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    Risk Factors for Cognitive Impairment in High-Grade Glioma Patients Treated with Postoperative Radiochemotherapy. Wang Qiang,Xiao Fengxia,Qi Fei,Song Xiaopeng,Yu Yonghua Cancer research and treatment : official journal of Korean Cancer Association PURPOSE:Fractionated radiotherapy as well as concomitant and adjuvant chemotherapy such as temozolomide for postoperative high-grade glioma (HGG) patients improves progression-free survival and overall survival. Multiple factors such as chemotherapy, radiotherapy, tumor grade, residual tumor volume, and genetic modifications might play a role in the formation of cognitive impairment. The risk factors of cognitive impairment in postoperative patients with HGG receiving radiotherapy and chemotherapy remains a concern in this population. The purpose of this study was to identify risk factors for cognitive impairment in patients of postoperative HGG. MATERIALS AND METHODS:A total of 229 patients with HGG who underwent surgery were analyzed. Cognitive impairment was defined as a decrease of Cognitive Assessment Montreal (MoCA)'s score in at least two cognitive domains or any MoCA's score of less than 26 points at the time of study compared with baseline level. Multiple potential risk factors including methylated status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter, glioma World Health Organization (WHO) grade, residual tumor volume, education, and sex were analyzed. Cox univariate and multivariate regression analysis was used to detect the significant risk factors for cognitive impairment. RESULTS:At the end of follow-up among the 229 patients, 147 patients (67%) developed cognitive impairment. 82 patients (36%) remained in normal cognitive condition. In multivariate analysis, unmethylated MGMT promoter (hazard ratio [HR], 1.679; 95% confidence interval [CI], 1.212 to 2.326; p=0.002), glioblastoma (HR, 1.550; 95% CI, 1.117 to 2.149; p=0.009), and residual tumor volume > 5.58 cm3 (HR, 1.454; 95% CI, 1.047 to 2.020; p=0.026) were independent risk factors for cognitive impairment. CONCLUSION:Methylated status of the MGMT promoter, glioma WHO grade, and residual tumor volume might be risk factors for the cognitive impairment in postoperative patients with HGG. 10.4143/crt.2019.242
    Role of Exosomes in Cancer-Related Cognitive Impairment. Koh Yong Qin,Tan Chia Jie,Toh Yi Long,Sze Siu Kwan,Ho Han Kiat,Limoli Charles L,Chan Alexandre International journal of molecular sciences A decline in cognitive function following cancer treatment is one of the most commonly reported post-treatment symptoms among patients with cancer and those in remission, and include memory, processing speed, and executive function. A clear understanding of cognitive impairment as a result of cancer and its therapy can be obtained by delineating structural and functional changes using brain imaging studies and neurocognitive assessments. There is also a need to determine the underlying mechanisms and pathways that impact the brain and affect cognitive functioning in cancer survivors. Exosomes are small cell-derived vesicles formed by the inward budding of multivesicular bodies, and are released into the extracellular environment via an exocytic pathway. Growing evidence suggests that exosomes contribute to various physiological and pathological conditions, including neurological processes such as synaptic plasticity, neuronal stress response, cell-to-cell communication, and neurogenesis. In this review, we summarize the relationship between exosomes and cancer-related cognitive impairment. Unraveling exosomes' actions and effects on the microenvironment of the brain, which impacts cognitive functioning, is critical for the development of exosome-based therapeutics for cancer-related cognitive impairment. 10.3390/ijms21082755
    Prechemotherapy Levels of Plasma Dehydroepiandrosterone and Its Sulfated Form as Predictors of Cancer-Related Cognitive Impairment in Patients with Breast Cancer Receiving Chemotherapy. Toh Yi Long,Shariq Mujtaba Juliana,Bansal Sumit,Yeo Angie,Shwe Maung,Lau Aik Jiang,Chan Alexandre Pharmacotherapy STUDY OBJECTIVE:Dehydroepiandrosterone (DHEA) and its sulfated form (DHEAS)-jointly referred to as DHEA(S)-are neurosteroids known to regulate brain development and function that have been found to be positively correlated with cognitive function. It is unknown whether prechemotherapy plasma DHEA(S) levels are associated with the onset of cancer-related cognitive impairment (CRCI). The objective of this study was to evaluate whether an association exists between prechemotherapy plasma DHEA(S) levels and onset of CRCI in patients with breast cancer receiving chemotherapy. DESIGN:Multicenter, prospective cohort study. SETTING:Two specialized cancer centers in Singapore. PATIENTS:Eighty-one patients with early-stage breast cancer (stages I-III) who had no prior exposure to chemotherapy and/or radiotherapy and were scheduled to receive anthracycline-based or taxane-based chemotherapy treatment with curative intent. MEASUREMENTS AND MAIN RESULTS:Patients completed assessments for self-perceived and objective cognitive function at three time points: prechemotherapy (T1), during chemotherapy (T2), and after chemotherapy (T3). Plasma samples were collected prior to chemotherapy, and DHEA(S) levels were quantified by using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariable logistic regression was used to adjust for clinically important factors and to evaluate the association between prechemotherapy plasma DHEA(S) levels and CRCI. Mean ± SD age was 48.9 ± 9.3 years, with 27.8% of patients experiencing clinically significant cognitive impairment based on global Functional Assessment of Cancer Therapy-Cognitive Function scores. The mean ± SD prechemotherapy plasma DHEAS and DHEA levels were 1.61 ± 0.91 μmol/L and 19.21 ± 13.13 nmol/L, respectively. Prechemotherapy DHEAS levels were found to be associated with impairment in the self-perceived cognitive domains of verbal fluency (adjusted odds ratio [OR] 0.27, 95% confidence interval [CI] 0.08-0.96) and mental acuity (adjusted OR 0.25, 95% CI 0.08-0.74). Conversely, DHEA levels were not associated with impairment in any cognitive subdomains. CONCLUSION:Our findings suggest that patients with higher prechemotherapy DHEAS levels had lower odds of developing self-perceived cognitive impairment. Future studies are required to further investigate the effect of DHEA(S) on specific cognitive domains and to validate our findings in independent cohorts. 10.1002/phar.2259
    Association between cognitive impairment patient with solid cancer and insulin resistance. Gonda Kenji,Yaginuma Kenji,Rokkaku Yuichi,Horita Shoichiro,Maejima Yuko,Shimomura Kenju BMC research notes OBJECTIVES:In an aging population, an increase in the number of elderly cancer patients with cognitive impairment is expected. The possible association between cancer and cognitive impairment is important to elucidate, because it can have a serious impact on quality of life. Here, we focused on glucose metabolism as a factor that links cancer and cognitive impairment. RESULTS:Thirteen subjects with solid cancers and cognitive impairment were recruited. As a control group, 14 subjects with cognitive impairment alone and 8 subjects with cancer alone were recruited. A Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and that of β-cell function (HOMA-B) were used. In comparison with patients with solid cancer alone, those with cognitive impairment alone and those with both cancer and cognitive impairment had increased HOMA-IR values. Insulin resistance was increased in patients with cognitive impairment alone and those with both cognitive impairment and solid cancer than in patients without cognitive impairment; however, β-cell function was not affected. The present data indicated that elderly cancer patients with high HOMA-IR score may be at a relatively high risk for developing cognitive impairment. Furthermore, early treatment to reduce insulin sensitivity may prevent cognitive impairment. 10.1186/s13104-019-4739-5
    Correlates of cognitive impairment in adult cancer survivors who have received chemotherapy and report cognitive problems. Gutenkunst Shannon L,Vardy Janette L,Dhillon Haryana M,Bell Melanie L Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer OBJECTIVE:Cognitive impairment negatively affects some cancer survivors who have completed chemotherapy; however, factors underlying this cognitive impairment remain poorly understood. We aimed to investigate (1) the relative importance of demographics, medical, and psychological characteristics associated with cognitive impairment and (2) the specific variables associated with cognitive impairment in adult cancer survivors who completed adjuvant chemotherapy. METHODS:We performed post hoc analyses of baseline data from early-stage cancer survivors with cognitive complaints who received adjuvant chemotherapy 0.5-5 years earlier and volunteered for a trial designed to improve cognition. The primary outcome of self-reported cognitive impairment was measured using a questionnaire; secondary outcome of objective cognitive impairment was measured using a computerized neuropsychological test battery. Hierarchical linear regression determined the relative importance of demographics, medical, and psychological characteristics in associations with both self-reported and objective cognitive impairment. RESULTS:The sample was 95% female and 89% breast cancer patients. The final model accounted for 33% of variation in self-reported cognitive impairment (n = 212, demographics 5%, medical 3%, and psychological 25%), with fatigue and stress as significant individual correlates (p values ≤ 0.0001). For the secondary analysis, the final model accounted for 19% of variation in objective cognitive impairment (n = 206, demographics 10%, medical 5%, and psychological 4%), with age, smoking history, and number of chemotherapy cycles as significant individual correlates. CONCLUSION:We found that psychological characteristics are more important than demographic and medical characteristics in self-reported cognitive impairment, whereas other characteristics are more important in objective cognitive impairment. This suggests clinicians should investigate possible psychological problems in cancer survivors who self-report cognitive impairment. 10.1007/s00520-020-05616-5
    Symptom Biomarkers for Children Receiving Treatment for Cancer: State of the Science. Mandrell Belinda N,Withycombe Janice S Journal of pediatric oncology nursing : official journal of the Association of Pediatric Oncology Nurses The Children's Oncology Group Nursing Discipline has identified the most concerning symptoms during childhood cancer treatment and the need for continued symptom assessment and intervention during treatment trajectory. To develop appropriate interventions, symptom science strategies must explore the biological mechanisms associated with symptoms of cancer and cancer treatment. To explore the associated biological mechanisms, biomarkers have been recommended for inclusion in symptom science studies, when applicable. The biomarker assessed, as well as the method of collection and storage, can affect the reliability and validity of the study results and clinical implication. This review will describe biomarkers that have been described in pediatric oncology symptom science research and provides special considerations for specimen collection and processing. 10.1177/1043454219859233
    Depressive symptom-associated IL-1β and TNF-α release correlates with impaired bronchodilator response and neutrophilic airway inflammation in asthma. Zhang Li,Zhang Xin,Zheng Jing,Liu Ying,Wang Ji,Wang Gang,Zhang Hong Ping,Kang De Ying,Peng Zu Gui,Ji Yu Lin,Wang Lei,Gibson Peter Gerard,Wang Gang Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology BACKGROUND:Depressive symptoms worsen asthma outcomes; however, the mechanism remains largely unexplored. OBJECTIVE:This study aimed to determine whether depressive symptom-associated immune inflammation correlates with impaired bronchodilator response (BDR) and airway inflammatory phenotypes. METHODS:Eligible adults with asthma (n = 198) underwent clinical assessment, sputum induction and blood sampling. Depressive symptoms were defined by scores on the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). Pre- and post-bronchodilator spirometry was performed for BDR. Airway inflammatory phenotypes were defined by sputum cell counts. CRP, IL-1β, IL-5, IL-6, IL-8, TNF-α, IFN-γ, CCL17 and CCL22 in serum and sputum were detected. RESULTS:Compared with the non-depressive group (n = 174), the depressive group (n = 24) exhibited impaired BDR (P = 0.032) and increased sputum neutrophils (P = 0.023), which correlated with the HADS-D scores (P = 0.027 and P = 0.029). Levels of IL-1β, TNF-α and IFN-γ in the serum and those of IL-1β and IFN-γ in the sputum were elevated in the depressive group compared to those in the non-depressive group (all P < 0.05). Multiple regression models indicated that TNF-α in the sputum and IL-1β, IL-6 and IFN-γ in both the serum and sputum were inversely associated with BDR; TNF-α in the sputum and IL-1β in both the serum and sputum were positively correlated with sputum neutrophils. Mediation analyses revealed that IL-1β and TNF-α in the sputum and IL-1β in both the serum and sputum mediate the correlations of the HADS-D scores with BDR and sputum neutrophils, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:Asthma patients with depressive symptoms present worse asthma control, which is most likely explained by impaired BDR and neutrophilic airway inflammation. IL-1β and TNF-α, which are two key pro-inflammatory cytokines that mediate the correlation of depressive symptoms with impaired BDR and neutrophilic airway inflammation, may serve as targeted biomarkers in the neuropsychological phenotype of asthma; however, this result needs to be further validated. 10.1111/cea.13346
    Association of Inflammatory Cytokines With the Symptom Cluster of Pain, Fatigue, Depression, and Sleep Disturbance in Chinese Patients With Cancer. Ji Yan-Bo,Bo Chun-Lu,Xue Xiu-Juan,Weng En-Ming,Gao Guang-Chao,Dai Bei-Bei,Ding Kai-Wen,Xu Cui-Ping Journal of pain and symptom management CONTEXT:Pain, fatigue, depression, and sleep disturbance are common in patients with cancer and usually co-occur as a symptom cluster. However, the mechanism underlying this symptom cluster is unclear. OBJECTIVES:This study aimed to identify subgroups of cluster symptoms, compare demographic and clinical characteristics between subgroups, and examine the associations between inflammatory cytokines and cluster symptoms. METHODS:Participants were 170 Chinese inpatients with cancer from two tertiary hospitals. Inflammatory markers including interleukin-6 (IL-6), interleukin-1 receptor antagonist, and tumor necrosis factor alpha were measured. Intergroup differences and associations of inflammatory cytokines with the cluster symptoms were examined with one-way analyses of variance and logistic regression. RESULTS:Based on cluster analysis, participants were categorized into Subgroup 1 (all low symptoms), Subgroup 2 (low pain and moderate fatigue), or Subgroup 3 (moderate-to-high on all symptoms). The three subgroups differed significantly in Eastern Cooperative Oncology Group (ECOG) performance status, sex, residence, current treatment, education, economic status, and inflammatory cytokines levels (all P < 0.05). Compared with Subgroup 1, Subgroup 3 had a significantly poorer ECOG physical performance status and higher IL-6 levels, were more often treated with combined chemoradiotherapy, and were more likely to be rural residents. IL-6 and ECOG physical performance status were significantly associated with 1.246-fold (95% CI 1.114-1.396) and 31.831-fold (95% CI 6.017-168.385) increased risk of Subgroup 3. CONCLUSION:Our findings suggest that IL-6 levels are associated with cluster symptoms in cancer patients. Clinicians should identify patients at risk for more severe symptoms and formulate novel target interventions to improve symptom management. 10.1016/j.jpainsymman.2017.05.003
    C-Reactive Protein/Albumin Ratio Is an Independent Prognostic Predictor of Survival in Advanced Cancer Patients Receiving Palliative Care. Zhang Jing,Zhang Chenbo,Li Qingxian,Zhang Jiawen,Gu Xiaoli,Zhao Weiwei,Chen Menglei,Liu Minghui,Zhang Zhe,Liao Xinghe,Cheng Wenwu Journal of palliative medicine The C-reactive protein/albumin (CRP/Alb) ratio has been reported as a prognostic factor of survival for patients with a variety of cancers. However, its prognostic impact for advanced cancer patients receiving palliative care remains presently unknown. The present study assessed the prognostic value of the CRP/Alb ratio, and compared this with that of the Glasgow Prognostic Score (GPS) and Palliative Prognostic Index (PPI) in a cohort of advanced cancer patients receiving palliative therapy. The medical records of 262 eligible patients who died of advanced cancer from February 1, 2013 to December 30, 2017 in the palliative care unit of the Fudan University Shanghai Cancer Center were retrospectively reviewed for the analysis. The present results revealed that a CRP/Alb ratio ≥1.31 (hazard ratio [HR], 2.33 [1.78-3.05],  < 0.001) can predict poor prognosis through univariate analysis. In addition, the multivariate analysis revealed that CRP/Alb (HR, 2.09 [1.54-2.84],  < 0.001), GPS (HR, 1.81 [1.07-3.07],  < 0.001), and PPI (HR, 3.35 [2.25-4.99],  < 0.001) were all independent prognosis factors. To compare the discriminatory performance of the CRP/Alb ratio with that of other established prognostic indexes in palliative care settings, the c-statistics, integrated discriminatory improvement index, net reclassification index, and receiver operating characteristic curves were generated, and it was demonstrated that the CRP/Alb ratio (c-statistics, 0.64 [0.61-0.68]) was able to discriminate advanced cancer patients with different survivals, with analogous discriminatory ability as GPS (c-statistics, 0.63 [0.59-0.66]) and PPI (c-statistics, 0.64 [0.60-0.68]). Notably, the combination of multiple prognostic indexes exerted higher discriminatory ability, compared with any single predictive index (c-statistics, 0.69 [0.66-0.73],  < 0.001). The present study suggests that the CRP/Alb ratio is a promising prognostic factor in predicting cancer patient survival in palliative care settings. Incorporating both objective parameters and the subjective index may improve the prediction accuracy of prognosis. 10.1089/jpm.2019.0102
    Development and validation of oral chemotherapy self-management scale. Peng Qi,Wu Wanying BMC cancer BACKGROUND:With the increase of oral chemotherapy drugs, patients receiving cancer treatment prefer oral chemotherapy versus intravenous, given equal efficacy and toxicity. However, they need to take an active part in their care, which is vital with home-based oral therapy, therefore the self-management is important for patients with oral chemotherapy. Unfortunately, the development of self-management assessment tools for oral chemotherapy still lags behind. METHODS:The OCSMS item pool was formulated based on literature review and semi-structured interviews, An initial scale containing 5 dimensions and 38 items was constructed through research seminar, Delphi survey and pilot testing. To assess the validity and reliability, We recruited 261 patients from cancer hospital in China. RESULTS:A 36-item scale was developed with five dimensions identified through factor analysis: daily life management, symptom management, medication management, emotional cognitive management and social support. Cronbach's coefficient Alpha, split-half coefficient, test-retest reliability and S-CVI/UA scores were 0.929, 0.773, 0.966 and 0.833, respectively, indicating that OCSMS has good reliability and validity. CONCLUSIONS:The OCSMS is a valid, reliable measurement method of the self-management ability of patients with oral chemotherapy. The OCSMS shows potential as a tool to ensure the safety of patients with cancer. The OCSMS may help evaluate the effectiveness of interventions to improve the self-management ability of patients. 10.1186/s12885-020-07404-0
    Effects of a nurse-led medication self-management programme in women with oral treatments for metastatic breast cancer: A mixed-method randomised controlled trial. Komatsu Hiroko,Yagasaki Kaori,Yamaguchi Takuhiro,Mori Ayako,Kawano Hiromi,Minamoto Noriko,Honma Orie,Tamura Kenji European journal of oncology nursing : the official journal of European Oncology Nursing Society PURPOSE:Adherence to medication is the most important challenge facing patients receiving oral anticancer treatment. This study aimed to evaluate the effects of a patient-centred medication self-management support programme in patients with metastatic breast cancer undergoing oral anticancer treatment. METHODS:This trial was a two-phased mixed-method randomised controlled study. Eligible participants were 155 patients with metastatic breast cancer newly prescribed an oral chemotherapy or targeted therapy agent. The intervention group received the patient-centred medication self-management support programme conducted by trained nurses. Primary outcome was adherence to medication at three months after the commencement of treatment, calculated by medication possession ratio (MPR). Secondary outcomes included self-efficacy, functional assessment, psychological distress, symptom severity and symptom interference, and patient satisfaction. After the completion of the intervention study, focus group interviews were conducted among intervention nurses. RESULTS:Both intervention and control groups maintained more than 90% of MPR and no significant difference was observed in the primary outcome. Regarding secondary outcomes, only general self-efficacy was significantly different in the two groups. In the qualitative study, the intervention nurses perceived improvement in the patients' self-efficacy, ability to anticipate the impact of treatment and adjust to life, and avoidance of loneliness. CONCLUSIONS:A significant effect of the programme was not found in the program because the adherence rate was high in both groups. Improvement in the patients' self-efficacy was observed both quantitatively and qualitatively. TRIAL REGISTRATION:UMIN Clinical Trials Registry (UMIN-CTR), Japan, UMIN000016597. (27 February 2015). 10.1016/j.ejon.2020.101780
    Biomarkers as Common Data Elements for Symptom and Self-Management Science. Page Gayle G,Corwin Elizabeth J,Dorsey Susan G,Redeker Nancy S,McCloskey Donna Jo,Austin Joan K,Guthrie Barbara J,Moore Shirley M,Barton Debra,Kim Miyong T,Docherty Sharron L,Waldrop-Valverde Drenna,Bailey Donald E,Schiffman Rachel F,Starkweather Angela,Ward Teresa M,Bakken Suzanne,Hickey Kathleen T,Renn Cynthia L,Grady Patricia Journal of nursing scholarship : an official publication of Sigma Theta Tau International Honor Society of Nursing PURPOSE:Biomarkers as common data elements (CDEs) are important for the characterization of biobehavioral symptoms given that once a biologic moderator or mediator is identified, biologically based strategies can be investigated for treatment efforts. Just as a symptom inventory reflects a symptom experience, a biomarker is an indicator of the symptom, though not the symptom per se. The purposes of this position paper are to (a) identify a "minimum set" of biomarkers for consideration as CDEs in symptom and self-management science, specifically biochemical biomarkers; (b) evaluate the benefits and limitations of such a limited array of biomarkers with implications for symptom science; (c) propose a strategy for the collection of the endorsed minimum set of biologic samples to be employed as CDEs for symptom science; and (d) conceptualize this minimum set of biomarkers consistent with National Institute of Nursing Research (NINR) symptoms of fatigue, depression, cognition, pain, and sleep disturbance. DESIGN AND METHODS:From May 2016 through January 2017, a working group consisting of a subset of the Directors of the NINR Centers of Excellence funded by P20 or P30 mechanisms and NINR staff met bimonthly via telephone to develop this position paper suggesting the addition of biomarkers as CDEs. The full group of Directors reviewed drafts, provided critiques and suggestions, recommended the minimum set of biomarkers, and approved the completed document. Best practices for selecting, identifying, and using biological CDEs as well as challenges to the use of biological CDEs for symptom and self-management science are described. Current platforms for sample outcome sharing are presented. Finally, biological CDEs for symptom and self-management science are proposed along with implications for future research and use of CDEs in these areas. FINDINGS:The recommended minimum set of biomarker CDEs include pro- and anti-inflammatory cytokines, a hypothalamic-pituitary-adrenal axis marker, cortisol, the neuropeptide brain-derived neurotrophic factor, and DNA polymorphisms. CONCLUSIONS:It is anticipated that this minimum set of biomarker CDEs will be refined as knowledge regarding biologic mechanisms underlying symptom and self-management science further develop. The incorporation of biological CDEs may provide insights into mechanisms of symptoms, effectiveness of proposed interventions, and applicability of chosen theoretical frameworks. Similarly, as for the previously suggested NINR CDEs for behavioral symptoms and self-management of chronic conditions, biological CDEs offer the potential for collaborative efforts that will strengthen symptom and self-management science. CLINICAL RELEVANCE:The use of biomarker CDEs in biobehavioral symptoms research will facilitate the reproducibility and generalizability of research findings and benefit symptom and self-management science. 10.1111/jnu.12378
    Symptom Clusters and Influencing Factors in Children With Acute Leukemia During Chemotherapy. Li Rongrong,Ma Jinling,Chan Yuying,Yang Qi,Zhang Chunxu Cancer nursing BACKGROUND:Acute leukemia is the most common malignancy in childhood. Identification of symptom clusters and their influencing factors in children with acute leukemia may improve the management of symptoms. OBJECTIVE:The aims of this study were to investigate symptom clusters in children with acute leukemia during chemotherapy and analyze the factors influencing their severity. METHODS:A cross-sectional survey was administered to 159 Chinese children with acute leukemia during chemotherapy. A demographic questionnaire and the Memorial Symptom Assessment Scale 10-18 were completed by the patients and their parents. Exploratory factor analysis was used to identify symptom clusters. Univariate analyses and multiple linear regression analyses were performed to analyze the factors affecting symptom clusters. RESULTS:Six clusters were identified, including gastrointestinal cluster, emotional cluster, head-related cluster, self-image disorder cluster, skin itching/irritation cluster, and somatic cluster. Factors influencing the severity of symptom clusters included age, gender, stage of chemotherapy, and medical reimbursement. CONCLUSIONS:There are multiple symptom clusters in children with acute leukemia during chemotherapy. Medical care staff should manage symptoms from the perspective of symptom cluster and carry out personalized interventions according to factors influencing these clusters. IMPLICATIONS FOR PRACTICE:The ability to predict symptom clusters in children with acute leukemia undergoing chemotherapy may assist with optimal clinical decision making in order to alleviate the symptom burden and improve children's quality of life. 10.1097/NCC.0000000000000716
    The level of oxidative stress and the expression of genes involved in DNA-damage signaling pathways in depressive patients with colorectal carcinoma. Wei Yong-chang,Zhou Fu-ling,He Da-lin,Bai Ji-rong,Hui Ling-yun,Wang Xin-yang,Nan Ke-jun Journal of psychosomatic research OBJECTIVES:This study investigated the connection among the oxidative stress, depression and expression of specific genes involved in DNA-damage signaling pathways in patients with colorectal carcinoma (CRC). METHODS:A unique Dukes'C subset of patients with newly diagnosed colorectal adenocarcinoma were assessed using the Hamilton Depression Rating Scale (HAMD), Zung Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale (SAS), Symptom Checklist 90 (SCL-90) and other multiple-item questionnaires. Oxidative-stress-related parameters in sera and the expression of genes were monitored during a pretreatment period. RESULTS:Eighty-two eligibility cases were divided into 2 groups based on an HAMD score cutoff of 20: the mean score was 28.29 in Group A (depression, n=52) and 16.50 in Group B (nondepression, n=30). The serum total antioxidant capacity, catalase, and superoxide dismutase concentrations were lower in Group A, whereas those of nitric oxide and malondialdehyde were higher in Group A. Importantly, the 8-hydroxy-deoxyguanosine level was higher in Group A than in Group B (P<.05). Microarray analysis revealed that the expressions of p34, PA26, and ABL were higher in Group A, whereas those of HRAD51, CR6, and XRCC3 were higher in Group B. CONCLUSION:Oxidative stress is capable of causing neuronal toxicity via lipid peroxidation, DNA damage, and abnormalities of gene expression, and therefore is a possible pathogenic mechanism underlying depression in patients with CRC. 10.1016/j.jpsychores.2008.09.001
    Self-care as a mediator between symptom-management self-efficacy and quality of life in women with breast cancer. Chin Chia-Hui,Tseng Ling-Ming,Chao Ta-Chung,Wang Tsae-Jyy,Wu Shu-Fang,Liang Shu-Yuan PloS one BACKGROUND:The important role of self-efficacy in facilitating health behavior and, in turn, promoting health outcomes has been widely presumed in the theoretical literature. However, little research has focused on the mechanism by which self-care mediates the relationship between symptom-management self-efficacy and quality of life (QOL) in breast cancer patients. OBJECTIVE:The purpose of this study was to examine the relationship between symptom-management self-efficacy and quality of life in Taiwanese oncology outpatients with breast cancer and then proposes self-care as a mediator between these two factors. METHODS:This cross-sectional study enrolled 201 oncology outpatients at one teaching hospital in metropolitan Taipei City, Taiwan. The research instruments included the Symptom-Management Self-Efficacy Scale-Cancer (SMSES-Breast Ca.), the Self-Care Scale, and the European Organization for Research & Treatment of Cancer Quality of Life Group Questionnaire (EORTC-QLQ-C30). RESULTS:Symptom-management self-efficacy (SMSE) was directly associated with the QOL of the participants (β = 5.94, p < .001). Moreover, SMSE was indirectly associated with QOL through self-care. Self-care was found to mediate the relationship between symptom-management self-efficacy and global QOL (indirect effect = 0.54, 95% CI 0.12 to 1.18). The level of 95% CI was significant. CONCLUSIONS:The present study supports that self-efficacy beliefs and self-care both significantly and positively influence the quality of life of patients. 10.1371/journal.pone.0246430
    Symptom burden among older breast cancer survivors: The Thinking and Living With Cancer (TLC) study. Mandelblatt Jeanne S,Zhai Wanting,Ahn Jaeil,Small Brent J,Ahles Tim A,Carroll Judith E,Denduluri Neelima,Dilawari Asma,Extermann Martine,Graham Deena,Hurria Arti,Isaacs Claudine,Jacobsen Paul B,Jim Heather S L,Luta George,McDonald Brenna C,Patel Sunita K,Root James C,Saykin Andrew J,Tometich Danielle B,Zhou Xingtao,Cohen Harvey J Cancer BACKGROUND:Little is known about longitudinal symptom burden, its consequences for well-being, and whether lifestyle moderates the burden in older survivors. METHODS:The authors report on 36-month data from survivors aged ≥60 years with newly diagnosed, nonmetastatic breast cancer and noncancer controls recruited from August 2010 through June 2016. Symptom burden was measured as the sum of self-reported symptoms/diseases as follows: pain (yes or no), fatigue (on the Functional Assessment of Cancer Therapy [FACT]-Fatigue scale), cognitive (on the FACT-Cognitive scale), sleep problems (yes or no), depression (on the Center for Epidemiologic Studies Depression scale), anxiety (on the State-Trait Anxiety Inventory), and cardiac problems and neuropathy (yes or no). Well-being was measured using the FACT-General scale, with scores from 0 to 100. Lifestyle included smoking, alcohol use, body mass index, physical activity, and leisure activities. Mixed models assessed relations between treatment group (chemotherapy with or without hormone therapy, hormone therapy only, and controls) and symptom burden, lifestyle, and covariates. Separate models tested the effects of fluctuations in symptom burden and lifestyle on function. RESULTS:All groups reported high baseline symptoms, and levels remained high over time; differences between survivors and controls were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy-exposed survivors, followed by hormone therapy-exposed survivors versus controls (P < .001). The burden score was related to physical, emotional, and functional well-being (eg, survivors with lower vs higher burden scores had 12.4-point higher physical well-being scores). The composite lifestyle score was not related to symptom burden or well-being, but physical activity was significantly associated with each outcome (P < .005). CONCLUSIONS:Cancer and its treatments are associated with a higher level of actionable symptoms and greater loss of well-being over time in older breast cancer survivors than in comparable noncancer populations, suggesting the need for surveillance and opportunities for intervention. 10.1002/cncr.32663
    Symptom burden in patients with cancer who are experiencing unplanned hospitalization. Newcomb Richard A,Nipp Ryan D,Waldman Lauren P,Greer Joseph A,Lage Daniel E,Hochberg Ephraim P,Jackson Vicki A,Fuh Charn-Xin,Ryan David P,Temel Jennifer S,El-Jawahri Areej R Cancer BACKGROUND:Inpatient supportive care programs often target patients with advanced solid tumors. To the authors' knowledge, few studies to date have characterized symptom burden in hospitalized patients with potentially curable cancers. The objective of the current study was to compare symptom burden, palliative care consultation, and readmission rates in hospitalized patients by cancer type and treatment intent. METHODS:The authors conducted a single-center study of hospitalized patients with cancer between 2014 and 2017. They assessed physical symptoms using the Edmonton Symptom Assessment System and psychological distress using the Patient Health Questionnaire-4 and the Primary Care PTSD (Posttraumatic Stress Disorder) Screen. Multivariate linear regression models were used to assess symptom burden, logistic regression was used to assess palliative care use, and competing risk regression was used to compare 90-day readmission risk. RESULTS:A total of 1549 patients were enrolled and surveyed. The majority of patients reported moderate to severe fatigue, poor well-being, and drowsiness with no significant differences noted by cancer type and treatment intent. Compared with other groups, patients with incurable solid cancer reported higher physical symptoms (beta coefficient [B], 4.73; P < .01) and symptoms of depression (B, 0.44; P < .01) and anxiety (B, 0.39; P < .01), but no difference in posttraumatic stress disorder. Among patients in the top quartile symptom burden according to the Edmonton Symptom Assessment System, the palliative care service was consulted in 14.7%, 7.9%, 25.0%, and 49.6%, respectively, of patients with potentially curable hematologic, potentially curable solid, incurable hematologic, and incurable solid cancers (P < .001). Compared with patients with potentially curable solid cancer, patients in each group experienced a higher risk of readmission within 90 days. CONCLUSIONS:Hospitalized patients with cancer experience substantial physical and psychological symptoms. Palliative care rarely is consulted for highly symptomatic patients with potentially curable cancers. Supportive care interventions should target the needs of symptomatic patients regardless of treatment intent. 10.1002/cncr.32833
    A Cognitive-Behavioral Intervention for the Symptom Clusters of Chinese Patients With Gastrointestinal Tract Cancer Undergoing Chemotherapy: A Pilot Study. Zhang Xinqiong,Wang Qin,Zhang Xiaomin,Wu Xiaoting,Wang Qiuping,Hong Jingfang Cancer nursing BACKGROUND:Patients with gastrointestinal tract (GIT) cancer undergoing chemotherapy often experience several symptoms that constitute symptom clusters and can cause patients to suffer. Effective interventions are lacking for this kind of patients. OBJECTIVE:The aims of this study were to test the feasibility and acceptability of a cognitive-behavioral (CB) intervention developed for Chinese patients with GIT cancer undergoing chemotherapy and to estimate the efficacy of the intervention for symptom clusters. METHODS:In this pilot, quasi-randomized controlled trial, 40 patients were assigned to the CB intervention or control group. The CB intervention, considering characteristics of patients and Chinese culture, contained 4 sections including cognitive reframing, cancer-diet education, relaxation, and exercise techniques. Symptom clusters, illness perception, anxiety, and depression were measured. RESULTS:Thirty-nine patients (97.5%) completed the study program and expressed willingness to follow the intervention. Compared with the control group, all outcomes were improved (all P < .05) in the CB group after the intervention, except for the gastrointestinal symptom cluster (t = 0.25, P = .802). In the CB group, the scores of all outcomes (all P < .05) decreased except for depression (t = 1.76, P = .095). CONCLUSION:The CB intervention is partially feasible and acceptable. It may also help to improve part of the symptom clusters of Chinese patients with GIT cancer undergoing chemotherapy. However, some modifications are needed in future studies to better test effectiveness. IMPLICATIONS FOR PRACTICE:Symptom management remains a major problem in clinical nursing. Such a CB intervention can be beneficial to the clinical management of symptom clusters. 10.1097/NCC.0000000000000625
    Real time remote symptom monitoring during chemotherapy for cancer: European multicentre randomised controlled trial (eSMART). Maguire Roma,McCann Lisa,Kotronoulas Grigorios,Kearney Nora,Ream Emma,Armes Jo,Patiraki Elisabeth,Furlong Eileen,Fox Patricia,Gaiger Alexander,McCrone Paul,Berg Geir,Miaskowski Christine,Cardone Antonella,Orr Dawn,Flowerday Adrian,Katsaragakis Stylianos,Darley Andrew,Lubowitzki Simone,Harris Jenny,Skene Simon,Miller Morven,Moore Margaret,Lewis Liane,DeSouza Nicosha,Donnan Peter T BMJ (Clinical research ed.) OBJECTIVE:To evaluate effects of remote monitoring of adjuvant chemotherapy related side effects via the Advanced Symptom Management System (ASyMS) on symptom burden, quality of life, supportive care needs, anxiety, self-efficacy, and work limitations. DESIGN:Multicentre, repeated measures, parallel group, evaluator masked, stratified randomised controlled trial. SETTING:Twelve cancer centres in Austria, Greece, Norway, Republic of Ireland, and UK. PARTICIPANTS:829 patients with non-metastatic breast cancer, colorectal cancer, Hodgkin's disease, or non-Hodgkin's lymphoma receiving first line adjuvant chemotherapy or chemotherapy for the first time in five years. INTERVENTION:Patients were randomised to ASyMS (intervention; n=415) or standard care (control; n=414) over six cycles of chemotherapy. MAIN OUTCOME MEASURES:The primary outcome was symptom burden (Memorial Symptom Assessment Scale; MSAS). Secondary outcomes were health related quality of life (Functional Assessment of Cancer Therapy-General; FACT-G), Supportive Care Needs Survey Short-Form (SCNS-SF34), State-Trait Anxiety Inventory-Revised (STAI-R), Communication and Attitudinal Self-Efficacy scale for cancer (CASE-Cancer), and work limitations questionnaire (WLQ). RESULTS:For the intervention group, symptom burden remained at pre-chemotherapy treatment levels, whereas controls reported an increase from cycle 1 onwards (least squares absolute mean difference -0.15, 95% confidence interval -0.19 to -0.12; P<0.001; Cohen's D effect size=0.5). Analysis of MSAS sub-domains indicated significant reductions in favour of ASyMS for global distress index (-0.21, -0.27 to -0.16; P<0.001), psychological symptoms (-0.16, -0.23 to -0.10; P<0.001), and physical symptoms (-0.21, -0.26 to -0.17; P<0.001). FACT-G scores were higher in the intervention group across all cycles (mean difference 4.06, 95% confidence interval 2.65 to 5.46; P<0.001), whereas mean scores for STAI-R trait (-1.15, -1.90 to -0.41; P=0.003) and STAI-R state anxiety (-1.13, -2.06 to -0.20; P=0.02) were lower. CASE-Cancer scores were higher in the intervention group (mean difference 0.81, 0.19 to 1.43; P=0.01), and most SCNS-SF34 domains were lower, including sexuality needs (-1.56, -3.11 to -0.01; P<0.05), patient care and support needs (-1.74, -3.31 to -0.16; P=0.03), and physical and daily living needs (-2.8, -5.0 to -0.6; P=0.01). Other SCNS-SF34 domains and WLQ were not significantly different. Safety of ASyMS was satisfactory. Neutropenic events were higher in the intervention group. CONCLUSIONS:Significant reduction in symptom burden supports the use of ASyMS for remote symptom monitoring in cancer care. A "medium" Cohen's effect size of 0.5 showed a sizable, positive clinical effect of ASyMS on patients' symptom experiences. Remote monitoring systems will be vital for future services, particularly with blended models of care delivery arising from the covid-19 pandemic. TRIAL REGISTRATION:Clinicaltrials.gov NCT02356081. 10.1136/bmj.n1647
    Symptom frequency and change of oldest old cancer patients. Pang Linda,de la Cruz Maxine,Wu Jimin,Liu Diane,Naqvi Mujtaba,Bruera Eduardo Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:The oldest old, described as those aged 85 and older, is a growing cancer population. There are limited studies evaluating the symptoms of the oldest old cancer patient population. Our study aimed to evaluate symptom frequency and clinical symptom change as assessed by the Edmonton Symptom Assessment System (ESAS) of the oldest old (≥ 85) compared to older adult (65-84) and general adult (18-64) outpatient cancer patients on initial consult and follow-up visit. METHODS:Retrospective review of a total of 441 patients, 200 randomly sampled patients in the general and older adult group and 41 consecutive patients in the oldest old group. Chart review was performed for demographic and clinical information including ESAS. RESULTS:The oldest old group had less advanced tumors and worse performance status and was receiving less cancer therapy. Eighty percent or more of these patients reported fatigue, sleep disturbance, appetite, and drowsiness. They experienced lower frequencies of pain (p < 0.0001), fatigue (p = 0.0338), nausea (p = 0.0151), feeling of well-being (p = 0.0245), sleep disturbance (p = 0.0484), financial distress (p = 0.0002), and spiritual distress (p = 0.0010) compared to the younger groups. Twenty-six to fifty-one percent of the oldest old patients' symptoms improved on the first follow-up visit. CONCLUSIONS:Oldest old cancer patients have high frequencies of multiple symptoms on initial referral. However, these symptom frequencies are lower when compared to younger age groups. Additionally, many of their symptoms improved on first follow-up visit in the palliative care clinic. More research is needed to address the needs of this growing cancer population and focus symptoms that can improve with palliative care intervention. 10.1007/s00520-019-04702-7
    Association of a Lay Health Worker Intervention With Symptom Burden, Survival, Health Care Use, and Total Costs Among Medicare Enrollees With Cancer. Patel Manali I,Ramirez David,Agajanian Richy,Agajanian Hilda,Coker Tumaini JAMA network open Importance:Undertreated patient symptoms require approaches that improve symptom burden. Objective:To determine the association of a lay health worker-led symptom screening and referral intervention with symptom burden, survival, health care use, and total costs among Medicare Advantage enrollees with a new diagnosis of solid or hematologic malignant neoplasms. Design, Setting, and Participants:This quality improvement study conducted at 9 community oncology practices from November 1, 2016, to October 31, 2018, compared newly diagnosed Medicare Advantage enrollees with solid or hematologic malignant neoplasms with patients diagnosed and treated 1 year prior. Analysis was conducted from August 1, 2019, to January 11, 2020. Interventions:Usual care augmented by a lay health worker trained to screen symptoms and refer patients to palliative care and behavioral medicine. Main Outcomes and Measures:The primary outcome was change in symptoms using the Edmonton Symptom Assessment Scale and the 9-item Patient Health Questionnaire at baseline and 6 and 12 months after enrollment. Secondary outcomes were between-group comparison of survival, 12-month health care use, and costs. Results:Among 425 patients in the intervention group and 407 patients in the control group, the mean (SD) age was 78.8 (8.3) years, 345 (41.5%) were female, and 407 (48.9%) were non-Hispanic white. Patients in the intervention group experienced a lower symptom burden as measured by the Edmonton Symptom Assessment Scale score over time compared with patients in the control group (mean [SD] difference, -1.9 [14.2]; 95% CI, -3.77 to -0.19; P = .01 for the intervention group and 2.32 [17.7]; 95% CI, 0.47 to 4.19; P = .02 for the control group). Similar findings were noted in 9-item Patient Health Questionnaire depression scores (mean [SD] difference, -0.63 [3.99]; 95% CI, -1.23 to -0.028; P = .04 for the intervention group and 1.67 [5.49]; 95% CI, 0.95 to 2.37; P = .01 for the control group). Patients in the intervention group compared with patients in the control group had fewer mean (SD) inpatient visits (0.54 [0.77]; 95% CI, 0.47-0.61 vs 0.72 [1.12]; 95% CI, 0.61-0.83; P = .04) and emergency department visits (0.43 [0.76]; 95% CI, 0.36-0.50 vs 0.57 [1.00]; 95% CI, 0.48-0.67; P = .002) per 1000 patients per year and lower total costs (median, $17 869 [interquartile range, $6865-$32 540] vs median, $18 473 [interquartile range, $6415-$37 910]; P = .02). A total of 180 patients in the intervention group and 189 patients in the control group died within 12 months. Among those who died, patients in the intervention group had greater hospice use (125 of 180 [69.4%] vs 79 of 189 [41.8%]; odds ratio, 3.16; 95% CI, 2.13-4.69; P < .001), fewer mean (SD) emergency department and hospital visits (emergency department: 0.10 [0.30]; 95% CI, 0.06-0.14 vs 0.30 [0.46]; 95% CI, 0.24-0.38; P = .001; hospital: 0.27 [0.44]; 95% CI, 0.21-0.34 vs 0.43 [0.82]; 95% CI, 0.32-0.55; P = .02), and lower costs (median, $3602 [interquartile range, $1076-$9436] vs median, $12 726 [interquartile range, $5259-$22 170]; P = .002), but there was no significant difference in inpatient deaths (18 of 180 [10.0%] vs 30 of 189 [15.9%]; P = .14). Conclusions and Relevance:This study suggests that a lay health worker-led intervention may be one way to improve burdensome and costly care. 10.1001/jamanetworkopen.2020.1023
    Symptom Experience, Management, and Outcomes According to Race and Social Determinants Including Genomics, Epigenomics, and Metabolomics (SEMOARS + GEM): an Explanatory Model for Breast Cancer Treatment Disparity. McCall Maura K,Connolly Mary,Nugent Bethany,Conley Yvette P,Bender Catherine M,Rosenzweig Margaret Q Journal of cancer education : the official journal of the American Association for Cancer Education Even after controlling for stage, comorbidity, age, and insurance status, black women with breast cancer (BC) in the USA have the lowest 5-year survival as compared with all other races for stage-matched disease. One potential cause of this survival difference is the disparity in cancer treatment, evident in many population clinical trials. Specifically, during BC chemotherapy, black women receive less relative dose intensity with more dose reductions and early chemotherapy cessation compared with white women. Symptom incidence, cancer-related distress, and ineffective communication, including the disparity in patient-centeredness of care surrounding patient symptom reporting and clinician assessment, are important factors contributing to racial disparity in dose reduction and early therapy termination. We present an evidence-based overview and an explanatory model for racial disparity in the symptom experience during BC chemotherapy that may lead to a reduction in dose intensity and a subsequent disparity in outcomes. This explanatory model, the Symptom Experience, Management, Outcomes and Adherence according to Race and Social determinants + Genomics Epigenomics and Metabolomics (SEMOARS + GEM), considers essential factors such as social determinants of health, clinician communication, symptoms and symptom management, genomics, epigenomics, and pharmacologic metabolism as contributory factors. 10.1007/s13187-019-01571-w
    Risk factors for clinician-reported symptom clusters in patients with advanced head and neck cancer in a phase 3 randomized clinical trial: RTOG 0129. Xiao Canhua,Hanlon Alexandra,Zhang Qiang,Movsas Benjamin,Ang Kian,Rosenthal David I,Nguyen-Tan P Félix,Kim Harold,Le Quynh,Bruner Deborah Watkins Cancer BACKGROUND:Chemoradiotherapy has become the standard of care for head and neck squamous cell carcinoma; however, those patients often experience multiple treatment-related symptoms or symptom clusters. Two symptom clusters have been identified for this population. Little is known about the risk factors of these symptom clusters. METHODS:Subjects comprised 684 patients who were treated with concurrent chemoradiotherapy in a phase 3 randomized clinical trial. This trial compared standard fractionation radiotherapy to accelerated fractionation radiotherapy. Symptom clusters were evaluated at the end of the first and the second cycle of chemotherapy, and 3 months after the start of radiotherapy. Mixed-effect modeling was used to observe risk factors for symptom clusters. RESULTS:Race and education were independent predictors for the head and neck cluster, whereas sex and history of tobacco use were independent predictors for the gastrointestinal cluster. Primary cancer site was only significant for the head and neck cluster when other factors were not controlled: patients with oropharyngeal cancer had more severe symptoms in the head and neck clusters than did patients with laryngeal cancer. In addition, patients receiving accelerated fractionation radiotherapy experienced more symptoms of radiomucositis, pain, and nausea at 3 months after the start of radiotherapy than those receiving standard fractionation radiotherapy. CONCLUSIONS:Demographic characteristics were more predictive to symptom clusters, whereas clinical characteristics, such as cancer site and treatment arms, were more significant for individual symptoms. Knowing the risk factors will enhance the capability of clinicians to evaluate patients' risk of severe symptom clusters and to personalize management strategies. 10.1002/cncr.28500
    Engaging high-risk groups in early lung cancer diagnosis: a qualitative study of symptom presentation and intervention preferences among the UK's most deprived communities. McCutchan Grace,Hiscock Julia,Hood Kerenza,Murchie Peter,Neal Richard D,Newton Gareth,Thomas Sara,Thomas Ann Maria,Brain Kate BMJ open OBJECTIVES:People at high-risk for lung cancer-current/former smokers, aged 40+ years, with serious lung comorbidity (ie, chronic obstructive pulmonary disease) and living in highly deprived areas-are more likely to delay symptom presentation. This qualitative study aimed to understand the influences on early presentation with lung cancer symptoms in high-risk individuals and intervention preferences. METHODS:Semi-structured qualitative interviews with 37 high-risk individuals (without a cancer diagnosis), identified through seven GP practices in socioeconomically deprived areas of England, Scotland and Wales (most deprived 20%). A symptom attribution task was used to explore lung symptom perception and help seeking, developed using Leventhal's Common Sense Model. Four focus groups with 16 high-risk individuals and 12 local stakeholders (healthcare professionals and community partners) were conducted to explore preferences for an intervention to promote early lung cancer symptom presentation. Data were synthesised using Framework analysis. RESULTS:Individual and area level indicators of deprivation confirmed that interview participants were highly deprived. Preoccupation with managing 'treatable' short-term conditions (chest infections), led to avoidance of acting on 'inevitable and incurable' long-term conditions (lung cancer). Feeling judged and unworthy of medical help because of their perceived social standing or lifestyle deterred medical help seeking, particularly when difficult life circumstances and traumatic events led to tobacco and alcohol addiction. . Participants recommended multifaceted interventions in community venues, with information about lung cancer symptoms and the benefits of early diagnosis, led by a trained and non-judgemental facilitator. CONCLUSIONS:This study was novel in engaging a high-risk population to gain an in-depth understanding of the broader contextual influences on lung cancer symptom presentation. Perceived lack of health service entitlement and complex lives facilitated avoidance of recognising and presenting with lung cancer symptoms. Community-based interventions have the potential to empower disadvantaged populations to seek medical help for lung symptoms. 10.1136/bmjopen-2018-025902
    Telephone interventions for symptom management in adults with cancer. Ream Emma,Hughes Amanda Euesden,Cox Anna,Skarparis Katy,Richardson Alison,Pedersen Vibe H,Wiseman Theresa,Forbes Angus,Bryant Andrew The Cochrane database of systematic reviews BACKGROUND:People with cancer experience a variety of symptoms as a result of their disease and the therapies involved in its management. Inadequate symptom management has implications for patient outcomes including functioning, psychological well-being, and quality of life (QoL). Attempts to reduce the incidence and severity of cancer symptoms have involved the development and testing of psycho-educational interventions to enhance patients' symptom self-management. With the trend for care to be provided nearer patients' homes, telephone-delivered psycho-educational interventions have evolved to provide support for the management of a range of cancer symptoms. Early indications suggest that these can reduce symptom severity and distress through enhanced symptom self-management. OBJECTIVES:To assess the effectiveness of telephone-delivered interventions for reducing symptoms associated with cancer and its treatment. To determine which symptoms are most responsive to telephone interventions. To determine whether certain configurations (e.g. with/without additional support such as face-to-face, printed or electronic resources) and duration/frequency of intervention calls mediate observed cancer symptom outcome effects. SEARCH METHODS:We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1); MEDLINE via OVID (1946 to January 2019); Embase via OVID (1980 to January 2019); (CINAHL) via Athens (1982 to January 2019); British Nursing Index (1984 to January 2019); and PsycINFO (1989 to January 2019). We searched conference proceedings to identify published abstracts, as well as SIGLE and trial registers for unpublished studies. We searched the reference lists of all included articles for additional relevant studies. Finally, we handsearched the following journals: Cancer, Journal of Clinical Oncology, Psycho-oncology, Cancer Practice, Cancer Nursing, Oncology Nursing Forum, Journal of Pain and Symptom Management, and Palliative Medicine. We restricted our search to publications published in English. SELECTION CRITERIA:We included randomised controlled trials (RCTs) and quasi-RCTs that compared one or more telephone interventions with one other, or with other types of interventions (e.g. a face-to-face intervention) and/or usual care, with the stated aim of addressing any physical or psychological symptoms of cancer and its treatment, which recruited adults (over 18 years) with a clinical diagnosis of cancer, regardless of tumour type, stage of cancer, type of treatment, and time of recruitment (e.g. before, during, or after treatment). DATA COLLECTION AND ANALYSIS:We used Cochrane methods for trial selection, data extraction and analysis. When possible, anxiety, depressive symptoms, fatigue, emotional distress, pain, uncertainty, sexually-related and lung cancer symptoms as well as secondary outcomes are reported as standardised mean differences (SMDs) with 95% confidence intervals (CIs), and we presented a descriptive synthesis of study findings. We reported on findings according to symptoms addressed and intervention types (e.g. telephone only, telephone combined with other elements). As many studies included small samples, and because baseline scores for study outcomes often varied for intervention and control groups, we used change scores and associated standard deviations. The certainty of the evidence for each outcome was interpreted using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS:Thirty-two studies were eligible for inclusion; most had moderate risk of bias,often related to blinding. Collectively, researchers recruited 6250 people and studied interventions in people with a variety of cancer types and across the disease trajectory, although many participants had breast cancer or early-stage cancer and/or were starting treatment. Studies measured symptoms of anxiety, depression, emotional distress, uncertainty, fatigue, and pain, as well as sexually-related symptoms and general symptom intensity and/or distress. Interventions were primarily delivered by nurses (n = 24), most of whom (n = 16) had a background in oncology, research, or psychiatry. Ten interventions were delivered solely by telephone; the rest combined telephone with additional elements (i.e. face-to-face consultations and digital/online/printed resources). The number of calls delivered ranged from 1 to 18; most interventions provided three or four calls. Twenty-one studies provided evidence on effectiveness of telephone-delivered interventions and the majority appeared to reduce symptoms of depression compared to control. Nine studies contributed quantitative change scores (CSs) and associated standard deviation results (or these could be calculated). Likewise, many telephone interventions appeared effective when compared to control in reducing anxiety (16 studies; 5 contributed quantitative CS results); fatigue (9 studies; 6 contributed to quantitative CS results); and emotional distress (7 studies; 5 contributed quantitative CS results). Due to significant clinical heterogeneity with regards to interventions introduced, study participants recruited, and outcomes measured, meta-analysis was not conducted. For other symptoms (uncertainty, pain, sexually-related symptoms, dyspnoea, and general symptom experience), evidence was limited; similarly meta-analysis was not possible, and results from individual studies were largely conflicting, making conclusions about their management through telephone-delivered interventions difficult to draw. Heterogeneity was considerable across all trials for all outcomes. Overall, the certainty of evidence was very low for all outcomes in the review. Outcomes were all downgraded due to concerns about overall risk of bias profiles being frequently unclear, uncertainty in effect estimates and due to some inconsistencies in results and general heterogeneity. Unsubstantiated evidence suggests that telephone interventions in some capacity may have a place in symptom management for adults with cancer. However, in the absence of reliable and homogeneous evidence, caution is needed in interpreting the narrative synthesis. Further, there were no clear patterns across studies regarding which forms of interventions (telephone alone versus augmented with other elements) are most effective. It is impossible to conclude with any certainty which forms of telephone intervention are most effective in managing the range of cancer-related symptoms that people with cancer experience. AUTHORS' CONCLUSIONS:Telephone interventions provide a convenient way of supporting self-management of cancer-related symptoms for adults with cancer. These interventions are becoming more important with the shift of care closer to patients' homes, the need for resource/cost containment, and the potential for voluntary sector providers to deliver healthcare interventions. Some evidence supports the use of telephone-delivered interventions for symptom management for adults with cancer; most evidence relates to four commonly experienced symptoms - depression, anxiety, emotional distress, and fatigue. Some telephone-delivered interventions were augmented by combining them with face-to-face meetings and provision of printed or digital materials. Review authors were unable to determine whether telephone alone or in combination with other elements provides optimal reduction in symptoms; it appears most likely that this will vary by symptom. It is noteworthy that, despite the potential for telephone interventions to deliver cost savings, none of the studies reviewed included any form of health economic evaluation. Further robust and adequately reported trials are needed across all cancer-related symptoms, as the certainty of evidence generated in studies within this review was very low, and reporting was of variable quality. Researchers must strive to reduce variability between studies in the future. Studies in this review are characterised by clinical and methodological diversity; the level of this diversity hindered comparison across studies. At the very least, efforts should be made to standardise outcome measures. Finally, studies were compromised by inclusion of small samples, inadequate concealment of group allocation, lack of observer blinding, and short length of follow-up. Consequently, conclusions related to symptoms most amenable to management by telephone-delivered interventions are tentative. 10.1002/14651858.CD007568.pub2
    Cancer symptom awareness in the US: Sociodemographic differences in a population-based survey of adults. Sarma Elizabeth A,Rendle Katharine A,Kobrin Sarah C Preventive medicine Symptom awareness may improve cancer outcomes by prompting timely help-seeking and diagnosis. Research in the UK has shown lower symptom awareness among sociodemographic groups at higher risk of poor cancer outcomes; however, no population-based surveys in the US have assessed whether cancer symptom awareness varies across sociodemographic groups. We therefore examined associations between sociodemographic factors and recognition of 11 cancer symptoms using a novel population-based survey of US adults. We conducted telephone interviews in 2014 with a population-representative sample of English-speaking adults (aged 50 and older) in the US (N = 1425) using an adapted Awareness and Beliefs about Cancer (ABC) survey. Socioeconomic status (SES) was indexed by education. Additional sociodemographic factors included gender, age, marital status, and race. We used multivariable logistic regression models to examine the association between sociodemographic factors and recognition of each symptom, adjusting for cancer experience. Participants recognized an average of 8.43 symptoms as potential signs of cancer. In multivariable analyses, less education consistently predicted lower recognition across the symptoms. As socioeconomic inequalities in cancer mortality widen, it is increasingly important to understand factors that may contribute to these disparities. Our results suggest that US adults of lower SES have lower cancer symptom awareness across symptoms, findings that echo results from other developed countries. With low rates of cancer screening, another approach to reducing cancer burden and disparities may be through greater symptom awareness for symptoms with lower awareness, though additional work is needed to identify mechanisms through which awareness may have its effects on cancer outcomes. 10.1016/j.ypmed.2020.106005
    [Effects of oxidative stress on cognitive impairment in first episode schizophrenia]. Wang Y P,Zhang P F,Yuan X X,Liu Y F,Li H H,Tao Q,Li X,Pang L J,Song X Q Zhonghua yi xue za zhi To observe the relationship between serum oxidative stress as well as brain-derived neurotrophic factor (BDNF) and cognitive function in first-episode drug-free schizophrenics, and to explore the possible effect of oxidative stress in cognitive impairment of first-episode schizophrenia. A total of 125 first-episode drug-free schizophrenics (schizophrenia group) from the First Affiliated Hospital of Zhengzhou University and 80 healthy individuals (control group) were enrolled. The serum concentration of oxidized glutathione (GSSG) was measured by the Microenzyme method the serum concentration of nitric oxide (NO) was measured by one-step method, the BDNF level was measured by enzyme linked immunosorbent assay and Matrics Consensus Cognitive Battery(MCCB) was used to evaluate the cognitive function. (1)The serum level of BDNF in schizophrenia group (2 763±1 728 pg/ml) was significantly lower than that in control group (4 165±1 299 pg/ml)(0.001). And the serum levels of GSSG and NO in schizophrenia group ((36±9), (81±65) μmol/L) were significantly higher than that in control group ((27±11), (24±16) μmol/L) (0.001). In comparison with the control group scores were significantly lower in the seven domains of cognitive function in the schizophrenia group (all 0.001). (2)After controlling the confounding factors like age, gender, cultural differences and course of disease by partial correlation analysis, the correlation analysis showed that: serum level of BDNF in schizophrenia group had positive correlation with Information processing rate T points, attentional facilitating T points, working memory T points and Reasoning and problem solving T points (0.417, 0.206, 0.247, 0.318, all 0.05). In schizophrenia group the serum level of GSSG had a negative correlation with information processing rate T points and reasoning and problem solving T points (-0.321, -0.231, all 0.05). The serum level of NO was negatively related to Information processing rate T points working memory T points Verbal learning T points(-0.201, -0.193, -0.237, all 0.05). Oxidative stress may be involved in the cognitive impairment of schizophrenia Oxidation products are risk factors for cognitive impairment of schizophrenia and BDNF is a protective factor of cognitive function. 10.3760/cma.j.issn.0376-2491.2019.01.003
    Deferoxamine regulates neuroinflammation and oxidative stress in rats with diabetes-induced cognitive dysfunction. Zeinivand Motahareh,Nahavandi Arezo,Zare Mahdie Inflammopharmacology Diabetic encephalopathy, a major complication of diabetes, is characterized by cognitive impairment and structural and neurochemical abnormalities. Neuroinflammation following impairment of iron homeostasis is a remarkable feature of several neurological disorders. In the present study, we investigated the role of deferoxamine (DFO), as a clinical iron chelator, in improvement of type 1 diabetes-induced cognitive dysfunction. Streptozotocin was utilized to induce type 1 diabetic in rat model. Animals were categorized into four groups: control, diabetic, diabetic + Iron and diabetic + DFO. Hence, DFO was administered at a dose of 100 mg/kg S.C and iron was administered at a dose of 12 mg/kg P.O for 8 weeks. Finally, Y-maze and passive avoidance were performed. Measurement of IL-6, ferritin, and the brain-derived neurotrophic factor (BDNF) expression was carried out using ELISA. Our results showed significant increased levels of ferritin (P < 0.001), IL-6 (P < 0.001), MDA (P < 0.01), as well as decreased levels of BDNF (P < 0.001) in the diabetic and iron groups compared to control. Post-treatment with DFO for 8 weeks after the induction of diabetes, markedly reduced levels of ferritin (P < 0.001), IL-6 (P < 0.01), and MDA (P < 0.001), as well as increased levels of BDNF (P < 0.01) compared to the diabetic and iron groups was observed. Collectively, these findings demonstrate the validity of DFO as a good candidate to attenuate cognitive dysfunction following diabetes by targeting oxidative stress, neuroinflammation, and modulation of iron homeostasis. 10.1007/s10787-019-00665-7
    Oxidative stress-induced cognitive impairment in obesity can be reversed by vitamin D administration in rats. Hajiluian Ghazaleh,Abbasalizad Farhangi Mahdieh,Nameni Ghazaleh,Shahabi Parviz,Megari-Abbasi Mehran Nutritional neuroscience BACKGROUND:There is evidence that obesity leads to cognitive impairments via several markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase and malondialdehyde (MDA) in the hippocampus. Increased inflammatory markers in the brain have obesity triggering effects. In the current study we aimed to investigate the effects of vitamin D on cognitive function, nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α concentration and markers of oxidative stress in the hippocampus of high-fat diet-induced obese rats. METHODS AND MATERIALS:Forty male Wistar rats were divided into two groups: control diet (CD) and high-fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: CD, CD + vitamin D, HFD and HFD + vitamin D. Vitamin D was administered at 500 IU/kg dosage for 5 weeks. Four weeks after supplementation, Morris water maze test was performed. NF-κB and TNF-α concentration in the hippocampus were determined using ELISA kits. Moreover, oxidative stress markers in the hippocampus including GPx, SOD, MDA and CAT concentrations were measured by spectrophotometry methods. RESULTS:HFD significantly increased TNF-α (P = 0.04) and NF-κB (P = 0.01) concentrations in the hippocampus compared with CD. Vitamin D treatment led to a significant reduction in hippocampus NF-κB concentrations in HFD + vitamin D group (P = 0.001); however, vitamin D had no effect on TNF-α concentrations. Moreover, HFD significantly induced oxidative stress by reducing GPx, SOD and increasing MDA concentrations in the hippocampus. Vitamin D supplementation in HFD group also significantly increased GPx, SOD and reduced MDA concentrations. CONCLUSION:Vitamin D improved hippocampus oxidative stress and inflammatory markers in HFD-induced obese rats and improved cognitive performance. Further studies are needed to better clarify the underlying mechanisms. 10.1080/1028415X.2017.1348436
    The Role of Oxidative Stress in Etiopathogenesis of Chemotherapy Induced Cognitive Impairment (CICI)-"Chemobrain". Gaman Amelia Maria,Uzoni Adriana,Popa-Wagner Aurel,Andrei Anghel,Petcu Eugen-Bogdan Aging and disease Chemobrain or chemotherapy induced cognitive impairment (CICI) represents a new clinical syndrome characterised by memory, learning and motor function impairment. As numerous patients with cancer are long-term survivors, CICI represent a significant factor which may interfere with their quality of life. However, this entity CICI must be distinguished from other cognitive syndromes and addressed accordingly. At the present time, experimental and clinical research suggests that CICI could be induced by numerous factors including oxidative stress. This type of CNS injury has been previously described in cancer patients treated with common anti-neoplastic drugs such as doxorubicine, carmustine, methotrexate and cyclophosphamide. It seems that all these pharmacological factors promote neuronal death through a final common pathway represented by TNF alpha (tumour necrosis factor). However, as cancer in general is diagnosed more commonly in the aging population, the elderly oncological patient must be treated with great care since aging per se is also impacted by oxidative stress and potentiually by TNF alpha deleterious action on brain parenchyma. In this context, some patients may develop cognitive dysfunction well before the appearance of CICI. In addition, chemotherapy may worsen their cognitive function. Therefore, at the present time, there is an acute need for development of effective therapeutic methods to prevent CICI as well as new methods of early CICI diagnosis. 10.14336/AD.2015.1022
    Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment ("chemobrain"), a condition that significantly impairs the quality of life of many cancer survivors. Ren Xiaojia,Boriero Diana,Chaiswing Luksana,Bondada Subbarao,St Clair Daret K,Butterfield D Allan Biochimica et biophysica acta. Molecular basis of disease Increasing numbers of cancer patients survive and live longer than five years after therapy, but very often side effects of cancer treatment arise at same time. One of the side effects, chemotherapy-induced cognitive impairment (CICI), also called "chemobrain" or "chemofog" by patients, brings enormous challenges to cancer survivors following successful chemotherapeutic treatment. Decreased abilities of learning, memory, attention, executive function and processing speed in cancer survivors with CICI, are some of the challenges that greatly impair survivors' quality of life. The molecular mechanisms of CICI involve very complicated processes, which have been the subject of investigation over the past decades. Many mechanistic candidates have been studied including disruption of the blood-brain barrier (BBB), DNA damage, telomere shortening, oxidative stress and associated inflammatory response, gene polymorphism of neural repair, altered neurotransmission, and hormone changes. Oxidative stress is considered as a vital mechanism, since over 50% of FDA-approved anti-cancer drugs can generate reactive oxygen species (ROS) or reactive nitrogen species (RNS), which lead to neuronal death. In this review paper, we discuss these important candidate mechanisms, in particular oxidative stress and the cytokine, TNF-alpha and their potential roles in CICI. 10.1016/j.bbadis.2019.02.007
    Chemotherapy-Induced Cognitive Impairment Is Associated with Increased Inflammation and Oxidative Damage in the Hippocampus. Bagnall-Moreau Ciara,Chaudhry Sovira,Salas-Ramirez Kaliris,Ahles Tim,Hubbard Karen Molecular neurobiology Increasing evidence indicates that chemotherapy results in long-term effects on cognitive dysfunction in some cancer survivors. While many studies have established the domains of cognition and corresponding regions in the brain most affected, little is revealed about the potential molecular mechanisms that mediate these adverse changes after treatment. The effects of chemotherapy on the brain are likely attributed to various mechanisms, including oxidative stress and immune dysregulation, features that are also reminiscent of cognitive aging. We have investigated the cognitive effects of a cocktail composed of doxorubicin and cyclophosphamide (AC-chemo) in a surgical ovariectomized rodent model. In this study, we address whether the levels of pro-inflammatory cytokines and oxidative stress-responsive gene markers are altered in the CNS of rats treated with systemic AC-chemo. We further evaluated the levels of nucleic acids modified by oxidative stress in the hippocampus using both immunohistochemical and Northern blotting techniques with a monoclonal antibody against 8-hydroxyguanosine (8-OHG) and 8-OHdG base lesions. We demonstrate that ERK 1/2 and JNK/SAPK signaling activities are elevated in the hippocampus of AC-chemo rats. The levels of pro-inflammatory, oxidative stress-responsive, and RNA/DNA damage markers were also higher in drug-injected animals relative to saline controls. The results indicate that the effects of AC chemotherapy are associated with oxidative damage and a global stress response in the hippocampus. These alterations in the molecular signature of the brain may underlie the processes that contribute to cognitive impairment after treatment. 10.1007/s12035-019-1589-z
    Chemotherapy-induced cognitive impairment: focus on the intersection of oxidative stress and TNFα. Rummel Nicole G,Chaiswing Luksana,Bondada Subbarao,St Clair Daret K,Butterfield D Allan Cellular and molecular life sciences : CMLS Chemotherapy-induced cognitive impairment (CICI) has been observed in a large fraction of cancer survivors. Although many of the chemotherapeutic drugs do not cross the blood-brain barrier, following treatment, the structure and function of the brain are altered and cognitive dysfunction occurs in a significant number of cancer survivors. The means by which CICI occurs is becoming better understood, but there still remain unsolved questions of the mechanisms involved. The hypotheses to explain CICI are numerous. More than 50% of FDA-approved cancer chemotherapy agents are associated with reactive oxygen species (ROS) that lead to oxidative stress and activate a myriad of pathways as well as inhibit pathways necessary for proper brain function. Oxidative stress triggers the activation of different proteins, one in particular is tumor necrosis factor alpha (TNFα). Following treatment with various chemotherapy agents, this pro-inflammatory cytokine binds to its receptors at the blood-brain barrier and translocates to the parenchyma via receptor-mediated endocytosis. Once in brain, TNFα initiates pathways that may eventually lead to neuronal death and ultimately cognitive impairment. TNFα activation of the c-jun N-terminal kinases (JNK) and Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathways may contribute to both memory decline and loss of higher executive functions reported in patients after chemotherapy treatment. Chemotherapy also affects the brain's antioxidant capacity, allowing for accumulation of ROS. This review expands on these topics to provide insights into the possible mechanisms by which the intersection of oxidative stress and TNFΑ are involved in chemotherapy-induced cognitive impairment. 10.1007/s00018-021-03925-4
    C-phycocyanin Mitigates Cognitive Impairment in Doxorubicin-Induced Chemobrain: Impact on Neuroinflammation, Oxidative Stress, and Brain Mitochondrial and Synaptic Alterations. Wang Chenying,Zhao Yuhang,Wang Lewei,Pan Shunji,Liu Yumei,Li Sanqiang,Wang Dongmei Neurochemical research Chemotherapy-induced cognitive impairment (CICI) is a common detrimental effect of cancer treatment, occurring in up to 75% of cancer patients. The widely utilized chemotherapeutic agent doxorubicin (DOX) has been implicated in cognitive decline, mostly via cytokine-induced neuroinflammatory and oxidative and mitochondrial damage to brain tissues. C-phycocyanin (CP) has previously been shown to have potent anti-inflammatory, antioxidant, and mitochondrial protective properties. Therefore, this present study was aimed to investigate the neuroprotective effects of CP against DOX-elicited cognitive impairment and explore the underlying mechanisms. CP treatment (50 mg/kg) significantly improved behavioral deficits in DOX-treated mice. Furthermore, CP suppressed DOX-induced neuroinflammation and oxidative stress, mitigated mitochondrial abnormalities, rescued dendritic spine loss, and increased synaptic density in the hippocampus of DOX-treated mice. Our results suggested that CP improves established DOX-induced cognitive deficits, which could be explained at least partly by inhibition of neuroinflammatory and oxidant stress and attenuation of mitochondrial and synaptic dysfunction. 10.1007/s11064-020-03164-2
    Nomogram-based parameters to predict overall survival in a real-world advanced cancer population undergoing palliative care. Zhao Weiwei,He Zhiyong,Li Yintao,Jia Huixun,Chen Menglei,Gu Xiaoli,Liu Minghui,Zhang Zhe,Wu Zhenyu,Cheng Wenwu BMC palliative care BACKGROUND:Although palliative care has been accepted throughout the cancer trajectory, accurate survival prediction for advanced cancer patients is still a challenge. The aim of this study is to identify pre-palliative care predictors and develop a prognostic nomogram for overall survival (OS) in mixed advanced cancer patients. METHODS:A total of 378 consecutive advanced cancer patients were retrospectively recruited from July 2013 to October 2015 in one palliative care unit in China. Twenty-three clinical and laboratory characters were collected for analysis. Prognostic factors were identified to construct a nomogram in a training cohort (n = 247) and validated in a testing cohort (n = 131) from the setting. RESULTS:The median survival time was 48.0 (95% CI: 38.1-57.9) days for the training cohort and 52.0 (95% CI: 34.6-69.3) days for the validation cohort. Among pre-palliative care factors, sex, age, tumor stage, Karnofsky performance status, neutrophil count, hemoglobin, lactate dehydrogenase, albumin, uric acid, and cystatin-C were identified as independent prognostic factors for OS. Based on the 10 factors, an easily obtained nomogram predicting 90-day probability of mortality was developed. The predictive nomogram had good discrimination and calibration, with a high C-index of 0.76 (95% CI: 0.73-0.80) in the development set. The strong discriminative ability was externally conformed in the validation cohort with a C-index of 0.75. CONCLUSIONS:A validated prognostic nomogram has been developed to quantify the risk of mortality for advanced cancer patients undergoing palliative care. This tool may be useful in optimizing therapeutic approaches and preparing for clinical courses individually. 10.1186/s12904-019-0432-7
    Reducing Cancer Costs Through Symptom Management and Triage Pathways. Barkley Ronald,Soobader Mah-Jabeen,Wang Jun,Blau Sibel,Page Ray D Journal of oncology practice PURPOSE:Value-based care infers care that is high quality at a comparatively low total cost. A key strategy for value-based oncology care is to avoid unnecessary emergency room (ER) visits and associated hospitalizations of patients receiving treatment for cancer. Early experience with this strategy showed that symptom management in patients with cancer can result in the reduction of ER events and hospitalizations. However, quantifying the actual savings achieved has been elusive. In this article, we present the impact of symptom management and triage pathways programs deployed at two midsize community oncology practices. We then quantify the actual dollar saving in their Medicare and commercial populations. METHODS:Symptom management records generated through the ER triage programs at the two practices were screened to identify avoided ER events. This approach was validated with an independent analysis using Medicare claim data from the Oncology Care Model program in which both practices participate. Bootstrap simulations were used to test for statistical significance of the ER event rate changes before and after the launch of the program. Average event and annual total cost savings from avoided ER incidents and ER-related hospitalizations were then calculated. RESULTS:Two hundred twenty-two avoided ER events were identified, for an estimated net annualized savings generated by the two practices of $3.85 million. Although the ER rate reduction was not statistically significant, these findings are consistent with the observed reduction of ER event rates among a subset of Oncology Care Model beneficiaries at the two practices. CONCLUSION:ER events and associated hospitalizations can be avoided as well as quantified as a result of the deployment of a practice-level integrated platform that incorporates physician-scripted symptom management protocols and telephone triage pathways. 10.1200/JOP.18.00082
    Palliative Care and the Management of Common Distressing Symptoms in Advanced Cancer: Pain, Breathlessness, Nausea and Vomiting, and Fatigue. Henson Lesley A,Maddocks Matthew,Evans Catherine,Davidson Martin,Hicks Stephanie,Higginson Irene J Journal of clinical oncology : official journal of the American Society of Clinical Oncology Good symptom management in oncology is associated with improved patient and family quality of life, greater treatment compliance, and may even offer survival advantages. With population growth and aging, the proportion of patients with multiple symptoms-both related and unrelated to their cancer-is anticipated to increase, supporting calls for a more routine and integrated approach to symptom management. This article presents a summary of the literature for the use of symptom assessment tools and reviews the management of four common and distressing symptoms commonly experienced by people with advanced cancer: pain, breathlessness, nausea and vomiting, and fatigue. We also discuss the role of palliative care in supporting a holistic approach to symptom management throughout the cancer trajectory. 10.1200/JCO.19.00470
    Polysymptomatology in Pediatric Patients Receiving Palliative Care Based on Parent-Reported Data. Feudtner Chris,Nye Russell,Hill Douglas L,Hall Matt,Hinds Pam,Johnston Emily E,Friebert Sarah,Hays Ross,Kang Tammy I,Wolfe Joanne, JAMA network open Importance:Pediatric palliative care treats patients with a wide variety of advanced illness conditions, often with substantial levels of pain and other symptoms. Clinical and research advancements regarding symptom management for these patients are hampered by the scarcity of data on symptoms as well as an overreliance on clinician report. Objective:To provide a detailed description of the symptoms among patients receiving pediatric palliative care based on parental report via a validated, structured symptom assessment measure. Design, Setting, and Participants:Baseline data for this cross-sectional analysis were collected between April 10, 2017, and February 5, 2020, from pediatric palliative care programs in 7 children's hospitals located in Akron, Ohio; Boston, Massachusetts; Birmingham, Alabama; Houston, Texas; Minneapolis, Minnesota; Philadelphia, Pennsylvania; and Seattle, Washington. Data were collected in the hospital, outpatient, and home setting from patients 30 years of age or younger who were receiving pediatric palliative care at 1 of the study sites. Exposures:Analyses were stratified by patients' demographic characteristics, including age, and by whether the patients had received a diagnosis of any of 10 non-mutually exclusive complex chronic condition categories. Main Outcomes and Measures:Twenty symptoms measured via the modified Memorial Symptom Assessment Scale, which scores the frequency and severity of any symptom that is present and provides a total symptom score. Results:Among the first 501 patients enrolled, the median age was 4.1 years (interquartile range, 0.8-12.9 years), 267 (53.3%) were male, and 356 (71.1%) were White. The most prevalent complex chronic conditions included gastrointestinal (357 [71.3%]), neurologic (289 [57.7%]), and cardiovascular (310 [61.9%]) conditions; 438 patients (87.4%) were technology dependent. Parents reported a mean (SD) of 6.7 (3.4) symptoms per patient and a median of 7 symptoms (interquartile range, 4-9 symptoms). A total of 367 patients (73.3%) had 5 or more symptoms. The 5 most prevalent symptoms were pain (319 [63.7%]; 95% CI, 59.4%-67.8%), lack of energy (295 [58.9%]; 95% CI, 54.5%-63.1%), irritability (280 [55.9%]; 95% CI, 51.5%-60.2%), drowsiness (247 [49.3%]; 95% CI, 44.9%-53.7%), and shortness of breath (232 [46.3%]; 95% CI, 41.9%-50.7%). Although older patients were reported by parents as having experienced more symptoms and having higher total symptom scores, variation across condition categories was relatively minor. Patients in the upper 10th percentile of total symptom scores had a median of 12.0 symptoms (interquartile range, 11-13). Conclusions and Relevance:In this cross-sectional study, most children receiving palliative care were experiencing polysymptomatology. An important subgroup of patients frequently experienced numerous severe symptoms. Assessment and management of patients with polysymptomatology are critical aspects of pediatric palliative care. 10.1001/jamanetworkopen.2021.19730
    Web and mobile-based symptom management interventions for physical symptoms of people with advanced cancer: A systematic review and meta-analysis. Saeidzadeh Seyedehtanaz,Kamalumpundi Vijayvardhan,Chi Nai-Ching,Nair Rajeshwari,Gilbertson-White Stephanie Palliative medicine BACKGROUND:Symptom management is a critical aspect of comprehensive palliative care for people with advanced cancer. Web and mobile-based applications are promising e-Health modalities that can facilitate timely access to symptom management interventions for this population. AIM:To evaluate the efficacy of web and mobile-based symptom management interventions in alleviating physical symptom burden in people with advanced cancer. DESIGN:A systematic review and meta-analysis was conducted. PROSPERO ID = CRD42020155295. DATA SOURCES:We searched databases including PubMed, PsycINFO, and CINAHL from 1991 until 2019. Inclusion criteria were: adults with advanced cancer, web or mobile-based interventions targeting symptom management, and report of physical symptom data. Risk of bias was assessed using the ROBINS-I and RoB2. Using RevMan, standardized mean difference (SMD) and 95% confidence intervals were calculated. Heterogeneity was assessed using the statistic. An assessment of interventions was conducted by evaluating the delivery mode, duration, and evaluation of application feature and theoretical elements. RESULTS:A total of 19 studies are included in the systematic review and 18 in the meta-analysis. Majority of the studies were deemed to have high risk of bias. Most of the interventions used a web-application for delivering their education ( = 17). While the interventions varied regarding duration and content, they were mainly guided by a symptom management theory. Web and mobile-based interventions significantly improved the overall physical symptom burden (SMD = -0.18; 95% CI = -0.28 to -0.09;  = 0%;  = 0.0002). CONCLUSIONS:Web and mobile-based intervention are efficacious in decreasing the overall physical symptom burden in people with advanced cancer. 10.1177/02692163211006317
    Vitamin C alleviates LPS-induced cognitive impairment in mice by suppressing neuroinflammation and oxidative stress. Zhang Xiao-Ying,Xu Zhi-Peng,Wang Wei,Cao Jiang-Bei,Fu Qiang,Zhao Wei-Xing,Li Yang,Huo Xiu-Lin,Zhang Li-Ming,Li Yun-Feng,Mi Wei-Dong International immunopharmacology Neuroinflammation is believed to be one of the primary causes of cognitive impairment. Previous studies showed that the antioxidant vitamin C (Vit C) performs many beneficial functions such as immunostimulant and anti-inflammatory actions, but its role in inflammatory cognitive impairment is unclear. In the current study, we investigated the effect and possible mechanism of action of Vit C in lipopolysaccharide (LPS)-induced cognitive impairment. Intracerebroventricular LPS-induced memory impairment was used as the model for neuroinflammatory cognitive dysfunction. Vit C was administered by intracerebroventricular microinjection 30 min prior to LPS exposure. It was found that Vit C significantly protected animals from LPS-induced memory impairment as evidenced by improved performance in the Morris water maze and novel object recognition tests without changes in spontaneous locomotor activity. Vit C pretreatment inhibited the activation of microglia and the production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Furthermore, Vit C pretreatment markedly decreased the malondialdehyde (MDA) level, increased superoxide dismutase (SOD) activity, and modulated the Bax/Bcl-2 ratio and p-p38 MAPK activation in the hippocampus of LPS-treated mice. Together, these results suggest that vitamin C pretreatment could protect mice from LPS-induced cognitive impairment, possibly through the modulation of oxidative stress and inflammatory responses. 10.1016/j.intimp.2018.10.020
    Association of Cerebrospinal Fluid Neurofilament Light Protein With Risk of Mild Cognitive Impairment Among Individuals Without Cognitive Impairment. Kern Silke,Syrjanen Jeremy A,Blennow Kaj,Zetterberg Henrik,Skoog Ingmar,Waern Margda,Hagen Clinton E,van Harten Argonde C,Knopman David S,Jack Clifford R,Petersen Ronald C,Mielke Michelle M JAMA neurology Importance:Accumulating data suggest that elevated cerebrospinal fluid (CSF) neurofilament light (NfL) and neurogranin (Ng) levels are associated with cognitive decline and may be useful markers of neurodegeneration. However, to our knowledge, previous studies have not assessed these CSF markers in the community, evaluated them with regards to risk of mild cognitive impairment (MCI), or compared their prognostic value with CSF total tau (T-tau) or phosphorylated tau (P-tau). Objective:To determine (1) whether CSF NfL and Ng levels were associated with risk of MCI, (2) the effect size of these markers compared with CSF T-tau or P-tau for risk of MCI, and (3) whether CSF amyloid-β (Aβ42) modified these associations. Design, Setting and Participants:The analyses included 648 participants without cognitive impairment who were enrolled into the prospective population-based Mayo Clinic Study of Aging between January 2004 and December 2015 with available CSF data and at least 1 follow-up visit. Participants were followed up for a median of 3.8 years (interquartile range, 2.6-5.4 years). The CSF NfL and Ng levels were measured using an in-house sandwich enzyme-linked immunosorbent assay. The CSF Aβ42, T-tau, and P-tau levels were measured with automated electrochemiluminescence immunoassays. Cox proportional hazards models, with age as the timescale, were used to assess the association between CSF NfL, Ng, Aβ42, T-tau, or P-tau with risk of MCI after adjusting for sex, education, apolipoprotein E genotype, and the Charlson comorbidity index. To examine CSF Aβ42 as an effect modifier, it was categorized into tertiles; the bottom tertile was defined as having elevated brain amyloid. Main Outcomes and Measures:Risk of MCI. Results:At baseline, the median age of the 648 participants without cognitive impairment was 72.3 years (range, 50.7-95.3 years) and 366 (56.5%) were men; 96 (14.8%) developed incident MCI. Compared with the bottom quartile, the top quartile of CSF NfL was associated with a 3.1-fold increased risk of MCI (hazard ratio, 3.13; 95% CI, 1.36-7.18) in multivariate models. Neither CSF T-tau, P-tau, nor Ng was associated with risk of MCI. There was no interaction between Aβ42 and CSF NfL for risk of MCI. Conclusions and Relevance:Elevated CSF NfL levels but not CSF T-tau, P-tau or Ng are a risk factor for MCI in a community population and are independent of brain amyloid. 10.1001/jamaneurol.2018.3459
    Profile of cognitive impairment and underlying pathology in multiple system atrophy. Koga Shunsuke,Parks Adam,Uitti Ryan J,van Gerpen Jay A,Cheshire William P,Wszolek Zbigniew K,Dickson Dennis W Movement disorders : official journal of the Movement Disorder Society BACKGROUND:The objectives of this study were to elucidate any potential association between α-synuclein pathology and cognitive impairment and to determine the profile of cognitive impairment in multiple system atrophy (MSA) patients. To do this, we analyzed the clinical and pathologic features in autopsy-confirmed MSA patients. METHODS:We retrospectively reviewed medical records, including neuropsychological test data, in 102 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank. The burden of glial cytoplasmic inclusions and neuronal cytoplasmic inclusions were semiquantitatively scored in the limbic regions and middle frontal gyrus. We also assessed concurrent pathologies potentially causing dementia including Alzheimer's disease, hippocampal sclerosis, and cerebrovascular pathology. RESULTS:Of 102 patients, 33 (32%) were documented to have cognitive impairment. Those that received objective testing, deficits primarily in processing speed and attention/executive functions were identified, which suggests a frontal-subcortical pattern of dysfunction. Of these 33 patients with cognitive impairment, 8 patients had concurrent pathologies of dementia. MSA patients with cognitive impairment had a greater burden of neuronal cytoplasmic inclusions in the dentate gyrus than patients without cognitive impairment, both including and excluding patients with concurrent pathologies of dementia. CONCLUSIONS:The cognitive deficits observed in this study were more evident on neuropsychological assessment than with cognitive screens. Based on these findings, we recommend that clinicians consider more in-depth neuropsychological assessments if patients with MSA present with cognitive complaints. Although we did not identify the correlation between cognitive deficits and responsible neuroanatomical regions, a greater burden of neuronal cytoplasmic inclusions in the limbic regions was associated with cognitive impairment in MSA. © 2016 International Parkinson and Movement Disorder Society. 10.1002/mds.26874
    Chronic acrylamide exposure induced glia cell activation, NLRP3 infl-ammasome upregulation and cognitive impairment. Liu Ying,Zhang Xing,Yan Dandan,Wang Yiqi,Wang Na,Liu Yufan,Tan Aijun,Chen Xiaoyi,Yan Hong Toxicology and applied pharmacology Acrylamide (ACR), a potential neurotoxin, is present in diet and drinking water. Dietary exposure contributes to cognitive impairment, but relevant mechanism information is limited. Neuroinflammation plays important roles in neurodegenerative disorders. This study aimed to explore whether chronic acrylamide exposure induced neuronal lesions, microglial activation, NLRP3 inflammasome-mediated neuroinflammation and cognitive impairment. For this purpose, 36 Sprague-Dawley (SD) rats were randomly divided into three groups (n = 12/group) and maintained on treated drinking water providing dosages of 0, 0.5, or 5 mg/kg/day ACR for 12 months. Chronic exposure to ACR caused gait abnormality and cognitive dysfunction, which was associated with neuronal lesions, decrease in synapse associated proteins including synapsin I (SYN1), synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), neurogenesis suppression as shown by reduced brain derived neurotrophic factor (BDNF) and doublecortin (DCX) in the hippocampus and frontal cortex. ACR stimulated glial proliferation and microglial activation by increasing GFAP, Iba-1, Iba-1CD68 positive cells. ACR markedly upregulated the protein levels of NLRP3 inflammasome constituents NLRP3, caspase-1 and increased pro-IL-1β and IL-1β. ACR elevated the protein P62 to suppress NLPR3 inflammasome cleavage. Inflammatory cytokines including TNF-α, IL-6 and Cox-2 were also significantly increased after NF-κB pathway activation, which aggravated neuronal lesions and caused memory deficits. This work helped to propose the possible mechanism of chronic exposure of ACR-induced neurotoxicity. 10.1016/j.taap.2020.114949
    MMP-9-BDNF pathway is implicated in cognitive impairment of male individuals with methamphetamine addiction during early withdrawal. Cheng Mei,Liu Qiang,Wang Yan,Hao Yuling,Jing Pengcheng,Jiao Shaoli,Ma Lin,Pan Chenmin,Wu Yulong Behavioural brain research Cognitive impairment is often concomitant with current and abstinent methamphetamine (METH) misuse. However, the mechanism underlying the pathogenesis of cognitive impairment induced by METH remains unclear. As evidence indicates that brain-derived neurotrophic factor (BDNF) is associated with METH addiction, the present study aimed to investigate whether BDNF and the proteins regulating the BDNF signaling pathway might be implicated in the cognitive impairment of the METH abusers during early withdrawal. A total of 171 male subjects were recruited, including 85 METH abstainers and 86 healthy controls. Cognitive function was evaluated with the Montreal Cognitive Assessment (MoCA) screening tool. The levels of serum proteins that regulate the BDNF signaling pathway were measured using enzyme-linked immunosorbent assay kits. 61.18% METH abstainers were determined to have cognitive impairment (MoCA<26). The serum levels of mBDNF, proBDNF, and MMP-9, as well as the ratio of the mBDNF/proBDNF (M/P) were significantly decreased in the cognition-impaired METH abstainers than in the cognition-unimpaired METH abstainers. mBDNF, proBDNF, TrkB, MMP-9, MMP-9 activity, and M/P were significantly correlated with the MoCA score in the METH abstainers. The combination of mBDNF, TrkB, MMP-9, and MMP-9 activity demonstrated excellent diagnostic potential for cognitive impairment of METH abusers during early withdrawal (AUC = 0.978). The results provide the prospective evidence that the MMP-9-BDNF pathway may underlie the pathogenesis of cognitive impairment in METH abusers during early withdrawal. 10.1016/j.bbr.2019.03.020
    Protective effects of tauroursodeoxycholic acid on lipopolysaccharide-induced cognitive impairment and neurotoxicity in mice. Wu Xian,Liu Caihong,Chen Liang,Du Yi-Feng,Hu Mei,Reed Miranda N,Long Yan,Suppiramaniam Vishnu,Hong Hao,Tang Su-Su International immunopharmacology Accumulating evidence has shown that tauroursodeoxycholic acid (TUDCA) is neuroprotective in different animal models of neurological diseases. However, whether TGR5 agonist TUDCA can improve lipopolysaccharide (LPS)-induced cognitive impairment in mice is less clear. Using a model of cognitive impairment with LPS (2.0 μg) we investigated the effects of TUDCA (200 or 400 μg) on cognitive dysfunction and neurotoxicity in mice. Both Morris water maze and Y-maze avoidance tests showed that TUDCA treatment significantly alleviated LPS-induced behavioral impairments. More importantly, we found that TUDCA treatment reversed TGR5 down-regulation, prevented neuroinflammation via inhibiting NF-κB signaling in the hippocampus of LPS-treated mice. Additionally, TUDCA treatment decreased LPS-induced apoptosis through decreasing TUNEL-positive cells and the overexpression of caspase-3, increasing the ratio of Bcl-2/Bax. TUDCA treatment also ameliorated synaptic plasticity impairments by increasing the ratio of mBDNF/proBDNF, the number of dendritic spines and the expression of synapse-associated proteins in the hippocampus. Our results indicated that TUDCA can improve cognitive impairment and neurotoxicity induced by LPS in mice, which is involved in TGR5-mediated NF-κB signaling. 10.1016/j.intimp.2019.03.065
    A Novel Angiotensin-(1-7) Glycosylated Mas Receptor Agonist for Treating Vascular Cognitive Impairment and Inflammation-Related Memory Dysfunction. Hay Meredith,Polt Robin,Heien Michael L,Vanderah Todd W,Largent-Milnes Tally M,Rodgers Kathleen,Falk Torsten,Bartlett Mitchell J,Doyle Kristian P,Konhilas John P The Journal of pharmacology and experimental therapeutics Increasing evidence indicates that decreased brain blood flow, increased reactive oxygen species (ROS) production, and proinflammatory mechanisms accelerate neurodegenerative disease progression such as that seen in vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer's disease and related dementias. There is a critical clinical need for safe and effective therapies for the treatment and prevention of cognitive impairment known to occur in patients with VCID and chronic inflammatory diseases such as heart failure (HF), hypertension, and diabetes. This study used our mouse model of VCID/HF to test our novel glycosylated angiotensin-(1-7) peptide Ang-1-6-O-Ser-Glc-NH2 (PNA5) as a therapy to treat VCID and to investigate circulating inflammatory biomarkers that may be involved. We demonstrate that PNA5 has greater brain penetration compared with the native angiotensin-(1-7) peptide. Moreover, after treatment with 1.0/mg/kg, s.c., for 21 days, PNA5 exhibits up to 10 days of sustained cognitive protective effects in our VCID/HF mice that last beyond the peptide half-life. PNA5 reversed object recognition impairment in VCID/HF mice and rescued spatial memory impairment. PNA5 activation of the Mas receptor results in a dose-dependent inhibition of ROS in human endothelial cells. Last, PNA5 treatment decreased VCID/HF-induced activation of brain microglia/macrophages and inhibited circulating tumor necrosis factor , interleukin (IL)-7, and granulocyte cell-stimulating factor serum levels while increasing that of the anti-inflammatory cytokine IL-10. These results suggest that PNA5 is an excellent candidate and "first-in-class" therapy for treating VCID and other inflammation-related brain diseases. 10.1124/jpet.118.254854
    The triangle of death of neurons: Oxidative damage, mitochondrial dysfunction, and loss of choline-containing biomolecules in brains of mice treated with doxorubicin. Advanced insights into mechanisms of chemotherapy induced cognitive impairment ("chemobrain") involving TNF-α. Ren Xiaojia,Keeney Jeriel T R,Miriyala Sumitra,Noel Teresa,Powell David K,Chaiswing Luksana,Bondada Subbarao,St Clair Daret K,Butterfield D Allan Free radical biology & medicine Cancer treatments are developing fast and the number of cancer survivors could arise to 20 million in United State by 2025. However, a large fraction of cancer survivors demonstrate cognitive dysfunction and associated decreased quality of life both shortly, and often long-term, after chemotherapy treatment. The etiologies of chemotherapy induced cognitive impairment (CICI) are complicated, made more so by the fact that many anti-cancer drugs cannot cross the blood-brain barrier (BBB). Multiple related factors and confounders lead to difficulties in determining the underlying mechanisms. Chemotherapy induced, oxidative stress-mediated tumor necrosis factor-alpha (TNF-α) elevation was considered as one of the main candidate mechanisms underlying CICI. Doxorubicin (Dox) is a prototypical reactive oxygen species (ROS)-generating chemotherapeutic agent used to treat solid tumors and lymphomas as part of multi-drug chemotherapeutic regimens. We previously reported that peripheral Dox-administration leads to plasma protein damage and elevation of TNF-α in plasma and brain of mice. In the present study, we used TNF-α null (TNFKO) mice to investigate the role of TNF-α in Dox-induced, oxidative stress-mediated alterations in brain. We report that Dox-induced oxidative stress in brain is ameliorated and brain mitochondrial function assessed by the Seahorse-determined oxygen consumption rate (OCR) is preserved in brains of TNFKO mice. Further, we show that Dox-decreased the level of hippocampal choline-containing compounds and brain phospholipases activity are partially protected in TNFKO group in MRS study. Our results provide strong evidence that Dox-targeted mitochondrial damage and levels of brain choline-containing metabolites, as well as phospholipases changes decreased in the CNS are associated with oxidative stress mediated by TNF-α. These results are consistent with the notion that oxidative stress and elevated TNF-α in brain underlie the damage to mitochondria and other pathological changes that lead to CICI. The results are discussed with reference to our identifying a potential therapeutic target to protect against cognitive problems after chemotherapy. 10.1016/j.freeradbiomed.2018.12.029
    A mechanistic cohort study evaluating cognitive impairment in women treated for breast cancer. Vardy Janette L,Stouten-Kemperman Myrle M,Pond Gregory,Booth Christopher M,Rourke Sean B,Dhillon Haryana M,Dodd Anna,Crawley Adrian,Tannock Ian F Brain imaging and behavior Some women report cognitive impairment after adjuvant chemotherapy (CTh) for breast cancer. Here we explore cognitive function, and underlying mechanisms with blood tests and functional magnetic resonance imaging (fMRI). Women treated for early breast cancer were recruited to three groups based on self-reported cognitive symptoms (CS) using FACT-Cog scores. CTh + CS+ (n = 44) had received chemotherapy and self-reported cognitive symptoms; CTh + CS- (n = 52) had chemotherapy but did not report cognitive problems; CTh- (n = 30) had not received chemotherapy. Clinical and computer-based neuropsychological tests were performed. Blood tests included 10 cytokines, sex hormones, coagulation factors, and apolipoprotein-E genotype. fMRI (n = 101) was performed while subjects performed an n-back memory task. Participants had median age 50 (range: 29-60) years and were a median of 17 months post-diagnosis. On clinical neuropsychological tests 19% had cognitive impairment using Global Deficit Score, and 36% using International Cancer and Cognition Task Force criteria with no significant differences in cognitive impairment rates between groups. CTh + CS+ had significantly more fatigue, anxiety/depression and poorer quality-of-life than other groups. There was no association between FACT-Cog and neuropsychological scores. There were significant differences in frontal and parietal regions on fMRI scans: CTh- showed hyperactivation compared to chemotherapy-treated groups, CTh + CS+ had more frontal activation than CTh + CS-. Elevated IL-1, IL-2 were associated weakly and IL-8 more strongly with neuropsychological impairment (rho > 0.20). There were no differences in global cognitive impairment between groups. Cognitive symptoms were associated with fatigue and anxiety/depression, but not with objective cognitive impairment. fMRI scans differed among the three groups. 10.1007/s11682-017-9728-5
    [A Structural Model for Chemotherapy Related Cognitive Impairment and Quality of Life in Breast Cancer Patients]. Lee Jung Ran,Oh Pok Ja Journal of Korean Academy of Nursing PURPOSE:This study aimed to develop and test a structural model for chemotherapy-related cognitive impairment of breast cancer patients based on a literature review and Hess and Insel's chemotherapy-related cognitive change model. METHODS:The Participants consisted of 250 patients who were ≥19 years of age. The assessment tools included the Menopause Rating Scale, Symptom Experience Scale, Hospital Anxiety and Depression Scale, Everyday Cognition, and Functional Assessment of Cancer Therapy-Breast Cancer. Data were analyzed using the SPSS 21.0 and AMOS 21.0 programs. RESULTS:The modified model was a good fit for the data. The model fit indices were χ²=423.18 (<.001), χ²/df=3.38, CFI=.91, NFI=.91, TLI=.89, SRMR=.05, RMSEA=.09, and AIC=515.18. Chemotherapy-related cognitive impairment was directly influenced by menopausal symptoms (β=.38, =.002), depression and anxiety (β=.25, =.002), and symptom experiences (β=.19, =.012). These predictors explained 47.7% of the variance in chemotherapy-related cognitive impairment. Depression and anxiety mediated the relations among menopausal symptoms, symptom experiences, and with chemotherapy related cognitive impairment. Depression and anxiety (β=-.51, =.001), symptom experiences (β=-.27, =.001), menopausal symptoms (β=-.22, =.008), and chemotherapy-related cognitive impairment (β=-.15, =.024) had direct effects on the quality of life and these variables explained 91.3%. CONCLUSION:These results suggest that chemotherapy-related toxicity is highly associated with cognitive decline and quality of life in women with breast cancer. Depression and anxiety increased vulnerability to cognitive impairment after chemotherapy. Nursing intervention is needed to relieve chemotherapy-related toxicity and psychological factor as well as cognitive decline for quality of life in patients undergoing chemotherapy. 10.4040/jkan.2019.49.4.375
    Cancer-related cognitive impairment: an update on state of the art, detection, and management strategies in cancer survivors. Lange M,Joly F,Vardy J,Ahles T,Dubois M,Tron L,Winocur G,De Ruiter M B,Castel H Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Advances in diagnostic and therapeutic strategies in oncology have significantly increased the chance of survival of cancer patients, even those with metastatic disease. However, cancer-related cognitive impairment (CRCI) is frequently reported in patients treated for non-central nervous system cancers, particularly during and after chemotherapy. DESIGN:This review provides an update of the state of the art based on PubMed searches between 2012 and March 2019 on 'cognition', 'cancer', 'antineoplastic agents' or 'chemotherapy'. It includes the most recent clinical, imaging and pre-clinical data and reports management strategies of CRCI. RESULTS:Evidence obtained primarily from studies on breast cancer patients highlight memory, processing speed, attention and executive functions as the most cognitive domains impaired post-chemotherapy. Recent investigations established that other cancer treatments, such as hormone therapies and targeted therapies, can also induce cognitive deficits. Knowledge regarding predisposing factors, biological markers or brain functions associated with CRCI has improved. Factors such as age and genetic polymorphisms of apolipoprotein E, catechol-O-methyltransferase and BDNF may predispose individuals to a higher risk of cognitive impairment. Poor performance on neuropsychological tests were associated with volume reduction in grey matter, less connectivity and activation after chemotherapy. In animals, hippocampus-based memory and executive functions, mediated by the frontal lobes, were shown to be particularly susceptible to the effects of chemotherapy. It involves altered neurogenesis, mitochondrial dysfunction or brain cytokine response. An important next step is to identify strategies for managing cognitive difficulties, with primary studies to assess cognitive training and physical exercise regimens. CONCLUSIONS:CRCI is not limited to chemotherapy. A multidisciplinary approach has improved our knowledge of the complex mechanisms involved. Nowadays, studies evaluating cognitive rehabilitation programmes are encouraged to help patients cope with cognitive difficulties and improve quality of life during and after cancer. 10.1093/annonc/mdz410
    Neuronal autoantibodies associated with cognitive impairment in melanoma patients. Bartels F,Strönisch T,Farmer K,Rentzsch K,Kiecker F,Finke C Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Cancer-related cognitive impairment is an important complication in cancer patients, yet the underlying mechanisms remain unknown. Over the last decade, the field of paraneoplastic neurological syndromes has been dramatically changed by the discovery of new neuronal autoantibodies, some of them associated with cognitive impairment. We aimed to assess the prevalence of neuronal autoantibodies in melanoma patients and their association with neurological and cognitive dysfunction. PATIENTS AND METHODS:A total of 157 consecutive melanoma patients with a median age of 63 years were recruited at the Department of Dermatology, Charité-Universitätsmedizin Berlin and tested for neuronal autoantibodies. A comprehensive neuropsychological assessment was carried out in a selected subgroup of 84 patients after exclusion of patients with confounding factors for a cognitive dysfunction, including brain metastases, relevant medication, and neurological disorders. RESULTS:Neuronal autoantibodies were found in 22.3% of melanoma patients. The most frequent antibodies were IgA/IgM anti-NMDAR antibodies. Applying the International Cognition and Cancer Task Force criteria, 36.9% had cognitive impairment, however, with a threefold higher odds in antibody-positive compared with antibody-negative patients (57.1% versus 30.2%, OR = 3.1, 95% CI: 1.1 to 8.6; P = 0.037). In patients with anti-NMDAR antibodies, this impairment increased with higher antibody titers (P = 0.007). Antibody-positive patients had a significantly impaired overall cognitive performance (z-value: -0.38 ± 0.69 versus 0.00 ± 0.56; P = 0.014) as well as significant impairments in tests of memory, attention, and executive function. In a multiple linear regression analysis, autoantibodies were an independent risk factor for cognitive impairment (B = -0.282; 95% CI: -0.492 to -0.071; P = 0.009). Autoantibody seropositivity was associated with immune checkpoint inhibitor treatment and a history of autoimmune diseases. CONCLUSIONS:A large number of melanoma patients harbor neuronal autoantibodies that are associated with significant cognitive impairment affecting memory, attention, and executive function. Neuronal autoantibodies might represent a pathophysiological factor and possible biomarker in the development of cancer-related cognitive impairment. 10.1093/annonc/mdz083
    Associations between inflammatory markers and cognitive function in breast cancer patients receiving chemotherapy. Williams AnnaLynn M,Shah Raven,Shayne Michelle,Huston Alissa J,Krebs Marcia,Murray Nicole,Thompson Bryan D,Doyle Kassandra,Korotkin Jenna,van Wijngaarden Edwin,Hyland Sharon,Moynihan Jan A,Cory-Slechta Deborah A,Janelsins Michelle C Journal of neuroimmunology BACKGROUND:Cancer-related cognitive impairment (CRCI) is often related to chemotherapy. Increased chronic inflammation is believed to play a key role in the development of CRCI related to chemotherapy but studies assessing this hypothesis specifically in patients receiving chemotherapy are rare. METHODS:We assessed several cognitive domains using the Cambridge Neuropsychological Test Automated Battery (CANTAB) in twenty-two breast cancer patients currently receiving chemotherapy. We also measured inflammatory cytokine and receptor (MCP-1, TNF-α, sTNFRI, sTNFRII) concentrations in patient sera using Luminex assays. These concentrations were log-transformed to obtain a normal distribution. Associations between log-transformed cytokines and cognition were evaluated using Pearson correlations and linear regression, taking into account relevant covariates. RESULTS:Increased concentrations of sTNFRI and sTNFRII were associated with poorer performance on the CANTAB Delayed Matching to Sample (DMS, tests visual memory). Increasing sTNFRI levels were negatively correlated with DMS percent correct (r=-0.47, p=0.029) and DMS percent correct after a 12 second (s) delay (r=-0.65, p=0.001). Increasing levels of sTNFRII negatively correlated with DMS percent correct after 12s delay (r=-0.57, p=0.006). After controlling for relevant demographic (i.e. age, education) and clinical variables (i.e. disease stage, regimen type), we found that increased sTNFRI remained significantly related to decline on the DMS at the 12s delay (p=0.018). CONCLUSION:This preliminary study shows a significant association between higher sTNFRI and lower scores on the short-term visual memory delayed match to sample test in breast cancer patients receiving chemotherapy, supporting the hypothesis that sTNFRI is involved in CRCI. 10.1016/j.jneuroim.2017.10.005
    Effect of dexmedetomidine on the cognitive function of patients undergoing gastric cancer surgery by regulating the PI3K/AKT signaling pathway. Wang Zhiyuan,Shen Zijin,Wang Haibin,Zhang Lin,Dong Rong Oncology letters Effect of dexmedetomidine on the cognitive function of patients undergoing gastric cancer surgery by regulating the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway was investigated. A total of 110 patients who were diagnosed and underwent radical gastrectomy in Ruijin Hospital North, Shanghai Jiaotong University School of Medicine from July 2016 to July 2018 were selected. In the experimental group, 60 patients were treated with dexmedetomidine infusion. In the control group, 50 patients were injected with 0.9% sodium chloride injection during the same period. The expression levels of serum inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), PI3K and AKT of patients were compared between the two groups before and after surgery for 1 day. The number of adverse reactions in the two groups was compared. The correlation between mini-mental state examination (MMSE) score and the expression levels of serum IL-6, PI3K and AKT was compared. The levels of serum TNF-α, IL-6, PI3K and AKT after operation for 1 day of patients in the two groups were significantly higher than those before operation (P<0.05), and were lower in the experimental than in the control group (P<0.05). The number of postoperative cognitive dysfunction of patients in the experimental group was lower than that of patients in the control group (P<0.05). The total number of adverse reactions in the control group was higher than that of patients in the experimental group (P<0.05). The MMSE scores of the two groups were decreased at 1 day after operation and were significantly lower in the control group than in the experimental group (P<0.05). The MMSE score was negatively correlated with the expression levels of serum TNF-α, IL-6, PI3K and AKT (P<0.001). Dexmedetomidine can effectively reduce the expression levels of postoperative inflammatory factors in patients undergoing gastric cancer surgery, improve the postoperative cognitive function by regulating PI3K-Akt signaling pathway and promotes the recovery of postoperative cognitive function. 10.3892/ol.2019.11224
    Influence of combined epidural anesthesia on cognitive function, inflammation and stress response in elderly liver cancer patients undergoing surgery. Su Yang,Pu Yanan,Zhao Zhengnan,Yang Xianglong Oncology letters Effects of combined epidural anesthesia on the cognitive function, inflammation and stress response in the elderly liver cancer patients undergoing surgery were explored. Elderly liver cancer patients (n=100) undergoing surgery in the Second Affiliated Hospital of Dalian Medical University from January 2015 to December 2018 were enrolled and randomly divided into observation group (n=50) and control group (n=50). In control group only conventional anesthesia was performed using 2 µg/kg fentanyl, 1.5 mg/kg propofol and 0.2 mg/kg atracurium, in addition to the procedures in the control group, combined epidural anesthesia was administered using 0.5% bupivacaine for 15 sec and maintained via 0.25% bupivacaine in the observation group. The anesthetic effect was observed and the arterial oxygen saturation (SaO), heart rate (HR), mean arterial pressure (MAP) and mini-mental state examination (MMSE) and cognitive function scores by cognitive abilities screening instrument (CASI) were evaluated in the patients, and their blood was drawn to detect the inflammatory factors interleukin (IL)-6, IL-1 and tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), norepinephrine and epinephrine. The observation group exhibited a better anesthetic effect and obviously smaller decreases in the SaO and MAP and increase in HR than the control group (P<0.05). The MMSE and CASI scores, and the content of IL-1, IL-6, TNF-α, MDA, CAT, norepinephrine and epinephrine in the observation group was obviously lower than that in the control group (P<0.05), while the content of SOD was evidently higher than that in the control group (P<0.05). Overall postoperative conditions in the observation group was superior to the control group (P<0.05), with the incidence rate of cognitive disorder lower than that in the control group (P<0.05). Combined epidural anesthesia dramatically improves the postoperative conditions and cognitive function and relieve inflammatory and stress responses in the patients with a better anesthetic effect, thus holding promise for application. 10.3892/ol.2020.11395
    Assessment of cognitive function in patients with metastatic cancer: Are we using the right tools? Kurita Geana Paula,Sandvad Marlene,Lundorff Lena,De Mattos-Pimenta Cibele Andrucioli,Højsted Jette,Sjøgren Per Palliative & supportive care OBJECTIVE:This study aimed at analyzing the validity and reliability of the continuous reaction time (CRT) test, the finger-tapping test (FTT), the Digit Span Test (DST), the Trail Making Test - part B (TMTB), and the Mini-Mental State Examination (MMSE) in patients with metastatic cancer. METHOD:Eighty adult patients and 81 healthy controls were assessed between July of 2010 and November of 2015. The neuropsychological tests were analyzed regarding construct/discriminant/criterion validity and reliability. RESULTS:In terms of construct validity, it was not possible to estimate a model for the MMSE because of a skewed response distribution. For discriminant validity, patients were slower on two measures of the CRT (p = 0.00483, p = 0.00030) and FTT dominant hand (p = 0.00306). Regarding sensitivity and specificity, only the DST and TMTB seemed to predict cognitive deficit; however, the ROC curve areas were ≤ 0.73. In terms of criterion validity, there were few significant correlations between the tests and the sociodemographic and clinical variables, and for the most part were very weak. Reliability was deemed to be adequate for the TMTB, DST, and FTT. SIGNIFICANCE OF RESULTS:The findings of the full validation analyses were not clear-cut. However, CRT test, DST, FTT, and TMTB demonstrated partial positive results, indicating that these tests have good potential for use in clinical settings and require further study. 10.1017/S1478951517000694
    Cognitive function and fatigue after diagnosis of colorectal cancer. Vardy J,Dhillon H M,Pond G R,Rourke S B,Xu W,Dodd A,Renton C,Park A,Bekele T,Ringash J,Zhang H,Burkes R,Clarke S J,Tannock I F Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Cognitive impairment and fatigue have been associated with cancer and its treatment. We present baseline data from a large longitudinal study that evaluates cognitive function, fatigue, and potential underlying mechanisms following diagnosis of colorectal cancer (CRC). PATIENTS AND METHODS:We evaluated CRC patients with stage I-III disease before or after surgery, participants with limited metastatic disease and healthy controls (HC). Neuropsychological evaluation included clinical and computerised tests. Participants completed questionnaires for fatigue and quality of life (QOL)-(FACT-F), anxiety/depression, and cognitive symptoms (FACT-Cog). Ten cytokines, clotting factors, sex hormones, carcinoembryonic antigen (CEA), and apolipoprotein E genotype were evaluated. Primary end points were cognitive function on clinical tests evaluated by a Global Deficit score (GDS) and fatigue. Associations between test results, demographic, and disease related factors were explored. RESULTS:We assessed 291 participants with early-stage disease [median age 59 (23-75) years, 63% men], 72 with metastatic disease, and 72 HC. Using GDS, 45% (126/281) of participants with early-stage CRC had cognitive impairment versus 15% (11/72) of HC (odds ratio 4.51, 95% confidence interval 2.28-8.93; P < 0.001), with complex processing speed, attention/working memory, and verbal learning efficiency being most affected. Women with early-stage CRC had greater cognitive impairment than men [55/105 (52%) versus 71/176 (40%), P < 0.050]. Cognitive symptoms were self-reported by 21% (59/286) of early-stage patients versus 17% (12/72) of HC; fatigue by 52% (149/287) of early-stage patients and 26% (19/72) of HC (P < 0.0001). Women reported more fatigue than men (P = 0.003). Fatigue, QOL, anxiety/depression, and cognitive symptoms were associated with each other (r = 0.43-0.71), but not with neuropsychological performance. Most cytokines were elevated in cancer patients. Cognitive function was not associated with cytokines, sex hormones, clotting factors, CEA, or apolipoprotein E genotype. CONCLUSIONS:The incidence of cognitive impairment was three to five times higher in CRC patients than HC, with women having higher impairment rates than men. The cognitive impairment profile suggests dysfunction primarily in fronto-subcortical brain systems. TRIAL REGISTRATION:NCT00188331. 10.1093/annonc/mdu448
    Role of stress, age and adjuvant therapy in the cognitive function of patients with breast cancer. Papanastasiou Artemis,Seliniotaki Theodora,Rizos Emmanouil,Kampoli Katerina,Ntavatzikos Anastasios,Arkadopoulos Nikolaos,Tsionou Christina,Spandidos Demetrios A,Koumarianou Anna Oncology letters According to data largely obtained from retrospective studies, it has been postulated that chemotherapy exerts an aggravating effect on the cognitive function of patients with breast cancer. Potential individual factors related to the effects of chemotherapy on cognitive function have been indicated, such as age-related cognitive dysfunction and stress. Elderly patients differ from non-elderly patients as regards higher cognitive related comorbidities, such as dementia, as well as regarding lower stress levels, indicating that 'chemobrain' may differentially affect these two age groups. The aim of this review was to discuss the effects of stress and chemotherapy on cognitive dysfunction and identify any potential age-related differences in patients with breast cancer treated with adjuvant chemotherapy. For this purpose, a systematic review of the literature was carried out on the PubMed, Scopus and Web of Science databases. The inclusion criteria were original articles published in peer-reviewed journals, elderly and non-elderly patients with breast cancer, reporting on stress and at least one cognitive parameter pre- and/or post-treatment. Eight studies met the preset criteria and were further analyzed. In total, the data of 1,253 women were included, of whom 800 patients with breast cancer were treated with surgery only, systemic treatment only, or both. Although all the studies included a non-elderly breast cancer patient subpopulation, only two of the studies included patients over 65 years of age. All studies indicated a statistically significant association of stress with various domains of cognitive dysfunction in patients, as shown by either self-completed questionnaires, neuropsychological testing or both. An age over 60 years was linked to fewer cognitive difficulties mediated by lower levels of stress. Thus, the evidence supports the association of stress with cognitive deficits in patients with breast cancer, regardless of the type of cancer-related treatment. Therefore, stress should be appropriately addressed. However, further research is required to investigate the association of stress with cognitive function in elderly patients with breast cancer. 10.3892/ol.2019.10361
    Remifentanil on T lymphocytes, cognitive function and inflammatory cytokines of patients undergoing radical surgery for cervical cancer. Lu X-Y,Chen M,Chen D-H,Li Y,Liu P-T,Liu Y European review for medical and pharmacological sciences OBJECTIVE:To explore the effects of remifentanil on cognitive function, T lymphocyte subsets and inflammatory cytokines of patients undergoing radical surgery for cervical cancer. PATIENTS AND METHODS:A total of 70 patients undergoing radical surgery for cervical cancer in our hospital from August 2014 to January 2017 were selected. They were divided into control group (n=35) and experimental group (n=35). The patients in the control group received intravenous drip of fentanyl, while those in the experimental group received intravenous drip of remifentanil in the surgery. All the patients returned to the wards after surgery. The eye-opening time, extubation time and awaking time of the patients were collected and recorded by specialized surgical nurses. Moreover, the cognitive function of the patients was assessed at the beginning of the surgery and 3 h, 6 h, 12 h, and 24 h after surgery. Blood was drawn at 24 h after surgery, and quantitative analysis of T lymphocyte subsets and inflammatory cytokines of the patients was conducted. RESULTS:The eye-opening time, extubation time, and awaking time in the remifentanil group were significantly earlier than those in the fentanyl group after surgery (p<0.05). At the same time after surgery, the score of mini-mental state examination (MMSE) in the remifentanil group was higher than that in the fentanyl group. The difference was statistically significant (p<0.05). The patients in the experimental group had a relatively low occurrence of cognitive disorder after surgery (p<0.05). The impacts of remifentanil on each type of T lymphocytes and inflammatory cytokines of the patients after surgery were smaller than those of fentanyl. The differences were statistically significant (p<0.05). CONCLUSIONS:Remifentanil can wake patients up early after surgery. Meanwhile, it results in small inflammatory response and stress response, and low occurrence of postoperative cognitive dysfunction in patients. Therefore, it is worthy of being vigorously promoted for clinical application. 10.26355/eurrev_201805_14987
    Cognitive Function in Patients With Colorectal Cancer Who Do and Do Not Receive Chemotherapy: A Prospective, Longitudinal, Controlled Study. Vardy Janette L,Dhillon Haryana M,Pond Gregory R,Rourke Sean B,Bekele Tsegaye,Renton Corrinne,Dodd Anna,Zhang Haibo,Beale Philip,Clarke Stephen,Tannock Ian F Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:Cognitive dysfunction is reported in people with cancer. Therefore, we evaluated longitudinal changes in cognitive function and underlying mechanisms in people with colorectal cancer (CRC) and healthy controls (HCs). PATIENTS AND METHODS:Participants completed cognitive assessments and questionnaires reporting cognitive symptoms, fatigue, quality of life, and anxiety/depression at baseline (before chemotherapy, if given) and 6, 12, and 24 months. Blood tests included cytokines, clotting factors, apolipoprotein E genotype, and sex hormones. Primary end point was overall cognitive function measured by the Global Deficit Score at 12 months. RESULTS:We recruited 289 patients with localized CRC (173 received chemotherapy; median age, 59 years; 63% male), 73 patients with limited metastatic/recurrent CRC, and 72 HCs. Cognitive impairment was more frequent in patients with localized CRC than HCs at baseline (43% v 15%, respectively; P < .001) and 12 months (46% v 13%, respectively; P < .001), with no significant effect of chemotherapy. Attention/working memory, verbal learning/memory, and complex processing speed were most affected. Cognitive impairment was similar in patients with localized and metastatic CRC. Cytokine levels were elevated in patients with CRC compared with HCs. There was no association between overall cognitive function and fatigue, quality of life, anxiety/depression, or any blood test. Cognitive symptoms at 12 months were reported in 25% of patients with localized CRC versus 17% of HCs (P = .19). More participants who received chemotherapy had cognitive symptoms at 6 months (32%) versus those who did not (16%; P = .007), with no significant difference at 12 months (29% v 21%, respectively; P = .19). Objective cognitive function was only weakly associated with cognitive symptoms. CONCLUSION:Patients with CRC had substantially more cognitive impairment at every assessment than HCs, with no significant added effect of chemotherapy. Mechanisms of cognitive impairment remain unknown. 10.1200/JCO.2015.63.0905
    Predicting Patient Reported Outcomes of Cognitive Function Using Connectome-Based Predictive Modeling in Breast Cancer. Henneghan Ashley M,Gibbons Chris,Harrison Rebecca A,Edwards Melissa L,Rao Vikram,Blayney Douglas W,Palesh Oxana,Kesler Shelli R Brain topography Being able to predict who will likely experience cancer related cognitive impairment (CRCI) could enhance patient care and potentially reduce economic and human costs associated with this adverse event. We aimed to determine if post-treatment patient reported CRCI could also be predicted from baseline resting state fMRI in patients with breast cancer. 76 newly diagnosed patients (n = 42 planned for chemotherapy; n = 34 not planned for chemotherapy) and 50 healthy female controls were assessed at 3 times points [T1 (prior to treatment); T2 (1 month post chemotherapy); T3 (1 year after T2)], and at yoked intervals for controls. Data collection included self-reported executive dysfunction, memory function, and psychological distress and resting state fMRI data converted to connectome matrices for each participant. Statistical analyses included linear mixed modeling, independent t tests, and connectome-based predictive modeling (CPM). Executive dysfunction increased over time in the chemotherapy group and was stable in the other two groups (p < 0.001). Memory function decreased over time in both patient groups compared to controls (p < 0.001). CPM models successfully predicted executive dysfunction and memory function scores (r > 0.31, p < 0.002). Support vector regression with a radial basis function (SVR RBF) showed the highest performance for executive dysfunction and memory function (r = 0.68; r = 0.44, p's < 0.001). Baseline neuroimaging may be useful for predicting patient reported cognitive outcomes which could assist in identifying patients in need of surveillance and/or early intervention for treatment-related cognitive effects. 10.1007/s10548-019-00746-4
    Sevoflurane Effect on Cognitive Function and the Expression of Oxidative Stress Response Proteins in Elderly Patients undergoing Radical Surgery for Lung Cancer. Qin Yang,Ni Jinping,Kang Li,Zhong Zhidong,Wang Liren,Yin Shuzhou Journal of the College of Physicians and Surgeons--Pakistan : JCPSP OBJECTIVE:To investigate the effects of sustained inhalation of sevoflurane on cognitive function and the expression of oxidative stress response proteins such as NADPH oxidase subunits NOX2 and NOX4 in elderly patients undergoing radical surgery for lung cancer. STUDY DESIGN:An experimental study. PLACE AND DURATION OF STUDY:Department of Anesthesiology, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, China, from February 2016 to October 2017. METHODOLOGY:Elderly patients who underwent radical surgery for lung cancer were divided into the sevoflurane group and the propofol group, with 52 cases in each group. Sustained inhalation of sevoflurane and propofol was administered to maintain anesthesia in the respective groups. Cognitive function and lung function parameters were compared between the two groups. Serum S100 &beta; levels and expression of NOX2 and NOX4 proteins in peripheral blood mononuclear cells of the two groups were determined. RESULTS:At 24 hours after surgery, the lung function indices of the sevoflurane group such as FEV1, FVC and VC were higher than those of the propofol group (p<0.001, p=0.008 and p=0.002, respectively). At the end of the surgery and at 24 hours after surgery, the MMSE scores of the sevoflurane group were higher than the propofol group (all p<0.001). S100 levels were lower than the propofol group (p=0.003 and p<0.001, respectively). Levels of NADPH oxidase subunits NOX2 and NOX4 proteins in peripheral blood mononuclear cells of the sevoflurane group were lower than the propofol group (p=0.033, p<0.001, p<0.001and p<0.001, respectively). CONCLUSION:Compared with intravenous anesthesia with propofol, general anesthesia with sevoflurane inhalation has little effect on the short-term cognitive function in elderly patients undergoing radical surgery for lung cancer, and can effectively improve lung function. The mechanism may be related to the reduction of the expression of NOX2 and NOX4 proteins. 10.29271/jcpsp.2019.01.12
    Potential Effect of Immunotherapy Agents on Cognitive Function in Cancer Patients. Joly Florence,Castel Hélène,Tron Laure,Lange Marie,Vardy Janette Journal of the National Cancer Institute A paradigm shift is occurring in cancer therapy, where instead of targeting tumor cells, immunotherapy agents (IA) target the immune system to overcome cancer tolerance and to stimulate an antitumor immune response. IA using immune checkpoint inhibitors (CPI) or chimeric antigen receptor T-cells have emerged as the most encouraging approaches to treat cancer patients. CPI are reported to induce moderate-to-severe neurologic immune-related adverse events in less than 1% of patients, whereas chimeric antigen receptor T-cell therapy is associated with frequent neurological toxicities that can be severe or even fatal. Cognitive difficulties have been described following chemotherapy and targeted therapy, but not specifically explored in patients receiving IA. The aim of this review is to establish a picture of the first published studies suggesting some biological and physiopathological effects of IA on cognitive functions among cancer patients. The first results originate from a preclinical study evaluating the role of CPI associated with peripheral radiation on cognitive dysfunction and the recent discovery of the central nervous lymphatic system allowing leukocytes to penetrate the central nervous system. Evaluating possible side effects of IA on cognitive function will be an important challenge for future clinical trials and for better understanding the underlying mechanisms through preclinical animal models. 10.1093/jnci/djz168
    The Role of Inflammation in the Pain, Fatigue, and Sleep Disturbance Symptom Cluster in Advanced Cancer. Kwekkeboom Kristine L,Tostrud Lauren,Costanzo Erin,Coe Christopher L,Serlin Ronald C,Ward Sandra E,Zhang Yingzi Journal of pain and symptom management CONTEXT:Symptom researchers have proposed a model of inflammatory cytokine activity and dysregulation in cancer to explain co-occurring symptoms including pain, fatigue, and sleep disturbance. OBJECTIVES:We tested the hypothesis that psychological stress accentuates inflammation and that stress and inflammation contribute to one's experience of the pain, fatigue, and sleep disturbance symptom cluster (symptom cluster severity, symptom cluster distress) and its impact (symptom cluster interference with daily life, quality of life). METHODS:We used baseline data from a symptom cluster management trial. Adult participants (N = 158) receiving chemotherapy for advanced cancer reported pain, fatigue, and sleep disturbance on enrollment. Before intervention, participants completed measures of demographics, perceived stress, symptom cluster severity, symptom cluster distress, symptom cluster interference with daily life, and quality of life and provided a blood sample for four inflammatory biomarkers (interleukin-1β, interleukin-6, tumor necrosis factor-α, and C-reactive protein). RESULTS:Stress was not directly related to any inflammatory biomarker. Stress and tumor necrosis factor-α were positively related to symptom cluster distress, although not symptom cluster severity. Tumor necrosis factor-α was indirectly related to symptom cluster interference with daily life, through its effect on symptom cluster distress. Stress was positively associated with symptom cluster interference with daily life and inversely with quality of life. Stress also had indirect effects on symptom cluster interference with daily life, through its effect on symptom cluster distress. CONCLUSION:The proposed inflammatory model of symptoms was partially supported. Investigators should test interventions that target stress as a contributing factor in co-occurring pain, fatigue, and sleep disturbance and explore other factors that may influence inflammatory biomarker levels within the context of an advanced cancer diagnosis and treatment. 10.1016/j.jpainsymman.2018.01.008
    Tumor-Associated Fatigue in Cancer Patients Develops Independently of IL1 Signaling. Grossberg Aaron J,Vichaya Elisabeth G,Christian Diana L,Molkentine Jessica M,Vermeer Daniel W,Gross Phillip S,Vermeer Paola D,Lee John H,Dantzer Robert Cancer research Fatigue is the most common symptom of cancer at diagnosis, yet causes and effective treatments remain elusive. As tumors can be highly inflammatory, it is generally accepted that inflammation mediates cancer-related fatigue. However, evidence to support this assertion is mostly correlational. In this study, we directly tested the hypothesis that fatigue results from propagation of tumor-induced inflammation to the brain and activation of the central proinflammatory cytokine, IL1. The heterotopic syngeneic murine head and neck cancer model (mEER) caused systemic inflammation and increased expression of in the brain while inducing fatigue-like behaviors characterized by decreased voluntary wheel running and exploratory activity. Expression of in the brain was not associated with any alterations in motivation, measured by responding in a progressive ratio schedule of food reinforcement, depression-like behaviors, or energy balance. Decreased wheel running occurred prior to detection in the brain, when systemic inflammation was minimal. Furthermore, mice null for two components of IL1β signaling, the type 1 IL1 receptor or the receptor adapter protein MyD88, were not protected from tumor-induced decreases in wheel running, despite attenuated cytokine action and expression. Behavioral and inflammatory analysis of four additional syngeneic tumor models revealed that tumors can induce fatigue regardless of their systemic or central nervous system inflammatory potential. Together, our results show that brain IL1 signaling is not necessary for tumor-related fatigue, dissociating this type of cancer sequela from systemic cytokine expression. These findings challenge the current understanding of fatigue in cancer patients, the most common and debilitating sequela associated with malignancy. . 10.1158/0008-5472.CAN-17-2168
    Sleep disturbance and cancer-related fatigue symptom cluster in breast cancer patients undergoing chemotherapy. Fox Rina S,Ancoli-Israel Sonia,Roesch Scott C,Merz Erin L,Mills Sarah D,Wells Kristen J,Sadler Georgia Robins,Malcarne Vanessa L Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:Sleep disturbance and cancer-related fatigue (CRF) are among the most commonly reported symptoms associated with breast cancer and its treatment. This study identified symptom cluster groups of breast cancer patients based on multidimensional assessment of sleep disturbance and CRF prior to and during chemotherapy. METHODS:Participants were 152 women with stage I-IIIA breast cancer. Data were collected before chemotherapy (T1) and during the final week of the fourth chemotherapy cycle (T2). Latent profile analysis was used to derive groups of patients at each timepoint who scored similarly on percent of the day/night asleep per actigraphy, the Pittsburgh Sleep Quality Index global score, and the five subscales of the Multidimensional Fatigue Symptom Inventory-Short Form. Bivariate logistic regression evaluated if sociodemographic/medical characteristics at T1 were associated with group membership at each timepoint. RESULTS:Three groups (Fatigued with sleep complaints, Average, Minimal symptoms) were identified at T1, and five groups (Severely fatigued with poor sleep, Emotionally fatigued with average sleep, Physically fatigued with average sleep, Average, Minimal symptoms) at T2. The majority of individuals in a group characterized by more severe symptoms at T1 were also in a more severe symptom group at T2. Sociodemographic/medical variables at T1 were significantly associated with group membership at T1 and T2. CONCLUSIONS:This study identified groups of breast cancer patients with differentially severe sleep disturbance and CRF symptom profiles prior to and during chemotherapy. Identifying groups with different symptom management needs and distinguishing groups by baseline sociodemographic/medical variables can identify patients at risk for greater symptom burden. 10.1007/s00520-019-04834-w
    Cognitive and motor aspects of cancer-related fatigue. Feng Li Rebekah,Regan Jeniece,Shrader Joseph A,Liwang Josephine,Ross Alexander,Kumar Saloni,Saligan Leorey N Cancer medicine BACKGROUND:Cancer-related fatigue (CRF) is a debilitating symptom frequently reported by patients during and after treatment for cancer. CRF is a multidimensional experience and is often solely assessed by self-report measures. The goal of the study is to examine the physical and cognitive aspects of self-reported CRF using a cognitive function test and a physical fatigue index in order to provide objective measures that can characterize the CRF phenotype. METHODS:A total of 59 subjects with nonmetastatic prostate cancer receiving external beam radiation therapy were included in the study. Fatigue was measured using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire. Cognitive characteristics of CRF was measured using the Stroop Color-Word Interference computerized test and the motor aspect of fatigue was measured using the static fatigue test using a handgrip dynamometer. FINDINGS:Functional Assessment of Cancer Therapy-Fatigue scores significantly correlated with the Stroop Interference score, but not performance accuracy in all test conditions. Fatigued subjects exhibited a more rapid decline to 50% of maximal strength and increased static fatigue index in the handgrip test, whereas maximal grip strength was not affected. CONCLUSIONS:The results suggest that CRF exhibits both cognitive and physical characteristics. Subjective fatigue was associated with increased time required to overcome cognitive interference, but not cognitive performance accuracy. Fatigued patients exhibited decreased physical endurance and the ability to sustain maximal strength over time. These objective measures may serve as valuable tools for clinicians to detect cognitive and physical impairment associated with CRF. 10.1002/cam4.2490
    Effects of an Exercise Intervention on Cancer-Related Fatigue and Its Relationship to Markers of Oxidative Stress. Repka Chris P,Hayward Reid Integrative cancer therapies BACKGROUND:Although the underlying mechanisms of cancer-related fatigue (CRF) are not fully characterized, treatment-associated oxidative stress may play a role. The purpose of this study was to determine the effect of an exercise intervention on the relationship between CRF and oxidative stress. METHODS:Upon cessation of radiation or chemotherapy, 8 cancer patients participated in a 10-week exercise intervention (EX), while 7 continued standard care (CON). Blood draws and fatigue questionnaires were administered to cancer patients before and after the intervention as well as to 7 age-matched individuals with no cancer history. Changes in plasma 8-hydroxy-deoxyguanosine (8-OHdG), protein carbonyls, antioxidant capacity, and fatigue were compared between groups. Correlations between CRF and oxidative stress were evaluated. RESULTS:Mean total fatigue scores decreased significantly (5.0 ± 2.2 to 2.6 ± 1.5, P < .05) in EX, but not in CON. Antioxidant capacity significantly increased (+41%; P < .05) and protein carbonyls significantly decreased (-36%; P < .05) in EX, but not in CON. Increases in antioxidant capacity were significantly correlated with reductions in affective ( r = -.49), sensory ( r = -.47), and cognitive fatigue ( r = -.58). Changes in total ( r = .46) and affective ( r = .47) fatigue exhibited significant correlations with changes in 8-OHdG over time, while behavioral ( r = .46) and sensory ( r = .47) fatigue changes were significantly correlated with protein carbonyls. CONCLUSIONS:Oxidative stress may be implicated in CRF, while improved antioxidant capacity following an exercise intervention may play a role in mitigating CRF in cancer survivors. 10.1177/1534735418766402
    Inflammation- and angiogenesis-related biomarkers are correlated with cancer-related fatigue in colorectal cancer patients: Results from the ColoCare Study. Himbert Caroline,Ose Jennifer,Lin Tengda,Warby Christy A,Gigic Biljana,Steindorf Karen,Schrotz-King Petra,Abbenhardt-Martin Clare,Zielske Lin,Boehm Juergen,Ulrich Cornelia M European journal of cancer care Cancer-related fatigue is one of the most common side effects of colorectal cancer treatment and is affected by biomedical factors. We investigated the association of inflammation- and angiogenesis-related biomarkers with cancer-related fatigue. Pre-surgery (baseline) serum samples were obtained from n = 236 newly diagnosed colorectal cancer patients. Meso Scale Discovery assays were performed to measure levels of biomarkers for inflammation and angiogenesis (CRP, SAA, IL-6, IL-8, MCP-1, sICAM-1, sVCAM-1, TNFα, VEGFA and VEGFD). Cancer-related fatigue was assessed with the EORTC QLQ-30 questionnaire at baseline and 6 and 12 months post-surgery. We tested associations using Spearman's partial correlations and logistic regression analyses, adjusting for age, sex and body mass index. sICAM-1 and VEGFD showed a significant positive correlation with cancer-related fatigue at baseline and 6-, and 12-month follow-up (sICAM-1: r = 0.19, p = 0.010; r = 0.24, p = 0.004; r = 0.25, p = 0.006; VEGFD: r = 0.20, p = 0.006; r = 0.15, p = 0.06; r = 0.23, p = 0.01 respectively). Biomarkers of inflammation and angiogenesis measured prior to surgery are associated with cancer-related fatigue in colorectal cancer patients throughout various time points. Our results suggest the involvement of overexpressed sICAM-1 and VEGFD in the development of fatigue. 10.1111/ecc.13055
    The role of neuro-immune interactions in cancer-related fatigue: Biobehavioral risk factors and mechanisms. Bower Julienne E Cancer Fatigue is a common and distressing symptom in both patients with cancer and cancer survivors. There is substantial variation in the severity and persistence of cancer-related fatigue that may be driven by individual differences in host factors, including characteristics that predate the cancer experience as well as responses to cancer and its treatment. This review examines biobehavioral risk factors linked to fatigue and the mechanisms through which they influence fatigue across the cancer continuum, with a focus on neuro-immune processes. Among psychosocial risk factors, childhood adversity is a strong and consistent predictor of cancer-related fatigue; other risk factors include history of depression, catastrophizing, lack of physical activity, and sleep disturbance, with compelling preliminary evidence for loneliness and trait anxiety. Among biologic systems, initial work suggests that alterations in immune, neuroendocrine, and neural processes are associated with fatigue. The identification of key risk factors and underlying mechanisms is critical for the development and deployment of targeted interventions to reduce the burden of fatigue in the growing population of cancer survivors. Given the multidimensional nature of fatigue, interventions that influence multiple systems may be most effective. 10.1002/cncr.31790
    Molecular epidemiology, cancer-related symptoms, and cytokines pathway. Reyes-Gibby Cielito C,Wu Xifeng,Spitz Margaret,Kurzrock Razelle,Fisch Michael,Bruera Eduardo,Shete Sanjay The Lancet. Oncology The Human Genome Project and HapMap have led to a better appreciation of the importance of common genetic variation in determining cancer risk, created potential for predicting response to therapy, and made possible the development of targeted prevention and therapeutic interventions. Advances in molecular epidemiology can be used to explore the role of genetic variation in modulating the risk for severe and persistent symptoms, such as pain, depression, and fatigue, in patients with cancer. The same genes that are implicated in cancer risk might also be involved in the modulation of therapeutic outcomes. For example, polymorphisms in several cytokine genes are potential markers for genetic susceptibility both for cancer risk and for cancer-related symptoms. These genetic polymorphisms are stable markers and easily and reliably assayed to explore the extent to which genetic variation might prove useful in identifying patients with cancer at high-risk of symptom development. Likewise, they could identify subgroups who might benefit most from symptom intervention, and contribute to developing personalized and more effective therapies for persistent symptoms. 10.1016/S1470-2045(08)70197-9
    Fatigue and sleep quality are associated with changes in inflammatory markers in breast cancer patients undergoing chemotherapy. Liu Lianqi,Mills Paul J,Rissling Michelle,Fiorentino Lavinia,Natarajan Loki,Dimsdale Joel E,Sadler Georgia Robins,Parker Barbara A,Ancoli-Israel Sonia Brain, behavior, and immunity Fatigue and sleep disturbances are two of the most common and distressing symptoms reported by cancer patients. Fatigue and sleep are also correlated with each other. While fatigue has been reported to be associated with some inflammatory markers, data about the relationship between cancer-related sleep disturbances and inflammatory markers are limited. This study examined the relationship between fatigue and sleep, measured both subjectively and objectively, and inflammatory markers in a sample of breast cancer patients before and during chemotherapy. Fifty-three women with newly diagnosed stage I-III breast cancer scheduled to receive at least four 3-week cycles of chemotherapy participated in this longitudinal study. Fatigue was assessed with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and objective sleep was measured with actigraphy. Three inflammatory markers were examined: Interleukin-6 (IL-6), Interleukin-1 receptor antagonist (IL-1RA) and C-reactive protein (CRP). Data were collected before (baseline) and during cycle 1 and cycle 4 of chemotherapy. Compared to baseline, more fatigue was reported, levels of IL-6 increased and IL-1RA decreased during chemotherapy. Reports of sleep quality remained poor. Mixed model analyses examining changes from baseline to each treatment time point revealed overall positive relationships between changes in total MFSI-SF scores and IL-6, between changes in total PSQI scores and IL-6 and IL-1RA, and between total wake time at night and CRP (all p's<0.05). These relationships suggest that cancer-related fatigue and sleep disturbances may share common underlying biochemical mechanisms. 10.1016/j.bbi.2012.02.001
    Exploring Relationships Among Peripheral Amyloid Beta, Tau, Cytokines, Cognitive Function, and Psychosomatic Symptoms in Breast Cancer Survivors. Henneghan Ashley,Haley Andreana P,Kesler Shelli Biological research for nursing OBJECTIVE:Accelerated brain aging has been proposed to explain cancer-related cognitive impairment, but empirical evidence for this relationship is lacking. The purpose of this study was to evaluate amyloid beta (Aβ) and tau, biomarkers of neurodegeneration, in relation to cognition in breast cancer survivors (BCSs). We explored relationships among peripheral concentrations of Aβ42, Aβ-40, tau, and cytokines; cognitive function; and psychosomatic symptoms in a cohort of BCSs post-chemotherapy. METHODS:This secondary analysis of a cross-sectional study was conducted with 65 BCSs. Serum total Aβ-42, Aβ-40, and tau levels were measured with single molecule array technology. Cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon [IFN]-g, IL-10, IL-12, IL-13, IL1-b, IL-2, IL-4, IL-5, IL-7, and IL-8) were simultaneously measured in serum using multiplex assays. Cognitive function was measured with five standardized neuropsychological tests and psychosomatic symptoms (stress, loneliness, anxiety, depressive symptoms, fatigue, sleep quality, and daytime sleepiness) with self-report questionnaires. Data analyses included correlations and random forest regression (RFR). RESULTS:Significant correlations were identified among hip-to-waste ratio, number of treatment modalities, Aβ-42, Aβ-40, and tau levels (s = .27-.35, s < .05). RFR modeling including Aβ-42, Aβ-40, tau, and cytokines as features explained significant variance in cognitive function ( = .71, = 9.01, < .0001) and psychosomatic symptoms ( = .74, = 10.22, < .0001). CONCLUSIONS:This study suggests that neurodegenerative biomarkers interact with cytokines to influence cognitive functioning and psychosomatic symptoms in BCSs following chemotherapy, but additional research is needed. 10.1177/1099800419887230
    C-reactive protein predicts fatigue independently of depression in breast cancer patients prior to chemotherapy. Pertl Maria M,Hevey David,Boyle Noreen T,Hughes Martina M,Collier Sonya,O'Dwyer Anne-Marie,Harkin Andrew,Kennedy M John,Connor Thomas J Brain, behavior, and immunity Heightened inflammatory activity has been proposed as a mechanism for the development of cancer-related fatigue (CRF), a common and distressing condition that can negatively affect quality of life. Inflammation is also implicated in the pathogenesis of depression, and depression is a strong predictor of CRF. Thus, the role of the pro-inflammatory cytokine network in CRF may be mediated by depression or both conditions may share similar underlying physiological processes. The current study investigated associations between fatigue, depression and inflammatory cytokine (IFN-γ, IL-6, TNF-α) and CRP concentrations, as well as kynurenine pathway (KP) activation, in 61 breast cancer patients prior to chemotherapy. Changes in inflammatory markers and KP activation over time were also explored, and associations with changes in fatigue and depression were examined. Higher levels of CRP were significantly correlated with fatigue and depression before chemotherapy; nevertheless, CRP predicted fatigue independently of depression. Although greater kynurenine concentrations were associated with increased immune activation, there was no evidence that the KP played a role in fatigue or depression. Furthermore, no relationships emerged between either fatigue or depression and IFN-γ, IL-6, or TNF-α before chemotherapy. Nevertheless, kynurenine levels pre- and post-treatment significantly predicted changes in depression, suggesting that heightened KP activation may contribute to depressive symptoms in patients treated for cancer. In addition, IL-6 significantly covaried with fatigue. These preliminary findings provide some support for the idea that low-grade inflammation contributes to the development of CRF, independently of depression; however, there was no evidence that this is mediated by KP activity. 10.1016/j.bbi.2013.07.177
    The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure. Lacourt Tamara E,Vichaya Elisabeth G,Chiu Gabriel S,Dantzer Robert,Heijnen Cobi J Frontiers in behavioral neuroscience Chronic or persistent fatigue is a common, debilitating symptom of several diseases. Persistent fatigue has been associated with low-grade inflammation in several models of fatigue, including cancer-related fatigue and chronic fatigue syndrome. However, it is unclear how low-grade inflammation leads to the experience of fatigue. We here propose a model of an imbalance in energy availability and energy expenditure as a consequence of low-grade inflammation. In this narrative review, we discuss how chronic low-grade inflammation can lead to reduced cellular-energy availability. Low-grade inflammation induces a metabolic switch from energy-efficient oxidative phosphorylation to fast-acting, but less efficient, aerobic glycolytic energy production; increases reactive oxygen species; and reduces insulin sensitivity. These effects result in reduced glucose availability and, thereby, reduced cellular energy. In addition, emerging evidence suggests that chronic low-grade inflammation is associated with increased willingness to exert effort under specific circumstances. Circadian-rhythm changes and sleep disturbances might mediate the effects of inflammation on cellular-energy availability and non-adaptive energy expenditure. In the second part of the review, we present evidence for these metabolic pathways in models of persistent fatigue, focusing on chronic fatigue syndrome and cancer-related fatigue. Most evidence for reduced cellular-energy availability in relation to fatigue comes from studies on chronic fatigue syndrome. While the mechanistic evidence from the cancer-related fatigue literature is still limited, the sparse results point to reduced cellular-energy availability as well. There is also mounting evidence that behavioral-energy expenditure exceeds the reduced cellular-energy availability in patients with persistent fatigue. This suggests that an inability to adjust energy expenditure to available resources might be one mechanism underlying persistent fatigue. 10.3389/fnbeh.2018.00078
    Interleukin 6-independent metabolic reprogramming as a driver of cancer-related fatigue. Grossberg Aaron J,Vichaya Elisabeth G,Gross Phillip S,Ford Bianca G,Scott Kiersten A,Estrada Darlene,Vermeer Daniel W,Vermeer Paola,Dantzer Robert Brain, behavior, and immunity Fatigue is a common and debilitating symptom of cancer with few effective interventions. Cancer-related fatigue (CRF) is often associated with increases in inflammatory cytokines, however inflammation may not be requisite for this symptom, suggesting other biological mediators also play a role. Because tumors are highly metabolically active and can amplify their energetic toll via effects on distant organs, we sought to determine whether CRF could be explained by metabolic competition exacted by the tumor. We used a highly metabolically active murine E6/E7/hRas model of head and neck cancer for this purpose. Mice with or without tumors were submitted to metabolic constraints in the form of voluntary wheel running or acute overnight fasting and their adaptive behavioral (home cage activity and fasting-induced wheel running) and metabolic responses (blood glucose, ketones, and liver metabolic gene expression) were monitored. We found that the addition of running wheel was necessary to measure activity loss, used as a surrogate for fatigue in this study. Tumor-bearing mice engaged in wheel running showed a decrease in blood glucose levels and an increase in lactate accumulation in the skeletal muscle, consistent with inhibition of the Cori cycle. These changes were associated with gene expression changes in the livers consistent with increased glycolysis and suppressed gluconeogenesis. Fasting also decreased blood glucose in tumor-bearing mice, without impairing glucose or insulin tolerance. Fasting-induced increases in wheel running and ketogenesis were suppressed by tumors, which was again associated with a shift from gluconeogenic to glycolytic metabolism in the liver. Blockade of IL-6 signaling with a neutralizing antibody failed to recover any of the behavioral or metabolic outcomes. Taken together, these data indicate that metabolic competition between the tumor and the rest of the organism is an important component of fatigue and support the hypothesis of a central role for IL-6-independent hepatic metabolic reprogramming in the pathophysiology of CRF. 10.1016/j.bbi.2020.05.043
    Perceived cognitive impairment in people with colorectal cancer who do and do not receive chemotherapy. Dhillon Haryana M,Tannock Ian F,Pond Gregory R,Renton Corrinne,Rourke Sean B,Vardy Janette L Journal of cancer survivorship : research and practice PURPOSE:Cognitive symptoms are common after cancer, but poorly associated with neuropsychological results. We previously reported colorectal cancer (CRC) patients had more cognitive impairment than controls. Here, we explore relationships between cognitive symptoms and neuropsychological domains. METHODS:Subjects with CRC (N = 362) and 72 healthy controls completed neuropsychological assessments and Functional Assessment of Cancer Therapy-Cognition (FACT-COG) at baseline (pre-chemotherapy) and 6, 12, and 24 months. Associations between neuropsychological and FACT-COG scores were explored: perceived cognitive impairment (PCI), perceived cognitive ability (PCA), impact of PCI on quality of life (CogQOL). RESULTS:Of 362 CRC subjects, 289 had loco-regional disease and 173 received chemotherapy (CTh+). At baseline, groups did not differ on total FACT-COG, PCI, or PCA scores. All scores, except PCA, were worse at 6 months in CTh+. CRC patients not receiving chemotherapy did not differ from controls on FACT-COG domains. PCA associated weakly (r = 0.28-0.34) with attention/executive function, visual memory, and global deficit score. There was no association between PCI and neuropsychological domains. Fatigue, anxiety/depression, and poorer quality of life were associated with PCI and CogQOL (r = 0.44-0.51) in CRC patients. CONCLUSIONS:No association was seen between total FACT-COG or PCI, and neuropsychological domains. A weak-moderate association was found between PCA and attention/executive function and visual memory. TRIAL REGISTRATION:The study was registered with clinicaltrials.gov (trial registration: NCT00188331). IMPLICATIONS FOR CANCER SURVIVORS:Cognitive symptoms are associated with fatigue, anxiety/depression, and poorer quality of life, and do not appear to be related to actual cognitive performance. Rates were lower than that reported in breast cancer survivors. Cognitive symptoms were greatest in those who received chemotherapy, with no significant difference between the non-chemotherapy survivors and healthy controls. 10.1007/s11764-017-0656-6
    Cognitive Dysfunction and Its Predictors in Adult Patients With Cancer Receiving Chemotherapy: A Cross-Sectional Correlational Study. Wazqar Dhuha Youssef The journal of nursing research : JNR BACKGROUND:Chemotherapy-related cognitive dysfunction, one of the most frequently reported symptoms in patients with cancer, has a negative impact on the daily lives of patients. No research has examined cognitive dysfunction and its potential predictors in adult patients with cancer receiving chemotherapy in Saudi Arabia. PURPOSE:The purpose of this study was to examine the sociodemographic, clinical, and psychological factors associated with cognitive dysfunction in adult patients with cancer receiving chemotherapy. METHODS:A cross-sectional correlational study was carried out with a convenience sample of 100 adult patients with cancer receiving chemotherapy at a university teaching hospital in Saudi Arabia. The Montreal Cognitive Assessment, the Hospital Anxiety and Depression Scale, and sociodemographic and clinical surveys were completed by participants. Descriptive statistics and linear regression were used to analyze the data. RESULTS:The data showed that the participants experienced moderate-to-severe cognitive dysfunction. Participants performed poorly in the divided attention and memory cognitive domains. Age, educational level, and depression factors were found to be significant predictors of cognitive dysfunction. CONCLUSIONS/IMPLICATIONS FOR PRACTICE:Cognitive dysfunction is commonly seen in patients with cancer receiving chemotherapy. Chemotherapy, age, and psychological factors increase susceptibility to cognitive dysfunction in adult patients with cancer. Oncology nurses should be aware that patients with cancer may be extremely vulnerable to cognitive dysfunction. Furthermore, age and psychological factors must be considered when developing symptom management and supportive care intervention programs to reduce the incidence of negative cognitive outcomes in this population. 10.1097/jnr.0000000000000340
    Chemotherapy-related cognitive impairment: mechanisms, clinical features and research perspectives. Cascella Marco,Di Napoli Raffaela,Carbone Domenico,Cuomo Gaia Francesca,Bimonte Sabrina,Muzio Maria Rosaria Recenti progressi in medicina The term chemotherapy-related cognitive impairment (CRCI), or cognitive dysfunction, or chemo fog, or chemo brain, is referred to a decline in a variety of neuropsychological tasks after chemotherapy, or following other anticancer treatments such as radiation therapy or surgery, in patients with non-central nervous system cancers. Furthermore, several pieces of evidence suggest that clinical manifestations of cognitive impairment may occur in cancer patients, prior to chemotherapy or in those not treated with cancer therapies. In these circumstances, it should be more appropriate to use the term cancer-related cognitive dysfunction. Because there is no consensus about its definition and diagnostic criteria, no specific test for CRCI diagnose exists. Whatever the cause, this manifestation of central nervous system toxicity is of increasing concern as the survival rates for cancer have improved steadily and, in turn, cognitive dysfunction can negatively impact the patients and cancer survivors' quality of life. The aim of this work is to offer an overview of the topic and recommendations for future research. 10.1701/3031.30289
    Age- and gender-dependent changes in circulating concentrations of tumor necrosis factor-α, soluble tumor necrosis factor receptor-1 and sulfated glycosaminoglycan in healthy people. Komosinska-Vassev Katarzyna,Olczyk Pawel,Winsz-Szczotka Katarzyna,Klimek Katarzyna,Olczyk Krystyna Clinical chemistry and laboratory medicine BACKGROUND:In this study, the effect of gender and physiological ageing on circulating concentrations of plasma sulfated glycosaminoglycans (sGAG) as well as molecules involved in pro- (tumor necrosis factor-α; TNF-α) and anti-inflammatory responses (soluble tumor necrosis factor receptor-1, sTNF-RI) were assessed. The relationships between sGAG and molecules involved in age-dependent extracellular matrix (ECM) remodeling during physiological ageing were also investigated. METHODS:Circulating TNF-α and sTNF-RI were measured in 91 healthy volunteers using enzyme-linked immunosorbent assays. sGAG were quantified using an Alcian blue-binding assay. RESULTS:A linear age-related decline in plasma sGAG was found during the first five decades of life (r=-0.61, p<0.05), followed by an increase occurring only in females (r=0.46, p<0.05). Circulating TNF-α concentrations were inversely correlated with age (r=-0.24, p<0.05) over the lifetime. For TNF-α, the observed changes were gender specific. Serum sTNF-RI concentrations were not affected by age in either men or women. A significant positive correlation was found between the concentrations of TNF-α and both sGAG (r=0.22, p<0.05) and sTNF-RI (r=0.21, p<0.05). CONCLUSIONS:Our data demonstrate that physiological ageing is associated with ECM remodeling, reflected by plasma sGAGs concentrations. Changes in the ECM metabolism during the ageing process were influenced by circulating TNF-α. Furthermore, serum concentrations of biomolecules involved in pro- and anti-inflammatory responses are not increased in healthy elderly subjects. 10.1515/CCLM.2011.007
    Symptom clusters in patients with breast cancer receiving radiation therapy. Chow Selina,Wan Bo Angela,Pidduck William,Zhang Liying,DeAngelis Carlo,Chan Stephanie,Yee Caitlin,Drost Leah,Leung Eric,Sousa Philomena,Lewis Donna,Lam Henry,Chow Ronald,Lock Michael,Chow Edward European journal of oncology nursing : the official journal of European Oncology Nursing Society PURPOSE:Symptoms experienced by breast cancer patients often cluster together in groups known as "symptom clusters". The aim was to determine the symptom clusters in women with non-metastatic breast cancer treated by radiation therapy (RT). METHODS:Edmonton Symptom Assessment Scale (ESAS) scores were taken from breast cancer patients receiving RT before, at completion of RT, and after RT. Exploratory factor analysis (EFA), principal component analysis (PCA), and hierarchical cluster analysis (HCA) were used to identify symptom clusters among the nine ESAS items at all three time points. RESULTS:This study included 1224 patients. The PCA and EFA identified the same two symptom clusters before the start of RT: 1) pain, tiredness, nausea, drowsiness, appetite, and dyspnea; 2) depression, anxiety, and wellbeing. The HCA further split the symptoms into three clusters. Wellbeing, depression, and anxiety consistently clustered together. Among the ESAS scores collected at the end of and after RT, each statistical method identified different symptom clusters. For the symptom clusters experienced at the end of RT, the following symptoms were always in the same cluster: wellbeing, depression, and anxiety; nausea and appetite; drowsiness and dyspnea. Following RT, depression and anxiety consistently clustered together, with nausea and appetite in a second cluster. CONCLUSION:Among the symptom clusters derived before, at the end of RT, and after RT, the following symptoms consistently presented together: depression and anxiety, nausea and appetite, pain and tiredness, and drowsiness, dyspnea, and tiredness. Understanding symptom clusters in this population can improve management of symptoms. 10.1016/j.ejon.2019.07.004