Citations

Background: While the benefits of physical activity (PA) for cancer survivors are well-documented, there is limited research specifically exploring its effects on health-related quality of life (HRQoL) among testicular cancer (TC) survivors. This review aims to examine the available literature on the relationship between PA and HRQoL in TC survivors post-treatment. Objective: To identify and synthesize existing studies on the effects of PA on HRQoL outcomes in TC survivors. Eligibility criteria: Studies that examined the relationship between PA, TC survivorship, and HRQoL across various phases of survivorship were included. Only peer-reviewed articles and gray literature addressing these topics were considered. Sources of evidence: A systematic search was conducted across seven databases and gray literature. Articles were evaluated based on titles, abstracts, and full-text reviews for inclusion. Charting methods: Following Arksey and O’Malley’s scoping review framework and PRISMA-ScR guidelines, studies were charted for key findings regarding the effects of PA on cancer-related fatigue, psychosocial outcomes, and HRQoL in TC survivors. The search also focused on identifying barriers to PA adherence and gaps in the current literature. Results: Three studies were examined: one experimental study, one feasibility study, and one cross-sectional study. Findings suggested that PA interventions could reduce cancer-related fatigue, improve psychosocial well-being, and enhance HRQoL indicators such as vitality, self-esteem, and social functioning. High-intensity interval training showed short-term benefits, while low-intensity activities demonstrated feasibility for broader adoption. Adherence barriers included treatment side effects and psychosocial factors. Limitations included small sample sizes, self-reported data, and lack of long-term follow-up. Conclusion: The findings suggest that PA can improve HRQoL in TC survivors, but significant gaps remain, particularly in terms of longitudinal studies, diverse populations, and tailored interventions. Future research should focus on developing scalable, sustainable PA interventions that address adherence and long-term health outcomes for TC survivors.

AbstractBackgroundAs low titer group O whole blood (LTOWB) increases in popularity, blood centers are finding innovative ways of maintaining the supply. One potential way is collecting LTOWB from parous female donors without testing for HLA antibodies. This in silico simulation predicted the risk of an LTOWB unit containing an HLA antibody and the subsequent risk for an HLA‐incompatible transfusion.MethodsAn LTOWB blood bank with 1 million units was simulated consisting of male, nulliparous, and parous female donors. The proportion of each donor type was modeled after the sex distribution at US blood centers. The parity of female donors was calculated based on the average number of live births per female depending on her age. HLA‐alloimmunization risk was determined by her parity status. The HLA haplotypes of the simulated recipients were derived from the 100 most common HLA haplotypes in the US National Marrow Registry Program database. The proportion of different race/ethnic groups in the US was used to simulate 100,000 LTOWB recipients to whom between 1 and 10 units were administered.ResultsOverall, the risk of an LTOWB unit containing at least one HLA antibody was 12.2% and the rate of receiving an HLA‐incompatible unit was 21.3%. The risk of receiving an HLA‐incompatible unit rose from 4.8% after receipt of one unit to 36.5% after 10 units.ConclusionBlood collectors and hospitals should evaluate the potential TRALI risk against the benefit of a potentially expanded inventory of LTOWB before collecting plasma‐containing products from non‐HLA‐tested parous female donors.

Introduction: Four randomized clinical trials have not demonstrated the superiority of anticoagulation over antiplatelet therapy in the prevention of recurrent embolic stroke of undetermined source (ESUS). In this multicenter observational cohort study, we evaluated long-term outcomes associated with various antithrombotic strategies according to potential embolic sources. Methods: A multicenter retrospective observational cohort of consecutive adult patients with ESUS was queried (n=27 sites). Comparisons were made between patients treated with single or combination antiplatelet therapy versus anticoagulation (direct oral anticoagulant, vitamin K antagonist, low molecular weight heparin) with or without antiplatelet therapy initiated within 7 days of stroke. The primary composite outcome of recurrent stroke, major bleeding, or death was assessed using unadjusted and adjusted Cox proportional hazards regression, with clustering by site. Causal inference was assessed using inverse probability of treatment weighted regression adjustment (IPTWRA), accounting for propensity for antiplatelet treatment, with effect estimates summarized as the average treatment effect (ATE) over time (in days). Adjusted models accounted for age, stroke severity, vascular risk factors, and major categories of potential embolic sources. Results: Of the 2201 included patients (n=218 treated with anticoagulation) followed over a median of 564 days (interquartile range [IQR] 154-1124), the median age was 65y (IQR 54-74) and 49.8% were female. Patients treated with anticoagulation were older with more frequent previous stroke, concomitant left ventricular dysfunction, and more severe deficits. Over 4541 person-years of follow-up, the annualized incidence rate of the primary outcome was 14.6% (95% confidence interval [CI], 13.6%-15.8%). Compared to anticoagulation, antiplatelet(s) use was not associated with a lower risk of the primary outcome in the adjusted Cox model (HR 0.91, 95% CI, 0.64-1.29) or in the IPTWRA model (average treatment effect 0.14, 95% CI, -1376.6 to 1376.9). Major bleeding events trended toward significance in the adjusted Cox model (HR 0.51, 95% CI 0.25-1.04) but were no different with IPTWRA (ATE 58.9, 95% CI, -125.4 to 243.2). Conclusions: These results validate the observations of randomized trials indicating a lack of benefit of anticoagulation over antiplatelet therapy in ESUS. A more detailed analysis of heterogeneity of treatment effect is under way.

Background: Left ventricular (LV) injury is a cardioembolic etiology of ischemic stroke. We aimed to 1) evaluate recurrent stroke risk among patients with cryptogenic stroke and LV injury, and 2) determine if there is a treatment effect with anticoagulation in this population. Methods: We analyzed the multicenter, retrospective Cardiac Abnormalities in Stroke Prevention and Recurrence cohort of patients with cryptogenic ischemic stroke. The exposure was LV injury defined by 1) LV ejection fraction (EF) 20-40% and/or 2) LV wall motion abnormality (hypokinesis or akinesis). The primary composite outcome included recurrent stroke, major bleeding, or death. Cox proportional hazard models were built and sequentially adjusted for 1) age and sex (Model 1), and 2) age, sex, race, ethnicity, anti-thrombotic use, and vascular risk factors (Model 2). We then assessed if there was heterogeneity in treatment effect by LV injury status with an interaction term of LV injury and oral anticoagulation use in Model 2. Results: Of 2,641 patients in CASPR, the analytic cohort included 2,191 patients with complete exposure and outcome data (median age 65 years, 49.8% female, median follow-up 1.55 years). There were 113 (5.2%) patients with LV injury (median LVEF 30%, interquartile range 25-34%). There were 559 incident events (321 recurrent strokes [288 ischemic], 71 major hemorrhages, 250 deaths). Among patients with LV injury, 15.9% were prescribed an anticoagulant within 7 days of index stroke (vs 9.6% without LV injury, p=0.03). The unadjusted risk of the primary outcome was non-significantly higher among patients with LV injury vs without (HR 1.40; 95% confidence interval [CI], 0.98-2.00), but became significant in Model 1 (HR 1.50; 95% CI, 1.21-1.85) and in Model 2 (HR 1.35, 95% CI, 1.11-1.64). In the LV injury subgroup, anticoagulation vs antiplatelet therapy was associated with a significant reduction in the primary outcome (HR 0.63, 95% CI, 0.43-0.94). In patients without LV injury, anticoagulation was associated with a higher risk of the composite outcome (HR 4.35, 95% CI, 1.69-11.16, p[interaction]=0.002). Conclusion: In this observational study, there was an increased risk of the primary outcome which included recurrent stroke among patients with cryptogenic stroke and LV injury. Anticoagulation use in LV injury is associated with a significant reduction in the risk of the primary outcome. These findings warrant confirmation in a dedicated randomized controlled trial.

Introduction: The lack of understanding about the genetic and molecular basis of young stroke (<55 years of age) has hindered development of diagnostic, management, and therapeutic approaches. Whole exome sequencing (WES) can be leveraged as a tool for studying etiological processes underlying stroke. At the time of study inception, this is the single largest WES study in this unique young stroke population to uncover elusive stroke etiologies. Methods: The Mayo Clinic TAPESTRY database is a research program conducting whole exome sequencing of 100,000 participants. Of these, 406 participants met the criteria for young stroke (18-54 years of age) based on ICD-9 and ICD-10 diagnostic codes. Controls were TAPESTRY participants without a stroke-related ICD diagnosis. Cases were matched for age, gender, and race for a 1:4 case-control ratio. Ischemic stroke etiology was classified using TOAST classification. To uncover genetic mechanisms, a gene centric approach was used to identify variants in our cohort. A list of 66 genes known to be associated with young stroke was curated based on existing genetic databases. Various filtration strategies were used to identify potentially damaging variants (graphic 1). Results: There were 406 cases (363 ischemic and 43 hemorrhagic; 291 female; age at stroke onset 39.8±10.4; 368 were White) and 3,857 controls. TOAST classification yielded 20 patients with large artery atherosclerosis, 58 cardioembolic, 10 small vessel disease, 148 other determined (58 patent foramen ovale, 50 dissection, 48 hypercoagulable state, 11 Moyamoya, 11 vasculitis, 10 fibromuscular dysplasia), and 165 undetermined etiologies. Several individuals had multiple competing etiologies. Of cerebral hemorrhages, there were 6 aneurysmal, 6 arteriovenous malformation, 5 hypertensive, 2 substance abuse, 3 trauma, and 21 other etiologies. Across the entire cohort, 35,054 variants were found within the 66 genes identified from the literature. Filtration identified 48 potentially damaging variants across 30 genes in 44 patients (20 cryptogenic and 21 other: 12 patent foramen ovale, 5 vasculitis, 4 dissection, 4 cardioembolic) that were absent in controls. Conclusion: WES is a powerful tool that can be used to uncover potential genetic mechanisms in the young stroke population. An improved understanding of etiologies would improve diagnostics and pave the way for new preventive and therapeutic approaches, thus improving the overall care of young stroke patients.

Introduction: Malignancy represents an important subgroup of embolic stroke of undetermined source (ESUS). We aim to compare infarct features, potential embolic sources, and long-term outcomes in ESUS patients with and without malignancy. Methods: In this pre-specified secondary analysis of the Cardiac Abnormalities in Stroke Prevention and Recurrence (CASPR) retrospective cohort study, active cancers were identified by site investigators and adjudicated as malignant if they were non-squamous or non-basal cell skin cancers. We compared the prevalence of various potential embolic sources (e.g., patent foramen ovale, left ventricular dysfunction, post-stroke atrial fibrillation) among patients with and without malignancy. The risk of recurrent stroke, major bleeding, or death was evaluated using adjusted Cox proportional hazards models, accounting for age, sex, vascular risk factors, competing potential embolic sources, and initial treatment with anticoagulation versus non-anticoagulant (e.g., antiplatelet) regimen. Results: Of the 2201 patients followed over a median of 564 days, 236 (10.7%) were diagnosed with cancer at the time of stroke. Patients with malignancy were older, more frequently hypertensive and did not differ with regards to prevalence of specific infarct patterns or potential cardiac embolic sources. No difference was observed in the composite outcome of recurrent stroke, major bleeding, or death (adjusted HR 1.02, 95% CI, 0.71-1.46). Age (adjusted HR per year 1.02, 95% CI, 1.01-1.03), baseline stroke severity (adjusted HR 1.03 per NIHSS point, 95% CI, 1.01-1.05), prior stroke (adjusted HR 1.68, 95% CI, 1.38-2.05), and multi-territorial infarct pattern (adjusted HR 1.67, 95% CI, 1.33-2.08) were significantly associated with this composite outcome, but anticoagulation was not. There was a nominally lower rate of major bleeding with malignancy (adjusted HR 0.45, 95% CI, 0.19-1.04), a significantly higher rate of death (adjusted HR 1.58, 95% CI, 1.09-2.30), but no significant difference in recurrent ischemic stroke (p=0.31). Conclusions: Patients with malignancy and ESUS had higher mortality but did not differ in recurrent stroke risk or major bleeding when compared to patients without malignancy. Anticoagulation was not independently associated with better outcomes. Further analysis of infarct topology and risk factors may better identify patients for whom anticoagulation may benefit.

Purpose: Fatigue is one of the most common and disabling symptoms experienced by people with inflammatory bowel disease; however, interventions to treat fatigue are limited. The purpose of this systematic review is to examine the relationship between sleep deficiency and fatigue in adults with inflammatory bowel disease and to describe the demographic and clinical factors associated with fatigue to inform future intervention work. Methods: We conducted a systematic review and reported the results using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search was conducted using MEDLINE, EMBASE, PsycINFO, CINAHL, and CENTRAL on 3/7/24. We included studies with adults (≥18 years of age) who had a diagnosis of inflammatory bowel disease (Crohn’s disease, ulcerative colitis, or indeterminate colitis) and measured fatigue and sleep using a validated self-report questionnaire or objective measurement. Results: Twenty-two studies met inclusion criteria for a total sample of 16 927, of whom 58.7% (n = 9937) had Crohn’s disease, and 66.3% (n = 11 226) were female. 56.1% of the participants experienced fatigue and 66.3% experienced sleep deficiency. Sleep quality and insomnia were consistently associated with fatigue. Baseline poor sleep quality was associated with persistent and worsening fatigue over 12 to 24 months. Clinical but not objective assessment of disease activity, anxiety, depression, female gender/sex, and younger age were also associated with more severe fatigue. Conclusions: Sleep quality and insomnia represent important modifiable contributors to fatigue. Future research should explore whether sleep interventions can improve fatigue in this population.