"Faith and a sunny day": Association of patient frailty with strain experienced by informal caregivers of older adults with non-muscle-invasive bladder cancer.

INTRODUCTION: Few studies have evaluated the potential effects of aging-related conditions like frailty in older adults with cancer on informal caregivers. Our objective was to evaluate the association between the sum total of the aging-related conditions of older adults with non-muscle-invasive bladder cancer (NMIBC) and the strain reported by their informal caregivers. MATERIALS AND METHODS: We conducted an explanatory sequential mixed methods cross-sectional survey study that recruited 81 dyads of older adults with NMIBC (age ≥ 65 at diagnosis) and their informal caregivers. Our outcome was measured by the Caregiver Strain Index (CSI), a self-reported measure of informal caregivers. Our exposure was the patient's deficit accumulation index (DAI), a validated composite measure of frailty derived from a geriatric assessment. A multivariable negative binomial regression was conducted to model CSI. We conducted qualitative thematic content analysis of responses to open-ended survey questions to understand specific types of caregiver strain and to identify coping strategies. RESULTS: Mean ages of patients and caregivers were 79.4 years and 72.5 years, respectively. Most caregivers were spouses (75.3 %) and lived with the patient (80.2 %). Of patients, 54.3 % were robust, 29.6 % were pre-frail, and 16.1 % were frail. In the multivariable model, we found that patient DAI was significantly associated with CSI (adjusted incidence rate ratio 1.05, 95 % CI 1.02-1.09). The top three sources of strain identified by caregivers were emotional adjustments, medical management, and family adjustments. Coping strategies for each included self-management of emotions, self-education about bladder cancer, and social support, respectively. DISCUSSION: In this cross-sectional study, we found that worsening frailty in an older adult with NMIBC was associated with greater informal caregiver strain. Informal caregivers reported challenges with emotional management, family dynamics, and medical tasks. These findings may inform longitudinal research and interventions to support informal caregivers who provide care for older adults with NMIBC.

Black Americans with sickle cell disease (SCD) demonstrate accelerated epigenetic pace of aging compared to Black Americans without SCD.

BACKGROUND: Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early mortality, we hypothesized that patients with SCD are experiencing accelerated biological aging compared to individuals without SCD. METHODS: We utilized the DunedinPACE measure to compare the epigenetic pace of aging in 131 Black Americans with SCD to 1391 Black American veterans without SCD. RESULTS: SCD patients displayed a significantly accelerated pace of aging (DunedinPACE mean difference of 0.057 points) compared to the veterans without SCD, whereby SCD patients were aging approximately 0.7 months more per year than those without SCD (p=4.49x10-8). This was true, even though the SCD patients were significantly younger according to chronological age than the individuals without SCD, making the epigenetic aging discrepancy even more apparent. This association became stronger when we removed individuals with PTSD from the non-SCD group (p=2.18x10-9), and stronger still when we restricted the SCD patients to those with hemoglobin SS and Sß0 thalassemia genotypes (p=1.61x10-10). CONCLUSIONS: These data support our hypothesis that individuals with SCD experience accelerated biological aging as measured by global epigenetic variation. The assessment of epigenetic measures of biological aging may prove useful to identify which SCD patients would most benefit from clinical interventions to reduce mortality.

Function, cognition, and quality of life among older adults with lung cancer who live alone: A prospective cohort study.

INTRODUCTION: Among older adults without cancer, living alone is associated with poor health outcomes. However, among older adults with non-small cell lung cancer (NSCLC) who live alone, data on function, cognition, and quality of life (QOL) during systemic treatment remain limited. MATERIALS AND METHODS: We enrolled adults aged ≥65 with advanced NSCLC starting a new chemotherapy, immunotherapy, and/or targeted therapy regimen with non-curative intent. Patients completed geriatric assessments including instrumental activities of daily living (IADL), Montreal Cognitive Assessment, and QOL pretreatment and at 1, 2, 4, and 6 months, or until treatment discontinuation, whichever occurred earlier. We categorized change in IADL, cognition, and QOL as stable/improved, declined with recovery, or declined without recovery using clinically meaningful definitions of change. We used multinomial logistic regression to compare change between patients who lived alone versus with others. RESULTS: Among 149 patients, median age was 73; 21% lived alone. Pretreatment IADL, cognition, and QOL scores were similar between older adults who lived alone versus with others. During NSCLC treatment, older adults who lived alone had similar trajectories of function (52% functional decline vs 38%), cognition (43% cognitive decline vs 50%), and QOL (45% QOL decline vs 44%) compared with those who lived with others. In unadjusted analyses, patients who lived alone were more likely to develop functional decline with recovery (reference category: stable/improved function) than those who lived with others (relative risk ratio 4.07, 95% CI 1.14-14.6, p = 0.03). However, this association was not observed after adjusting for age, race, prior NSCLC treatment, current treatment group, and pretreatment geriatric assessment differences. There were no differences in cognitive or QOL trajectories in unadjusted or adjusted analyses. DISCUSSION: Approximately half of older adults with advanced NSCLC who lived alone were able to maintain their function, cognition, and QOL during NSCLC treatment, which was similar to older adults who lived with others. Many older adults with advanced NSCLC who live alone can receive systemic treatment with individualized supportive care.

Physical Activity and Cognition: Longitudinal findings from the Thinking and Living with Cancer Study.

BACKGROUND: Physical activity can improve cognition; however, little is known regarding the relationships between longitudinal objectively-measured physical activity, cognition, and inflammation in older breast cancer survivors. METHODS: Older (≥60 yrs) breast cancer survivors (n = 216) and frequency-matched non-cancer controls (n = 216) were assessed at baseline (pre-systemic therapy for survivors) and annually for up to five years. Assessments included hip-worn ActiGraphs worn for seven days, neuropsychological tests, the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI) subscale, and circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6). Data were analyzed using linear mixed-effect, random-effect contemporaneous fluctuation, and multi-level mediation models, considering covariates; p < .05 (two-sided) was considered significant. RESULTS: Survivors had fewer minutes of moderate-to-vigorous physical activity (MVPA) than controls at 36-, 48-, and 60-month time points (p < .03). Fewer survivors met Aerobic Physical Activity Guidelines at 36 months than controls (17.7% vs 33.0%, p = .030). When Guidelines were met (vs not), FACT-Cog PCI scores were 2.1 ± 1.0 (p = .034) points higher. Higher MVPA and meeting Aerobic Guidelines were not related to objective neuropsychological performance. MVPA was inversely associated with CRP and IL-6 (p < .001), but inflammation did not mediate physical activity effects on perceived cognition. CONCLUSIONS: Older breast cancer survivors were less physically active than older non-cancer controls, especially farther from baseline. Meeting Aerobic Guidelines was associated with better perceived cognition in survivors. Survivorship care should consider physical activity monitoring and referral to rehabilitation and supervised exercise programs to promote physical activity and improve recovery in older survivors.

EFFICACY OF INTRAVENOUS IMMUNOGLOBULIN ALONE ON CORONARY ARTERY LESION REDUCTION IN KAWASAKI DISEASE.

Background: Though Aspirin and intravenous immunoglobulin (IVIG) remain the standard treatments for Kawasaki Disease (KD) to minimize coronary artery damage, the duration and dosage of aspirin are inconsistent across hospitals. However, the lack of multi-center randomized trials prevents definitive answers to the impact of high-dose aspirin. Methods: This clinical trial was structured as a prospective, evaluator-blinded, multi-center randomized controlled trial with two parallel arms, aiming to assess the effectiveness of IVIG as a standalone primary therapy of KD in comparison to the combination of IVIG with high-dose aspirin therapy. KD patients were enrolled between September, 2016 and August, 2019. A final cohort of 134 patients were randomly assigned to the standard and test groups with 69 and 65 patients, respectively. The Standard group received IVIG (2 g/kg) along with aspirin (80-100 mg/kg/day) until fever subsided for 48 hours. The test group received IVIG (2 g/kg) alone. Following the initial treatment, both groups received a daily aspirin dose (3-5 mg/kg) for six weeks. The primary outcome measure was the occurrence of coronary artery lesions (CAL) at the 6-8 weeks mark. The secondary outcome is IVIG resistance. Results: The overall rate of CAL in test group decreased from 10.8% at diagnosis to 1.5% and 3.1% at 6 weeks and 6 months, respectively. The CAL rate of standard group declined from 13.0% to 2.9% and 1.4%, with no statistically significant difference (P>0.1) in the frequency of CAL between the two groups. Furthermore, no statistically significant differences were found for treatment (P>0.1) and prevention (P>0.1) effect between the two groups. Conclusions: This marks the first prospective multi-center randomized controlled trial comparing the standard treatment of KD using IVIG plus high-dose aspirin against IVIG alone. Our analysis indicates that addition of high-dose aspirin during initial IVIG treatment is neither statistically significant nor clinically meaningful for CAL reduction. Registration: URL: http://www.clinicaltrials.gov ; identifier: NCT02951234. What is New?: This study represents the first multi-center randomized controlled trial investigating the efficacy of high-dose aspirin or intravenous immunoglobulin (IVIG) during the acute stage of KD. This study assessed the impact of discontinuing high-dose aspirin (80-100 mg/kg/day) on the occurrence of CAL during the acute phase treatment of Kawasaki Disease.No significant differences were observed between high-dose aspirin plus IVIG treatment and IVIG alone treatment in terms of the frequency of abnormal coronary artery abnormalities. Additionally, our analysis revealed no statistically significant differences in either the treatment effect (the number of cases successfully treated) or prevention effect (the prevention of new cases) between these two treatments. What Are the Clinical Implications?: Comparison analysis indicated the non-inferiority between two groups with or without high-dose aspirin.Administering the standard 2 g/kg/day IVIG without high-dose aspirin (80-100 mg/kg/day) during the acute phase therapy for KD does not increase the risk of coronary artery lesions, which are a primary cause of morbidity and mortality in KD patients.Addition of high-dose aspirin during initial IVIG treatment is not statistically significant or clinically meaningful.

Vegetable Gardening and Health Outcomes in Older Cancer Survivors: A Randomized Clinical Trial.

Importance: Cancer survivors experience accelerated functional decline that threatens independence and quality of life. Previous studies have suggested that vegetable gardening may improve diet, physical activity, and physical function in this vulnerable population, which comprises more than 5% of the US population. Objective: To assess whether diet, physical activity and functioning, and other outcomes improved in older cancer survivors assigned to a vegetable gardening intervention compared with a waitlist. Design, Setting, and Participants: From May 11, 2016, to May 2, 2022, a 2-arm, assessor-blinded, crossover-designed, intent-to-treat, randomized clinical trial was conducted at cancer survivors' homes across Alabama. Medicare-eligible survivors of cancers with 5-year survival of 60% or more were registry ascertained and screened for suboptimal vegetable and fruit consumption (<5 servings per day), physical activity (<150 moderate-to-vigorous minutes per week), and physical function (36-Item Short Form Health Survey [SF-36] subscale score ≤90). Consented participants underwent baseline assessments, were randomly assigned to intervention or waitlisted arms, and were reassessed at 1-year follow-up. Intervention: One-year, home-based vegetable gardening intervention providing gardening supplies and mentorship by cooperative extension-certified master gardeners to plant and maintain spring, summer, and fall gardens. Waitlisted participants received the identical intervention after 12 months. Main Outcomes and Measures: The main outcome was a composite index of improvements in self-reported vegetable and fruit consumption, physical activity, and physical function corroborated by plasma α-carotene levels, accelerometry, and physical performance assessments, respectively. Results: Of 381 enrolled participants (mean [SD] age, 69.8 [6.4] years; range, 50-95 years; 263 [69.0%] female), 194 were assigned to the gardening intervention and 187 were waitlisted (attrition rates, 7.2% and 7.0%, respectively). Intent-to-treat analyses did not detect a significant improvement in the composite index of vegetable and fruit intake, moderate-vigorous physical activity, and physical function (intervention arm vs waitlisted arm, 4.5% vs 3.1%; P = .53) or between-arm differences in vegetable and fruit intake (mean difference, 0.3 [95% CI, -0.1 to 0.7] servings per day; P = .10). The intervention arm experienced a significant improvement in vegetable and fruit intake (mean increase, 0.3 [95% CI, 0.0-0.6] servings per day; P = .04). Significant improvements also were observed in the intervention arm vs waitlisted arm in physical performance (mean difference for 2-minute step test, 6.0 [95% CI, 0.8-11.2] steps; P = .03; for 30-second chair stand, 0.8 [95% CI, 0.1-1.5] repetitions; P = .02), perceived health (8.4 [95% CI, 3.0-13.9] points on a 100-point scale [higher scores indicate better health]; P = .003), and gut microbiome alpha diversity (84.1 [95% CI, 20.5-147.6] more observed species; P = .01). The COVID-19 pandemic significantly moderated effects (eg, odds of improvement in self-reported physical functioning were greater before vs during the pandemic: odds ratio, 2.17; 95% CI, 1.12-4.22; P = .02). Conclusions and Relevance: In this randomized clinical trial including older cancer survivors, a vegetable gardening intervention did not significantly improve a composite index of diet, physical activity, and physical function; however, survivors assigned to the intervention had significantly increased vegetable and fruit consumption and, compared with waitlisted survivors, experienced significant improvements in perceived health and physical performance. Further study in broader populations and during pandemic-free periods is needed to determine definitive benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT02985411.

Palbociclib in adults aged 70 years and older with advanced breast cancer: A phase 2 multicenter trial (Alliance A171601).

INTRODUCTION: Palbociclib is a widely used treatment for advanced breast cancer in older adults. However, the existing evidence regarding its safety and tolerability in this age group is inconsistent and limited to retrospective subgroup or pooled analyses. MATERIALS AND METHODS: We conducted a prospective single-arm multicenter phase 2 study to evaluate the safety and tolerability of palbociclib in participants aged 70 years or older with advanced hormone receptor-positive breast cancer. Participants were given palbociclib in combination with their physician's choice of endocrine therapy (letrozole or fulvestrant). The primary endpoint was the incidence of grade 3+ adverse events (AEs) by six months. Secondary endpoints included AE-related dose delays, dose reductions, early discontinuations, and hospitalizations. Additionally, we compared these endpoints by age groups (70-74 and ≥ 75 years). RESULTS: Of the 90 participants (median age 74 years [70-87]) enrolled, 75.6% (95% confidence interval [CI], 65.4-84.0) had grade 3+ AEs by six months. The most frequent grade 3+ AEs were neutropenia (61%), fatigue (4%), and nausea (3%). Febrile neutropenia was uncommon (1.1%). Due to AEs, 36% had dose delays, 34% had dose reductions, 10% had early discontinuations, and 10% had hospitalizations. Compared to those aged 70-74 years, participants aged ≥75 years had higher rates of early discontinuations (5.9% vs 15.9%, a difference of 9.5% [95% CI 3.5%-22.5%]). DISCUSSION: Palbociclib has an overall favorable safety profile in adults aged ≥70 with advanced breast cancer. However, adults ≥75 years had a trend toward higher rates of AE-related early discontinuations compared to those 70-74 years. Further research is needed to evaluate tolerability and improve the delivery of palbociclib in older adults. CLINICALTRIALS: gov:NCT03633331.

Alzheimer disease-related biomarkers and cancer-related cognitive decline: the Thinking and Living with Cancer study.

PURPOSE: We evaluated whether plasma Alzheimer disease (AD)-related biomarkers were associated with cancer-related cognitive decline among older breast cancer survivors. METHODS: We included survivors aged 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched noncancer control paricipant (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (presystemic therapy) and annually for up to 60 months. Cognition was measured using tests of attention, processing speed, and executive function and learning and memory; perceived cognition was measured by the Functional Assessment of Cancer Therapy-Cognitive Function v3 Perceived Cognitive Impairments. Baseline plasma neurofilament light, glial fibrillary acidic protein, ß-amyloid 42 and 40 and phosphorylated tau 181 were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD biomarkers, time, group (survivor vs control participant), and their 2- and 3-way interactions, controlling for age, race, Wide Range 4 Achievement Test Word Reading score, comorbidity, and body mass index; 2-sided P values of .05 were considered statistically significant. RESULTS: There were no group differences in baseline AD-related biomarkers except survivors had higher baseline neurofilament light levels than control participants (P = .013). Survivors had lower adjusted longitudinal attention, processing speed, and executive function than control participants starting from baseline and continuing over time (P ≤ .002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except control participants had lower attention, processing speed, and executive function scores with higher glial fibrillary acidic protein levels (P = .008). CONCLUSION: The results do not support a relationship between baseline AD-related biomarkers and cancer-related cognitive decline. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers, and examine other mechanisms and factors affecting cognition presystemic therapy.

Functional decline in older breast cancer survivors treated with and without chemotherapy and non-cancer controls: results from the Hurria Older PatiEnts (HOPE) prospective study.

PURPOSE: This study aimed to assess whether physical functional decline in older women with early-stage breast cancer is driven by cancer, chemotherapy, or a combination of both. METHODS: We prospectively sampled three groups of women aged ≥ 65: 444 with early-stage breast cancer receiving chemotherapy (BC Chemo), 98 with early-stage breast cancer not receiving chemotherapy (BC Control), and 100 non-cancer controls (NC Control). Physical function was assessed at two timepoints (T1 [baseline] and T2 [3, 4, or 6 months]) using the Physical Functioning Subscale (PF-10) of the RAND 36-item Short Form. The primary endpoint was the change in PF-10 scores from T1 to T2, analyzed continuously and dichotomously (Yes/No, with "yes" indicating a PF-10 decline > 10 points, i.e., a substantial and clinically meaningful difference). RESULTS: Baseline PF-10 scores were similar across all groups. The BC Chemo group experienced a significant decline at T2, with a median change in PF-10 of -5 (interquartile range [IQR], -20, 0), while BC Control and NC Control groups showed a median change of 0 (IQR, -5, 5; p < 0.001). Over 30% of BC Chemo participants had a substantial decline in PF-10 vs. 8% in the BC Control and 5% in the NC Control groups (p < 0.001). CONCLUSION: In this cohort of older adults with early-stage breast cancer, the combination of breast cancer and chemotherapy contributes to accelerated functional decline. Our findings reinforce the need to develop interventions aimed at preserving physical function, particularly during and after chemotherapy. IMPLICATIONS FOR CANCER SURVIVORS: The high prevalence of accelerated functional decline in older women undergoing breast cancer chemotherapy underscores the urgency to develop interventions aimed at preserving physical function and improving health outcomes. CLINICAL TRIAL: NCT01472094, Hurria Older PatiEnts (HOPE) with Breast Cancer Study.

genRCT: a statistical analysis framework for generalizing RCT findings to real-world population.

When evaluating the real-world treatment effect, the analysis based on randomized clinical trials (RCTs) often introduces generalizability bias due to the difference in risk factors between the trial participants and the real-world patient population. This problem of lack of generalizability associated with the RCT-only analysis can be addressed by leveraging observational studies with large sample sizes that are representative of the real-world population. A set of novel statistical methods, termed "genRCT", for improving the generalizability of the trial has been developed using calibration weighting, which enforces the covariates balance between the RCT and observational study. This paper aims to review statistical methods for generalizing the RCT findings by harnessing information from large observational studies that represent real-world patients. Specifically, we discuss the choices of data sources and variables to meet key theoretical assumptions and principles. We introduce and compare estimation methods for continuous, binary, and survival endpoints. We showcase the use of the R package genRCT through a case study that estimates the average treatment effect of adjuvant chemotherapy for the stage 1B non-small cell lung patients represented by a large cancer registry.

A parental communication assessment initiative in the paediatric cardiovascular ICU.

OBJECTIVE: Challenges to communication between families and care providers of paediatric patients in intensive care units (ICU) include variability of communication preferences, mismatched goals of care, and difficulties carrying forward family preferences from provider to provider. Our objectives were to develop and test an assessment tool that queries parents of children requiring cardiac intensive care about their communication preferences and to determine if this tool facilitates patient-centred care and improves families' ICU experience. DESIGN: In this quality improvement initiative, a novel tool was developed, the Parental Communication Assessment (PCA), which asked parents with children hospitalised in the cardiac ICU about their communication preferences. Participants were prospectively randomised to the intervention group, which received the PCA, or to standard care. All participants completed a follow-up survey evaluating satisfaction with communication. MAIN RESULTS: One hundred thirteen participants enrolled and 56 were randomised to the intervention group. Participants who received the PCA preferred detail-oriented communication over big picture. Most parents understood the daily discussions on rounds (64%) and felt comfortable expressing concerns (68%). Eighty-six percent reported the PCA was worthwhile. Parents were generally satisfied with communication. However, an important proportion felt unprepared for difficult decisions or setbacks, inadequately included or supported in decision-making, and that they lacked control over their child's care. There were no significant differences between the intervention and control groups in their communication satisfaction results. CONCLUSIONS: Parents with children hospitalised in the paediatric ICU demonstrated diverse communication preferences. Most participants felt overall satisfied with communication, but individualising communication with patients' families according to their preferences may improve their experience.

Prediction of cognitive decline in older breast cancer survivors: the Thinking and Living with Cancer study.

PURPOSE: Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment. METHODS: We used the Thinking and Living with Cancer study, a large ongoing multisite prospective study of older breast cancer survivors with complete assessments pre-systemic therapy, 12 months and 24 months after initiation of systemic therapy. Cognition was measured using neuropsychological testing of attention, processing speed, and executive function (APE). CRCD was defined as a 0.25 SD (of observed changes from baseline to 12 months in matched controls) decline or greater in APE score from baseline to 12 months (transient) or persistent as a decline 0.25 SD or greater sustained to 24 months. We used machine learning approaches to predict CRCD using baseline demographics, tumor characteristics and treatment, genotypes, comorbidity, and self-reported physical, psychosocial, and cognitive function. RESULTS: Thirty-two percent of survivors had transient cognitive decline, and 41% of these women experienced persistent decline. Prediction of CRCD was good: yielding an area under the curve of 0.75 and 0.79 for transient and persistent decline, respectively. Variables most informative in predicting CRCD included apolipoprotein E4 positivity, tumor HER2 positivity, obesity, cardiovascular comorbidities, more prescription medications, and higher baseline APE score. CONCLUSIONS: Our proof-of-concept tool demonstrates our prediction models are potentially useful to predict risk of CRCD. Future research is needed to validate this approach for predicting CRCD in routine practice settings.

Cognitive and Cerebrospinal Fluid Alzheimer's Disease-related Biomarker Trajectories in Older Surgical Patients and Matched Nonsurgical Controls.

BACKGROUND: Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults. METHODS: The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid ß (Aß) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls. RESULTS: The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aß, tau, or p-tau levels, or tau/Aß or p-tau/Aß ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 [95% CI, -0.06 to 0.43]; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (ß, -0.31 [95% CI, -0.45 to -0.17]; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up. CONCLUSIONS: During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aß) changes or greater cognitive decline.

Anti-CMV IgG Seropositivity is Associated with Plasma Biomarker Evidence of Amyloid-ß Accumulation.

Background: Some human studies have identified infection with cytomegalovirus (CMV), a member of the alpha herpesvirus family, as a risk factor for Alzheimer's disease and related dementias (ADRD). To our knowledge, no studies have evaluated associations of CMV seropositivity with plasma biomarkers of ADRD risk in middle-aged adults. Objective: In participants recruited for an exercise study, we evaluated cross-sectional associations of CMV seropositivity with: Aß42/Aß40 ratio, a low ratio suggestive of central nervous system Aß accumulation; glial fibrillary acidic protein (GFAP), a measure of neuroinflammation; and neurofilament light (NfL), a measure of neurodegeneration. Methods: Anti-CMV IgG was quantified by ELISA. Plasma ADRD biomarkers were quantified using the ultrasensitive SIMOA assay. We used linear regression to evaluate associations of CMV seropositivity with the ADRD biomarkers, adjusting for age, sex, and race (n = 303; Age = 55.7±9.2 years). For ADRD biomarkers significantly associated with CMV seropositivity, we evaluated continuous associations of anti-CMV IgG levels with the ADRD biomarkers, excluding CMV seronegative participants. Results: 53% of participants were CMV seropositive. CMV seropositivity was associated with a lesser Aß42/Aß40 ratio (ß=-3.02e-03 95% CI [-5.97e-03, -7.18e-05]; p = 0.045). In CMV seropositive participants, greater anti-CMV IgG levels were associated with a lesser Aß42/Aß40 ratio (ß=-4.85e-05 95% CI[-8.45e-05, -1.25e-05]; p = 0.009). CMV seropositivity was not associated with plasma GFAP or NfL in adjusted analyses. Conclusions: CMV seropositivity was associated with a lesser plasma Aß42/Aß40 ratio. This association may be direct and causally related to CMV neuro-cytotoxicity or may be indirect and mediated by inflammatory factors resulting from CMV infection burden and/or the immune response.

Global metabolomics revealed deviations from the metabolic aging clock in colorectal cancer patients.

Background: Markers of aging hold promise in the context of colorectal cancer (CRC) care. Utilizing high-resolution metabolomic profiling, we can unveil distinctive age-related patterns that have the potential to predict early CRC development. Our study aims to unearth a panel of aging markers and delve into the metabolomic alterations associated with aging and CRC. Methods: We assembled a serum cohort comprising 5,649 individuals, consisting of 3,002 healthy volunteers, 715 patients diagnosed with colorectal advanced precancerous lesions (APL), and 1,932 CRC patients, to perform a comprehensive metabolomic analysis. Results: We successfully identified unique age-associated patterns across 42 metabolic pathways. Moreover, we established a metabolic aging clock, comprising 9 key metabolites, using an elastic net regularized regression model that accurately estimates chronological age. Notably, we observed significant chronological disparities among the healthy population, APL patients, and CRC patients. By combining the analysis of circulative carcinoembryonic antigen levels with the categorization of individuals into the "hypo" metabolic aging subgroup, our blood test demonstrates the ability to detect APL and CRC with positive predictive values of 68.4% (64.3%, 72.2%) and 21.4% (17.8%, 25.9%), respectively. Conclusions: This innovative approach utilizing our metabolic aging clock holds significant promise for accurately assessing biological age and enhancing our capacity to detect APL and CRC.

Falls prechemotherapy and toxicity-related hospitalization during adjuvant chemotherapy for breast cancer in older women: Results from the prospective multicenter HOPE trial.

BACKGROUND: Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer. METHODS: In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates. RESULTS: Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003). CONCLUSIONS: In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors.

Geriatric assessment-derived deficit accumulation and patient-reported treatment burden in older adults with bladder cancer.

BACKGROUND: When a person's workload of healthcare exceeds their resources, they experience treatment burden. At the intersection of cancer and aging, little is known about treatment burden. We evaluated the association between a geriatric assessment-derived Deficit Accumulation Index (DAI) and patient-reported treatment burden in older adults with early-stage, non-muscle-invasive bladder cancer (NMIBC). METHODS: We conducted a cross-sectional survey of older adults with NMIBC (≥65 years). We calculated DAI using the Cancer and Aging Research Group's geriatric assessment and measured urinary symptoms using the Urogenital Distress Inventory-6 (UDI-6). The primary outcome was Treatment Burden Questionnaire (TBQ) score. A negative binomial regression with LASSO penalty was used to model TBQ. We further conducted qualitative thematic content analysis of responses to an open-ended survey question ("What has been your Greatest Challenge in managing medical care for your bladder cancer") and created a joint display with illustrative quotes by DAI category. RESULTS: Among 119 patients, mean age was 78.9 years (SD 7) of whom 56.3% were robust, 30.3% pre-frail, and 13.4% frail. In the multivariable model, DAI and UDI-6 were significantly associated with TBQ. Individuals with DAI above the median (>0.18) had TBQ scores 1.94 times greater than those below (adjusted IRR 1.94, 95% CI 1.33-2.82). Individuals with UDI-6 greater than the median (25) had TBQ scores 1.7 times greater than those below (adjusted IRR 1.70, 95% CI 1.16-2.49). The top 5 themes in the Greatest Challenge question responses were cancer treatments (22.2%), cancer worry (19.2%), urination bother (18.2%), self-management (18.2%), and appointment time (11.1%). CONCLUSIONS: DAI and worsening urinary symptoms were associated with higher treatment burden in older adults with NMIBC. These data highlight the need for a holistic approach that reconciles the burden from aging-related conditions with that resulting from cancer treatment.

How I treat anemia in older adults.

ABSTRACT: With the global growing older adult population, clinicians face the common, yet complex challenge of how to evaluate and manage anemia in this population. Older age predisposes to common causes of anemia such as nutritional deficiencies, inflammatory disorders, chronic kidney disease, and hematologic malignancies. Failure to diagnose and appropriately manage anemia may result in decreased quality of life, impaired cognition, impaired mobility, and increased mortality. Anemia diagnosis in older adults presents a diagnostic conundrum because anemia may have a single cause, may be multifactorial, or may have no apparent cause even after an extensive evaluation. We believe a systematic approach to diagnosis ensures appropriate testing and avoids the pitfall of undertreatment and overtreatment. In this article we present our recommended approach through common scenarios for the management of anemia in the older adult.

Exploring the feasibility of using long-term stored newborn dried blood spots to identify metabolic features for congenital heart disease screening.

Congenital heart disease (CHD) represents a significant contributor to both morbidity and mortality in neonates and children. There's currently no analogous dried blood spot (DBS) screening for CHD immediately after birth. This study was set to assess the feasibility of using DBS to identify reliable metabolite biomarkers with clinical relevance, with the aim to screen and classify CHD utilizing the DBS. We assembled a cohort of DBS datasets from the California Department of Public Health (CDPH) Biobank, encompassing both normal controls and three pre-defined CHD categories. A DBS-based quantitative metabolomics method was developed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). We conducted a correlation analysis comparing the absolute quantitated metabolite concentration in DBS against the CDPH NBS records to verify the reliability of metabolic profiling. For hydrophilic and hydrophobic metabolites, we executed significant pathway and metabolite analyses respectively. Logistic and LightGBM models were established to aid in CHD discrimination and classification. Consistent and reliable quantification of metabolites were demonstrated in DBS samples stored for up to 15 years. We discerned dysregulated metabolic pathways in CHD patients, including deviations in lipid and energy metabolism, as well as oxidative stress pathways. Furthermore, we identified three metabolites and twelve metabolites as potential biomarkers for CHD assessment and subtypes classifying. This study is the first to confirm the feasibility of validating metabolite profiling results using long-term stored DBS samples. Our findings highlight the potential clinical applications of our DBS-based methods for CHD screening and subtype classification.