Comparison of serum metabolomics in women with breast Cancer Prior to Chemotherapy and at 1 year: cardiometabolic implications.

OBJECTIVE: Early-stage breast cancer (BC) is the second most common malignancy in women, worldwide. Early-detection and treatment advances have led to 5-year survival rates of 90% for early-stage breast cancer. However, the long-term morbidity of breast cancer remains high, with a majority of survivors facing increased risk of cardiometabolic conditions as well as secondary cancers. In particular, African American women with breast cancer experience higher morbidity and mortality than other women. Metabolomics is the comprehensive study of metabolites in biological samples to elucidate the role of monosaccharides, amino acids, and their respective metabolic pathways. Although some studies have found differential metabolites in women with breast cancer compared to normal controls, there has been little study of women with breast cancer across time and the active treatment trajectory. This study examines and compares the serum metabolomic profile of women with BC, prior to initial chemotherapy and at 1 year after inception of chemotherapy. METHODS: This study examined serum metabolites through a secondary analysis of a longitudinal parent study (EPIGEN) of women diagnosed with early-stage BC. Participants were evaluated across 5 time points: prior to their receipt of chemotherapy (T1), at the time of their 4th chemotherapy treatment (T2), 6 months after the initiation of chemotherapy (T3), one year after the initiation of chemotherapy (T4) and two years after the initiation of chemotherapy (T5). This analysis focused on the metabolomic data from 70 participants from T1 to T4. Using ultra high-pressure liquid chromatography high resolution mass spectrometry (UHPLC-HRMS), we performed Friedman Rank Sum Test followed by Nemenyi post-hoc pairwise tests to identify which metabolite levels differed between time points, focusing on metabolites with a Benjamini-Hochberg false discovery rate (FDR) from the overall Friedman test < 0.05 and then specifically examined the p-values from the T1 vs. T4 pairwise comparison. RESULTS: The untargeted serum metabolomics yielded a total of 2,395 metabolites identified on the basis of the accurate mass and MS/MS fragmentation, 1,264 of which were significant after Friedman's test (FDR < 0.05). The analysis then focused on the levels of 124 metabolites from the T1 vs. T4 post-hoc comparison that had a combined FDR < 0.05 and fold change (FC) > 2.0. Metabolite set enrichment analysis (MSEA) as part of Metaboanalyst 3.0 was performed to identify pathways that were significantly altered. The known metabolites identified from the functional analysis were used to evaluate the up and down regulated pathways. The 40metabolites from the Functional Analysis were mainly attributed to amino acids (specifically lysine regulation), fatty acids (particularly unsaturated) and steroid hormone synthesis (lysophosphatidic acid). CONCLUSION: There were multiple significant changes in the serum metabolomic profile of women with breast cancer at one-year post inception of chemotherapy compared to pre-chemotherapy, most notably associated with lysine degradation, branched-chain amino acid synthesis, linoleic acid metabolism, tyrosine metabolism and biosynthesis of unsaturated fatty acids as the top 5 metabolic pathways. Some of these changes could be associated with metabolic perturbations that are consistent with heightened risk of cardiometabolic morbidity. Our results provide new insights into the mechanisms underlying potential heightened cardiovascular health risks in this population.

The association of wound factors and symptoms of fatigue and pain with wound healing in chronic venous leg ulcers.

The purpose of this study was: (1) to characterise the association of wound area, wound exudate C-reactive protein (CRP), broad-spectrum matrix metalloprotease protein (MMPs), and symptoms of fatigue and pain in individuals with chronic venous leg ulcers (CVLUs) over time and (2) to identify factors associated with the wound healing trajectory in CVLUs. Seventy four participants with CVLU who received weekly sharp debridement were recruited from a wound care clinic during the 8-week study period. To examine associations among wound CRP, MMPs, pain, fatigue, and wound healing trajectory over time, we calculated Bayes factors (BF) based on a linear mixed model. The mean age of participants was 71.8 (SD = 9.8) and the mean wound area was 2278 mm2 (SD = 7085 mm2 ) at baseline. Higher fatigue was strongly associated with higher MMPs (BF = 9, 95% HDI: [-.05, .43]), lower CRP (BF = 11, 95% HDI: [-.02, .002]), and large areas of wound (BF = 20, 95% HDI: [-.001, .01]). Higher CRP and MMPs activity in wound exudate and higher fatigue were associated with a larger wound area. To facilitate wound healing, clinicians need to utilise the multifactorial approach, which includes wound treatment and management of symptoms such as pain and fatigue, because of the molecular and psycho-behavioural factors involved in wound healing.

Exploring the relationship between DNA methylation age measures and psychoneurological symptoms in women with early-stage breast cancer.

PURPOSE: The epigenetic clock has been acknowledged as an indicator for molecular aging, but few studies have examined possible associations of DNA methylation (DNAm) age or age acceleration (AA) with symptom burden in individuals who are treated for cancer. This study explored the association of DNAm age or AA with psychoneurological (PN) symptoms, including cognitive impairment, fatigue, sleep disturbances, pain, and depressive symptoms, in breast cancer survivors over a 2-year period. METHODS: We measured PN symptoms using reliable instruments and DNAm levels by Infinium HumanMethylation450K BeadChip (N = 72). DNAm age was calculated by the Horvath, Grim, and Hannum-based intrinsic and extrinsic age estimations. AA was defined by the residual regressing estimated epigenetic age on chronological age. Mixed regression models were fitted for AA and changes in AA to study the association over time. Separate linear regression models and a mixed-effects model were fitted for AA at each time point. RESULTS: Horvath-AA, Grim-AA, and extrinsic epigenetic AA were significantly changed over time, while intrinsic epigenetic AA did not exhibit any temporal changes. Increased AA was associated with greater anxiety and fatigue, as well as worse cognitive memory, adjusting for race, BMI, income, chemotherapy, radiation therapy, and chronological age. Increased DNAm age was associated with greater anxiety over 2 years. CONCLUSION: Our findings suggest DNAm age and AA may be associated with PN symptoms over the course of cancer treatment and survivorship. Some PN symptoms may be amenable to preventive interventions targeted to epigenetic clocks that influence aging-associated processes.

Longitudinal Analysis of Sleep Disturbance in Breast Cancer Survivors.

BACKGROUND: Breast cancer survivors (BCS) often report poor sleep quality and wakefulness throughout the night as the greatest challenges experienced during and posttreatment. OBJECTIVES: This study aimed to elucidate characteristics of sleep disturbances and determine potential predictors that affect sleep disturbances in BCS for 2 years postchemotherapy. METHODS: This is a secondary analysis of data from the EPIGEN study, which longitudinally examined sociodemographic and cancer-related factors, lifestyle, symptom characteristics, and epigenetic factors at baseline prior to chemotherapy (T1), the midpoint (T2), 6-month (T3), 1-year (T4), and 2-year (T5) time points postchemotherapy. Temporal lifestyle changes, symptom characteristics, and epigenetic factors were explored using linear mixed-effects models with a random intercept. A linear regression model was fitted to identify significant predictors of sleep disturbances at each time point. RESULTS: In 74 BCS with an average age of 51 years and 70% non-Hispanic White, BCS experienced severe sleep disturbances at T2, which gradually improved over time. Significant temporal changes in midsleep awakenings, early awakenings, and fatigue at work were observed, with disturbances being elevated at T2. Anxiety (T1, T2, and T4), fatigue (T3 and T4), and perceived stress (T3) were significant predictors after adjusting for radiation therapy, surgery, and adjuvant endocrine therapy. DISCUSSION: This study highlights that predictors of sleep disturbances change over time, with anxiety being a factor earlier in the treatment trajectory (prechemotherapy) and continuing over time with fatigue and perceived stress being involved later in the treatment trajectory. Our results indicate that symptom management strategies to address sleep disturbances should be tailored to the temporal factors that may change in severity during active treatment and early survivorship period. Findings gained from this study on sleep disturbance patterns and the potential risk factors can be incorporated into clinical practice in planning education and developing interventions.

Telomere lengths in women treated for breast cancer show associations with chemotherapy, pain symptoms, and cognitive domain measures: a longitudinal study.

BACKGROUND: Survival rates for breast cancer (BC) have improved, but quality of life post-diagnosis/treatment can be adversely affected, with survivors reporting a constellation of psychoneurological symptoms (PNS) including stress, anxiety, depression, pain, fatigue, sleep disturbance, and cognitive dysfunction. METHODS: To assess a potential relationship between telomere length (TL) and the development/persistence of PNS, we longitudinally studied 70 women (ages 23-71) with early stage BC (I-IIIA) at 5 time-points: prior to treatment (baseline), the mid-point of their chemotherapy cycle, 6 months, 1 year, and 2 years following the initiation of chemotherapy. Measures quantified included assessments of each of the PNS noted above and TL [using both a multiplex qPCR assay and a chromosome-specific fluorescence in situ hybridization (FISH) assay]. RESULTS: Variables associated with qPCR mean TLs were age (p = 0.004) and race (T/S ratios higher in Blacks than Whites; p = 0.019). Significant differences (mostly decreases) in chromosome-specific TLs were identified for 32 of the 46 chromosomal arms at the mid-chemo time-point (p = 0.004 to 0.049). Unexpectedly, the sequential administration of doxorubicin [Adriamycin], cyclophosphamide [Cytoxan], and docetaxel [Taxotere] (TAC regimen) was consistently associated with higher TLs, when compared to TLs in women receiving a docetaxel [Taxotere], Carboplatin [Paraplatin], and trastuzumab [Herceptin] [TCH] chemotherapy regimen [association was shown with both the qPCR and FISH assays (p = 0.036)]. Of the PNS, pain was significantly negatively associated with TL (higher pain; shorter telomeres) for a subset of chromosomal arms (5q, 8p, 13p, 20p, 22p, Xp, Xq) (p = 0.014-0.047). Chromosomal TLs were also associated with 7 of the 8 cognitive domains evaluated, with the strongest relationship being noted for chromosome 17 and the visual memory domain (shorter telomeres; lower scores). CONCLUSIONS: We showed that race and age were significantly associated with telomere length in women treated for early stage BC and that acquired telomere alterations differed based on the woman's treatment regimen. Our study also demonstrated that pain and cognitive domain measures were significantly related to telomere values in this study cohort. Expanding upon the knowledge gained from this longitudinal study could provide insight about the biological cascade of events that contribute to PNS related to BC and/or its treatment.

Global Metabolomics in Allogeneic Hematopoietic Cell Transplantation Recipients Discordant for Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) remains a significant late effect issue for allogeneic hematopoietic cell transplantation (allo-HCT) survivors, contributing to morbidity and mortality. The etiology of cGVHD is not well elucidated. Owing to a lack of early diagnostic tests and pathophysiology ambiguity, targeted treatments remain limited. Biomarkers for prediction, control response, or prognostication have not yet been identified. Metabolomics, the quantification of metabolites, is a potential biomarker of cGVHD but has not been evaluated in this population. In this study, we examined global metabolites of stored plasma to identify differentially expressed metabolites of individuals discordant for cGVHD following allo-HCT. A descriptive, comparative, cross-sectional study design was used to examine differentially expressed metabolites of plasma samples obtained from 40 adult allo-HCT recipients (20 with cGVHD and 20 without cGVHD) from 2 parent studies. Metabolomics profiling was conducted at the University of Florida's Southeast Center for Integrative Metabolomics. Full experimental methods followed a previously published method. All statistical analyses were performed by a PhD-prepared, trained bioinformatics statistician. There were 10 differentially expressed metabolites between participants with cGVHD and those without cGVHD. Differential metabolites included those related to energy metabolism (n = 3), amino acid metabolism (n = 3), lipid metabolism (n = 2), caffeine metabolism (n = 1), and neurotransmission (n = 1). Serotonin had the greatest fold change (21.01). This study suggests that cGVHD may be associated with expanded cellular energy and potentially mitochondrial dysfunction. The differential metabolic profile between patients with and without cGVHD indicates metabolic perturbations that merit further exploration as potential biomarkers of cGVHD. These findings support the need for further examination using a larger, prospective study design to identify metabolomic risk factors that may signal the need for earlier preventive measures and earlier treatment to reduce cGVHD.

Baseline Gut Microbiota Composition Is Associated with Major Infections Early after Hematopoietic Cell Transplantation.

Infection is a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Gut microbiota (GM) composition and metabolites provide colonization resistance against dominance of potential pathogens, and GM dysbiosis following HCT can be deleterious to immune reconstitution. Little is known about the composition, diversity, and evolution of GM communities in HCT patients and their association with subsequent febrile neutropenia (FN) and infection. Identification of markers before HCT that predict subsequent infection could be useful in developing individualized antimicrobial strategies. Fecal samples were collected prospectively from 33 HCT recipients at serial time points: baseline, post-conditioning regimen, neutropenia onset, FN onset (if present), and hematologic recovery. GM was assessed by 16S rRNA sequencing. FN and major infections (ie, bloodstream infection, typhlitis, invasive fungal infection, pneumonia, and Clostridium difficile enterocolitis) were identified. Significant shifts in GM composition and diversity were observed during HCT, with the largest alterations occurring after initiation of antibiotics. Loss of diversity persisted without a return to baseline at hematologic recovery. GM in patients with FN was enriched in Mogibacterium, Bacteroides fragilis, and Parabacteroides distasonis, whereas increased abundance of Prevotella, Ruminococcus, Dorea, Blautia, and Collinsella was observed in patients without fever. A baseline protective GM profile (BPGMP) was predictive of protection from major infection. The BPGMP was associated with subsequent major infections with 77% accuracy and an area under the curve of 79%, with sensitivity, specificity, and positive and negative predictive values of 0.71, 0.91, 0.77, and 0.87, respectively. Our data show that large shifts in GM composition occur early after HCT, and differences in baseline GM composition are associated with the development of subsequent major infections.

Dietary Intake and Diet Quality of Hematopoietic Stem Cell Transplantation Survivors.

Hematopoietic stem cell transplantation (HCT) survivors are burdened by a high prevalence and early onset of chronic diseases. Healthy dietary patterns have been associated with lower risks of chronic health conditions in the general population. HCT survivors are susceptible to multiple complications that may result in chronic illness. Unfortunately, no study to date has comprehensively documented the adherence of HCT survivors to the Dietary Guidelines for Americans (DGA), which are designed specifically to provide guidance for making healthy food choices. The primary aim of this study was to evaluate diet quality and nutrient intake adequacy of HCT survivors. A secondary aim was to assess these survivors' willingness to take part in a future dietary intervention. The dietary intake of adults who had undergone autologous or allogeneic HCT for a hematologic disease and were at least 1 year post-transplantation was assessed using the Block 2014 food frequency questionnaire, and diet quality was estimated using the Healthy Eating Index 2015. Nutrient intake adequacies of the group were estimated by the estimated average requirement cutpoint method. Survivors' (n = 90) HEI-2015 scores averaged 61.6 ± 1.1. Adherence to a good-quality diet was reported by only 10% of survivors. Intakes of vitamins A, C, and D, as well as magnesium and calcium, suggested inadequacy. Fiber intake at 8.9 g per 1000 kcal/day fell below the recommended adequate intake. "Change in taste" was associated with lower quality of diet (P = .02). HCT survivors within 2 years post-transplantation were more receptive than survivors beyond 2 years to participating in a dietary intervention (95% versus 65%; P = .0013). Adult HCT survivors reported less-than-optimal adherence to the 2015-2020 DGA and had numerous shortfall nutrient intakes; however, their willingness to participate in a dietary intervention was relatively high. These findings reinforce the need to incorporate nutrition into HCT survivor care.

Consortium Building for Nurse Scientists Interested in Symptoms Research in the Era of Precision Health.

PURPOSE: This article aims to provide perspectives on the establishment of a consortium for nurse scientists with similar career trajectories interested in cancer-related symptoms (CRS) research. Hereby, we describe the development of and recent outcomes from the CRS consortium, the lessons learned in establishing the consortium, and future directions to advance the science of CRS. MODEL AND METHODS: New and innovative strategies are needed to address the complexity of CRS research. A CRS consortium was created to allow a mechanism for oncology nurse scientists with varying expertise to collaborate to advance CRS research. The National Institutes of Health (NIH) Symptom Science Model (SSM) guides the research of the CRS Consortium. DISCUSSION AND CONCLUSIONS: A need for improved CRS assessment and management has been identified. The CRS consortium was created as a collaborative think tank to begin to address this need. Guided by the NIH SSM, CRS consortium members have worked to define symptom phenotypes, enhance understanding of the biologic mechanisms that can contribute to symptom phenotypes, and develop tailored interventions to improve symptom management. Dissemination of the CRS consortium efforts involve publications and presentations. CLINICAL IMPLICATIONS: Nurse scientists interested in symptom science and biobehavorial research face many challenges on how to initiate and sustain independent programs of research. Through the formation of a CRS consortium, oncology nurse scientists can work together to address identified issues in symptom measurement and management.

Ocular Graft-versus-Host Disease after Hematopoietic Cell Transplantation: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.

Ocular graft-versus-host disease (GVHD) occurs in more than one-half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity that affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed. Ocular GVHD involves at least 3 biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have identified several novel pathogenic mechanisms, including the renin angiotensin system and endoplasmic reticulum stress signaling, which can be targeted by therapeutic agents. Numerous studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. The efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important that all health professionals caring for HCT recipients have adequate knowledge of ocular GVHD to provide optimal care.

Relationship of fatigue with cognitive performance in women with early-stage breast cancer over 2 years.

OBJECTIVE: Fatigue and cognitive dysfunction are major concerns for women with early-stage breast cancer during treatment and into survivorship. However, interrelationships of these phenomena and their temporal patterns over time are not well documented, thus limiting the strategies for symptom management interventions. In this study, changes in fatigue across treatment phases and the relationship among fatigue severity and its functional impact with objective cognitive performance were examined. METHODS: Participants (N = 75) were assessed at five time points beginning prior to chemotherapy to 24 months after initial chemotherapy. Fatigue severity and impact were measured on the Brief Fatigue Inventory. Central nervous system (CNS) Vital Signs was used to measure performance based cognitive testing. Temporal changes in fatigue were examined, as well as the relationship between fatigue and cognitive performance, at each time point using linear mixed effect models. RESULTS: Severity of fatigue varied as a function of phase of treatment. Fatigue severity and its functional impact were moderate at baseline, increased significantly during chemotherapy, and returned to near baseline levels by 2 years. At each time point, fatigue severity and impact were significantly associated with diminished processing speed and complex attention performance. CONCLUSIONS: A strong association between fatigue and objective cognitive performance suggests that they are likely functionally related. That cognitive deficits were evident at baseline, whereas fatigue was more chemotherapy dependent, implicates that two symptoms share some common bases but may differ in underlying mechanisms and severity over time. This knowledge provides a basis for introducing strategies for tailored symptom management that vary over time.

Development of the PROMIS-based Research Assessment and Clinical Tool-Fatigue (ReACT-F).

PURPOSE: Evidence has shown that cancer-related fatigue (CRF) may be a treatment-limiting symptom and often impairs health-related quality of life. Accurate assessment of the multidimensional nature of CRF could help drive interventions to mitigate this debilitating symptom. Currently, there are no clinical tools to effectively and efficiently assess the multidimensionality of CRF. The purpose of this paper is to introduce a CRF-specific short form that can assess the multidimensional nature of CRF for use in the clinical setting. METHODS: The CRF-specific short form was developed using the 95-item PROMIS® fatigue bank. Bi-factor analysis was used to evaluate dimensionality of the alternative model using fatigue for the general factor and physical, cognitive, affective, global, and motivational for the local factors. After unidimensionality was confirmed (loading factor > 0.3), one item from each local factor was selected using discrimination power for inclusion in the CRF-specific short form. RESULTS: The Research Assessment and Clinical Tool-Fatigue (ReACT-F) was created from the 95-item PROMIS fatigue bank using established item parameters. The ReACT-F assesses five common dimensions of CRF as well as perceived burden of the fatigue dimensions. CONCLUSIONS: The ReACT-F is a CRF-specific self-report short form that addresses the need for a brief, clinically useful tool to quickly assess the multidimensional nature of CRF. We anticipate that the ReACT-F can be completed in the clinical setting in approximately 3 minutes, providing clinicians with meaningful data to drive personalized interventions. Further validation of the ReACT-F is highly encouraged.

Systematic review of genetic polymorphisms associated with psychoneurological symptoms in breast cancer survivors.

PURPOSE: Psychoneurological (PN) symptoms, such as anxiety, cognitive impairment, depression, fatigue, sleep disturbances, and pain, are highly prevalent in breast cancer patients undergoing cancer treatment. Emerging evidence suggests that genetic polymorphisms may contribute to differential symptom susceptibility. We aimed to systematically review associations between genetic polymorphisms and PN symptoms during or after cancer treatment for early-stage breast cancer. METHODS: Twenty-six eligible articles published until October 2017 were identified in PubMed, PsycINFO, Web of Science, and additional records. Information on study characteristics, genetic polymorphisms, and PN symptoms was extracted. Study quality was evaluated by the STrengthening the REporting of Genetic Association (STREGA) guideline. Genes included in the analysis were categorized by biological pathways based on the Reactome database. RESULTS: A total of 54 single nucleotide polymorphisms and haplotypes that are significantly associated with PN symptoms were identified; half of them were associated with increased severity of PN symptoms, while the other half contributed to the decrease of PN symptoms. Pain has the known highest number of associated genetic polymorphisms reported, followed by fatigue, cognitive impairment, depressive symptoms, sleep disturbances, and anxiety. The majority of genetic polymorphisms were involved in immune system and neuronal system pathways. Most studies were unsuccessful in meeting the STREGA guideline, which requires transparent reporting of methods and results. CONCLUSIONS: This review provides comprehensive evidence of genetic polymorphisms underlying PN symptoms, which may pave the way for the development of personalized therapeutics targeting these symptoms. More well-designed genome-wide association studies are required to validate and replicate these findings.

Neurocognitive Dysfunction in Hematopoietic Cell Transplant Recipients: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Complications and Quality of Life Working Party of the European Society for Blood and Marrow Transplantation.

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and nonmalignant diseases. Despite increasing survival rates, long-term morbidity after HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction after HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction after HCT. In this review we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Finally, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae after HCT.

Relationships among psychoneurological symptoms and levels of C-reactive protein over 2 years in women with early-stage breast cancer.

PURPOSE: The aim of the present study was to explore clusters of psychoneurological symptoms and inflammation (levels of C-reactive protein) over time in a cohort of women with early-stage breast cancer. Specifically, we examined the relationships among affective symptoms (depression, anxiety, fatigue, sleep disturbances, pain, and perceived stress), domains of cognitive performance, and levels of peripheral C-reactive over a period of 2 years. METHODS: This was a prospective, longitudinal study of 77 women diagnosed with early-stage breast cancer. Data collection, including symptom questionnaires, performance-based cognitive testing, and blood draws, took place at 5 time points: prior to initiating adjuvant chemotherapy, prior to the fourth chemotherapy treatment, and at 6, 12, and 24 months after the initiation of chemotherapy. RESULTS: Exploratory factor analysis with varimax orthogonal rotation was used to examine the covariance among symptoms at each visit. Using the factor scores and weighted sums, three clusters were identified: global cognition, affective symptoms, and cognitive efficiency. Peripheral levels of C-reactive protein were inversely correlated with the cognitive efficiency factor across time. CONCLUSIONS: The findings suggest that objectively measured domains of cognitive function occur independently of other affective symptoms that are commonly reported by women with breast cancer in long-term survivorship. The cognitive efficiency symptom cluster may be amenable to interventions targeted to biological influences that reduce levels of C-reactive protein.

Daily olive oil intake is feasible to reduce trigeminal neuralgia facial pain: A pilot study.

Extra virgin olive oil (EVOO) is thought to contribute to neuroprotection and, thus, may influence pain symptoms experienced by adults with demyelination-related trigeminal neuralgia (TN). This study aimed to determine the feasibility of daily intake of EVOO and its potential to alleviate facial pain of TN. Adults, self-reporting as female and affected by TN, were enrolled in a 16-week nonblinded, parallel study. After a 4-week baseline, participants were randomized to 60 mL/day EVOO or control (usual diet and no supplemental EVOO) for 12 weeks. Participants completed a daily questionnaire on pain intensity and compliance, the Penn Facial Pain Scale weekly, the 36-Item Short Form Survey monthly, and dietary assessment during baseline and intervention. Participants (n = 52; 53.3 ± 12.9 years) were recruited nationally; 42 completed the study. The EVOO group, with 90% intake compliance, showed significant decreases in the Penn Facial Pain Scale items of interference with general function, interference with orofacial function, and severity of pain from baseline, whereas the control group showed no improvements. EVOO benefit, compared with control, trended for the interference with orofacial function (P = .05). The 36-Item Short Form Survey items of role limitations resulting from emotional problems and role limitations from physical health favored EVOO. The EVOO group significantly improved their Healthy Eating Index 2015 component scores of fatty acids (primarily from increased oleic acid), sodium, and refined grains. EVOO intake of 60 mL/day was feasible for participants experiencing TN and may mitigate pain and improve quality of life. This trial was registered at clinicaltrials.gov (NCT05032573).

Sleep, Fatigue, and Inflammatory Biomarkers in Older Adults with Chronic Venous Leg Ulcers Receiving Intensive Outpatient Wound Care.

Objective: Chronic venous ulcers are a relatively common and distressing condition that disproportionately affects older individuals. Along with multiple concomitant issues such as wound drainage, pain, and mobility impairments, individuals with chronic venous leg ulcers (CVLUs) commonly report sleep disturbances and fatigue; however, limited research has examined these symptoms in relation to inflammatory biomarkers in this population over the intensive wound care treatment trajectory. This study aimed at describing the symptoms of sleep and fatigue in older adults with CVLUs receiving intensive wound treatment with weekly debridement and exploring the relationships between these symptoms and tumor necrosis factor-alpha (TNF-α), c-reactive protein (CRP), and interleukin (IL)-6. Approach: Demographics, clinical characteristics, Pittsburgh Sleep Quality Index (PSQI) scores, Brief Fatigue Inventory (BFI), TNF-α, CRP, and IL-6 levels were collected from 84 older adults with CVLUs at three time points (baseline, week 4, and week 8). Data analysis included descriptive statistics and Bayesian estimation of associations. Results: Findings showed a consistent pattern of poor sleep quality and mild fatigue among these individuals. Lower IL-6 levels at week 4 and higher CRP levels at week 8 were linked to poor sleep quality. Higher CRP levels were linked to greater fatigue at baseline and week 8. Sleep and fatigue were correlated at all time points. Innovation and Conclusion: This study highlights the importance of clinicians evaluating sleep and fatigue in those with CVLUs. Further research is needed to validate circulating inflammatory biomarkers to enhance our understanding of sleep and fatigue's role in wound healing.

Association of Tryptophan: Kynurenine Metabolites with Healing in Chronic Venous Leg Ulcers.

OBJECTIVE: Chronic wound healing is a complex process that is still not well understood. The tryptophan (TRP)-L-Kynurenine (KYN) pathway has recently been under increased scrutiny in regards to wound healing. The study applied metabolomics to elucidate the TRP-L- KYN pathway associated with wound healing in chronic venous leg ulcers (CVLUs). APPROACH: This study used a longitudinal comparative design of 60 serum samples collected from 30 older adult patients with CVLUs, receiving weekly sharp debridement at a wound clinic. The serum samples were collected at baseline and week 4 (healed wounds) or week 8 (non-healed wounds). Liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to analyze targeted metabolites. A Bayesian approach was employed to examine robust correlations between changes in metabolite values and linear healing slope and to compare by group. RESULTS: The mean age was 71.13 (±9.46). Half of the sample were female and the minority (17%) were Black. The mean values of evaluated metabolites for the non-healed group were consistently lower than those for the healed group. The healed group (n=12) had higher KYN values; Those on a healing trajectory (n=23) had lower KYN levels and higher TRP levels at baseline and over time. There was moderate support (Bayes Factor = 3.70) for a negative association between change in Kynurenic Acid and linear healing slope (r = -0.35, CrI = -0.62, -0.04, PD= 98%). Results suggest KYN and TRP may be markers for healing in individuals with CVLUs. INNOVATION AND CONCLUSION: Gaining a better understanding of the associations between the TRP-L- KYN pathway and the healing of CVLUs may help to clarify the links of inflammation with the rate and success of wound healing. Biomarker development focused on the TRP-L- KYN pathway could be pursued, if the associations are further supported by focused research studies.

Biomarkers of sleep disturbance in adults with chronic illness: A scoping review.

OBJECTIVES: The purpose of this scoping review was to identify which biomarkers for sleep disturbance were the most prevalent and significant in the literature across chronic illnesses. METHODS: A scoping review was conducted, following Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, to provide a map of the existing literature on the biomarkers of sleep disturbance in adults with chronic illness. Peer-reviewed articles published between 2010-2020 were included if they measured a biomarker and discussed sleep deprivation, disturbance, or dysfunction secondary to a chronic illness. RESULTS: A total of 21 articles were included and synthesized using data charting. There were 24 different biomarkers identified, most commonly collected through serum. Biomarkers were grouped, then biomarkers and correlations with sleep were identified and mapped. DISCUSSION: Overall, the most common biomarkers studied were interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), c-reactive protein (CRP), and interleukin-1 beta (IL-1ß). Cytokines were the most commonly studied biomarkers, with a majority of studies focusing on pro-inflammatory cytokines. Based on the results of this review, CRP, IL-6, TNF-α, and erythrocyte sedimentation rate (ESR) showed themost significant correlations with sleep across all chronic illnesses. Future research is still needed to identify an ideal biomarker for sleep disturbance that can be used across chronic illnesses.

A scoping review of psychological distress instruments in women with early-stage breast cancer during chemotherapy.

BACKGROUND: Psychological distress is associated with worsening symptoms during the active treatment period and lower quality of life in women with early-stage breast cancer. Many studies have indicated risk for heightened psychological distress across the breast cancer trajectory. PURPOSE: The aim of this review is to examine the literature for instruments used to measure psychological distress among women with breast cancer during chemotherapy. METHODS: This study used the Arksey and O'Malley framework of scoping reviews. Two databases, PubMed & CINAHL, were searched for peer-reviewed original articles that were published within the last ten years, included participants with a diagnosis of breast cancer stages I to III, and receiving chemotherapy, English text articles, and studies that report psychological distress measures. FINDINGS: The initial screening yielded 529 relevant studies. After applying the exclusion criteria, a total of 17 studies concerning the assessment of psychological distress during chemotherapy were retained for the analysis of variables and measures of psychological distress. The instruments used to measure psychological distress varied, with a total of 21 measures. The most frequently utilized measure was the Hospital Anxiety and Depression Scale (n = 5), followed by the Impact of Event Scale (n = 2), the Distress Thermometer (n = 2), and the Perceived Stress Scale (n = 2). CONCLUSION: This review identified the gaps related to inconsistencies in the operationalization and instruments used to measure psychological distress among breast cancer survivors during chemotherapy. Standardization of measures assessing psychological distress, along with conceptual clarity, is essential for measuring distress in research and clinical practice.