A service-oriented approach to clinical trial recruitment for dementia and brain health: Methods and case examples of MyAlliance for Brain Health.

INTRODUCTION: Recruitment of sufficient and diverse participants into clinical research for Alzheimer's disease and related dementias remains a formidable challenge. The primary goal of this manuscript is to provide an overview of an approach to diversifying research recruitment and to provide case examples of several methods for achieving greater diversity in clinical research enrollment. METHODS: The University of Kansas Alzheimer's Disease Research Center (KU ADRC) developed MyAlliance for Brain Health (MyAlliance), a service-oriented recruitment model. MyAlliance comprises a Primary Care Provider Network, a Patient and Family Network, and a Community Organization Network, each delivering tailored value to relevant parties while facilitating research referrals. RESULTS: We review three methods for encouraging increased diversity in clinical research participation. Initial outcomes reveal an increase in underrepresented participants from 17% to 27% in a research registry. Enrollments into studies supported by the research registry experienced a 51% increase in proportion of participants from underrepresented communities. DISCUSSION: MyAlliance shifts power, resources, and knowledge to community advocates, promoting brain health awareness and research participation, and demands substantial financial investment and administrative commitment. MyAlliance offers valuable lessons for building sustainable, community-centered research recruitment infrastructure, emphasizing the importance of localized engagement and cultural understanding. Highlights: MyAlliance led to a significant increase in the representation of underrepresented racial and ethnic groups and individuals from rural areas.The service-oriented approach facilitated long-term community engagement and trust-building, extending partnerships between an academic medical center and community organizations.While effective, MyAlliance required substantial financial investment, with costs including infrastructure development, staff support, partner organization compensation, and promotional activities, underscoring the resource-intensive nature of inclusive research recruitment efforts.

Detection of early-stage NASH using non-invasive hyperpolarized 13C metabolic imaging.

Non-alcoholic steatohepatitis (NASH) is characterized from its early stages by a profound remodeling of the liver microenvironment, encompassing changes in the composition and activities of multiple cell types and associated gene expression patterns. Hyperpolarized (HP) 13C MRI provides a unique view of the metabolic microenvironment, with potential relevance for early diagnosis of liver disease. Previous studies have detected changes in HP 13C pyruvate to lactate conversion, catalyzed by lactate dehydrogenase (LDH), with experimental liver injury. HP ∝ -ketobutyrate ( ∝ KB) is a close molecular analog of pyruvate with modified specificity for LDH isoforms, specifically attenuated activity with their LDHA-expressed subunits that dominate liver parenchyma. Building on recent results with pyruvate, we investigated HP ∝ KB in methionine-choline deficient (MCD) diet as a model of early-stage NASH. Similarity of results between this new agent and pyruvate (~ 50% drop in cytoplasmic reducing capacity), interpreted together with gene expression data from the model, suggests that changes are mediated through broad effects on intermediary metabolism. Plausible mechanisms are depletion of the lactate pool by upregulation of gluconeogenesis (GNG) and pentose phosphate pathway (PPP) flux, and a possible shift toward increased lactate oxidation. These changes may reflect high levels of oxidative stress and/or shifting macrophage populations in NASH.

An exploratory study of service user and clinical outcomes in telehealth-delivered dialectical behavior therapy for adolescents skills groups.

The COVID-19 pandemic led many in-office therapeutic programs to pivot to virtual programming without empirical data supporting the acceptability and efficacy of the remote-delivered adaptations. These adaptations were essential for continuing care and addressing surging youth psychological problems at the time. To serve adolescents with comorbid psychiatric disorders and associated problems (e.g., emotion dysregulation), we adapted and implemented virtual and hybrid formats of a dialectical behavior therapy for adolescents (DBT-A; Rathus & Miller, 2015) program within a public university training clinic, such as separating the traditional multifamily group into adolescent-only and caregiver-only groups. Building on qualitative reports on virtual DBT-A, we explored preliminary service user and clinical outcomes of the virtual and hybrid DBT-A adolescent skills group component in a longitudinal retrospective cohort study for teenagers treated during the first 2 years of the pandemic (N = 21; 81% Hispanic/Latinx; 100% White). Aim 1 described service user outcomes (e.g., retention, group cohesion, client satisfaction) in the remote-delivered skills groups. Most youth completed treatment. Caregiver satisfaction was high, whereas adolescent satisfaction was mild. Aim 2 explored preliminary clinical outcomes of remote-delivered skills group adaptations. Overall anxiety, panic, and two emotion regulation facets (i.e., emotional awareness; goal pursuit when upset) significantly reduced across treatment. There were no significant reductions in depression. No suicide attempts or suicides occurred during the program. Further work is needed to clarify the efficacy of telehealth formats of DBT-A skills groups in larger, more racially diverse samples and to identify which adolescents are most appropriate for virtual and/or hybrid DBT-A. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Using Focus Groups to Explore Older Black Men's Perception of Dietary Interventions.

Older Black men are underrepresented in research despite being disproportionately affected by Alzheimer's disease (AD) and cardiovascular (CV) risk factors related to AD compared with non-Hispanic Whites. Although dietary interventions have shown promise to reduce modifiable CV risk factors related to AD, Black Americans have lower adherence likely due to lack of cultural considerations. Using a noninterventional convergent parallel mixed-methods approach, this study examined the cultural contexts that inform perceptions of dietary interventions among older Midwestern Black men. All participants completed an online demographic and dietary habit survey prior to focus group discussions. Two focus group discussion sessions were conducted with a total of 10 cognitively normal Black men aged 55 years and older. Survey data were analyzed using a frequency analysis and qualitative data were analyzed using a six-step thematic analysis process. Most men indicated having hypertension (N = 7, 77.8%) and currently not following a dietary eating pattern (N = 8, 88.9%). Emerging themes identified included (1) knowledge of dementia, (2) perceptions of dietary interventions, (3) barriers impacting participation in dietary interventions, and (4) overcoming barriers to engage Black men in dietary interventions. Findings from this study should inform the design of future dietary interventions for AD prevention to enhance participation among older Black men.

Hyperpolarized 15N caffeine, a potential probe of liver function and perfusion.

PURPOSE: To demonstrate hyperpolarization of 15N-caffeine and report exploratory findings as a potential probe of liver function and perfusion. METHODS: An amorphous formulation of [1,3-15N2]caffeine was developed for hyperpolarization via dissolution dynamic nuclear polarization. Polarizer hardware was augmented to support monitoring of solid-state 15N MR signals during the buildup of hyperpolarization. Liquid state hyperpolarized 15N MR signals were obtained in a preclinical 3T magnet by interfacing an external spectrometer console with home-built RF surface coils. 15N signal decay constants were estimated in H2O and in vivo in liver and brain regions of rats at 3 T. Decays were also measured at 9.4 T to assess the effect of B0, and in the presence of albumin to assess the impact of protein binding. RESULTS: Polarization levels of 3.5% and aqueous T1 relaxation times of nearly 200 s were attained for both N1 and N3 positions at 3 T. Shorter apparent decay constants were observed in vivo, ranging from 25 s to 43 s, with modest extensions possible by exploiting competitive binding of iophenoxate with plasma albumin. Downstream products of caffeine could not be detected on in vivo 15N-MR spectra of the liver region, even with metabolic stimulation by ß $$ \beta $$ -naphthoflavone treatment. Considering the high perfusion rate of brain, persistence of caffeine signal in this region is consistent with potential value as a perfusion imaging agent. CONCLUSION: These results establish the feasibility of hyperpolarization of hyperpolarized 15N-caffeine, but further work is necessary to establish the role of this new agent to probe liver metabolism and perfusion.

A vendor-neutral EPI sequence for hyperpolarized 13C MRI.

PURPOSE: To develop a flexible, vendor-neutral EPI sequence for hyperpolarized 13C metabolic imaging. METHODS: An open-source EPI sequence consisting of a metabolite-specific spectral-spatial RF excitation pulse and a customizable EPI readout was created using the Pulseq framework. To explore the flexibility of our sequence, we tested several versions of the sequence including a symmetric 3D readout with different spatial resolutions for each metabolite (1.0 cm3 and 1.5 cm3). A multichamber phantom constructed with a Shepp-Logan geometry, containing two chambers filled with either natural abundance 13C compounds or hyperpolarized (HP) [1-13C]pyruvate, was used to test each sequence. For experiments involving HP [1-13C]pyruvate, a single chamber was prefilled with nicotinamide adenine dinucleotide hydride and lactate dehydrogenase to facilitate the conversion of [1-13C]pyruvate to [1-13C]lactate. All experiments were performed on a Siemens Prisma 3T scanner. RESULTS: All the sequence variations localized natural-abundance 13C ethylene glycol and methanol to the appropriate compartment of the multichamber phantom. [1-13C]pyruvate was detectable in both chambers following the injection of HP [1-13C]pyruvate, whereas [1-13C]lactate was only found in the chamber containing nicotinamide adenine dinucleotide hydride and lactate dehydrogenase. The conversion rate from [1-13C]pyruvate to [1-13C]lactate (kPL) was 0.01 s-1 (95% confidence interval [0.00, 0.02]). CONCLUSION: We have developed and tested a vendor-neutral EPI sequence for imaging HP 13C agents. We have made all of our sequence creation and image reconstruction code freely available online for other investigators to use.

Abbreviated Dialectical Behavior Therapy Virtual Skills Group for Caregivers of Adolescents: An Exploratory Study of Service User and Clinical Outcomes.

Prior work emphasizes involving caregivers in youth mental health services. To support youth with emotion dysregulation, dialectical behavior therapy for adolescents (DBT-A) includes a multi-family skills group, wherein adolescents and caregivers learn skills together. However, limited work has examined the impact of caregiver involvement within DBT-A. The current study examines outcomes of two caregiver-only DBT-A skills groups adapted for abbreviated telehealth delivery. We report on caregivers' (N = 11, 100% mothers, 55% Hispanic) service user outcomes (e.g. self-efficacy at skill usage, group cohesion, therapeutic alliance) and clinical outcomes (i.e. their own emotion functioning, criticism, responses to their adolescent's negative emotions). Results indicate caregiver-only groups were feasible and acceptable, and suggest preliminary efficacy, including improvements in caregiver emotion functioning, distress during interactions with their adolescents, and adolescent-reported criticism. Caregivers also reported reductions in unsupportive responses with their adolescents. Overall, while we caution interpretation due to a small sample size, findings support the preliminary feasibility and efficacy of modifying caregiver participation in DBT-A to be less time-consuming and administered via telehealth.

A retrospective analysis of serious adverse events and deaths in U.S.-based lifestyle clinical trials for cognitive health.

Objective: This retrospective analysis examined serious adverse events (SAEs) and deaths in U.S. lifestyle clinical trials aimed at enhancing cognitive health in older adults. Methods: Data was gathered from trials completed between January 1, 2000, and July 19, 2023, via ClinicalTrials.gov's API. Results: Among these trials, 76% did not report results. The remaining studies fell into four intervention categories: Cognitive/Behavioral, Exercise/Movement, Diet/Supplement, and Multi-modal. When considering all trial types collectively, the findings suggest that lifestyle clinical trials are generally safe. There was no significant increase in the relative risk of experiencing an SAE in the intervention group compared to the control group. However, in terms of relative risk of death, an increase of 28% was observed in the intervention compared to the control, which was statistically significant (X2 (1, N = 36), p < 0.00688). Nevertheless, this increase did not surpass age-adjusted U.S. mortality rates. Assessing the data by intervention type, Diet/Supplement, and Multi-modal trials displayed an elevated relative risk of SAEs in the intervention. Diet/Supplement trials had a 16% increase (X2 (1, N = 2), p < 0.0263), and Multi-modal trials had a 365% increase (X2 (1, N = 5), p < 0.000213). Diet/Supplement trials also showed a 67% increased risk of death (X2 (1, N = 2), p < 0.000197). Conclusions: These findings should be cautiously considered due to the low rate of reporting, but underscore the significance of reporting clinical trial results, enhancing transparency, and facilitating more accurate safety assessments in cognitive aging and lifestyle interventions for older adults.

Learning from Adolescents and Caregivers to Enhance Acceptability and Engagement Within Virtual Dialectical Behavior Therapy for Adolescents Skills Groups: A Qualitative Study.

Despite the significant increase in adolescent mental health challenges in recent years, structural barriers continue to limit access to and engagement in mental health services. As such, opportunities to learn directly from adolescents and their families on how to best structure and deliver services are paramount. The current study assumes a multi-informant approach and reports on adolescents' and caregivers' (N = 33) experiences in an adapted telehealth/hybrid Dialectical Behavior Therapy for Adolescents (DBT-A) program. Focus groups were conducted across two cohorts of families who participated in DBT-A skills groups, to collect family-centered data on the acceptability of program modifications, engagement in the adapted telehealth/hybrid DBT-A, and recommendations for improvement. Participants were predominately Latine White and were from a broad range of socioeconomic backgrounds. Additionally, 45.5% of the adolescents identified as LGBTQ + . Focus group findings emphasized how the telehealth platform was both convenient and disengaging, and how in-person sessions offered improved group connection and content engagement. Participants underscored the importance of balancing multi-family group sessions with adolescent- and caregiver-only group sessions in the program, and adolescents emphasized a need for the DBT-A program to better center adolescents' unique experiences and voices throughout sessions. Both adolescents and caregivers suggested modifications to synthesize the content and improve generalizability of the DBT-A skills to their real lives. Overall, these findings add to a new and evolving branch of DBT-A qualitative inquiry, as well as the growing body of work that recommends incorporating the voices of people with lived experiences into the development and modification of psychological services.

An open-source system for efficient clinical trial support: The COMET study experience.

Exercise clinical trials are complex, logistically burdensome, and require a well-coordinated multi-disciplinary approach. Challenges include managing, curating, and reporting on many disparate information sources, while remaining responsive to a variety of stakeholders. The Combined Exercise Trial (COMET, NCT04848038) is a one-year comparison of three exercise modalities delivered in the community. Target enrollment is 280 individuals over 4 years. To support rigorous execution of COMET, the study team has developed a suite of scripts and dashboards to assist study stakeholders in each of their various functions. The result is a highly automated study system that preserves rigor, increases communication, and reduces staff burden. This manuscript describes system considerations and the COMET approach to data management and use, with a goal of encouraging further development and adaptation by other study teams in various fields.

A Retrospective Analysis of Serious Adverse Events and Deaths in US-Based Lifestyle Clinical Trials for Cognitive Health.

This retrospective analysis assessed the serious adverse events and deaths reported in lifestyle clinical trials designed to enhance cognitive health in older adults living in the United States. Data was collected from studies conducted between January 1, 2000, and July 19, 2023, using the ClinicalTrials.gov application programming interface. Our query revealed that 76% of these studies did not report trial results. The remaining studies with reported results were categorized under one of four intervention types: Cognitive/Behavioral, Exercise/Movement, Diet/Supplement, and Multi-modal. When all trial types are considered together, the results indicate that lifestyle clinical trials are safe, with no significant increase in relative risk of experiencing an SAE in an intervention group over a control group. And although the increase in relative risk of death in an intervention group over a control group was significant at 28% (X2 (1, N = 36), p < 0.00688), the probability of death was not higher than the U.S. mortality rates by age. When assessing the data using intervention type, Diet/Supplement trials and Multi-modal trials both had an increase in relative risk of experiencing an SAE in the intervention over the control group, with Diet/Supplement trials at 16% (X2 (1, N = 2), p < 0.0263) and Multi-modal trials at 365% (X2 (1, N = 5), p < 0.000213). The Diet/Supplement trials also had an increased risk of death at 67% (X2 (1, N = 2), p < 0.000197). These results should be taken with careful consideration. Due to such a low reporting rate, the 36 studies included in this analysis do not accurately represent the majority of lifestyle clinical trials conducted in the U.S. This study is valuable in that it highlights the importance of reporting clinical trial results, which will improve transparency in trial results and allow for more accurate assessments of safety in the growing field of cognitive aging and lifestyle interventions for older adults.

Development of a Culturally Adapted Dietary Intervention to Reduce Alzheimer's Disease Risk among Older Black Adults.

The objective of this study is to identify and understand knowledge and attitudes that influence dietary practices among older Black adults using a community-engaged approach. This is a non-interventional mixed methods study designed to inform the development of an adapted brain-healthy soul food diet intervention. A purposive sampling approach was used to conduct seven semi-structured focus group discussions and an online quantitative survey. In total, 39 participants who self-identified as Black, aged 55 years and older, English speaking, and who were cognitively normal with an AD8 < 2; (25.6% men; 74.4% women) participated in the online survey and one of the seven 60 min virtual focus group discussions (5-7 per focus group). Quantitative frequency data from the online surveys were analyzed using descriptive statistics. Qualitative focus group data were analyzed using a 6-step thematic analysis process. Five themes emerged: dementia awareness; practices shaping food choices and consumption; barriers to eating healthy; instrumental support; and elements of a culturally adapted brain-healthy dietary intervention. Older Black adults perceived an adapted MIND dietary model as the most acceptable with the incorporation of salient cultural characteristics and strategies within both the design and delivery phases.

A Virtual Photovoice Study of Older African Americans Perceptions of Neurovascular Clinical Trials.

BACKGROUND: Alzheimer disease (AD) poses a major public health crisis, especially among African Americans (AAs) who are up to 3 times more likely to develop AD compared with non-Hispanic Whites. Moreover, cardiovascular risk factors represent a precursor to cognitive decline, which contributes to racial/ethnic disparities seen within AD. Despite these disparities, AAs are underrepresented in neurovascular research. The purpose of this qualitative virtual photovoice project is to explore how older Midwestern AAs perceive neurovascular clinical trials. METHODS: Five photovoice sessions were held virtually over a 3-month period. Participants took photos each week that captured the salient features of their environment that described their perceptions and experiences related to neurovascular clinical trials. Structured discussion using the SHOWED method was used to generate new understandings about the perspectives and experiences in neurovascular clinical trials. Data was analyzed using strategies in participatory visual research. RESULTS: A total of 10 AAs aged 55 years and older participated and a total of 6 themes emerged from the photovoice group discussions. CONCLUSION: Findings from this study inform the development of culturally appropriate research protocols and effective recruitment strategies to enhance participation among older AAs in neurovascular clinical trials.

Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study.

OBJECTIVE: Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population. This group is pivotal to healthcare system resilience during the COVID-19, and future, pandemics. We investigated demographic, social, behavioural and occupational risk factors for SARS-CoV-2 infection among HCWs. DESIGN/SETTING/PARTICIPANTS: HCWs enrolled in a large-scale sero-epidemiological study at a UK university teaching hospital were sent questionnaires spanning a 5-month period from March to July 2020. In a retrospective observational cohort study, univariate logistic regression was used to assess factors associated with SARS-CoV-2 infection. A Least Absolute Shrinkage Selection Operator regression model was used to identify variables to include in a multivariate logistic regression model. RESULTS: Among 2258 HCWs, highest ORs associated with SARS-CoV-2 antibody seropositivity on multivariate analysis were having a household member previously testing positive for SARS-CoV-2 antibodies (OR 6.94 (95% CI 4.15 to 11.6); p<0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p<0.0001). Occupational factors associated with a higher risk of seropositivity included working as a physiotherapist (OR 2.78 (95% CI 1.21 to 6.36); p=0.015) and working predominantly in acute medicine (OR 2.72 (95% CI 1.57 to 4.69); p<0.0001) or medical subspecialties (not including infectious diseases) (OR 2.33 (95% CI 1.4 to 3.88); p=0.001). Reporting that adequate personal protective equipment (PPE) was 'rarely' available had an OR of 2.83 (95% CI 1.29 to 6.25; p=0.01). Reporting attending a handover where social distancing was not possible had an OR of 1.39 (95% CI 1.02 to 1.9; p=0.038). CONCLUSIONS: The emergence of SARS-CoV-2 variants and potential vaccine escape continue to threaten stability of healthcare systems worldwide, and sustained vigilance against HCW infection remains a priority. Enhanced risk assessments should be considered for HCWs of black ethnicity, physiotherapists and those working in acute medicine or medical subspecialties. Workplace risk reduction measures include ongoing access to high-quality PPE and effective social distancing measures.

The different faces of metastatic melanoma in the gastrointestinal tract.

Melanoma is the most aggressive form of skin cancer, with tendency to spread to any organ of the human body, including the gastrointestinal tract (GIT). The diagnosis of metastases to the GIT can be difficult, as they may be clinically silent for somewhile and may occur years after the initial melanoma diagnosis. CT imaging remains the standard modality for staging and surveillance of melanoma patients, and in most cases, it will be the first imaging modality to identify GIT lesions. However, interpretation of CT studies in patients with melanoma can be challenging as lesions may be subtle and random in distribution, as well as sometimes mimicking other conditions. Even so, early diagnosis of GIT metastases is critical to avoid emergency hospitalisations, whilst surgical intervention can be curative in some cases. In this review, we illustrate the various imaging presentations of melanoma metastases within the GIT, discuss the clinical aspects and offer advice on investigation and management. We offer tips intended to aid radiologists in their diagnostic skills and interpretation of melanoma imaging scans.

A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital.

OBJECTIVES: To describe the risk factors for SARS-CoV-2 infection in UK healthcare workers (HCWs). METHODS: We conducted a prospective sero-epidemiological study of HCWs at a major UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression. RESULTS: 410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71]; p=0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42]; p=0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25]; p<0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 - 2·07; p<0·001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever, and myalgia; 31% of staff testing positive reported no prior symptoms. CONCLUSIONS: Risk of SARS-CoV-2 infection amongst HCWs is highly heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.

Implementation of a Pediatric Population Health Asthma Program in Academic Medical Center-Affiliated Urban and Suburban Practices.

A tiered pediatric Asthma Population Health Management Program (APHMP), based on evidence-based practices, that differentially targets populations for intervention based on rising risk for high utilization and disease complications was implemented at 6 urban and suburban practices affiliated with an academic medical center. In addition to standard pediatric asthma care, APHMP adds regular administration of the asthma control test (ACT), provider education on performance variation, and monitoring through the electronic health record-based asthma registry. As patients' use of acute health care services and complications increases, APHMP integrates multidisciplinary interventions, including an asthma coach who conducts environmental assessments in addition to addressing social needs, into their primary care. A retrospective cohort study method was used to assess population-level effects on asthma event rates and practice- and provider-level variation from 2017 to 2019. Consistent with well-documented health disparities in pediatric asthma, the analysis demonstrated that patients who were male (odds ratio [OR] = 1.21, 95% confidence interval [CI] = 1.02-1.43), 4-8 years old (OR = 4.91, 95% CI = 3.27-7.37), Spanish speaking (OR = 1.67, 95% CI = 1.54-1.81), from low-income neighborhoods (OR = 1.56, 95% CI = 1.53-2.46), and with ACT <20 (OR = 2.88, 95% CI = 1.97-4.21) had higher odds of having asthma events. Six percent of patients studied were found to be at risk for high health care utilization and disease complications. Study limitations include the absence of a control group, the mixed model data collection approach, and the effects of seasonal variation on asthma events. Future directions include analyzing disease management program outcomes of incorporating an asthma coach into a patient's primary care team and addressing provider-level variation in asthma event rates.

The forgotten appearance of metastatic melanoma in the small bowel.

BACKGROUND: Melanoma is the most aggressive form of skin cancer, with a tendency to metastasise to any organ of the human body. While the most common body organs affected include liver, lungs, brain and soft tissues, spread to the gastrointestinal tract is not uncommon. In the bowel, it can present with a multitude of imaging appearances, more rarely as an aneurysmal dilatation. This appearance is classically associated with lymphoma, but it has more rarely been associated with other forms of malignancy. CASE PRESENTATION: We report a case series of three patients with aneurysmal dilatation in the small bowel (SB) confirmed to be due to metastatic melanoma (MM). All patients had non-specific symptoms; most times being attributed initially to causes other than melanoma. On CT the identified aneurysmal SB dilatations were diagnosed as presumed lymphoma in all cases. In two cases, the aneurysmal dilatation was the first presentation of metastatic disease and in two of the cases more than one site of the gastrointestinal tract was concomitantly involved. All patients underwent surgical resection with histological confirmation of MM. CONCLUSIONS: Recognition of unusual SB presentation of MM, such as aneurysmal SB dilatation, is important to expedite diagnosis, provide appropriate treatment, and consequently improve quality of life and likely survival of these patients. As the most common cancer to metastasise to the SB and as a known imaging mimicker, MM should remain in any radiologist's differential diagnosis for SB lesions with aneurysmal dilatation.

COMbined Exercise Trial (COMET) to improve cognition in older adults: Rationale and methods.

Substantial evidence suggests physical exercise may sustain cognitive function and perhaps prevent Alzheimer's Disease (1, 2). Current public health recommendations call for older adults to do at least 150 min a week of aerobic exercise (e.g. walking) and twice a week resistance exercise (e.g. weight lifting) for physical health. Yet, much remains unknown about how these exercise modalities support brain health independently or in combination. The COMbined Exercise Trial (COMET) is designed to test the combined and independent effects of aerobic and resistance training specifically focusing on exercise-related changes in 1) cognitive performance, 2) regional brain volume, 3) physical function, and 4) blood-based factors. To explore these questions, we will enroll 280 cognitively normal older adults, age 65-80 years, into a 52-week community-based exercise program. Participants will be randomized into one of four arms: 1) flexibility/toning- control 2) 150 min of aerobic exercise only, 3) progressive resistance training only, or 4) combined aerobic and progressive resistance training. Outcomes assessed include a comprehensive cognitive battery, blood biomarkers, brain magnetic resonance imaging, physiological biomarkers, cardiorespiratory fitness, physical function, and battery of psychosocial questionnaires is assessed at baseline, 6 and 12-months. COMET will provide rigorous randomized controlled trial data to understand the effects of the most common exercise modalities, and their combination (i.e., the standard public health recommendation), on brain health.