bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of cancer diagnosis with frailty status in high need, high risk veterans.
Authors: Resendes Natasha M , Oomrigar Shivan M , Tannous Toufic , Ruiz Jorge G , Hammel Iriana M 
Published: June 2022

e24024 Background: Frailty, a common geriatric condition, is characterized by a vulnerability to stressors caused by multisystem dysfunction associated with poor clinical outcomes. Patients with frailty are often High-Need High-Risk (HNHR), a group with higher levels of healthcare utilization. Cancer diagnosis could increase the incidence of frailty in this group by several mechanisms: immunosenescence, chronic inflammation, potentially harmful effects of therapies and associated comorbidities. The study aim was to determine the cross-sectional association of cancer with frailty status in High Need, High Risk veterans. Methods: This was a cross-sectional study of HNHR Veterans in the Veterans Integrated Service Network 8 identified through quarterly reports run by VA predictive analytic models. We compared Veterans with and without cancer in terms of frailty status, sociodemographic characteristics, substance or alcohol abuse and number of medications. Frailty was defined using a 30-item VA Frailty Index (VA-FI, excluding cancer) generated as a proportion based on the number of items present. We compared non-frail (robust = 0–0.1, and pre-frail = 0.11–0.20), and frail (mild = 0.21–0.30, moderate = 0.31–0.40, and severe = > 0.4). After adjusting for gender, age, alcohol abuse, tobacco abuse and number of medications, we performed a multinomial logistic regression using odds ratios (OR) with 95% confidence intervals (CI) with cancer as the independent variable and frailty status as the dependent variable. Results: A total of 10916 Veterans were included in the analysis, mean age 68.5 (SD = 11.8) years, 93.4% male, 74.7% Caucasian, 18.0% Black, 7.4% Hispanic, 8710 (79.8%) frail and 3641 (36.1%) had Cancer. Of those with cancer, frail = 3358 (85.2%) vs. non-frail = 583 (14.8%) (p < .0001). After multivariate multinomial logistic regression, the presence of cancer was associated with being severely frail as compared to robust, adjusted OR:2.3(95%C.I.:1.8-2.9), p < 0.0001. Conclusions: In this HNHR veteran population, cancer had a positive, cross-sectional association with frailty. Identifying HNHR patients with cancer may assist clinicians in the implementation of targeted clinical interventions that may prevent or reverse frailty status and associated poor clinical outcomes. More research is needed to better determine the impact of cancer on frailty diagnosis.
Impact of specific oncologic and geriatric parameters in predicting chemotherapy toxicity and death in elderly cancer patients.
Authors: Gholam Dani E , Stephan Elie , Bassil Nazem , El Haddad Kamal , Antonios Diane , Gerges Zeina , Chebib Amale , Haydar Mazen , El Bikai Rana 
Published: June 2022

e24026 Background: Cancer is mainly a disease of the elderly with more than 75% of patients aged 65 years and more at diagnosis. Comprehensive geriatric assessment (CGA) is usually used to assess elderly cancer patients¹. However, its sensitivity in predicting their outcome is questionable. Methods: We investigated whether specific oncologic and geriatric markers could predict chemotherapy toxicity and cancer-related death in a prospective single center study with 110 chemo-naive patients with advanced cancer. All patients underwent a CGA. Frailty markers as defined by Fried2 as well as basic oncologic data were collected. Bivariate and multivariate analysis were done to assess the relation between the different variables and major toxicity. A Cox regression model for survival analysis was also performed. Results: Median age is 74 years [65-90 years]. 46% have stage IV disease. 27% have aggressive cancer as defined by Hurria et al3. Grade III-IX chemotherapy-related toxicity occurred in 22% of patients. Combined chemotherapy drug regimens, loss of appetite in the last 3 months and polypharmacy at baseline were predictive of chemotherapy toxicity in multivariate analysis. After a median follow-up of 12 months, 59% died of disease progression. In multivariate analysis, advanced cancer stage, initial loss of > 5% body weight within 1 year, altered physical activity and Activity of Daily Living (ADL), anemia and heavy comorbidities (CIRS – G score) were predictive of poor outcome (Table). Conclusions: In elderly cancer patients, poor nutritional status and heavy comorbidities are predictive of both chemotherapy intolerance and death. In addition, markers such as anemia, advanced cancer stage, altered physical activity and impaired ADL predict early death. Balducci L. The Oncologist 2000. Fried LP. J Gerontol A Biol Sci Med Sci 2001. Hurria A. J Clin Oncol 2011. Clinical trial information: 02-02-18. [Table: see text]
Evaluation of the geriatric 8 (G8) screening tool in a multi-ethnic Asian population of older adults with cancer: Results from Geriatric Oncology Longitudinal End to eNd (GOLDEN) Study.
Authors: Chen Matthew Zhixuan , Rais Nydia Camelia , Tey Jeremy Chee Seong , Ling Natalie Mun Wai , Ng Yean Shin , Chun Meiling , Said Noorhanah Mohd , Eng Wan Nghee , Ho Francis , Pang Shien Ling Angela 
Published: June 2022

e24029 Background: The Geriatric 8 (G8) questionnaire has been validated predominantly in Western populations as a screening tool to identify vulnerable older adults with cancer who would benefit from comprehensive geriatric assessment (CGA). Given the paucity of evidence of the performance of this tool in a multi-ethnic Asian population, there is a need to determine whether the established cut-off score of 14 should be adjusted for improved performance in this population of older adults. Methods: Prospective cross-sectional study was done in older adults aged ≥ 65 years in the outpatient setting of an academic tertiary cancer center, the National University Cancer Institute, Singapore (NCIS). G8 questionnaire and CGA were conducted for eligible patients. The performance of the G8 screening tool in identifying patients who would benefit from a CGA was evaluated using receiver operating characteristic (ROC) curve analysis: area under the curve (AUC), sensitivity (Sn), and specificity (Sp). Results: 180 participants (mean age 74 years) were included in the study. 40.5% were female. 90% were Chinese, 7% were Malay, 2% were Indian. 57.8% were pre-frail and 12.8% were frail. The top five cancers in our study population were colorectal (30%), lung (25%), head and neck (12%), upper gastrointestinal (10%) and gynecological (7.0%). ROC analysis showed an AUC of 0.73 (95% CI 0.65 – 0.80) with an optimal cut-off score of 13 (Sn 71.7%, Sp 74.0%). Conclusions: G8 performed well in identifying older adults with cancer who would benefit from a CGA, in a multi-ethnic Asian population. In our cohort, we found that a slightly lower cut-off score of 13 performed better, and should be taken into consideration as part of daily oncology practice in Asia. Future research efforts should go into examining the biological aspects of frailty in this population.
Immuno-senescence and elevated central carbon metabolism in hematopoietic stem cell compartment upon aging.
Authors: Beiro-Poisa Laura , Landry Jonathan J.M. , Ho Anthony D. 
Published: June 2022

e24030 Background: Aging is associated with decline of hematopoiesis, compromised innate immunity, and propensity for malignancies. Aging of the hematopoietic stem and progenitor cell (HSPC) compartment is caused by accumulation of senescent cells and elimination of the latter rejuvenates innate immunity in animal models. Methods: HSC (CD34+) were isolated from the bone marrow of healthy human subjects (age range 20 – 74 years; n = 18) and separated by FACS in 3 distinct subsets with high, intermediate, and low glucose uptake (GU) capacity (GUhigh, GUinter, GUlow). Single-cell RNA-sequencing (scRNAseq) studies, followed by gene ontology (GO) analysis of biological processes, analysis of cell cycle, and gene set enrichment analysis (GSEA) were performed. Results: While the percentages of GUinter and GUlow subpopulations remain relatively constant with age, the proportion of GUhigh subset increases continuously with age (from 0.2% in adults < 30 years to 6,7% in > 60 years). GO analysis revealed that the GUhigh subset showed a significantly higher expression of genes involved in myeloid development, cell cycle arrest, inflammation and stress response, apoptosis, and significantly lower expressions of genes involved in lymphoid development. GSEA confirmed that the gene sets for cell cycle arrest, senescence associated secretory phenotype (SASP), anti-apoptosis/survival and P53 pathways are significantly up-regulated in the GUhigh subset. The latter shows therefore all deregulations that are inherent hallmarks of senescence. Most of the molecular deregulations are similar to those found in murine models of aging, but there are significant differences. In addition, cell cycle analysis revealed that the proportion of cells in the G1 phase was significantly reduced in the GUhigh subset. Comparing the frequencies of old to young GUhigh, GUlow cells along the cell cycle progression ranks showed a significant depletion of cells in late G1 phase among GUhigh cells but not in the other subsets. The frequencies of non-cycling cells in the GUlowsubset have remained high (> 70%) irrespective of age, thus providing evidence for the quiescence status of the GUlow subset, as well as for persistence of HSPC with “young phenotype”. Conclusions: Our series of proteome and single cell transcriptome analyses have shown that the GUhigh subpopulation is highly enriched in senescent HSPCs. This property may be exploited to enrich, visualize, and trace senescence in human bone marrow. Cell cycle analysis has revealed a significantly shortened G1 phase that is linked to dedifferentiated state in the senescent HSPC. Our results indicate a dependency of senescent HSPCs on elevated glucose metabolism as well as on anti-apoptotic factors for survival. These may represent ideal targets for elimination of senescent HSPC to restore innate immunity as demonstrated in murine models.
Active Living After Cancer (ALAC) program: An avenue to improve physical functioning and moderate-intensity physical activity in gynecologic cancer survivors.
Authors: Unke Jenna , Wilson Jordan , Mitchell Stacy J , Montes Giselle , Basen-Engquist Karen , Fleming Nicole D. 
Published: June 2022

e24034 Background: Active Living After Cancer (ALAC) is a 12-week evidence-based program funded by the Cancer Prevention and Research Institute of Texas (CPRIT) to provide physical activity and survivorship education to cancer survivors. Given the limited data evaluating the effects of physical activity educational programs in gynecologic cancer survivors, we aim to assess the effects of the ALAC intervention in this patient population. Methods: A retrospective analysis was performed on gynecologic cancer survivors who participated in ALAC from 2017 to 2021. The 12-week ALAC program included weekly meetings (in-person or virtual) led by a facilitator providing physical activity behavioral skills training, leading 10 minutes of exercise, and discussing topics related to cancer survivorship. Surveys and functional testing assessments were collected pre- and post-program which included: The Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ) and 30-second sit-to-stand. A patient-reported outcomes survey was used to assess patient perceived benefits and program satisfaction. Results: Thirty-two patients participated in ALAC and 22 completed pre- and post-program assessments. The mean age of participants was 60.2 years (range 50.7-69.7 years) and mean number of classes attended was 8 (range 0-12 classes). Prior cancer diagnoses included 14 cervical, 11 uterine, and 7 ovarian cancers. A significant improvement was seen pre- and post-ALAC in moderate-intensity physical activity minutes (n = 17, 97 vs 252 minutes, p = 0.007) by GSLTPAQ and 30-second sit-to-stand test (n = 16, 12.3 vs 15.8 repetitions, p = 0.003) in our cohort. The post-ALAC patient reported outcome survey (n = 22) revealed improvement in emotional well-being (90%), physical well-being (91%), physical activity level (100%), comfort speaking openly in a group (85%), and willingness to discuss their cancer journey (66%). Overall, 95.3% of participants were satisfied with the ALAC program and 100% of participants would recommend the ALAC program to other cancer survivors. Conclusions: Educational physical activity-based programs like ALAC improve physical functioning and moderate-intensity physical activity in gynecologic cancer survivors. Further studies on the long-term health benefits of structured educational programs which promote active lifestyles in gynecologic cancer survivors are needed in larger patient cohorts.
Completion of electronic patient reported outcome measures among diverse cancer patients treated in an integrated health system.
Authors: Adjei Boakye Eric , Tam Samantha , Zatirka Theresa , Neslund-Dudas Christine , Su Wan-Ting , Cannella Cara E , Chang Steven S. , Movsas Benjamin 
Published: June 2022

e24035 Background: Patient reported outcome measures (PROMs) are derived entirely from patients’ perspectives and complementary to traditional clinical assessment. Use of PROMs as a symptom communication tool has been demonstrated to improve quality of life, decrease health care utilization, and improve overall survival in clinical trial settings. However, clinical trial enrollment is known to be biased, often excluding those with the most difficulty accessing care. Henry Ford Cancer Institute has implemented a PROMs platform integrated with routine clinical care throughout the vertically integrated health system for all cancer disease sites. The purpose of this study is to compare patient characteristics in those responding to and those without response to PROMs to understand potential disparities. Methods: All patients with a diagnosis of cancer and a visit with an oncologic provider were offered an opportunity to complete PROMs between September 16, 2020 to July 19, 2021. Domain-specific National Institute of Health’s computer adaptive technology Patients-Reported Outcomes Measurement Information System (PROMIS) instruments in pain interference, physical function, fatigue, and depression were offered prior to a visit using a patient-facing electronic portal or via iPAD at the time of visit. Patient level demographic, insurance, ZIP code level socioeconomic status and clinical data were compared across PROMs responders and non-responders using multivariable logistic regression. Results: A total of 3,226 patients were included in the study, of whom 1,652 (51.2%) responded to PROMs. The mean age of the patients was 60 years (SD = 13) and 60.5% were females. Most were of white race (68.8%) and were married (56.1%). There was similar distribution of patients with private (43.7%) and Medicare (41.6%) insurance. After adjusting for age, sex, race, marital status, education, income, insurance and stage, patients who were single (aOR = 0.78; 95% CI: 0.65—0.94) or had Medicare insurance (aOR = 0.68; 95% CI: 0.55—0.83) were less likely to respond to the PROMs. Patients diagnosed with early-stage (stages 0,1,2) disease (aOR = 0.79; 95% CI: 0.67—0.93) were less likely to respond to PROMs, but those with unknown stage (aOR = 1.27; 95% CI: 1.04—1.56) were more likely to respond to PROMs compared to those diagnosed with late-stage (stages 3,4) disease. There was no significant association between race and PROMs response. Conclusions: Patients who are single, have Medicare insurance, and early-stage disease are less likely to respond to PROMs. Future implementation efforts need to focus on these populations to ensure equitable availability of PROMs as a tool for symptom communications in patients with cancer.
A cross sectional survey to assess knowledge, attitude, and practice of Yoga among cancer patients at a tertiary care hospital in Rishikesh, India.
Authors: Sehrawat Amit , Malik Sweta , Mudgal Shikha , Dogra Twinkle , Barnwal Suresh Lal , Chaturvedi Jaya , Nath Uttam Kumar , sundriyal Deepak 
Published: June 2022

e24040 Background: The global cancer burden continues to rise, putting individuals under severe physical, mental, and financial stress. Yoga may aid chemotherapy patients to improve their quality of life. The purpose of this survey is to learn more about the gaps in knowledge, attitude, and practice of Yoga and barriers. Methods: The cross-sectional time-bound survey was conducted on cancer patients of age 18 years and above receiving cancer treatment at the outpatient clinic of AIIMS Rishikesh. We collected data of 738 cancer patients, bivariate and multivariate analysis was done to understand the level of awareness of the importance of Yoga as an alternative therapy. Results: Of 738 cancer patients who participated, 90.2% had heard about Yoga. Among those aware of yogic practices, only 15.9% knew that Yoga is an alternative therapy across the world. Knowledge of yogic importance was associated with age (OR = 1.16, 95% CI = 1.07-1.26, p = 0.002), education (OR = 0.5, 95%CI = 0.4-0.6, p < < .001), religion (OR = 1.16, 95%CI = 1.1-1.2, p < < .001). Attitude towards Yoga with the belief that it helps maintain mental health has a positive association with education (OR = 0.9, 95% CI = 0.8-0.9, p = 0.03). Almost 56% of cancer patients had never practiced Yoga. The identified barriers in yogic kriya practice were lack of time, interest, and facilities. Conclusions: The knowledge of the benefits of Yoga on health was high in adolescent young cancer patients. Still, the motivation towards yoga practice is limited due to various factors like lack of infrastructure, time, belief. The gap between knowledge, attitude, practice, and barriers can be overcome by conducting effective yogic programs for this population.
Low doses of advanced glycation end-products and fructosilation products promotes premature cell death of human cardiac cells and increases drug resistance of human breast cancer cells exposed to doxorubicin through NLRP3 and MyD88 pathways.
Authors: Quagliariello Vincenzo , Iovine Martina , D'Aiuto Giuseppe , Buccolo Simona , Maurea Carlo , Bonelli Annamaria , Paccone Andrea , Canale Maria Laura , Maurea Nicola 
Published: June 2022

e24055 Background: Advanced glycosylation end-products (AGEs) are non-enzyme, protein glycosylation products caused by glucose-induced metabolic disorder, and play an important role in aging, cancer, metabolic syndrome and cardiovascular diseases. We aimed to assess whether AGEs and fructosilation products, such as methylglyoxal (MG) and N-carboxymethyllysine (N-CML) could increase susceptibility to cell damages induced by doxorubicin. Methods: Human cardiomyocytes were pre-exposed for 24h with low doses (50 mmol/L) of methylglyoxal (MG) or N-carboxymethyllysine (N-CML). After, cells were exposed to subclinical concentration of doxorubicin (at 100 and 200 nM) for 48 and 72h. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular Malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of peroxisome proliferator-activated receptor-α; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6). Expression of p53 was also performed through western blot method. Results: Pre-exposure to methylglyoxal (MG) but especially to N-carboxymethyllysine (N-CML) increase cell mortality to doxorubicin of 48-53% compared to control. Pre-exposure to N-CML promotes premature death of cardiomyocytes to doxorubicin through NLRP3-driven pathways. Notably, MG and N-CML increased significantly the cardiotoxicity through NLRP3 inflammasome, Myd88 myddosome and cytochrome C-mediated apoptosis. Pre-exposure to N-CML and MG increase the secretion of interleukin-6 that increase cell apoptosis through a paracrine and autocrine mechanism. Induction of IL-6 reduces the expression of p53 resulting in the induction of the apoptotic process. Conclusions: These observations suggest that AGEs and fructosilation producs promotes premature cardiotoxicity of human cardiac cells exposed to doxorubicin by activation of NLRP3, Myd88-related pathways and downregulation of p53.
A nutraceutical combination of spirulina, reishi and moringa exerts significant cytoprotective effects againts doxorubicin and trastuzumab cardiotoxicity.
Authors: Paccone Andrea , Quagliariello Vincenzo , De Anseris Raffaele , Ostacolo Carmine , Buccolo Simona , Iovine Martina , Maurea Carlo , Conforti Gabriele , Caronna Antonietta , Maurea Nicola 
Published: June 2022

e24056 Background: Anthracycline and trastuzumab are essential adjuvant therapies for a variety of cancers, particularly breast, and gastric and esophageal cancers. Whilst prolonging cancer-related survival, these agents can induce drug-related cardiotoxicity. Cardioprotective agents used to mitigate cardiotoxicity, such as angiotensin antagonists, angiotensin receptor blockers and beta‐blockers, are often poorly tolerated in these patients due to intravascular volume fluctuations, which are further escalated by the hemodynamic side effects of these agents. Spiruline, Reishi and Moringa are nutaceuticals with anti-inflammatory effects that are currently used in cancer patients to improve quality of life and fatigue. We hypothesize that the combination of Spirulina, Reishi and Moringa could reduce inflammation and cardiotoxicity of anthracyclines and trastuzumab. Methods: Human cardiomyocytes were exposed to subclinical concentration of doxorubicin and trastuzumab (200 nM) alone or in combination with a formulation composed by Spiruline, Reishi and Moringa (at 10, 25 and 50 µg/ml) for 48h. Cell viability, apoptosis and necrosis were performed. Quantification of malondialdehyde and intracellular Ca2+ were performed through spectrophotometric methods. Anti-inflammatory studies were also performed (expression of NLRP3, TLR4/MyD88 pathways, nuclear expression of NF-kB). Intracellular concentration of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL17-α were also performed. Results: Spiruline, Reishi and Moringa in combination increased synergistically the cell viability during exposure to doxorubicin and trastuzumab. The nutraceutical formulation reduces intracellular Ca2+ overload (-48,8% vs cells treated only to anticancer drugs; p < 0,001), lipid peroxidation (- 47,2 % compared to cells exposed only to anticancer drugs; p < 0,001). The expression of MyD88 and NLRP3 inflammasome were also reduced (-36,3 and -28,58 % vs cells exposed only to anticancer drugs, respectively; p < 0.001). Notably, Spiruline, Reishi and Moringa increased of 26,3% the production of IL-10 and IL-2. Cytokines involved in cardiotoxicity and chemoresistance were reduced, such as IL-1α and IL-1β (-18,3 and -27,4 % vs DOXO-TRA group), IL-6 (-31,2 % vs DOXO-TRA group) and IL17-α (-27,3 % vs DOXO-TRA group) (p < 0.01 for all). Conclusions: During exposure to doxorubicin and trastuzumab, the combination of Spiruline, Reishi and Moringa exerts cardioprotective and anti-inflammatory effects. Their properties are mediated by the reduction of iCa2+ content that consequently reduces lipid peroxidation and the expression of NLRP3- MyD88. These results indicating the potential use of this nutraceutical formulation in preclinical models of anthracycline and anti HER2 antibodies-mediated cardiotoxicity.