Effect of Yoga and Mediational Influence of Fatigue on Walking, Physical Activity, and Quality of Life Among Cancer Survivors.

BACKGROUND: Cancer-related fatigue (CRF) negatively affects survivors' walking, engagement in physical activity (PA), and quality of life (QoL). Yoga is an effective therapy for treating CRF; however, evidence from large clinical trials regarding how reducing CRF through yoga influences CRF's interference with survivors' walking, engagement in PA, and QoL is not available. We examined the effects of yoga and the mediational influence of CRF on CRF's interference with walking, PA, and QoL among cancer survivors in a multicenter phase III randomized controlled trial. PATIENTS AND METHODS: Cancer survivors (n=410) with insomnia 2 to 24 months posttreatment were randomized to a 4-week yoga intervention-Yoga for Cancer Survivors (YOCAS)-or standard care. A symptom inventory was used to assess how much CRF interfered with survivors' walking, PA, and QoL. The Multidimensional Fatigue Symptom Inventory-Short Form was used to assess CRF. Two-tailed t tests and analyses of covariance were used to examine within-group and between-group differences. Path analysis was used to evaluate mediational relationships between CRF and changes in CRF's interference with walking, PA, and QoL among survivors. RESULTS: Compared with standard care controls, YOCAS participants reported significant improvements in CRF's interference with walking, PA, and QoL at postintervention (all effect size = -0.33; all P≤.05). Improvements in CRF resulting from yoga accounted for significant proportions of the improvements in walking (44%), PA (53%), and QoL (45%; all P≤.05). CONCLUSIONS: A significant proportion (44%-53%) of the YOCAS effect on CRF's interference with walking, PA, and QoL was due to improvements in CRF among cancer survivors. Yoga should be introduced and included as a treatment option for survivors experiencing fatigue. By reducing fatigue, survivors further improve their walking, engagement in PA, and QoL.

Advances in methods to analyse cardiolipin and their clinical applications.

Cardiolipin (CL) is a mitochondria-exclusive phospholipid, primarily localised within the inner mitochondrial membrane, that plays an essential role in mitochondrial architecture and function. Aberrant CL content, structure, and localisation have all been linked to impaired mitochondrial activity and are observed in the pathophysiology of cancer and neurological, cardiovascular, and metabolic disorders. The detection, quantification, and localisation of CL species is a valuable tool to investigate mitochondrial dysfunction and the pathophysiological mechanisms underpinning several human disorders. CL is measured using liquid chromatography, usually combined with mass spectrometry, mass spectrometry imaging, shotgun lipidomics, ion mobility spectrometry, fluorometry, and radiolabelling. This review summarises available methods to analyse CL, with a particular focus on modern mass spectrometry, and evaluates their advantages and limitations. We provide guidance aimed at selecting the most appropriate technique, or combination of techniques, when analysing CL in different model systems, and highlight the clinical contexts in which measuring CL is relevant.

Chemotherapy-induced peripheral neuropathy (CIPN) and its treatment: an NIH Collaboratory study of claims data.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling complication of many chemotherapies. We investigated the feasibility of using health plan claims and administrative data to identify CIPN occurrence by comparing patients who received neurotoxic and non-neurotoxic chemotherapies. METHODS: The sample included over 53,000,000 patients from two regional and one national insurer in the USA (> 400,000 exposed to chemotherapy). Peripheral neuropathy was identified using a broad definition (definition 1) and a specific definition (i.e., drug-induced polyneuropathy code) (definition 2). RESULTS: CIPN incidence as measured by definition 1 within 6 months of chemotherapy initiation was 18.1% and 6.2% for patients who received neurotoxic and non-neurotoxic chemotherapy, respectively (relative risk neurotoxic vs. non-neurotoxic (RR), 2.93 (95% CI, 2.87-2.98)). For definition 2, these incidences were 3.6% and 0.1% (RR, 25.2 (95% CI, 22.8-27.8)). The incidences of new analgesic prescriptions for neurotoxic and non-neurotoxic groups were as follows: gabapentin, 7.1%/1.7%; pregabalin, 0.69%/0.31%; and duloxetine, 0.78%/0.76%. The incidence of CIPN as defined by definitions 1 and 2 was low compared with that of published research studies, but the relative risk of CIPN among patients who received neurotoxic chemotherapies compared with those who received non-neurotoxic chemotherapies was high using definition 2. CONCLUSIONS: These data suggest that as used currently by clinicians, administrative codes likely underestimate CIPN incidence. Thus, studies using administrative data to estimate CIPN incidence are not currently feasible. However, the drug-induced polyneuropathy code is a specific indicator of CIPN in administrative data and may be useful for investigating predictors or potentially preventive therapies of CIPN.

Utility of topical agents for radiation dermatitis and pain: a randomized clinical trial.

PURPOSE: Although topical agents are often provided during radiation therapy, there is limited consensus and evidence for their use prophylactically to prevent or reduce radiation dermatitis. METHODS: This was a multi-site, randomized, placebo-controlled, blinded study of 191 breast cancer patients to compare the prophylactic effectiveness of three topical agents (Curcumin, HPR Plus™, and Placebo) for reducing radiation dermatitis and associated pain. Patients applied the topical agent to their skin in the radiation area site three times daily starting the first day of radiation therapy (RT) until 1 week after RT completion. RESULTS: Of the 191 randomized patients, 171 patients were included in the final analyses (87.5% white females, mean age = 58 (range = 36-88)). Mean radiation dermatitis severity (RDS) scores did not significantly differ between study arms (Curcumin = 2.68 [2.49, 2.86]; HPR Plus™ = 2.64 [2.45, 2.82]; Placebo = 2.63 [2.44, 2.83]; p = 0.929). Logistic regression analyses showed that increased breast field separation positively correlated with increased radiation dermatitis severity (p = 0.018). In patients with high breast field separation (≥ 25 cm), RDS scores (Curcumin = 2.70 [2.21, 3.19]; HPR Plus™ = 3.57 [3.16, 4.00]; Placebo = 2.95 [2.60, 3.30]; p = 0.024) and pain scores (Curcumin = 0.52 [- 0.28, 1.33]; HPR Plus™ = 0.55 [- 0.19, 1.30]; Placebo = 1.73 [0.97, 2.50]; p = 0.046) significantly differed at the end of RT. CONCLUSIONS: Although there were no significant effects of the treatment groups on the overall population, our exploratory subgroup analysis suggests that prophylactic treatment with topical curcumin may be effective for minimizing skin reactions and pain for patients with high breast separation (≥ 25 cm) who may have the worst skin reactions.

Pharmacogenetics of platinum-based chemotherapy: impact of DNA repair and folate metabolism gene polymorphisms on prognosis of non-small cell lung cancer patients.

Chemotherapy based on platinum compounds is the standard treatment for NSCLC patients with EGFR wild type, and is also used as second line in mutated EGFR patients. Nevertheless, this therapy presents poor clinical outcomes. ERCC1, ERCC2, XRCC1, MDM2, MTHFR, MTR, and SLC19A1 gene polymorphisms may contribute to individual variation in response and survival to platinum-based chemotherapy. The aim of this study was to investigate the influence of these polymorphisms on response and survival of NSCLC patients treated with platinum-based chemotherapy. A retrospective-prospective cohorts study was conducted, including 141 NSCLC patients. Polymorphisms were analyzed by PCR real-time with Taqman® probes. Patients with ERCC1 rs3212986-GG (p = 0.0268; OR = 2.50; CI95% = 1.12-5.69) and XRCC1 rs25487-GG (p = 0.0161; OR = 2.99; CI95% = 1.26-7.62) genotype showed significantly better ORR. Cox survival analysis revealed that patients carrying the MDM2 rs1690924-GG genotype (p = 0.0345; HR = 1.99; CI95% = 1.05-3.80) presented higher risk of death. Furthermore, carriers of MTR rs1805087-A alleles (p = 0.0060; HR = 8.91; CI95% = 1.87-42.42) and SLC19A1 rs1051266-AA genotype (p = 0.0130; HR = 1.74; CI95% = 1.12-2.68) showed greater risk of progression. No influence of ERCC1 rs11615, ERCC2 rs13181, ERCC2 rs1799793, XRCC1 rs1799782, MDM2 rs1470383, MTHFR rs1801131, and MTHFR rs1801133 on platinum-based chemotherapy clinical outcomes was found. In conclusion, our results suggest that ERCC1 rs3212986, XRCC1 rs25487, MDM2 rs1690924, MTR rs1805087, and SLC19A1 rs1051266 gene polymorphisms may significantly act as predictive factors in NSCLC patients treated with platinum-based chemotherapy.

Response of Zea mays to multimetal contaminated soils: a multibiomarker approach.

Heavy metals present in mine tailings pollute agroecosystems, put the integrity of the environment at risk and become a major route of exposure to humans. The present study was carried out in Taxco, Guerrero, Mexico, where millions of tons of mine tailings have been deposited. Soils from this region are used for agricultural activities. Maize (Zea mays) was selected as a test plant, because it is one of the most common and important cereal crops in Mexico and worldwide. Thirteen metals were selected and their bioaccumulation in roots, leaves and fruits were measured in plants cultivated in soils contaminated with mine tailings and those cultivated in non-contaminated soils. The effect of metal bioaccumulation on: macro and micromorphology, size, biomass, coloration leaf patterns and on DNA damage levels in different structures were determined. The bioaccumulation pattern was: root > leaf > fruit, being only Mn and Cr bioaccumulated in all three structures and V in the roots and leaves. A significant effect of metal bioaccumulation on 50% of the size and leaf shape and 55% of the biomass characters in Z. mays exposed plants was detected. Regarding micromorphological characters, a significant effect of metal bioaccumulation on 67% of the leaf characters and on 100% of the color basal leaf characters was noted. The effect of metal bioaccumulation on the induction of DNA damage (leaf > fruit > root) was detected employing single cell gel electrophoresis analysis. An approach, in which multi endpoints are used is necessary to estimate the extent of the detrimental effects of metal pollution on agroecosystem integrity contaminated with mine tailings.

Cytokine single-nucleotide polymorphisms and risk of non-small-cell lung cancer.

OBJECTIVE: Lung cancer, particularly the non-small-cell lung cancer (NSCLC) subtype, is the leading cause of cancer-related death worldwide. Several functional polymorphisms in inflammatory cytokine genes, such as IL1B, IL6, IL12A, IL13 and IL16, have been associated with the risk of NSCLC. The aim of this study was to evaluate the association between ILs gene polymorphisms and the risk of developing NSCLC. PARTICIPANTS AND METHODS: A retrospective case-control study was carried out, including 174 NSCLC cases and 298 controls of Spanish origin. IL1B (rs1143634), IL1B (rs12621220), IL1B (rs1143623), IL1B (rs16944), IL1B (rs1143627), IL12A (rs662959), IL13 (rs1881457), IL6 (rs1800795) and IL16 (rs7170924) gene polymorphisms were analysed by TaqMan. RESULTS: The genotypic logistic regression model adjusted by smoking status showed that the IL1B rs1143634-TT genotype was associated with a lower risk of NSCLC (P=0.04312; odds ratio=0.226; 95% confidence interval=0.044-0.840). No other gene polymorphisms showed an association with NSCLC in any of the models tested. CONCLUSION: In conclusion, IL1B rs1143634 was significantly associated with a higher risk of NSCLC. No influence of IL1B rs12621220, rs1143623, rs16944, rs1143627, IL12A rs662959, IL13 rs1881457 and IL16 rs7170924 on the risk of developing NSCLC was found in our study.

Ischemic Stroke as an Initial Manifestation of Antiphospholipid Syndrome in an Adolescent: A Case Report.

Cerebrovascular diseases in pediatric patients are relatively rare. Ischemic stroke in adolescents is associated with a poor prognosis. The most common causes include systemic diseases, such as heart disease and hypercoagulation disorders. It is important to mention that one of the most common acquired hypercoagulation states is the antiphospholipid syndrome (APS). Patients with this disease may present stroke as the first clinical manifestation, which not only increases morbidity in these patients but presents a diagnostic challenge. This case presents one example of how APS can present as a pediatric stroke. The diagnostic approach should always be through the presence of specific antibodies accompanied by the presence of a thromboembolic episode proven by catheterization or an imaging study. In the brain, the preferred imaging study is magnetic resonance imaging. Management is based on anticoagulation therapy and continuous monitoring in the intensive care unit.

Effects of mammary cancer and chemotherapy on neuroimmunological markers and memory function in a preclinical mouse model.

Treatment modalities for breast cancer, including cyclophosphamide chemotherapy, have been associated with the development of cognitive decline (CRCD), which is characterized by impairments in memory, concentration, attention, and executive functions. We and others have identified a link between inflammation and decreased cognitive performance in patients with breast cancer receiving chemotherapy. In order to better understand the inflammation-associated molecular changes within the brain related to tumor alone or in combination with chemotherapy, we orthotopically implanted mouse mammary tumors (E0771) into female C57BL/6 mice and administered clinically relevant doses of cyclophosphamide and doxorubicin intravenously at weekly intervals for four weeks. We measured serum cytokines and markers of neuroinflammation at 48 h and up to one month post-treatment and tested memory using a reward-based delayed spatial alternation paradigm. We found that breast tumors and chemotherapy altered systemic inflammation and neuroinflammation. We further found that the presence of tumor and chemotherapy led to a decline in memory over time at the longest delay, when memory was the most taxed, compared to shorter delay times. These findings in a clinically relevant mouse model shed light on possible biomarkers for CRCD and add to the growing evidence that anti-inflammatory strategies have the potential to mitigate cancer- or treatment-related side effects.

Characterization of Beta-Lactam Resistome of Escherichia coli Causing Nosocomial Infections.

Nosocomial infections caused by Escherichia coli pose significant therapeutic challenges due to the high expression of genes encoding antimicrobial drug resistance. In this study, we investigated the conformation of the beta-lactam resistome responsible for the specific pattern of resistance against beta-lactam antibiotics. A total of 218 Escherichia coli strains were isolated from in-hospital patients diagnosed with nosocomial infections, obtained from various sources such as urine (n = 49, 22.48%), vaginal discharge (n = 46, 21.10%), catheter tips (n = 14, 6.42%), blood (n = 13, 5.96%), feces (n = 12, 5.50%), sputum (n = 11, 5.05%), biopsies (n = 8, 3.67%), cerebrospinal fluid (n = 2, 0.92%) and other unspecified discharges (n = 63, 28.90%). To characterize the beta-lactam resistome, all strains were subjected to antibiotic dilution tests and grown in beta-lactam antibiotics supplemented with Luria culture medium. Subsequently, multiplex PCR and next-generation sequencing were conducted. The results show a multi-drug-resistance phenotype, particularly against beta-lactam drugs. The primary determinant of this resistance was the expression of the blaTEM gene family, with 209 positive strains (95.87%) expressing it as a single gene (n = 47, 21.6%) or in combination with other genes. Common combinations included blaTEM + blaCTX (n = 42, 19.3%), blaTEM + blaCTX + blaSHV (n = 13, 6%) and blaTEM + blaCTX + blaBIL (n = 12, 5.5%), among others. The beta-lactam resistome of nosocomial Escherichia coli strains isolated from inpatients at the "October first" Regional Hospital of ISSSTE was predominantly composed of members of the blaTEM gene family, expressed in various configurations along with different members of other beta-lactamase gene families.

Antimicrobial and immunosuppressive drug interactions in solid organ transplant recipients.

Infections are frequent and can be severe in recipients of solid organ transplantation. Prevention and treatment are priority objectives of multidisciplinary transplant teams. Interactions between antimicrobials (indicated for prevention and therapy) and immunosuppressants (for preventing rejection) make treatment more complex than in the general population. Co-administration of immunosuppressants and antibiotics can cause harmful interactions, modifying the pharmacokinetic and pharmacodynamic characteristics of both groups of drugs. The loss of the transplanted organ due to reduced levels of immunosuppressants is a unique consequence of the often lethal interactions in this group of patients. By contrast, elevated levels of these drugs cause toxicity, and reduced concentrations of antimicrobial treatment fail to contain the infection. Azoles, rifabutin, protease inhibitors, non-nucleoside reverse transcriptase inhibitors and antimicrobial macrolides all interact with immunosuppressants. In this article, we review interactions between antibiotics and immunosuppressants in order to adopt the most appropriate clinical approach (dosage adjustments, close monitoring of plasma levels and organ function) and determine whether they can be used together with any measure of safety.

Associations of Uncertainty With Psychological Health and Quality of Life in Older Adults With Advanced Cancer.

CONTEXT: Older adults with advanced cancer face uncertainty related to their disease and treatment. OBJECTIVES: To evaluate the associations of uncertainty with psychological health and quality of life (QoL) in older adults with advanced cancer. METHODS: Secondary cross-sectional analysis of baseline data from a national clustered geriatric assessment trial. Patients 70 years and older with advanced cancer considering a new line of chemotherapy were recruited. We measured uncertainty using the modified nine-item Mishel Uncertainty in Illness Scale. Dependent variables included anxiety (Generalized Anxiety Disorder-7), depression (Generalized Depression Scale-15), distress (distress thermometer), QoL (Functional Assessment of Cancer Therapy-General), and emotional well-being (Functional Assessment of Cancer Therapy-General subscale). We used multivariate linear regression analyses to evaluate the association of uncertainty with each dependent variable. We conducted a partial least squares analysis with a variable importance in projection (VIP) plot to assess the contribution of individual variables to the model. Variables with a VIP <0.8 were considered less influential. RESULTS: We included 527 patients (median age 76 years; range 70-96). In multivariate analyses, higher levels of uncertainty were significantly associated with greater anxiety (ß = 0.11; SE = 0.04), depression (ß = 0.09; SE = 0.02), distress (ß = 0.12; SE = 0.02), as well as lower QoL (ß = -1.08; SE = 0.11) and emotional well-being (ß = -0.29; SE = 0.03); the effect sizes were considered small. Uncertainty items related to disease and treatment were most strongly associated with psychological health and QoL scores (all VIP >0.8). CONCLUSION: Uncertainty among older patients with advanced cancer is associated with worse psychological health and QoL. Tailored uncertainty management strategies are warranted.

PD-L1 testing and clinical management of newly diagnosed metastatic non-small cell lung cancer in Spain: MOREL study.

AIM: To describe the clinical management and PD-L1 testing of patients with newly diagnosed stage IV non-small cell lung cancer (NSCLC) without driver mutations in Spain. METHODS: Multicenter, retrospective study. RESULTS: Among 297 evaluated patients, 89.2% received systemic treatment for stage IV disease, of whom 53.6% received platinum doublet therapy, 26.8% immunotherapy as monotherapy and 14.7% immunotherapy + chemotherapy, with 9.4% receiving treatment as part of a clinical trial. Treatment was initiated 1 month after histological diagnosis, with PD-L1 test results available in most cases (92.6%). PD-L1 testing was performed in 287 patients, 95.1% by in-house tests, mostly with the 22C3 pharmDx assay. The factor most strongly associated with treatment selection was, as expected, the expression of PD-L1. CONCLUSION: PD-L1 testing is implemented in clinical practice and seems to guide treatment decisions in patients with NSCLC in Spain.

Relationships of self-perceived age with geriatric assessment domains in older adults with cancer.

OBJECTIVES: Older self-perceived age is associated with poor health and higher healthcare utilization in the geriatric population. We evaluated the associations of self-perceived age with geriatric assessment (GA) domain impairments in older adults with cancer. METHODS: This was a secondary analysis of baseline data from a GA cluster-randomized trial (URCC 13070; PI: Mohile). We included patients aged ≥70 with incurable stage III/IV solid tumor or lymphoma considering or receiving treatment and had ≥1 GA domain impairment other than polypharmacy. Multivariate analyses were used to evaluate the associations of age difference between chronological and self-perceived age (categorized into "feeling younger than chronological age" vs. "feeling the same or older than their chronological age") with GA domain impairments. RESULTS: We included 533 patients; mean age was 76.6 (SD 5.2). On multivariate analyses, compared to those who felt younger than their chronological age, those who felt the same or older were more likely to have impairments in physical performance [Adjusted Odds Ratio (AOR) 5.42, 95% Confidence Interval (CI) 1.69-17.40)], functional status (AOR 2.31, 95% CI 1.73-3.07), comorbidity (AOR 1.62, 95% CI 1.20-2.19), psychological health (AOR 2.62, 95% CI 1.85-3.73), and nutrition (AOR 1.65, 95% CI 1.20-2.28). They were also more likely to screen positively for polypharmacy (AOR 1.86, 95% CI 1.30-2.65). CONCLUSIONS: Older adults with cancer who felt the same or older than their chronological age were more likely to have GA domain impairments. Further studies are needed to better understand the relationships between self-perceived age, aging-related conditions, and outcomes in this population.

Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective study.

BACKGROUND: Little is known about the effects of chemotherapeutic drugs on DNA methylation status of leukocytes, which may be predictive of treatment benefits and toxicities. Based on a prospective national study, we characterize the changes in leukocyte DNA methylome from pre- to post-chemotherapy (approximately 4 months apart) in 93 patients treated for early stage breast cancer and 48 matched non-cancer controls. We further examined significant methylation changes with perceived cognitive impairment, a clinically significant problem related to cancer and chemotherapy. RESULTS: Approximately 4.2% of the CpG sites measured using the Illumina 450K methylation array underwent significant changes after chemotherapy (p < 1e-7), in comparison to a stable DNA methylome in controls. Post-chemotherapy, the estimated relative proportions of B cells and CD4+ T cells were decreased by a median of 100% and 39%, respectively, whereas the proportion of monocytes was increased by a median of 91%. After controlling for leukocyte composition, 568 CpGs from 460 genes were still significantly altered following chemotherapy. With additional adjustment for chemotherapy regimen, cumulative infusions, growth factors, and steroids, changes in four CpGs remained significant, including cg16936953 in VMP1/MIR21, cg01252023 in CORO1B, cg11859398 in SDK1, and cg19956914 in SUMF2. The most significant CpG, cg16936953, was also associated with cognitive decline in breast cancer patients. CONCLUSIONS: Chemotherapy profoundly alters the composition and DNA methylation landscape of leukocytes in breast cancer patients. Our results shed light on the epigenetic response of circulating immune cell populations to cytotoxic chemotherapeutic drugs and provide possible epigenetic links to the degeneration of cognitive function associated with chemotherapy.

Longitudinal Relationship Between Frailty and Cognition in Patients 50 Years and Older with Breast Cancer.

OBJECTIVES: To evaluate relationships between frailty and cognition longitudinally in adults 50 years and older with breast cancer receiving chemotherapy. DESIGN: Secondary analysis of a prospective longitudinal observational study. SETTING: University of Rochester NCI Community Oncology Research Program community oncology clinics. PARTICIPANTS: Patients with breast cancer age 50 and older receiving adjuvant/neoadjuvant chemotherapy (n = 376) and age-matched controls without cancer (n = 234). MEASUREMENTS: Frailty was assessed using a modified frailty score from self-reported assessments (weakness, exhaustion, physical activity, and gait speed). Cognition was assessed by patient report (Functional Assessment of Cancer Therapy-Cognition [FACT-Cog]) and objective measures. Frailty and cognition were measured at three time points (prechemotherapy [A1], postchemotherapy [A2], and 6 months postchemotherapy [A3]; similar time interval for controls). Linear regression models evaluated associations between frailty and cognition adjusting for covariates. RESULTS: The average age was 59 years (standard deviation = 6.4 y). At baseline, patients with cancer had a higher mean frailty score (1.21 vs .73; P < .001) and lower mean FACT-Cog score (158.4 vs 167.3; P < .001) compared with controls. Objective cognitive measures were not statistically different. Longitudinal decline in FACT-Cog between A1 and A2 (P < .05) and between A1 and A3 (P < .01) was associated with increased frailty score in patients compared with controls. Longitudinal worsening in Controlled Oral Word Association (P < .05) and Trail-Making Test (P < .01) were associated with an increase in frailty between A1 and A2 in patients compared with controls; longitudinal decline in the Delayed Match to Sample test was associated with an increase in frailty between A1 and A3 (P < .05) in patients compared with controls. This finding remained significant for a subset analysis of those aged 65 and older. CONCLUSION: In patients with breast cancer aged 50 and older, longitudinal decline in FACT-Cog and objective measures of attention and memory were associated with increased frailty during treatment and up to 6 months posttreatment. Overall, our study suggests cognition and frailty are both important factors to assess in breast cancer patients. J Am Geriatr Soc 67:928-936, 2019.

Effects of a Home-based Exercise Program on Anxiety and Mood Disturbances in Older Adults with Cancer Receiving Chemotherapy.

BACKGROUND/OBJECTIVE: Exercise interventions improve anxiety and mood disturbances in patients with cancer. However, studies are limited in older adults with cancer. We assessed the effects of exercise on anxiety, mood, and social and emotional well-being in older patients with cancer during their first 6 weeks of chemotherapy. DESIGN: Exploratory secondary analysis of a randomized controlled trial (RCT). SETTING: Community oncology practices. PARTICIPANTS: Older patients (aged 60 years or older) undergoing chemotherapy (N = 252). INTERVENTION: Patients were randomized to Exercise for Cancer Patients (EXCAP) or usual care (control) for the first 6 weeks of chemotherapy. EXCAP is a home-based, low- to moderate-intensity progressive walking and resistance training program. MEASUREMENTS: Analysis of covariance, with study arm as the factor, baseline value as the covariate, and study arm × baseline interaction, was used to evaluate arm effects on postintervention anxiety (State Trait Anxiety Inventory [STAI]), mood (Profile of Mood States [POMS]), and social and emotional well-being (Functional Assessment of Cancer Therapy-General subscales) after 6 weeks. RESULTS: Median age was 67 years; 77% had breast cancer. Statistically significant group differences were observed in the STAI score (P = .001), POMS score (P = .022), social well-being (P = .002), and emotional well-being (P = .048). For each outcome, EXCAP patients with worse baseline scores had larger improvements at 6 weeks; these improvements were clinically significant for STAI score and social well-being. CONCLUSIONS: Among older cancer patients receiving chemotherapy, a 6-week structured exercise program improved anxiety and mood, especially among those participants with worse baseline symptoms. Additional RCTs are needed to confirm these findings and evaluate the appropriate exercise prescription for managing anxiety, mood, and well-being in this patient population. J Am Geriatr Soc 67:1005-1011, 2019.

Elucidating the associations between sleep disturbance and depression, fatigue, and pain in older adults with cancer.

OBJECTIVES: Sleep disturbance is prevalent and often coexists with depression, fatigue, and pain in the cancer population. The aim of this study was to describe the prevalence of sleep disturbance with co-existing depression, fatigue, and pain in older patients with cancer. We also examined the associations of several socio-demographic and clinical variables with sleep disturbance. METHODS: This cross-sectional study consisted of 389 older patients with solid and hematologic malignancies who were referred to the Specialized Oncology Care & Research in the Elderly (SOCARE) clinics at the Universities of Rochester and Chicago between May 2011 and October 2015 and completed a sleep and geriatric assessment (that inquires about fatigue, pain, and depression). Multivariate logistic regression was used to identify variables associated with sleep disturbance. RESULTS: The prevalence of sleep disturbance was 40%. Of those with sleep disturbance (n = 154), 84% also had at least one of the other three symptoms (25% had one symptom, 38% had two symptoms, and 21% had three symptoms). Sleep disturbance was more likely to be reported in those with comorbidities (45% vs. 28%, P = 0.002), depression (49% vs. 36%, P = 0.015), fatigue (49% vs. 23%, P < 0.001), and pain (45% vs. 31%, P = 0.010). On multivariable analysis, only fatigue (adjusted odds ratio (AOR) 1.90, 95% CI 1.10-3.30, P = 0.020) was independently associated with sleep disturbance. CONCLUSIONS: Sleep disturbance is prevalent and often co-occurs with depression, fatigue, or pain in older patients with cancer. Fatigue was significantly associated with sleep disturbance and future studies should explore interventions that target sleep disturbance and fatigue.

In vitro proliferation and expansion of hematopoietic progenitors present in mobilized peripheral blood from normal subjects and cancer patients.

In the present study, we have assessed, in a comparative manner, the in vitro proliferation and expansion potentials of hematopoietic progenitor cells (HPC) present in mobilized peripheral blood from normal subjects (MPB-n; n = 18) and cancer patients (MPB-c; n = 18). The latter included patients with breast cancer (BrCa; n = 8), Hodgkin disease (HD; n = 4), non-Hodgkin lymphoma (NHL; n = 3), and acute myeloid leukemia (AML; n = 3). Progenitor cells from normal bone marrow (BM) and umbilical cord blood (UCB) were included as controls. HPC, enriched by a negative selection procedure, were cultured for 25 days, in serum-free liquid media in the presence of a cytokine combination including early- and late-acting cytokines. Our results demonstrate that the in vitro biological properties of progenitor cells present in MPB differ, depending on whether they are derived from healthy individuals, from patients with solid tumors, or from patients with hematological neoplasias. Among all cell sources analyzed, UCB-derived progenitors showed the greatest proliferation and expansion potentials (1000-fold increase in total cell numbers on day 15, and a 22-fold increase in myeloid progenitor cell numbers, at day 10). Progenitor cells present in MPB from hematologically normal individuals showed proliferation and expansion potentials comparable to those of HPC from normal BM (500-fold increase in total cell numbers on day 15, and a 14-fold increase in myeloid progenitor cell numbers, at day 10). The proliferation/expansion potentials of MPB progenitors from BrCa patients were also within the normal range, although in the lower levels (327-fold increase in total cell numbers, on day 15, and 11.8-fold increase in myeloid progenitors, at day 10). In contrast, progenitors present in MPB from patients with HD, NHL, and especially AML, showed reduced in vitro capacities (119-, 102-, and 51-fold increase in total cell numbers, respectively; and 8-, 4-, and 2.6-fold increase in myeloid progenitor cells, respectively). To our knowledge, this is the first report in which the in vitro proliferation and expansion potentials of HPC from MPB from normal subjects and cancer patients are assessed simultaneously in a comparative manner.

Does polarized training improve performance in recreational runners?

PURPOSE: To quantify the impact of training-intensity distribution on 10K performance in recreational athletes. METHODS: 30 endurance runners were randomly assigned to a training program emphasizing low-intensity, sub-ventilatory-threshold (VT), polarized endurance-training distribution (PET) or a moderately high-intensity (between-thresholds) endurance-training program (BThET). Before the study, the subjects performed a maximal exercise test to determine VT and respiratory-compensation threshold (RCT), which allowed training to be controlled based on heart rate during each training session over the 10-wk intervention period. Subjects performed a 10-km race on the same course before and after the intervention period. Training was quantified based on the cumulative time spent in 3 intensity zones: zone 1 (low intensity, RCT). The contribution of total training time in each zone was controlled to have more low-intensity training in PET (±77/3/20), whereas for BThET the distribution was higher in zone 2 and lower in zone 1 (±46/35/19). RESULTS: Both groups significantly improved their 10K time (39min18s ± 4min54s vs 37min19s ± 4min42s, P < .0001 for PET; 39min24s ± 3min54s vs 38min0s ± 4min24s, P < .001 for BThET). Improvements were 5.0% vs 3.6%, ~41 s difference at post-training-intervention. This difference was not significant. However, a subset analysis comparing the 12 runners who actually performed the most PET (n = 6) and BThET (n = 16) distributions showed greater improvement in PET by 1.29 standardized Cohen effect-size units (90% CI 0.31-2.27, P = .038). CONCLUSIONS: Polarized training can stimulate greater training effects than between-thresholds training in recreational runners.