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.

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.

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.

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.

Predictors of Time to Aneurysm Repair and Mortality in Aneurysmal Subarachnoid Hemorrhage.

ABSTRACT: BACKGROUND : Prompt aneurysm repair is essential to prevent rebleeding after aneurysmal subarachnoid hemorrhage. To date, most studies on this topic have focused on 1 set of predictors (eg, hospital or patient characteristics) and on 1 outcome (either time to aneurysm repair or mortality). The purpose of this study was to test a model that includes hospital and patient characteristics as predictors of time to aneurysm repair and mortality, controlling for disease severity and comorbidity, and considering time to aneurysm repair as a potential influence in these relationships. METHODS : A sample of aneurysmal subarachnoid hemorrhage patients with a principal procedure of clipping or coiling was selected (n = 387) from a statewide administrative database for cross-sectional retrospective analysis. The primary study outcome was in-hospital mortality. Independent variables were level of stroke center, age, race, sex, and type of aneurysm repair. Hierarchical logistic regression was used to estimate the probability of in-hospital death. RESULTS : Patients who underwent a coiling procedure were more likely to be treated within the first 24 hours of admission compared with those undergoing clipping (odds ratio, 0.54; 95% CI, 0.35-0.84; P = .01). Patients treated at a certified comprehensive stroke center (CSC) had a 72% reduction in odds of death compared with those treated at primary stroke centers (odds ratio, 0.28; 95% CI, 0.10-0.77; P = .01), after controlling for disease severity and comorbid conditions. Time to aneurysm repair was not significantly associated with mortality and did not influence the relationship between hospital and patient characteristics and mortality. CONCLUSION : Our results indicate that treatment at a CSC was associated with a lower risk of in-hospital mortality. Time to aneurysm repair did not influence mortality and did not explain the mortality benefit observed in CSCs. Research is needed to explore interdisciplinary hospital factors including nursing and nurse-sensitive interventions that may explain the relationship between CSCs and mortality outcomes.

Biobehavioral Implications of Covid-19 for Transplantation and Cellular Therapy Recipients.

A growing body of literature has emphasized the importance of biobehavioral processes - defined as the interaction of behavior, psychology, socioenvironmental factors, and biological processes - for clinical outcomes among transplantation and cellular therapy (TCT) patients. TCT recipients are especially vulnerable to distress associated with pandemic conditions and represent a notably immunocompromised group at greater risk for SARS-CoV-2 infection with substantially worse outcomes. The summation of both the immunologic and psychologic vulnerability of TCT patients renders them particularly susceptible to adverse biobehavioral sequelae associated with the Covid-19 pandemic. Stress and adverse psychosocial factors alter neural and endocrine pathways through sympathetic nervous system and hypothalamic-pituitary-adrenal axis signaling that ultimately affect gene regulation in immune cells. Reciprocally, global inflammation and immune dysregulation related to TCT contribute to dysregulation of neuroendocrine and central nervous system function, resulting in the symptom profile of depression, fatigue, sleep disturbance, and cognitive dysfunction. In this article, we draw upon literature on immunology, psychology, neuroscience, hematology and oncology, Covid-19 pathophysiology, and TCT processes to discuss how they may intersect to influence TCT outcomes, with the goal of providing an overview of the significance of biobehavioral factors in understanding the relationship between Covid-19 and TCT, now and for the future. We discuss the roles of depression, anxiety, fatigue, sleep, social isolation and loneliness, and neurocognitive impairment, as well as specific implications for sub-populations of interest, including pediatrics, caregivers, and TCT donors. Finally, we address protective psychological processes that may optimize biobehavioral outcomes affected by Covid-19.

Blood-based biomarkers of cancer-related cognitive impairment in non-central nervous system cancer: A scoping review.

This scoping review was designed to synthesize the extant literature on associations between subjective and/or objective measures of cancer-related cognitive impairment (CRCI) and blood-based biomarkers in adults with non-central nervous system cancers. The literature search was done for studies published from the start of each database searched (i.e., MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, grey literature) through to October 20, 2021. A total of 95 studies are included in this review. Of note, a wide variety of biomarkers were evaluated. Most studies evaluated patients with breast cancer. A variety of cognitive assessment measures were used. The most consistent significant findings were with various subjective and objective measures of CRCI and levels of interleukin-6 and tumor necrosis factor. Overall, biomarker research is in an exploratory phase. However, this review synthesizes findings and proposes directions for future research.

Factors Associated With Emergency Department Length of Stay and In-hospital Mortality in Intracerebral Hemorrhage Patients.

ABSTRACT: BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is a medical emergency that requires rapid identification and focused assessment early to ensure the best possible outcomes. The purpose of this study is to evaluate the associations between system and patient factors and emergency department (ED) length of stay and in-hospital mortality in patients given a diagnosis of ICH. METHODS: A sample of 3108 ICH patients was selected from a statewide administrative database for cross-sectional retrospective analysis. System characteristic (hospital stroke certification), patient characteristics (age, sex, and race), and covariate conditions (stroke severity and comorbidities) were analyzed using descriptive statistics and hierarchical logistic regression models to address the study questions. RESULTS: The mean ED length of stay is 2.9 ± 3 hours (range, 0-42 hours) before admission to an inpatient unit. Inpatient mortality is 14.9%. Stroke center certification (P < .000) and stroke severity (P ≤ .000) are significant predictors of ED length of stay, whereas age (P < .000), stroke severity (P < .000), comorbidities (P = .047), and ED length of stay (P = .04) are significant predictors of in-hospital mortality. Most notably, an ED length of stay of 3 hours or longer has a 37% increase in the odds of in-hospital mortality. CONCLUSION: Our findings support age, stroke severity, and ED length of stay as predictors of in-hospital mortality for ICH patients. The importance of timely admission to an inpatient unit is emphasized. Optimal systems of care and expedited inpatient admission are vital to reduce morbidity and mortality for ICH stroke patients.

Gut Microbiota Dysbiosis Associated with Persistent Fatigue in Hematopoietic Cell Transplantation Survivors.

Fatigue is one of the most prevalent and distressing complications among hematopoietic stem cell transplantation (HCT) survivors, negatively affecting physical, social, and emotional domains of quality of life. Chronic systemic inflammation has been linked to alterations in nervous system activity and initiation of distressing symptoms, such as fatigue. Damage to gut mucosa due to alteration in gut microbiota (GM) composition and microbial translocation has been shown to increase systemic proinflammatory cytokines. The aim of this study was to evaluate the relationship between fatigue and GM by measuring the differences in GM composition in HCT survivors with and without persistent fatigue. This cross-sectional study included 30 adults who underwent HCT for a hematologic disease and were at least 1 year post-HCT. Patients with chronic graft-versus-host disease were excluded. Fatigue severity was assessed by the Brief Fatigue Inventory (BFI). Based on the BFI score, patients were grouped into 2 categories: 0 to 3 (without fatigue) and ≥4 (with fatigue). The V1 to V3 region of the 16S rRNA gene from fecal specimens was sequenced using the Illumina MiSeq. Sequencing reads were processed, denoised, and replicated, chimeras were filtered, amplicon sequence variants (ASVs) were generated, and taxonomy was assigned using DADA2. Beta diversity analysis through principal coordinate analysis was generated using the Bray-Curtis dissimilarity matrix, and the difference was tested using linear model with generalized least squares in R. An alpha diversity analysis was performed using Chao1. Linear discriminant analysis effect size (LEfSe) was used to find markers that differ between the 2 groups. Based on the BFI results, patients were categorized into 2 cohorts: with fatigue (n = 14) and without fatigue (n = 16). The 2 cohorts were similar in terms of demographics, disease, and transplant characteristics. Based on the GM analysis, there was a significant difference in GM composition (beta diversity) between the 2 cohorts (P = .001). Alpha diversity (richness) was also significantly lower in survivors with fatigue (P =.002). LEfSe analysis identified 46 discriminative features (P < .05; linear discriminant analysis score >2) whose relative abundance varied significantly among individuals with fatigue and those without fatigue. Ten ASVs were associated with the patients with fatigue, and 36 ASVs were associated with those without fatigue. Several ASVs enriched in survivors with fatigue included organisms such as Klebsiella and Enterococcus, which have been implicated in inflammatory bowel diseases. The ASVs enriched in the cohort without fatigue were members of the Ruminococcaceae family (Oscillospira spp) and the Lachnospiraceae family (Fusicatenibacter and Coprococcus spp), which are known to have the ability to ferment complex plant carbohydrates. These findings show an association between GM composition and fatigue and suggest a microbial contribution to clinically significant fatigue post-HCT, which may guide the development of new approaches to treating fatigue based on manipulation of the GM.

Exploring Associations Between Metabolites and Symptoms of Fatigue, Depression and Pain in Women With Fibromyalgia.

Fibromyalgia (FM) is a chronic noncommunicable disorder characterized by a constellation of symptoms that include fatigue, depression and chronic pain. FM affects 2%-8% of the U.S. population, 2% of the global population, with 61%-90% of FM diagnoses attributed to women. Key causal factors leading to the development and severity of FM-related symptoms have not yet been identified. The purpose of this article is to report relationships among identified metabolites and levels of fatigue, depression, pain severity, and pain interference in a sample of 20 women with FM. In this secondary analysis, we conducted global metabolomic analysis and examined the data for relationships of metabolite levels with self-reported symptoms of fatigue, depression, pain severity, and pain interference. Results revealed six metabolites (6-deoxy-hexose; pantothenic acid; ergothioneine; l-carnitine; n-acetylserotonin; butyrobetaine) and their associated metabolic pathways such as carnitine synthesis, lipid oxidation, tryptophan metabolism, beta-alanine metabolism and pantothenic and Coenzyme-A biosynthesis that were either positively or inversely related to pain severity, pain interference, or both. The preliminary data presented suggest that metabolites representing energy, amino acid, or lipid classification may be associated with pain symptom severity and interference in women with FM. Future work will confirm these findings in a large, comparative cohort, targeting metabolites and metabolite pathways to better understand the relationships of metabolites and symptomology.

Biobehavioral Research and Hematopoietic Stem Cell Transplantation: Expert Review from the Biobehavioral Research Special Interest Group of the American Society for Transplantation and Cellular Therapy.

Hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for many hematologic conditions. Despite advances in conditioning and supportive measures, however, there remain significant comorbidities that threaten survivorship. Adverse effects of stress-related biobehavioral processes-defined here as the interactions of behavioral, psychological, and socioenvironmental factors with biology-impact immune recovery and function and are particularly salient in the HCT context, given the importance of immune reconstitution for improved survivorship. However, biobehavioral processes have been underinvestigated in this vulnerable group compared with other cancer populations. Here the Biobehavioral Research Special Interest Group (SIG) of the American Society for Transplantation and Cellular Therapy provides an expert review to inform research directions explicating the biological correlates of behavioral symptoms and evaluate the impact of these on HCT outcomes. The goal of this expert review is to provide a foundation for advancing science that effectively integrates behavioral and biological processes to optimize quality of life and improve clinical outcomes for HCT recipients.

Relationships Among Fatigue, Anxiety, Depression, and Pain and Health-Promoting Lifestyle Behaviors in Women With Early-Stage Breast Cancer.

BACKGROUND: With a nearly 89% 5-year survival rate for women with early-stage breast cancer, symptoms are a priority. Healthy lifestyle behaviors may be temporally associated with symptoms; however, evidence is lacking. OBJECTIVE: This research examined temporal relationships among healthy lifestyle behaviors and symptoms in women diagnosed with breast cancer receiving chemotherapy. METHODS: This research was part of a study (R01NR012667) approved by the institutional review board. Women (n = 76) providing written informed consent participated in this longitudinal study examining health-promoting lifestyle behaviors and symptoms (fatigue, anxiety, depression, and pain). Participants completed well-validated self-report questionnaires primarily at a clinic visit. Statistical methods included descriptive statistics, linear mixed-effects models, and pairwise comparisons using SAS 9.4; α was set at .05. RESULTS: Lowest healthy lifestyle behavior scores for physical activity and highest scores for spiritual growth were reported. Significant changes in physical activity and stress management were noted. Fatigued patients had lower physical activity and nutrition scores than did patients without fatigue. Patients with anxiety had lower spiritual growth and interpersonal relation scores than did patients without anxiety. Relationships demonstrated temporal differences. CONCLUSIONS: Breast cancer survivors did not routinely engage in healthy lifestyle behaviors. Significant temporal changes in healthy lifestyle behaviors and symptoms and significant associations among healthy lifestyle behaviors, symptoms, and demographic and clinical factors were noted in this study. IMPLICATIONS FOR PRACTICE: Knowing the temporal relationships among these variables provides insight that could be useful for nurses so they can encourage healthy lifestyle behaviors to mitigate symptoms throughout the cancer trajectory.

Reducing chest radiography utilization in the medical intensive care unit.

BACKGROUND AND PURPOSE: Daily chest radiographs (CXRs) have long been a routine part of care. However, evidence as well as changing technology has promoted on-demand CXRs as beneficial to patient care. We found that a substantial number of routine daily CXRs were being ordered, with some of the orders staying active even after extubation. METHODS: Within a 19-bed adult medical ICU, we prospectively utilized 3 intervention phases from October 1, 2014, to February 28, 2018, to reduce routine CXRs. Nurse Practitioners (NP) initiated this quality improvement (QI) project, aiming to reduce the number of unnecessary of CXRs. Interventions included staff survey, routine CXR order removal, duplicate alerts, visual reminders, and an electronic clinical decision support tool. Monthly education of appropriate CXRs and bedside ultrasound were facilitated by NPs. The outcome measures of interest include: the number of CXRs per patient-day, the number of routine and on-demand CXRs, mortality rate, ICU length of stay, and ventilator days, radiation and cost. CONCLUSIONS: Total number of CXRs per patient-day decreased by 36.1%. The proportion of routine CXRs decreased from 55.37% to 13.18%; on-demand orders increased, from 44.63% to 86.82%; and calculated radiation-exposure per census decreased, from 0.011 to 0.008 mSv. In addition, charges to patients for CXRs decreased by $7,750/month. ICU mortality and ventilator days per census remained stable. IMPLICATIONS FOR PRACTICE: By an orchestrated process that included creating awareness and desire to change CXR ordering practices, we were able to decrease routine CXRs and increase on-demand utilization while maintaining counterbalance measures.