Exploring the links of skeletal muscle mitochondrial oxidative capacity, physical functionality, and mental well-being of cancer survivors.

Physical impairments following cancer treatment have been linked with the toxic effects of these treatments on muscle mass and strength, through their deleterious effects on skeletal muscle mitochondrial oxidative capacity. Accordingly, we designed the present study to explore relationships of skeletal muscle mitochondrial oxidative capacity with physical performance and perceived cancer-related psychosocial experiences of cancer survivors. We assessed skeletal muscle mitochondrial oxidative capacity using in vivo phosphorus-31 magnetic resonance spectroscopy (31P MRS), measuring the postexercise phosphocreatine resynthesis time constant, τPCr, in 11 post-chemotherapy participants aged 34-70 years. During the MRS procedure, participants performed rapid ballistic knee extension exercise to deplete phosphocreatine (PCr); hence, measuring the primary study outcome, which was the recovery rate of PCr (τPCr). Patient-reported outcomes of psychosocial symptoms and well-being were assessed using the Patient-Reported Outcomes Measurement Information System and the 36-Item Short Form health survey (SF-36). Rapid bioenergetic recovery, reflected through a smaller value of τPCr was associated with worse depression (rho ρ = - 0.69, p = 0.018, and Cohen's d = - 1.104), anxiety (ρ = - 0.61, p = .046, d = - 0.677), and overall mental health (ρ = 0.74, p = 0.010, d = 2.198) scores, but better resilience (ρ = 0.65, p = 0.029), and coping-self efficacy (ρ = 0.63, p = 0.04) scores. This is the first study to link skeletal muscle mitochondrial oxidative capacity with subjective reports of cancer-related behavioral toxicities. Further investigations are warranted to confirm these findings probing into the role of disease status and personal attributes in these preliminary results.

Feasibility of DNA Methylation Age as a Biomarker of Symptoms and Resilience among Cancer Survivors with Multiple Chronic Conditions.

This study aims to examine the feasibility of DNA methylation age as a biomarker for symptoms and resilience in cancer survivors with multiple chronic conditions (MCCs). We included ten participants from our parent study, an ongoing randomized control trial study. Participants' symptoms and resilience were assessed, and peripheral blood was collected. DNA methylation age calculation was performed using DNAge® analysis. Data were analyzed using Spearman's correlation analysis and the Mann-Whitney U test. Participants in the intervention group tended to have a decrease in DNA methylation age and age acceleration after completing an exercise program (mean difference = -0.83 ± 1.26). The change in DNA methylation age was significantly correlated with the change in resilience score (r = -0.897, p = 0.015). The preliminary results suggest that DNA methylation age can be a potential biomarker for improving resilience in cancer survivors with multiple chronic conditions. This finding is limited by the small sample size, and a larger study is needed.

Nurse-Administered Auricular Point Acupressure for Cancer-Related Pain.

PURPOSE: The study aimed to (1) examine the feasibility of providing a training course on auricular point acupressure (APA) for clinical oncology nurses to integrate APA into real-world nursing care settings, and (2) examine the effectiveness of APA on cancer-related pain (CRP) under usual inpatient oncology ward conditions. METHODS: This was a 2-phase feasibility study. Phase 1, an in-person, 8 hour training program was provided to oncology nurses. Phase 2, a prospective and feasibility study was conducted to evaluate the integration of APA into nursing care activities to manage CRP. Oncology patients were included if their pain was rated at ≥4 on a 0 to 10 numeric rating scale in the past 24 hours. Patients received 1 APA treatment administered by the nurses and were instructed to stimulate the points for 3 days. Study outcomes (pain intensity, fatigue, and sleep disturbance), pain medication use, and APA practice were measured by a phone survey daily. RESULTS: Ten oncology nurses received APA training in phase 1. APA had been added to the hospital's electronic health records (EHRs) as a pain treatment. In phase 2, 33 oncology patients received APA treatment with a 100% adherence rate (pressing the seeds 3 times per day, 3 minutes per time based on the suggestion). The side effects of APA were minimal (~8%-12% felt tenderness on the ear). After 3 days of APA, patients reported 38% pain relief, 39% less fatigue, and 45% improvement in sleep disturbance; 24% reduced any type of pain medication use and 19% reduced opioid use (10 mg opioids using milligram morphine equivalent). The major barrier to integrating APA into routine nursing practice was time management (how to include APA in a daily workflow). CONCLUSION: It is feasible to provide 8-hour training to oncology nurses for mastering APA skill and then integrating APA into their daily nursing care for patients with CRP. Based on the promising findings (decreased pain, improved fatigue and sleep disturbance, and less opioid use), the next step is to conduct a randomized clinical trial with a larger sample to confirm the efficacy of APA for oncology nurses to treat CRP in real-world practice.ClinicalTrial.gov identifier number: NCT04040140.

Biobehavioral Influences of Stress and Inflammation on Mucositis in Adolescents and Young Adults with Cancer: Results from a Pilot Study.

Purpose: Chemotherapy-induced mucositis is a prevalent and burdensome toxicity among adolescent and young adults (AYAs) with cancer and impedes the delivery of optimal therapy. Its development is not well understood, but baseline stress and inflammation may be contributory factors. This pilot study evaluates stress and inflammation as risk factors for mucositis, identifies effect size estimates, and evaluates the feasibility of a prospective study to investigate mucositis development. Methods: Thirty AYAs receiving chemotherapy with substantial risk of mucositis completed baseline stress measures, and serum was collected for inflammatory biomarker analysis. Regression and mediation analyses determined the relationship between stress/inflammation and mucositis. Results: Stress appears to be a significant risk factor for incidence of mucositis (odds ratio 1.13, p = 0.125) and predicts total mucositis score (ß = 0.281, p = 0.023) as well as peak incidence (ß = 0.052, p = 0.018). Baseline levels of interleukin (IL)-1a and epidermal growth factor (EGF) predicted mucositis development, and EGF and IL-8 may mediate the relationship between stress and mucositis. Findings suggest that stress-induced inflammation exacerbates symptom development. Conclusion: Results from this pilot study inform mucositis symptom models, suggesting that psychosocial and physiologic factors are involved in development. Importantly, this pilot study provides initial effect size estimates, including magnitude and direction of relationships, that are essential to informing larger, more robustly powered studies. High enrollment, low attrition, and minimal missing data in this study suggest this model is feasible for research in this population. Importantly, this work is a first step in identifying new risk factors for mucositis and targets for nurse-led interventions to prevent toxicity development.

Biological Correlates of the Effects of Auricular Point Acupressure on Pain.

BACKGROUND: To identify candidate inflammatory biomarkers for the underlying mechanism of auricular point acupressure (APA) on pain relief and examine the correlations among pain intensity, interference, and inflammatory biomarkers. DESIGN: This is a secondary data analysis. METHODS: Data on inflammatory biomarkers collected via blood samples and patient self-reported pain intensity and interference from three pilot studies (chronic low back pain, n = 61; arthralgia related to aromatase inhibitors, n = 20; and chemotherapy-induced neuropathy, n = 15) were integrated and analyzed. This paper reports the results based on within-subject treatment effects (change in scores from pre- to post-APA intervention) for each study group (chronic low back pain, cancer pain), between-group differences (changes in scores from pre- to post-intervention between targeted-point APA [T-APA] and non-targeted-point APA [NT-APA]), and correlations among pain intensity, interference, and biomarkers. RESULTS: Within-group analysis (the change score from pre- to post-APA) revealed statistically significant changes in three biomarkers: TNF-α (cancer pain in the APA group, p = .03), ß-endorphin (back pain in the APA group, p = .04), and IL-2 (back pain in the NT-APA group, p = .002). Based on between-group analysis in patients with chronic low back pain (T-APA vs NT-APA), IL-4 had the largest effect size (0.35), followed by TNF-α (0.29). A strong positive monotonic relationship between IL-1ß and IL-2 was detected. CONCLUSIONS: The current findings further support the potential role of inflammatory biomarkers in the analgesic effects of APA. More work is needed to gain a comprehensive understanding of the underlying mechanisms of APA on chronic pain. Because it is simple, inexpensive, and has no negative side effects, APA can be widely disseminated as an alternative to opioids.

Dynamic Brain Activity Following Auricular Point Acupressure in Chemotherapy-Induced Neuropathy: A Pilot Longitudinal Functional Magnetic Resonance Imaging Study.

BACKGROUND: The objective of this study was to investigate the dynamic brain activity following auricular point acupressure (APA) in chemotherapy-induced neuropathy (CIN). METHODS: Participants received 4 weeks of APA in an open-pilot trial with repeated observation. Along with the clinical self-reported CIN outcomes, objective outcomes were measured over the course of the treatment by physiological changes in pain sensory thresholds from quantitative sensory testing (QST) and repeated functional magnetic resonance imaging scans. RESULTS: After 4 weeks of APA, participants had reported clinically significant improvements (ie, ≥30%) in a reduction of CIN symptoms (including pain, numbness, tingling, and stiffness) in lower extremity stiffness (32%), reduced foot sensitivity (13%), and higher pain threshold (13%). Across the 11 intrinsic brain networks examined, there was a trend toward significance of the connectivity of the basal ganglia network (BGN) to the salience network (SAL), which was decreased pre-APA versus immediate-APA (effect size [ES] = 1.04, P = .07). The BGN also demonstrated decreased connectivity with the language network pre-APA versus delayed imaging post-APA (ES = -0.92, P = .07). Furthermore, there was increased executive control network (ECN) and SAL within-network connectivity comparing pre-APA to delayed imaging post-APA, trending toward significance (ES = 0.41, P = .09 and ES = 0.17, P = .09, respectively). CONCLUSION: The changes in connectivity and activity within or between the ECN, SAL, and BGN from pre- to post-APA suggest ongoing alterations in brain functional connectivity following APA, particularly in the insula, anterior cingulate, and dorsolateral prefrontal cortices, which play significant roles in pain, memory, and cognitive function.

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.

Preliminary Effectiveness of Auricular Point Acupressure on Chemotherapy-Induced Neuropathy: Part 2 Laboratory-Assessed and Objective Outcomes.

PURPOSE: To manage chemotherapy-induced neuropathy (CIN), this paper explores reliable and valid objectives measures to evaluate the treatment effects of auricular point acupressure (APA). DESIGN/METHOD: This study was a repeated-measures one-group design. Participants received four weeks of APA to manage their CIN. The laboratory-assessed and objective outcomes included quantitative sensory testing, grip and pinch strength, and inflammatory biomarkers. Wilcoxon matched pairs signed-rank tests were conducted to determine change scores of outcomes at pre- vs. post- and pre- vs. 1-month follow-up. Spearman's rho correlation coefficient was used to examine the linear association of score changes of all objective study outcomes. RESULTS: Comparing pre-and-post APA, (1) the mean score of the monofilament for all lower extremity sites tested decreased after APA, indicating sensory improvement; (2) the suprathreshold pinprick stimuli mean scores on the upper extremities increased, except the scores from the index finger and thumb; (3) the pain tolerance of thumb and trapezius areas increased; (4) decreasing IL1ß (p = .05), IFNγ (p = .02), IL-2 (p = .03), IL-6 (p = .05), IL-10 (p = .05), and IP10/CXCL10 (p = .04) were observed pre-post APA. Conditional pain modulation was significantly (p< .05) associated with pain intensity (r = 0.55), tingling (r = 0.59); and IL1ß concentration (r = 0.53) pre-post APA. The sustained effects of 4-week APA were observed at the 1-month follow-up. CONCLUSIONS: Our study findings demonstrated the promising effectiveness of APA in the management of CIN, and these treatment effects can be assessed using reliable and valid objective measures. CLINICAL IMPLICATIONS: If the efficacy of APA to manage CIN is confirmed in a larger sample, APA has the potential to be a scalable treatment for CIN because it is a reproducible, standardized, and easy-to-perform intervention.

Preliminary Effectiveness of Auricular Point Acupressure on Chemotherapy-Induced Neuropathy: Part 1 Self-Reported Outcomes.

PURPOSE: To reduce chemotherapy-induced neuropathy (CIN)-a significant challenge among cancer patients following chemotherapy-we explored the effects of auricular point acupressure (APA), which involves needleless, acupuncture-like stimulation on specific ear points. DESIGN/METHOD: This pilot study examined the effects of a 4-week APA intervention in the management of CIN. Descriptive analysis was used to examine the changes in study outcomes. RESULTS: Fifteen participants were enrolled. Two participants dropped out because they developed new medical conditions. Thirteen participants completed the study (87% retention rate). Study participants had more severe symptoms in their lower extremities (i.e., toes, feet, soles) than in their upper extremities (i.e., fingers, wrists, elbows). After the 4-week APA intervention, the mean percentage change scores ranged from 38% (tingling) to 49% (numbness); compared to pre-intervention, the therapeutic effects of APA were sustained at the 1-month follow-up. Function in both upper and lower extremities improved after the APA intervention (≥28%) and continued to improve at the 1-month follow-up (≥36%). CONCLUSIONS: Preliminary results from this small sample provide initial evidence of the effectiveness of APA on CIN. Future studies should confirm these results using a larger sample, a comparative sham control, and an examination of the underlying physiological mechanisms of the anti-CIN effects of APA. CLINICAL IMPLICATIONS: APA may provide an inexpensive and effective complementary approach for the self-management of CIN. Once the seeds have been taped to the patient's ear by the provider, patients are empowered to self-manage their CIN in their own environment.

The Use of Mobile Health to Assist Self-management and Access to Services in a Rural Community.

The purpose of this study was to explore the barriers to and needs for using mobile health technology to assist low-income Asian American and Pacific Islander participants living in rural Hawaii in their healthcare. Three focus groups consisting of patients, family support/significant others, and providers (N = 19) were conducted to assess the unique needs of low-income Asian American and Pacific Islander patients in rural Hawaii. The electronic health literacy scale was also used among participants in the patients and family support/significant other groups. The total electronic health literacy means were 23.57 (SD = 9.71) among participants in the patient group, 34.50 (SD = 7.78) in the family support/significant others group, and 35.67 (SD = 4.56) in the providers group. The qualitative analysis yielded categories with three main themes: value of mobile health, stumbling blocks to mobile health, and mobile health wish list and subthemes. Practice implications include uses of these findings to integrate future versions of mobile health that will promote effective communication and information specifically to diverse low-income populations.

A predictive algorithm to identify genes that discriminate individuals with fibromyalgia syndrome diagnosis from healthy controls.

OBJECTIVES: Fibromyalgia syndrome (FMS) is a chronic and often debilitating condition that is characterized by persistent fatigue, pain, bowel abnormalities, and sleep disturbances. Currently, there are no definitive prognostic or diagnostic biomarkers for FMS. This study attempted to utilize a novel predictive algorithm to identify a group of genes whose differential expression discriminated individuals with FMS diagnosis from healthy controls. METHODS: Secondary analysis of gene expression data from 28 women with FMS and 19 age-and race-matched healthy women. Expression of discriminatory genes were identified using fold-change differential and Fisher's ratio (FR). Discriminatory accuracy of the differential expression of these genes was determined using leave-one-out-cross-validation. Functional networks of the discriminating genes were described from the Ingenuity's Knowledge Base. RESULTS: The small-scale signature contained 57 genes whose expressions were highly discriminatory of the FMS diagnosis. The combination of these high discriminatory genes with FR higher than 1.45 provided a leave-one-out-cross-validation accuracy for the FMS diagnosis of 85.11%. The discriminatory genes were associated with 3 canonical pathways: hepatic stellate cell activation, oxidative phosphorylation, and airway pathology related to COPD. CONCLUSION: The discriminating genes, especially the 2 with the highest accuracy, are associated with mitochondrial function or oxidative phosphorylation and glutamate signaling. Further validation of the clinical utility of this finding is warranted.

Altered Cd8+ T lymphocyte Response Triggered by Arginase 1: Implication for Fatigue Intensification during Localized Radiation Therapy in Prostate Cancer Patients.

Fatigue, the most common side effect of cancer treatments, is observed to intensify during external-beam radiation therapy (EBRT). The underlying molecular mechanisms remain unclear. This study investigated the differentially expressed genes/proteins and their association with fatigue intensification during EBRT. Fatigue scores measured by FACT-F and peripheral blood were collected prior to treatment (baseline D0), at midpoint (days 19-21, D21) and endpoint (days 38-42, D42) from men (n=30) with non-metastatic prostate cancer undergoing EBRT. RNA extracted from peripheral blood was used for gene expression analysis. Plasma arginase I and arginine were examined using ELISA and liquid chromatography-tandem mass spectrometry. Differences in fatigue scores, gene and protein expression between times points following EBRT were analyzed by one way ANOVA followed by Post Hoc t-test. Fatigue scores decreased significantly from baseline (44.6 ± 8.1) to midpoint (37.3 ± 10.6, p=0.000, low scores indicating high fatigue) and to endpoint (37.4 ± 10.1, p=0.001) during EBRT. ARG1 (encoding arginase type 1) was significantly up regulated from baseline to midpoint of EBRT (fold change =2.41, p<0.05) whereas genes associated with the adaptive immune functional pathway (CD28, CD27, CCR7, CD3D, CD8A and HLA-DOB) were significantly downregulated >2-fold between the study time points. The changes in gene expression were associated with patient reported fatigue intensity. Moreover, the upregulation of ARG1 was negatively correlated with the absolute lymphocyte count (R2=0.561, p=0.01) only in the high level of fatigue group (n=17) during EBRT. Increased ARG1 expression is known to result in arginine deficiency, which leads to immunosuppression by impairing lymphocyte proliferation and activation. EBRT-induced ARG1 upregulation may play an essential role in fatigue intensification via the arginine deficiency and suppression of T-cell proliferation pathways. These findings may provide novel insights into the molecular-genetic mechanisms underlying the development and intensification of cancer treatment-related fatigue.

Exploratory Investigation of Early Biomarkers for Chronic Fatigue in Prostate Cancer Patients Following Radiation Therapy.

BACKGROUND: Fatigue is one of the most debilitating adverse effects of cancer therapy. Identifying biomarkers early during cancer therapy may help us understand the biologic underpinnings of the persistence of fatigue following therapy. OBJECTIVE: We aimed to identify early biomarkers of fatigue by examining correlations of levels of cytokines during external beam radiation therapy (EBRT) with persistence of fatigue 1 year following treatment completion in men with nonmetastatic prostate cancer (NM-PC). METHODS: A sample of 34 men with nonmetastatic prostate cancer scheduled to receive EBRT were followed up at baseline (T1), midpoint of EBRT (T2), and 1 year following EBRT (T3). Demographic and clinical data were obtained by chart review. The Functional Assessment of Cancer Therapy-Fatigue was administered to measure fatigue levels. Plasma cytokine levels were determined at T1 and T2 using the Bio-Rad Bio-Plex Cytokine Assay Kits. RESULTS: Significant correlations were observed between levels of interleukin 2 (IL-3), IL-8, IL-9, IL-10, IL-16, interferon γ-induced protein 10, interferon α2, interferon γ, and stromal cell-derived factor 1α at T2 with worsening of fatigue from T1 to T3. CONCLUSIONS: Immunological changes prior to chronic fatigue development may reflect the long-term response to radiation therapy-induced damage. IMPLICATIONS FOR PRACTICE: Early biomarkers for chronic fatigue related to cancer therapy will help advance our understanding of the etiology of this distressing symptom and will help nurses identify patients at risk of developing chronic fatigue after cancer treatment. This information will also aid in patient education, as well as symptom management.

Biological Basis for the Clustering of Symptoms.

OBJECTIVES: Identification of biologic pathways of symptom clusters is necessary to develop precision therapies for distressing symptoms. This review examined extant literature evaluating relationships between biomarkers and symptom clusters in cancer survivors. DATA SOURCES: PubMed, CINAHL, Web of Science and Cochrane Library were searched using terms "biological markers" or "biomarkers" and "symptom cluster" or "symptom complex" or "multiple symptoms." CONCLUSION: Biomarkers related to inflammation (eg, cytokines) were the most studied and showed the most significant relationships with clusters of symptoms. This review suggests that clustering of symptoms related to cancer or cancer therapy is linked to immune/inflammatory pathways. IMPLICATIONS FOR NURSING PRACTICE: Understanding the etiology of symptom clusters may guide future nursing interventions for symptom management.

Relationship of Mitochondrial Enzymes to Fatigue Intensity in Men With Prostate Cancer Receiving External Beam Radiation Therapy.

PURPOSE: Mitochondrial dysfunction is a plausible biological mechanism for cancer-related fatigue. Specific aims of this study were to (1) describe the levels of mitochondrial oxidative phosphorylation complex (MOPC) enzymes, fatigue, and health-related quality of life (HRQOL) before and at completion of external beam radiation therapy (EBRT) in men with nonmetastatic prostate cancer (PC); (2) examine relationships over time among levels of MOPC enzymes, fatigue, and HRQOL; and (3) compare levels of MOPC enzymes in men with clinically significant and nonsignificant fatigue intensification during EBRT. METHODS: Fatigue was measured by the revised Piper Fatigue Scale and the Functional Assessment of Cancer Therapy-Fatigue subscale (FACT-F). MOPC enzymes (Complexes I-V) and mitochondrial antioxidant superoxide dismutase 2 were measured in peripheral blood using enzyme-linked immunosorbent assay at baseline and completion of EBRT. Participants were categorized into high or low fatigue (HF vs. LF) intensification groups based on amount of change in FACT-F scores during EBRT. RESULTS: Fatigue reported by the 22 participants with PC significantly worsened and HRQOL significantly declined from baseline to EBRT completion. The HF group comprised 12 men with clinically significant change in fatigue (HF) during EBRT. Although no significant changes were observed in MOPC enzymes from baseline to EBRT completion, there were important differences in the patterns in the levels of MOPC enzymes between HF and LF groups. CONCLUSION: Distinct patterns of changes in the absorbance of MOPC enzymes delineated fatigue intensification among participants. Further investigation using a larger sample is warranted.

Understanding the Association of Fatigue With Other Symptoms of Fibromyalgia: Development of a Cluster Model.

OBJECTIVE: To develop a symptoms cluster model that can describe factors of fibromyalgia syndrome (FMS) associated with fatigue severity as reported by the sample and to explore FMS clinical symptom subclusters based on varying symptom intensities. METHODS: FMS individuals (n = 120, 82% ages 31-60 years, 90% women, 59% white) diagnosed with the 1990 or 2010 American College of Rheumatology diagnostic criteria were enrolled. Participants completed multiple validated self-report questionnaires to measure fatigue, pain, depression, anxiety, pain catastrophizing, daytime sleepiness, cognitive function, and FMS-related polysymptomatic distress. Cluster analysis using SPSS 19.0 and structural equation modeling using AMOS 17.0 were used. RESULTS: Final structural equation modeling the symptoms cluster model showed good fit and revealed that FMS fatigue was associated with widespread pain, symptoms severity, pain intensity, pain interference, cognitive dysfunction, catastrophizing, anxiety, and depression (χ(2) = 121.72 (98df), P > 0.05, χ(2) /df = 1.242, comparative fit index = 0.982, root mean square error of approximation = 0.045). Two distinct clinical symptom subclusters emerged: subcluster 1 (78% of total subjects), defined by widespread pain, unrefreshed waking, and somatic symptoms, and subcluster 2 (22% of total subjects), defined by fatigue and cognitive dysfunction with pain being a less severe and less widespread occurrence. CONCLUSION: Overall, subcluster 1 had more intense symptoms than subcluster 2. FMS symptoms may be categorized into 2 clinical subclusters. These findings have implications for an illness whose diagnosis and management are symptom dependent. A longitudinal study capturing the variability in the symptom experience of FMS subjects is warranted.

Clinical Predictors of Fatigue in Men With Non-Metastatic Prostate Cancer Receiving External Beam Radiation Therapy.

BACKGROUND: Fatigue is one of the most distressing symptoms experienced by people with cancer receiving radiation therapy. OBJECTIVES: The goal of this study is to evaluate clinical predictors of worsening fatigue during external beam radiation therapy (EBRT) in men with non-metastatic prostate cancer. METHODS: Thirty-five men with non-metastatic prostate cancer scheduled for EBRT were followed at baseline, midpoint, and completion of EBRT. The Functional Assessment of Cancer Therapy-Fatigue scale was administered. Demographic and clinical data were obtained by chart review. Paired t-tests, correlations, general linear models, and logistic regressions were used to determine associations between fatigue scores and clinical data. FINDINGS: Red blood cells, hemoglobin, and hematocrit levels were highly intercorrelated and, therefore, were grouped as one composite variable termed heme. Heme levels at baseline and androgen-deprivation therapy (ADT) were significantly correlated with worsening of fatigue symptoms from baseline to midpoint and endpoint. ADT alone did not have a significant correlation with fatigue, but it indirectly affected fatigue levels by influencing heme markers as treatment progressed. These findings provide evidence that hematologic markers and the use of ADT assist in predicting radiation therapy-related fatigue and guide symptom management.

Comparing Genomic Profiles of Women With and Without Fibromyalgia.

BACKGROUND: Fibromyalgia syndrome (FMS), a chronic musculoskeletal condition characterized by diffuse pain, fatigue, sleep impairment, and cognitive dysfunction, is associated with significant functional disability. Its underlying biological mechanisms are unknown. This study investigated differentially expressed genes between women with FMS and healthy volunteers. METHODS: Women who met the 1990 or 2010 American College of Rheumatology fibromyalgia criteria were compared to age- and race-matched pain-free healthy women. Peripheral blood samples were collected, and a full genome microarray gene expression analysis was performed. One-way analysis of variance was used to identify differentially expressed genes using the filtering criterion of 1% false discovery rate. Analysis of canonical pathways associated with these genes was performed. Confirmatory quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay verified microarray results. Independent t-tests compared gene and protein expression between groups. RESULT: Participants were 54 women with FMS and 25 controls. Expression arrays from a subset of women with FMS (n = 29) and controls (n = 20) showed upregulation of 12 genes (>1.8-fold change, p < .05) in the FMS sample. Differentially expressed genes were related to B-cell development, primary immunodeficiency signaling, and mitotic roles of polo-like kinase. CENPK and HSP90AA1 were the most differentially expressed genes (p < .01). CONCLUSION: Activity of interrelated pathways related to immune response, and homeostasis appears to be relevant to the experience of FMS. Replication and exploration of the relationship between gene expression and symptom severity will help determine clinical relevance of these findings.

Proteomic serum profile of fatigued men receiving localized external beam radiation therapy for non-metastatic prostate cancer.

CONTEXT: Fatigue is the most distressing side effect of radiation therapy, and its progression etiology is unknown. OBJECTIVES: This study describes proteome changes from sera of fatigued men with non-metastatic prostate cancer receiving external beam radiation therapy (EBRT). METHODS: Fatigue scores, measured by the Functional Assessment of Chronic Illness Therapy-Fatigue, and serum were collected from 12 subjects at baseline (before EBRT) and at midpoint (Day 21) of EBRT. Depleted sera from both time points were analyzed using two-dimensional difference gel electrophoresis, and up/down regulated proteins were identified using liquid chromatography-tandem mass spectrometry. Western blot analyses confirmed the protein changes observed. RESULTS: Results showed that apolipoprotein (Apo)A1, ApoE, and transthyretin (TTR) consistently changed from baseline (Day 0) to midpoint (Day 21). The mean ApoE level of subjects with high change in fatigue (HF: n = 9) increased significantly from baseline to midpoint and were higher than in subjects with no change in fatigue. The mean ApoA1 level was higher in HF subjects at baseline and at midpoint than in no fatigue subjects at both time points. The mean TTR level of no fatigue subjects was higher at baseline and midpoint than in HF subjects. CONCLUSION: These ApoE, ApoA1, and TTR results may assist in understanding pathways that can explain fatigue progression etiology in this clinical population.

Gene expression profiles of fatigued fibromyalgia patients with different categories of pain and catastrophizing: a preliminary report.

BACKGROUND: Fibromyalgia (FM) is a chronic condition characterized by diffused musculoskeletal pain and overwhelming fatigue. PURPOSE: To compare the gene expression profiles of fatigued FM women with different levels of pain and catastrophizing. METHODS: Nine women with FM enrolled in an active Medstar Research Institute protocol were included in the gene expression analyses of peripheral blood RNA via Affymetrix GeneChip Human Genome U133 Plus 2.0 array (Santa Clara, CA). Scores from Brief Pain Inventory, Pain Catastrophizing Scale, and Multidimensional Fatigue Inventory categorized the nine participants into pain (high, n = 3; low, n = 6) and catastrophizing groups (high, n = 5; low, n = 4). DISCUSSION: Differential expression of 107 genes between the high and low pain groups and 139 genes between the high and low catastrophizing groups (over 2.0-fold change, p < .05) were observed. Network analyses showed interferon signaling and interferon regulatory activation factor pathways distinguished between the pain groups whereas dendritic cell maturation delineated between the catastrophizing groups. CONCLUSION: Findings provide preliminary evidence that specific physiological pathways may possibly delineate pain and catastrophizing mechanisms. Further investigation via the use of a larger and more homogenous sample is warranted.