA. Another unique transcriptional module also associated with the agitation domain was enriched with genes involved in post-synaptic signaling, including DRD1, PDE1B, CAMK4, and GABRA4. By comparing context-dependent changes in DEGs between cases and control networks, ESR1 and PARK2 were implicated as two high impact genes associated with agitation that mediated significant information flow through the biological network. Overall, our work establishes unique targets for future study of the biological mechanisms of BPSD and resultant drug development.

Biomarker panel increases accuracy for identification of an MS relapse beyond sNfL.

BACKGROUND: For relapsing-remitting multiple sclerosis (RRMS), there is a need for biomarker development beyond clinical manifestations and MRI. Soluble neurofilament light chain (sNfL) has emerged as a biomarker for inflammatory activity in RRMS. However, there are limitations to the accuracy of sNfL in identifying relapses. Here, we sought to identify a panel of biomarkers that would increase the precision of distinguishing patients in relapse compared to sNfL alone. METHODS: We used a multiplex approach to measure levels of 724 blood proteins in two distinct RRMS cohorts. Multiple t-tests with covariate correction determined biomarkers that were differentially regulated in relapse and remission. Logistic regression models determined the accuracy of biomarkers to distinguish relapses from remission. RESULTS: The discovery cohort identified 37 proteins differentially abundant in active RRMS relapse compared to remission. The verification cohort confirmed four proteins, including sNfL, were altered in active RRMS relapse compared to remission. Logistic regression showed that the 4-protein panel identified active relapse with higher accuracy (AUC = 0.87) than sNfL alone (AUC = 0.69). CONCLUSION: Our studies confirmed that sNfL is elevated during relapses in RRMS patients. Furthermore, we identified three other blood proteins, uPA, hK8 and DSG3 that were altered during relapse. Together, these four biomarkers could be used to monitor disease activity in RRMS patients.

KIR+CD8+ T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19.

In this work, we find that CD8+ T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49+CD8+ regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8+ T cells efficiently eliminated pathogenic gliadin-specific CD4+ T cells from the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis. Selective ablation of Ly49+CD8+ T cells in virus-infected mice led to autoimmunity after infection. Our results indicate that in both species, these regulatory CD8+ T cells act specifically to suppress pathogenic T cells in autoimmune and infectious diseases.

Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM.

Multiple sclerosis (MS) is a heterogenous autoimmune disease in which autoreactive lymphocytes attack the myelin sheath of the central nervous system. B lymphocytes in the cerebrospinal fluid (CSF) of patients with MS contribute to inflammation and secrete oligoclonal immunoglobulins1,2. Epstein-Barr virus (EBV) infection has been epidemiologically linked to MS, but its pathological role remains unclear3. Here we demonstrate high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM) and provide structural and in vivo functional evidence for its relevance. A cross-reactive CSF-derived antibody was initially identified by single-cell sequencing of the paired-chain B cell repertoire of MS blood and CSF, followed by protein microarray-based testing of recombinantly expressed CSF-derived antibodies against MS-associated viruses. Sequence analysis, affinity measurements and the crystal structure of the EBNA1-peptide epitope in complex with the autoreactive Fab fragment enabled tracking of the development of the naive EBNA1-restricted antibody to a mature EBNA1-GlialCAM cross-reactive antibody. Molecular mimicry is facilitated by a post-translational modification of GlialCAM. EBNA1 immunization exacerbates disease in a mouse model of MS, and anti-EBNA1 and anti-GlialCAM antibodies are prevalent in patients with MS. Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.

Considerations about risk of ongoing distress: what can we learn from repeat screening?

The importance of routine distress screening in cancer patients is widely acknowledged, though non-compliance with screening protocols is common. Cited reasons for non-adherence include lack of time and expertise and concerns about the resources associated with the identification and management of clinically relevant distress. This commentary examines changes in distress among people with cancer who participated in a tele-based psychosocial intervention, from the point of initial distress screening to 12 months after commencing the intervention. The goal is to contribute to the discussion about the potential infrastructure requirements of implementing screening programs among screening 'hesitant' cancer care services. Secondary analysis showed a general downward distress trajectory though the greatest reduction occurred between recruitment and baseline and before receiving a low-intensity psychosocial intervention (ß = - 1.84, 95% CI - 2.12, - 1.56). While acknowledging transience of distress in some patients, our results support the possible therapeutic benefit of assessing and validating individuals' distress in the hope of preventing the development of more overt health problems associated with undiagnosed and untreated symptoms.

Consensus Curriculum for Fellowship Training in Multiple Sclerosis and Neuroimmunology.

Management of multiple sclerosis and neuroimmunologic disorders has become increasingly complex because of the expanding number of recognized neuroimmune disorders, increased number of therapeutic options, and multidisciplinary care management needs of people with multiple sclerosis and neuroimmunologic disorders. More subspecialists are needed to optimize care of these patients, and many fellowship programs have been created or expanded to increase the subspecialty workforce. Consequently, defining the scope and standardizing fellowship training is essential to ensure that trainees receive high-quality training. A workgroup was created to develop a consensus fellowship curriculum to serve as a resource for all current and future training programs. This curriculum may also serve as a basis for future accreditation efforts.

Evolving knowledge of the unmet needs in dry eye disease.

Dry eye disease is a common but underdiagnosed disorder in the United States, and its prevalence is likely to increase as the nation's population ages. Although still regarded as little more than a nuisance by many clinicians and payers alike, dry eye disease is known to have both clinical consequences for ocular health and effects on vision-related quality of life in many people, impairing their ability to function well in vocational and social settings. Pharmaceutical treatments consist mainly of over-the-counter ocular lubricants ("artificial tears") and a few prescription drugs that address the inflammatory component of dry eye disease through immunomodulation and/or inhibition of T-cell activity. In September 2020, Oyster Point Pharma, Inc (Oyster Point Pharma), convened a panel-consisting of 7 managed care executives with experience in management of dry eye disease treatments and 2 eye care practitioners with expertise in dry eye disease-to discuss how the growth of knowledge about dry eye disease in the past 2 decades has altered their thinking about and approach to dry eye disease, as well as how they would like to see the field advance. They pointed to an existing unmet need in knowledge and therapeutics that can address the underlying causes of dry eye disease. Oyster Point Pharma supported the authorship of this article; the authors were members of the panel, and all panelists were compensated by Oyster Point Pharma. This article provides an overview of dry eye disease and summarizes the panel discussion.

Human KIR + CD8 + T cells target pathogenic T cells in Celiac disease and are active in autoimmune diseases and COVID-19.

Previous reports show that Ly49 + CD8 + T cells can suppress autoimmunity in mouse models of autoimmune diseases. Here we find a markedly increased frequency of CD8 + T cells expressing inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalent of the Ly49 family, in the blood and inflamed tissues of various autoimmune diseases. Moreover, KIR + CD8 + T cells can efficiently eliminate pathogenic gliadin-specific CD4 + T cells from Celiac disease (CeD) patients' leukocytes in vitro . Furthermore, we observe elevated levels of KIR + CD8 + T cells, but not CD4 + regulatory T cells, in COVID-19 and influenza-infected patients, and this correlates with disease severity and vasculitis in COVID-19. Expanded KIR + CD8 + T cells from these different diseases display shared phenotypes and similar T cell receptor sequences. These results characterize a regulatory CD8 + T cell subset in humans, broadly active in both autoimmune and infectious diseases, which we hypothesize functions to control self-reactive or otherwise pathogenic T cells. ONE-SENTENCE SUMMARY: Here we identified KIR + CD8 + T cells as a regulatory CD8 + T cell subset in humans that suppresses self-reactive or otherwise pathogenic CD4 + T cells.

An International Standardized Magnetic Resonance Imaging Protocol for Diagnosis and Follow-up of Patients with Multiple Sclerosis: Advocacy, Dissemination, and Implementation Strategies.

Standardized magnetic resonance imaging (MRI) protocols are important for the diagnosis and monitoring of patients with multiple sclerosis (MS). The Consortium of Multiple Sclerosis Centers (CMSC) convened an international panel of MRI experts to review and update the current guidelines. The objective was to update the standardized MRI protocol and clinical guidelines for diagnosis and follow-up of MS and develop strategies for advocacy, dissemination, and implementation. Conference attendees included neurologists, radiologists, technologists, and imaging scientists with expertise in MS. Representatives from the CMSC, Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, US Department of Veteran Affairs, National Multiple Sclerosis Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis companies were present. Before the meeting, CMSC members were surveyed about standardized MRI protocols, gadolinium use, need for diffusion-weighted imaging, and the central vein sign. The panel worked to make the CMSC and MAGNIMS MRI protocols similar so that the updated guidelines could ultimately be accepted by international consensus. Advocacy efforts will promote the importance of standardized MS MRI protocols. Dissemination will include publications, meeting abstracts, educational programming, webinars, "meet the expert" teleconferences, and examination cards. Implementation will require comprehensive and coordinated efforts to make the protocol easy to access and use. The ultimate vision, and goal, is for the guidelines to be universally useful, usable, and used as the standard of care for patients with MS.

Tandospirone, a Partial 5-HT1A Receptor Agonist, Administered Systemically or Into Anterior Cingulate Attenuates Repetitive Behaviors in Shank3B Mice.

BACKGROUND: Several cases of autism spectrum disorder have been linked to mutations in the SHANK3 gene. Haploinsufficiency of the SHANK3 gene contributes to Phelan-McDermid syndrome, which often presents an autism spectrum disorder phenotype along with moderate to severe intellectual disability. A SHANK3 gene deletion in mice results in elevated excitation of cortical pyramidal neurons that alters signaling to other brain areas. Serotonin 1A receptors are highly expressed on layer 2 cortical neurons and are known to have inhibitory actions. Serotonin 1A receptor agonist treatment in autistic cases with SHANK3 mutations and possibly other cases may restore excitatory and inhibitory balance that attenuates core symptoms. METHODS: A series of experiments investigated the effects of acute tandospirone treatment on spatial learning and self-grooming, subchronic treatment of tandospirone on self-grooming behavior, and the effect of tandospirone infusion into the anterior cingulate on self-grooming behavior. RESULTS: Only male Shank3B+/- mice exhibited a spatial learning deficit and elevated self-grooming. Acute i.p. injection of tandospirone, 0.01 and 0.06 mg/kg in male Shank3B+/- mice, attenuated a spatial acquisition deficit by improving sensitivity to positive reinforcement and reduced elevated self-grooming behavior. Repeated tandospirone (0.06 mg/kg) treatment attenuated elevated self-grooming behavior in male Shank3B+/- mice. Tandospirone injected into the anterior cingulate/premotor area reduced self-grooming behavior in male Shank3B+/- mice. CONCLUSIONS: These results suggest that stimulation of cortical serotonin 1A receptors may reduce repetitive behaviors and cognitive impairments as observed in autism spectrum disorder, possibly by attenuating an excitation/inhibition imbalance. Further, tandospirone may serve as a treatment in autism spectrum disorder and other disorders associated with SHANK3 mutations.

Repopulation of T, B, and NK cells following alemtuzumab treatment in relapsing-remitting multiple sclerosis.

OBJECTIVE: To characterize long-term repopulation of peripheral immune cells following alemtuzumab-induced lymphopenia in relapsing-remitting MS (RRMS), with a focus on regulatory cell types, and to explore associations with clinical outcome measures. METHODS: The project was designed as a multicenter add-on longitudinal mechanistic study for RRMS patients enrolled in CARE-MS II, CARE-MS II extension at the University of Southern California and Stanford University, and an investigator-initiated study conducted at the Universities of British Columbia and Chicago. Methods involved collection of blood at baseline, prior to alemtuzumab administration, and at months 5, 11, 17, 23, 36, and 48 post-treatment. T cell, B cell, and natural killer (NK) cell subsets, chemokine receptor expression in T cells, in vitro cytokine secretion patterns, and regulatory T cell (Treg) function were assessed. Clinical outcomes, including expanded disability status score (EDSS), relapses, conventional magnetic resonance imaging (MRI) measures, and incidents of secondary autoimmunity were tracked. RESULTS: Variable shifts in lymphocyte populations occurred over time in favor of CD4+ T cells, B cells, and NK cells with surface phenotypes characteristic of regulatory subsets, accompanied by reduced ratios of effector to regulatory cell types. Evidence of increased Treg competence was observed after each treatment course. CD4+ and CD8+ T cells that express CXCR3 and CCR5 and CD8+ T cells that express CDR3 and CCR4 were also enriched after treatment, indicating heightened trafficking potential in activated T cells. Patterns of repopulation were not associated with measures of clinical efficacy or secondary autoimmunity, but exploratory analyses using a random generalized estimating equation (GEE) Poisson model provide preliminary evidence of associations between pro-inflammatory cell types and increased risk for gadolinium (Gd+) enhancing lesions, while regulatory subsets were associated with reduced risk. In addition, the risk for T2 lesions correlated with increases in CD3+CD8+CXCR3+ cells. CONCLUSIONS: Lymphocyte repopulation after alemtuzumab treatment favors regulatory subsets in the T cell, B cell, and NK cell compartments. Clinical efficacy may reflect the sum of interactions among them, leading to control of potentially pathogenic effector cell types. Several immune measures were identified as possible biomarkers of lesion activity. Future studies are necessary to more precisely define regulatory and effector subsets and their contributions to clinical efficacy and risk for secondary autoimmunity in alemtuzumab-treated patients, and to reveal new insights into mechanisms of immunopathogenesis in MS. TRIAL REGISTRATION: Parent trials for this study are registered with ClinicalTrials.gov: CARE-MS II: NCT00548405, CARE-MS II extension: NCT00930553 and ISS: NCT01307332.

Prostate cancer survivorship priorities for men and their partners: Delphi consensus from a nurse specialist cohort.

AIMS & OBJECTIVES: To describe the prostate cancer survivorship experience and priorities from the perspective of prostate cancer specialist nurses. BACKGROUND: Specialist nurses are providing long-term survivorship care to men and their partners however, few prostate cancer survivorship interventions are effective and priorities for nurse-led survivorship care are poorly understood. DESIGN: A three-round modified Delphi approach. METHODS: The study was conducted between 1 December 2018 and 28 February 2019 to develop a consensus view from an expert nurse cohort (43 prostate cancer specialist nurses: 90% response). First, participants described men's prostate cancer survivorship experience and priorities for improving care for men and partners. In subsequent rounds, participants identified key descriptors of the survivorship experience; rated priorities for importance and feasibility; and identified a top priority action for men and for partners. Thematic analysis and descriptive statistics were applied. Guidelines for Reporting Reliability and Agreement Studies informed the conduct of the study. RESULTS: Prostate cancer specialist nurses characterised the prostate cancer survivorship experience of men as under-resourced, disjointed and distressing. In all, 11 survivorship priorities for men and three for partners were identified within five broad areas: capacity building; care coordination; physical and psychosocial care; community awareness and early detection; and palliative care. However, feasibility for individual items was frequently described as low. CONCLUSION: Internationally, prostate cancer survivorship care for men and their partners requires urgent action to meet future need and address gaps in capacity and care coordination. Low feasibility of survivorship priorities may reflect translational challenges related to capacity. Prostate cancer survivorship care guidelines connected to practice priorities are urgently needed. RELEVANCE TO CLINICAL PRACTICE: These findings address key gaps in the evidence for developing national nurse-led prostate cancer survivorship priorities. These priorities can be used to inform survivorship guidelines including nursing care for men with prostate cancer and their partners.