bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel screening approach for cancer cachexia using metagenomic gut microbiome profiling in patients with advanced non-small cell lung cancer.
Authors: Hakozaki Taiki , Salazar Eder Mendez , Kobayashi Takayuki , Fukuoka Shota , Koyama Shohei , Nishikawa Hiroyoshi , Motooka Daisuke , Nakamura Shota , Okuma Yusuke , Hosomi Yukio , Takeyama Haruko , Hosokawa Masahito , Routy Bertrand 
Published: June 2024

12090 Background: Cancer cachexia (CC) is a multifactorial syndrome involving immune-metabolic crosstalk across multiple organs and has been associated with a negative clinical impact in patients with non-small cell lung cancer (NSCLC) amenable to immune checkpoint inhibitors (ICIs). In parallel, the gut microbiome (GM) has emerged as a key contributor to ICI response. In this study, we aimed to evaluate the association between CC and GM composition and its metabolic potentials. Methods: We collected fecal samples from 139 patients with advanced NSCLC treated with ICI. In addition to 16S rRNA sequencing for all patients, shotgun metagenomic microbiome profiling was performed for 69 patients to estimate the species-level composition and functional capacity of the GM. Cancer cachexia was diagnosed according to the international consensus based on the body weight changes over the previous six months. Survival time was calculated using the Kaplan-Meier method. GM diversity indices, differential abundance, and functional profiles based on the MetaCyc database were compared between the patients with and without CC. Results: Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the cachexia group compared to the non-cachexia group [4.5 vs. 11.5 months (p < 0.001) and 10.8 vs. 44.9 months (p < 0.01), respectively]. Both GM profiling techniques revealed a significant difference in beta diversity between both groups (p < 0.01). In addition, metagenomic analyses revealed the distinct characteristics of GM at the species level between the groups. The CC group showed an overrepresentation of the commensal bacteria, such as Escherichia coli, Ruthenibacterium lactatiformans, Hungatella hathewayi,and Eggerthella lenta, whereas the non-CC group showed an enrichment of Parabacteroides distasonis, Eubacterium rectale,and Roseburia inulinivorans. Moreover, functional analysis revealed the significantly different metabolic potentials of GM in the CC group. The CC group showed an enrichment of pathways, such as D-arabinose degradation II, L-lysine degradation, and octan oxidation. Finally, the clustering of patients based on significant metabolic pathways or gene reactions provided a high predictive ability to discriminate between patients with and without CC. Conclusions: The shotgun metagenomic approach allowed for the characterization of the altered gut microbes and their metabolic potentials in patients with CC. Stratification based on the GM profiles may be useful as a novel screening method for CC, which is progressive and may involve more multistage pathology than identified by the conventional approach.
Sleep apnea and glymphatic dysfunction as a mediator of executive dysfunction and neurodegenerative risk in cancer related cognitive impairment (CRCI).
Authors: Kushman Sophie , Topalian Alique Gabrielle , Shatz Rhonna 
Published: June 2024

12091 Background: Cancer survivors often experience cognitive changes, formally known as Cancer-Related Cognitive Impairment (CRCI), during or after treatment. CRCI commonly consists of executive dysfunction, which includes impairments in short-term memory, sustained attention/inhibitory control, cognitive flexibility, processing speed, and top-down processing. CRCI may be impacted by comorbidities and can increase neurodegenerative disease risk. Sleep disorders and disruptions (SDs) impair executive function in the general population. SDs may contribute to CRCI by impeding progression to deep sleep stages associated with enhanced glymphatic flow (GF) and clearance of inflammatory byproducts, leading to ventriculomegaly (VM- enlarged ventricles). VM is associated with cognitive impairment in other disorders, such as normal pressure hydrocephalus. Using data from the University of Cincinnati Cancer Cognitive Registry, we investigated relationships between the incidence and type of SD in CRCI, SDs and executive dysfunction, and evidence of altered GF in SD as measured by Evans Indices (EIs). SDs are known to be prevalent in CRCI patients. We hypothesize that evidence of impaired GF as measured by EIs will be present and associated with SDs and executive dysfunction. Identifying modifiable contributors to CRCI and their mechanisms of action are critical steps towards increasing quality of life in survivors. Methods: 174 patients referred for CRCI between 10/2021-10/2023 underwent assessments for CRCI and sleep hygiene with a cognitive battery, subjective questionnaires, and nocturnal polysomnography. Retrospective data gathered from Epic was entered into a REDCap registry. MRIs were analyzed in McKesson to calculate EIs. Results: Our data demonstrated the presence of SDs in 84% of patients and obstructive sleep apnea in 45%. Measures of apnea severity (apnea-hypopnea index-AHI) and GF (EIs) inversely correlated with executive function scores. This implicates sleep-related GF as a potential mediator of CRCI. Conclusions: CRCI and accompanying increased neurodegenerative risk may be the result of restricted cerebral spinal fluid exchange due to SDs in conjunction with systemic inflammation from cancer and its treatment. Sleep assessments should be routine in CRCI evaluations. Longitudinal assessments will help determine the relationship of SDs and their treatment to the course of CRCI and risk of neurodegenerative disease.
Mental healthcare utilization and psychosocial outcomes among patients with recently diagnosed cancer: A National Health Interview Survey report.
Authors: Parmet Tamar , Sannes Timothy S. , Kilbourn Kristin 
Published: June 2024

12096 Background: Individual's diagnosed with cancer (IWC) often experience heightened psychosocial distress. Studies suggest 25-50% of IWC experience some form of psychosocial distress (Mehnert-Theuerkauf et al., 2023). Further, research shows that an individual's risk of developing a new mental disorder increases by 30% during the first year after being diagnosed with cancer (Hu et al., 2023). Although many IWC experience distress, literature depicts the underutilization of psychosocial services, with estimates suggesting that fewer then 10% of IWC receive support for their distress (Forsyth et al., 2013). This is concerning as research in rodents and humans shows that unaddressed distress can lead to faster growing tumors and rapidly advancing disease (Eckerling et al., 2021). The present study aimed to characterize mental healthcare utilization among Americans recently diagnosed with various types of cancer. We also aimed to illustrate prevalence of anxiety and depression in this population. Methods: Data from the 2022 National Health Interview Survey was used in this report. A total of 667 recently diagnosed IWC were included in the final analytic sample. Cancer type was divided into five subcategories: blood cancers (n=76), breast cancer (n=193), gynecologic cancer (n=87), colorectal cancer (n=72), lung cancer (n=62), and prostate cancer (n=177). Participants’ mental healthcare utilization at the time of the survey and within the last 12 months was assessed. The General Anxiety Disorder-7 (GAD-7) was used to measure participants’ anxiety levels and the Personal Health Questionnaire Depression Scale (PHQ-8) was used to assess depressive symptoms. Results: Over 28% of recently diagnosed IWC reported moderate-severe levels of anxiety on the GAD7, and 43% of participants reported high levels depression on the PHQ8. One-way ANOVA demonstrated significant differences in PHQ8 (F(5, 666)=3.332, p=0.006) and GAD7 (F(5,666)=3.35, p=0.005) scores across cancer groups. Post Hoc testing found that participants coping with colorectal cancers reported the highest levels of anxiety and depression compared to other cancer types. Of newly diagnosed patients, only 1.2% of patients reported currently receiving psychosocial support from a mental health professional, and only 13.6% reported receiving therapy from a mental health professional in the last year. Conclusions: Consistent with many studies, psychosocial distress among recently diagnosed IWC was very common, yet mental health care utilization remained low. These results indicate that efforts to target newly diagnosed IWC with psychosocial support interventions remains challenged. As such, our results underscore the importance of developing novel means of reaching IWC, and particularly colorectal cancer, as these individuals continue to struggle with significant levels of psychosocial distress.
Efficacy of mammography screening in women aged 40–49 years: An updated systematic review and meta-analysis.
Authors: Reis Pedro Cotta Abrahão , Oliveira João Pedro , Vellaichamy Swathi , Cagnacci Renato 
Published: June 2024

e22513 Background: The screening of women aged over 50 through mammography has proven to significantly reduce breast cancer mortality in randomized controlled trials (RCTs). Despite prior trials and meta-analyses, new trials have been published and debates persist regarding the effectiveness of mammography screening for women aged 40–49. Therefore, we conducted an updated meta-analysis to assess the impact of mammography screening on reducing breast cancer mortality within this age group. Methods: In adherence to PRISMA guidelines, we systematically searched Pubmed, Cochrane, and Embase libraries for RCTs evaluating the efficacy of mammography screening in lowering breast cancer mortality among patients aged 40–49. Exclusion criteria encompassed non-RCTs, studies lacking reports on breast cancer mortality for individuals aged 40–49, and secondary analyses of included trials. Data extraction was carried out based on the latest available follow-up. We synthesized the relative risk (RR) for breast cancer mortality along with their corresponding 95% confidence intervals (95% CI). Employing a random-effects model, statistical analysis was conducted using RevMan 5.4 version, with an evaluation of I2 statistics for heterogeneity. Results: From 797 initial studies, 10 RCTs were included, comprising 163,634 women in the intervention group and 206,130 in the control group. Median follow-up ranged from 14 to 30 years. In individual studies, statistical significance was only reached in one trial (Table). Breast cancer mortality in the intervention group was significantly lower than in the control group RR 0.86 [95% CI 0.77–0.95]; p = 0.004; I2 = 0%. Conclusions: Despite limited data availability for this age group in certain recent publications with extended follow-up periods, raised questions about the design and reported results in some trials, the comprehensive findings of this meta-analysis suggest that mammography screening retains its effectiveness in reducing breast cancer mortality among women aged 40–49 years. [Table: see text]
Psilocybin, peyote, mescaline, and lysergic acid diethylamide (LSD) use in a nationally representative population by cancer history.
Authors: Baral Amrit , Pan Yue , Caban Martinez Alberto J. , Pinheiro Paulo S. , Hlaing WayWay M. , Vidot Denise Christina 
Published: June 2024

e22518 Background: Classic psychedelics (Peyote, Psilocybin, Mescaline, and LSD) are re-emerging in the oncology toolbox. Peyote is the oldest known psychedelic, yet underexplored in clinical research. Preclinical studies suggest its extract stimulates lymphocyte proliferation, kills tumor cells, and may regulate sleep. This study aims to estimate the prevalence of classic psychedelic use among a US-representative sample of adults with and without a history of cancer. Methods: Data ( N= 208,220, weighted N: 239,589,661) from adults >18y in the 2015 - 2019 National Surveys on Drug Use and Health (52.8% female, 68.4% non-Hispanic White, 45.6% aged ≥50y) were analyzed to estimate lifetime classic psychedelic use among those with no cancer history, past history (diagnosed > 1y ago), or recently (≤1y ago) diagnosed. Weighted prevalence of psychedelic use, 95% confidence intervals, and adjusted (sex, race, income, education) odds ratio were calculated using logistic regression analysis in SAS. Results: Overall, 6.2% had a cancer history and 14.0% reported lifetime classic psychedelics use. LSD was the most prevalent in the sample (10.6%, 95% CI:10.4-10.8) compared to Psilocybin (9.6%, 95% CI: 9.4-9.9), Mescaline (3.1%, 95% CI:3.0-3.2), and Peyote (2.3%, 95% CI:2.2-2.4). Psychedelic use was lowest in adults with past cancer diagnosis (12.3%, 95% CI:11.4-13.1) vs recently diagnosed [14.0% (95% CI:12.0-16.0] and cancer naive (14.1%, 95% CI:13.8-14.4). Each classic psychedelic was used more often among recent cancer diagnosed adults than past diagnosed (p < 0.05). Specifically, LSD (11.1%, 95% CI:9.3-12.9 vs 9.3%, 95% CI:8.5-10.0), Psilocybin (8.3%, 95% CI:6.6-10.0 vs 7.3%, 95% CI: 6.7-8.0), Mescaline (5.4%, 95% CI:4.0-6.8 vs 4.6%, 95% CI: 3.9-5.2), and Peyote (3.7%, 95% CI: 2.5-5.0 vs 2.9%, 95% CI: 2.5-3.4) use was higher in recently diagnosed cancer patients than past diagnosed. There were no significant differences in age, except among Peyote. Among 18-to-34-year-olds, recent cancer patients had 3-fold greater odds (aOR:3.55, 95%CI: 1.11-11.31) of using peyote vs cancer naïve. In ≥50-year-olds, those with past cancer diagnosis had 21% lower odds (aOR:0.79, 95% CI:0.63-0.97) of using peyote vs cancer naïve. Conclusions: Results suggest differential psychedelic use by cancer history and age. These findings, while limited by temporality of diagnosis and initiation of psychedelic use, underscore the need to investigate reasons and long-term impact of specific psychedelic use with more rigor among adults with a cancer history.
Impact of obesity on breast cancer clinicopathological characteristics in underserved community dweller women of Chicagoland: An experience from a US safety-net hospital.
Authors: Proskuriakova Ekaterina , Aryal Barun Babu , Shrestha Dhan , Valencia Stephanie , Kovalenko Iuliia , Adams Megan , Boxwala Mubaraka , Verda Larissa , Khosla Paramjeet Grewal 
Published: June 2024

e22519 Background: Breast cancer (BC) continues to pose a significant public health challenge, with its incidence and disproportionate impact on underserved populations in the United States. The relationship between obesity and clinicopathological characteristics at presentation remains a critical area of investigation. Safety-net hospitals catering to diverse, underserved, and often marginalized communities provide a unique setting to explore these associations, shedding light on potential disparities and informing targeted interventions. This study seeks to address a critical gap in knowledge on obesity and BC characteristics in underserved populations in the United States. Methods: In this retrospective study, 927 BC patients were included. Analysis was conducted to assess the association between body mass index (BMI), age of diagnosis, tumor clinicopathologic characteristics, and molecular types. The analysis was stratified by menopausal status at diagnosis. Results: The average age at diagnosis was 57.52 ± 12.40 years; 60.2% were postmenopausal women. Patients were categorized based on BMI into underweight/normal, overweight, and obese categories. One-way ANOVA analysis revealed no significant difference in mean age at presentation between BMI groups (p = 0.08). A significant association was found between BMI and menopausal status (p < 0.05). Disease stage at presentation was significantly associated with BMI (p < 0.05). Further investigation into BMI categories and tumor characteristics revealed a significant correlation in postmenopausal women, with obesity linked to tumor size and lymph node status (p < 0.05). No significant associations were observed between HER-2 status, ER/PR status, and obesity in either premenopausal or postmenopausal groups. In the subgroup analysis focusing on ethnic groups, African American patients (with an average BMI of 32.8 ± 8.2 kg/m2) demonstrated a higher prevalence of obesity at BC diagnosis in both pre and post-menopausal females compared to other ethnic groups (p < 0.05). Conclusions: Obesity was associated with the disease stage and menopause status at diagnosis. In postmenopausal patients, obesity was associated with tumor size and lymph node disease status. Additionally, ethnic variations were evident, with African American patients displaying a higher prevalence of obesity. We need further investigations to tailor interventions addressing diverse demographic factors in BC management.
Implementation of video assisted point-of-care germline genetic education and testing for patients with peri-diagnostic pancreatic cancer.
Authors: King Daniel , Mitnick Nathan , Mann Aman , Kauff Noah D. 
Published: June 2024

e22530 Background: Germline genetic testing is universally recommended for patients with exocrine pancreatic cancer (PC). Pretest consultation with a genetics professional is recommended to ensure patients are informed about risks, benefits, and limitations of testing. This is a resource intensive process and is associated with a suboptimal testing rate (~30%). Prior work demonstrates that video-assisted pre-test education does not increase patient anxiety compared to traditional pre-test genetic counseling in peridiagnostic ovarian cancer patients. In this report, we assess the feasibility of using a similar video assisted, streamlined genetic education and testing approach in peridiagnostic PC patients. Methods: As part of a pilot quality improvement initiative, patients with a diagnosis of exocrine PC seen in a single academic practice were offered streamlined, video-assisted genetic education followed by germline testing. Patient eligibility for this pilot included: new diagnosis or radiographic suspicion of PC; English language proficiency; and no prior germline testing. After this approach was presented by the medical oncology team, eligible patients viewed a 9-minute educational video describing the goals, pros, and cons of germline genetic testing. After watching the video, patients were given the option to proceed with testing that day. Patients with pathogenic mutations were referred for formal post-test genetic counseling, and patients with variants of uncertain significance (VUSs) were referred on a case-by-case basis. Following IRB approval, we conducted a retrospective review of the experience of all patients presenting to this pilot site from April-Dec 2023. Results: During the study period, 56 new patients with exocrine PC presented to the pilot site. 50 patients were eligible for participating in the pilot program. All patients, except one who declined on the basis of transferring care, consented to testing (49/50; 98%). Median patient age was 71, 49% were female. Race distribution was: White (30), Asian (6), Black (4), Other (2), Declined (7). Median time from patient diagnosis to testing was 11 days. One patient had a germline ATM mutation, and this patient was seen for formal posttest counseling 18 days after testing was initiated. Seven patients had VUSs. Six new patients presenting during the study period were not eligible for this pilot, all due to limited English proficiency. All 6 of these patients underwent genetic testing after translation service assisted counseling by either the primary oncology or cancer genetics team. Conclusions: Video assisted point-of-care genetics education and testing led to nearly universal uptake of genetic testing in peridiagnostic PC patients. This workflow was feasible, timely, and optimized use of genetic counseling resources.
Co-occurrence of germline pathogenic variants in a Brazilian cohort of patients with breast cancer.
Authors: Souto Andreza Karine de Barros Almeida , Santana Thaiana Aragao , Oliveira Leandro Jonata Carvalho , Bulcao Marcela Lima , Farias João Paulo Gonzaga de , de Bustamante Fernandes Carolina , Christtanini Koyama Fernanda , Tiaki Uehara Daniela , Rego Fernanda Orpinelli Ramos do , Testa Galindo Layla , Ferrari Bruno Lemos , Mano Max S. , Dienstmann Rodrigo , Zalis Mariano , Garicochea Bernardo 
Published: June 2024

e22532 Background: The estimated prevalence of germline pathogenic variants (PV) or likely pathogenic variants (LPV) in high and moderate penetrance genes is around 7-10% among women with breast cancer (BC). The emergence of next-generation sequencing (NGS) technology allowed multi-gene panel testing (MGPT) analysis at a lower cost. However, the detection of incidental findings with unknown significance (VUS) and challenges with variant interpretation increase substantially with MGPT. The effect of co-existing PV/LPV in two or more genes is still understudied. Here, we present the prevalence of concurrent germline LPV/PV in a cohort of Brazilian women with BC who underwent a MGPT in a single reference laboratory. Methods: Retrospective observational study using a laboratory cohort (Oncoclínicas Precision Medicine). This study includes women with BC who performed a germline MGPT (able to call SNVs, indels and CNVs) from 2019 to 2023. All patients were tested in a single reference laboratory (OC Precision Medicine) and originated from several Brazilian centers within the Oncoclínicas network. Two distinct germline NGS assays were used: breast and ovarian cancer (BOC) panel (36 genes) and a pan-cancer (PC) panel (105 genes). Results: In the overall cohort, 2,651 women with BC were included in this analysis. The median age at genetic testing was 51 years. 1,867 pts (70.4%) underwent a PC panel testing and the remaining 784 pts (29.6%) a BOC panel.Overall, 314 (12%) pts carrier of LP/PV in high- and/or moderate-penetrance genes. Two or more heterozygous LP/PV were found in 35 pts (1.32%), including 8 pts (1.02%) in the BOC panel and 27 pts (1.44%) in the PC panel subgroups. There were no differences in age of onset of BC in single vs co-occurring double mutants. The most frequent co-existing PV/LPV were found in BRCA2 (11) / BRCA1 (8) / PALB2 (4) / TP53 (3) and MUTYH (7) / CHEK2 (3) in the high and moderate penetrance genes, respectively. Six pts (0.23%) had a double heterozygous involving high and/or moderate penetrance genes. Interestingly, there was a case with four heterozygous variants in TP53, MUTYH, MUTYH and APC. Conclusions: In times of rapid incorporation of MGPT in the clinical practice, our real-world data showed that a small proportion of BC patients could be carriers of two or more germline heterozygous LP/PV in cancer genes. However, this represents a challenging scenario for patient and family management, especially in a co-occurrence of high and moderate penetrance genes.