bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychoneurological symptoms, inflammatory biomarkers and gut microbiome richness and diversity in individuals receiving hematopoietic cell transplantation (HCT).
Authors: Samami Elham , Starkweather Angela , Lyon Debra , Lynch Kelly Debra , Weaver Michael T. 
Published: June 2024

e24053 Background: Hematopoietic Stem Cell Transplantation (HCT) is a potentially curative treatment for certain hematologic cancers. Although survival rates are markedly higher than in the past, there are a growing number of long-term HCT survivors who are at risk for short and long-term sequela, which can negatively affect quality of life. Psychoneurological (PN) symptoms are common occurrences associated with heightened inflammation in other cancers and chronic conditions. Emerging research links the gut microbiota to inflammatory biomarkers and suggests that gut-microbiota-brain crosstalk impacts the severity of psychoneurological symptoms among HCT recipients. Methods: This longitudinal descriptive study investigated the relationship among a cluster of PN symptoms (pain, fatigue, and depression), inflammatory biomarkers (IL-6, IL-10, C-reactive protein (CRP), and microbiota diversity measures (Shannon and Chao Beta diversity indexes) in 55 individuals receiving HCT for a hematologic malignancy. The time periods examined covered pre-transplant, 30-days, and 100-days following transplant. The PN symptoms were collected through self-reported questionnaires via computer with assistance from study staff, along with blood samples and stool specimens obtained at each study visit. Inflammatory marker values were log-transformed when used as dependent variables. Gut microbiota samples were analyzed using 16S ribosomal gene (V4 region) amplicons using Illumina MiSeq. Data analysis was performed using SAS 9.4, with PROC MIXED used for the mixed model analyses. Results: The analysis characterized mean changes in microbiota diversity over time for both Shannon and Chao indexes. IL6 levels were consistent over time, with an inverse association with Chao but not Shannon index. IL10 and CRP levels changed over time, but without associations with either Shannon or Chao. Pain severity and interference changed over time, but with no associations with inflammatory markers or gut microbiome beta diversity. Fatigue severity and interference changed over time and were positively associated with IL10. Depression did not change over time and was not associated with inflammatory markers or diversity. Conclusions: This study provides preliminary information related to associations between PN symptoms, inflammatory markers, and selected measures of gut microbiome diversity in HCT recipients. Further research is needed to explore and validate these findings to examine the implications for microbiota diversity on inflammatory factors and PN symptoms. Clinical trial information: NCT02398708 .
Comparison of concurrent care and traditional hospice at a regional VA.
Authors: Zhang Jeremy Shi , Hadler Rachel A. , Broderick Ann , Zeitler William Andrew 
Published: June 2024

e24065 Background: While hospice care offers many patients services promoting comfort and quality of life, the traditional hospice model described in Medicare policy presents numerous barriers to utilization. Notably, since hospice pays for all therapies related to a terminal illness, patients are often forced to make a difficult choice to stop disease-directed therapies in order to enroll in hospice. Poor provider understanding of hospice also contributes to the common scenario in which hospice is offered too late to make a meaningful impact for patients and their families. These issues were prominent in the VA population in 2006, when only 5% of eligible Veterans received hospice services. Consequently, the VA Comprehensive End-of-Life Care Initiative in 2009 created the concurrent care hospice model in where Veterans no longer had to stop all disease-directed therapies to enroll. Initial national VA data in lung cancer suggested that concurrent care may be better than traditional hospice by decreasing aggressive treatments, ICU hospitalizations, and medical costs. Our regional VA developed a Hospice Flag system that tagged patients in the electronic medical record who had either a concurrent or traditional hospice enrollment to better inform health care providers. This project investigates how the concurrent care hospice model may help achieve an important Veteran-centered outcome, which is to die in the home setting and improve access to hospice care. Methods: We retrospectively reviewed all Veterans with a hospice flag from October 2017 to July 2021 and cancer as the primary hospice diagnosis. Our primary aim was to establish correlation between hospice type and Veterans’ ultimate location of death with the percentage at home versus institution (e.g. care center, hospital, or hospice house). A secondary measure was median length-of-stay (LOS) in hospice. Results: 317 total Veterans were enrolled in concurrent care hospice (96) and traditional hospice (221) from Oct 2017 to July 2021. 72% of Veterans in concurrent care (69/96) died at home compared to only 57% in traditional hospice (125/221) with the remainder dying in an institution; this result was statistically significant by Chi-square analysis (p = 0.01). Median LOS in hospice was 62 days for concurrent care and 26 days for traditional hospice. Conclusions: This project demonstrates that concurrent care hospice is significantly associated with Veterans being able to die in their own home. Concurrent care was also correlated with longer median LOS in hospice, suggesting greater duration of support services provided to patients and families.
Impact of COVID-19 on referrals to outpatient palliative care for patients with advanced cancer in a safety-net health system.
Authors: DiMartino Lisa , Merrill Vincent , Hogan Timothy P. , Skinner Celette Sugg , Sadeghi Navid , Roche-Green Alva , Hong Arthur S. 
Published: June 2024

e24071 Background: Medically underserved adults with cancer experience challenges with access to care and tend to present at later disease stage. Amidst the complex needs of safety-net patients, the value of early palliative care (PC) services can go unrecognized. Few studies have examined PC referral patterns in the outpatient setting among advanced cancer patients within a safety-net system, and none has studied how or whether referrals have evolved since the most acute stages of the COVID-19 pandemic. This study examined PC referrals for cancer patients seen as outpatients in the urban safety-net primary provider of cancer care for uninsured individuals in Dallas, TX, and assessed changes from before to after the acute pandemic phase. Methods: We used tumor registry records linked to outpatient PC referral data from the safety-net health system’s electronic health record from January 1, 2018 to July 31, 2023. The primary outcome was a binary indicator for receipt of PC referral among patients diagnosed with advanced-stage solid tumor cancer. Using a multivariate logistic regression model, we evaluated whether our independent variable – a binary indicator for pre-pandemic (January 1, 2018 to February 28, 2020) and post-pandemic (March 1, 2020 to July 31, 2023) time periods – was associated with PC referrals. We included age, sex, race/ethnicity, cancer type, preferred language, and insurance as covariates. Results: Among 1,590 eligible patients (mean age 58.1, range: 21-94), 44% were female and 75% were non-White. Diagnoses included lung (20%), gastrointestinal (17%), colorectal (14%), breast (9%), prostate (9%), head/neck (9%), pancreatic (8%), gynecologic (6%), and other (8%) cancers. Across both time periods, a total of 785 (49%) of patients received a PC referral. Whereas 53% of the 754 patients in the pre-pandemic cohort received a PC referral, 46% of the 836 in the post-pandemic cohort received a referral. In the adjusted regression model, pre-pandemic patients were 1.26 times more likely to have a PC referral than post-pandemic patients (95% CI, 1.02-1.56). Referrals varied by cancer type across both time periods – compared to breast cancer patients, gynecologic cancer patients had lower odds of PC referral (aOR, 0.19; 95% CI, 0.10-0.36) and pancreatic cancer patients had higher odds of PC referral (aOR, 2.93; 95% CI, 1.71-5.00). Conclusions: Our analysis showed that referrals declined during the COVID-19 pandemic and revealed differing underlying patterns of PC referral along disease groups. Understanding pre-existing referral patterns and lasting practice changes post-pandemic can support clinicians to integrate PC and improve cancer outcomes. Findings can be used to develop interventions, such as clinical triggers, to improve PC delivery for underserved cancer patients.
Feasibility of hydromorphone PCA 10-day simple mode home management of patients in severe pain: A prospective multicenter study.
Authors: Zhao Kelei , Han Yu , Li Chunqing , Zhang Guifang , He Junling , Chang Wei , Yin Haiqing , Cui Yuelong , Dong Yanhu , Yao Yibo , Chen Guorong , Wang Pei , Tang Dongxia , Dong Hua , Zhang Qiang , Li Bo , Zhang Min , Ji Yinghua , Lu Ping 
Published: June 2024

e24072 Background: Pain is a common symptom affecting patients with cancer. In clinical practice patients with advanced refractory cancer pain often face multiple anti-tumor treatments and prefer treatment at home or in community clinics versus hospitalization; thus, pain relief and drug management are challenging. Patient-controlled analgesia (PCA) is an essential component of analgesic treatment. However, difficulties associated with PCA configuration, unified pump configuration mode, and tube blockage may limit its use by both doctors and patients, negatively affecting large-scale promotion of PCA technology in hospitals and at home. In this study we optimized PCA parameters to resolve problems around cumbersome operation and tube blockage, thereby increasing pump utility and feasibility. We refer to this mode as the "10-day simple mode." The study objective is to evaluate the analgesic effect of the "10-day simple mode" of hydromorphone PCA and to explore its home-based convenience and use. Methods: A total of 100 patients with refractory cancer pain were included in this study. The pump configuration mode was divided into two stages. The first (titration) stage was: hydromorphone + normal saline with a total volume of 24 ml and pump speed of 1.0 ml/h. The second (maintenance) stage was: hydromorphone + normal saline with a total volume of 288 ml and pump speed of 1.2 ml/h with PCA of 2.4 ml. During the maintenance stage, if pain control was unsatisfactory the background dose was increased based on the number of PCA presses in the previous 24 hours. Patients' numeric rating scale (NRS) scores, quality of life scores, and adverse reactions were recorded before and after treatment. Results: Patients' average NRS score before treatment was 7.4 (7-10). Average time to successful titration was 49.6 minutes (35.6-56.9) and 40.7% of patients achieved successful titration within 30 minutes. After titration, the average NRS score was 3.2 (0-6). There was a statistically significant difference in NRS scores before and after titration (p < 0.05). During maintenance, 56.0% of patients experienced breakthrough pain on day 1, when the average NRS score was 5.2. As background dosing continued breakthrough pain and average NRS score gradually decreased (p < 0.05). Quality of life scores and patient satisfaction measured before and after 10 days of PCA pump use showed significant improvement (p < 0.001). Conclusions: For patients with refractory cancer pain, the hydromorphone PCA "10-day simple mode" produces good analgesic effect, is easy to manage, and suitable for patients seeking home-based pain relief. These results warrant further clinical study. Clinical trial information: NCT05744089 .
Preclinical development of ATR04-484, an auxotrophic strain of Staphylococcus epidermidis, for the topical treatment of epidermal growth factor receptor (EGFR) inhibitor-induced dermal toxicity.
Authors: Whitfill Travis M. , Mootien Sara , Leger Roger 
Published: June 2024

e24074 Background: Agents targeting the EGFR-mediated signaling pathway are commonly used for the treatment of advanced lung, pancreatic, colorectal, and head and neck cancers. Significant dermal toxicities, which occur in up to 90% of patients treated with EGFR inhibitors (EGFRis) and other therapies inhibiting downstream signaling pathways, may be disruptive to a patient’s quality of life and adherence to therapy. Inhibition of the EGFR pathway may suppress host defenses and lead to opportunistic pathogenic colonization or infection. EGFRi-induced dermal toxicity is associated with elevated levels of Staphylococcus aureus and IL-36γ. ATR04-484 is a topical ointment containing S. epidermidis strain SE484, isolated from a healthy human volunteer that was selected for its ability to inhibit S. aureus and IL-36γ . Methods: Reconstructed human epidermis (RHE) and ex vivo pig skin were used to measure the effect of ATR04-484 on S. aureus in therapeutic and prophylactic settings with S. aureus added prior to or after ATR04-484, respectively. To evaluate the anti-inflammatory effects of ATR04-484, IL-36γ levels were measured on untreated RHE and RHE treated with erlotinib alone or in combination with ATR04-484. 104 colony-forming units (CFU) of methicillin-resistant (MRSA) or methicillin-sensitive (MSSA) S. aureus were used. Toxicology was assessed by measuring cell viability in three in vitro toxicology assays: the eye irritant potential was tested on 3D reconstituted human cornea-like epithelium (RhCE), the skin irritant potential of the strain in the ointment was assessed on 3D RHE, and the skin corrosive potential was evaluated on RHE. Results: ATR04-484 comparably inhibited growth of both MRSA and MSSA in therapeutic and prophylactic settings. In a therapeutic setting, ATR04-484 inhibited MRSA growth by 1 log (90%) compared to untreated MRSA in both RHE and pig skin. In a prophylactic setting, ATR04-484 inhibited MRSA growth by approximately 5 logs on RHE and 2 logs on pig skin. Additionally, application of ATR04-484 reduced IL-36γ to a level comparable to untreated RHE. The effect was dose-dependent; application of 109CFU/cm2 of ATR04-484 showed more potent IL-36γ reduction compared to 108 CFU/cm2. The three toxicology assays indicate that ATR04-484 does not cause irritation or corrosion. Conclusions: In these preclinical studies, ATR-04-484 showed a promising preclinical profile for the treatment of EGFRi-induced dermal toxicity by significantly reducing S. aureus growth, completely ameliorating IL-36γ levels, and showing no safety concerns.
Quality of life in patients with malignant wounds treated at a wound care clinic.
Authors: Chen Anna , Dusza Stephen W. , Bromberg Jacqueline , Chandarlapaty Sarat , Goldfarb Shari Beth , Sanford Rachel Ann , Markova Alina 
Published: June 2024

e24075 Background: Malignant wounds can present in up to 14.5% of patients with advanced cancer, significantly reducing quality of life (QoL). Patients with chronic leg ulcers experienced improved QoL, as determined by a reduction in Skindex-16 score after treatment at a dedicated wound care clinic. We sought to assess the effect of wound care clinics on QoL in patients with malignant wounds. Objectives: To describe the baseline QoL, physical symptoms, and treatment modalities that affect QoL in patients with malignant wounds. To assess changes in QoL over time of patients attending a wound care clinic. Methods: This retrospective study included 36 patients seen from 1/1/2016 - 4/1/2023 at a wound care clinic at an oncologic hospital with at least one completed Skindex-16 questionnaire, which is a validated measure of the effects of skin diseases on QoL. Data were extracted from the electronic medical record. Descriptive statistics, graphical methods, and random effects models for change were used to describe the patient population and the QoL measures over time. Results: Of the 36 patients who completed at least one Skindex-16 questionnaire, 69% were female, and 50% developed malignant wounds from metastatic breast cancer, 22.2% from cutaneous squamous cell carcinoma, and 27.8% from various malignancies such as sarcoma. Most patients had advanced cancer; 9.7% were stage II, 41.9% stage III, and 48.4% stage IV. At the initial visit, patients had drainage associated with their wound 86.1% of the time, odor 47.2%, bleeding 63.9%, pain 69.4%, and itch 50% of the time. Patients were treated with dressings 100% of the time, and 88.2% of patients received topical treatment for odor, 73.9% received topical treatment for bleeding, 55.6% topical itch treatment, 44% topical pain treatment, 36% gabapentin, and 24% received an opioid. The median baseline Skindex-16 score was 59.5, falling into the “extremely severe” category, with a median score of 17.5, 21, and 23 for the symptom, emotion, and function domains, respectively. Nineteen patients completed an additional Skindex-16 questionnaire at follow up visits (visit two 52.8%, visit three 33.3%, visit four 19.4%, visit five or greater 13.9%). Compared to the median Skindex-16 score at baseline, there was a 34.5% improvement at visit two, 45.4% at visit three, 73.1% at visit four, and 83.2% improvement in QoL at visit five or more. Conclusions: Malignant wounds severely reduce patients’ quality of life; however, patients experienced significantly improved quality of life after being treated at dedicated wound clinics.
Effect of lactobacillus rhamnosus DY801 on methionine metabolism and Th17 cells in the treatment of acute radiochemotherapy induced bowel injury.
Authors: Yu Lu , Chen Zhenhui , Fan Hongying , Ding Yi 
Published: June 2024

e24099 Background: Radiation and chemotherapy are important treatments for patients with pelvic malignant tumors, and they will inevitably lead to the occurrence of radiochemotherapy-induced intestinal injury. Acute radiochemotherapy-induced intestinal injury reduces the quality of life and treatment compliance of patients, which ultimately affects overall survival. However, at present, the treatment of acute intestinal injury is limited. Therefore, alleviating acute radiochemotherapy-induced intestinal injury is an important scientific problem to be solved urgently in tumor treatment. Methods: The stool samples of patients before and after treatment were analyzed by 16S rRNA sequencing to explore the intestinal bacteria associated with radiochemotherapy-induced intestinal injury. The changes in intestinal bacteria and metabolism related to radiochemotherapy-induced intestinal injury were explored through mice in vivo experiments, metagenomics, and non-target metabolomics analysis. New strains of Lactobacillus were obtained from fresh human fecal samples. The molecular mechanism of the therapeutic effect of Lactobacillus rhamnosus DY801 was explored through in vivo experiments, RNA-sequencing, Crispr/cas9 gene knockout, immunohistochemistry, flow cytometry, LC/MS, and western blot. Results: 16S rRNA sequencing of stool samples from patients before and after treatment suggested that the abundance of Lactobacillus and Bacteroides decreased after radiotherapy and chemotherapy. In vivo experiments in mice showed that the decrease in abundance of Lactobacillus and Bacteroides, the decrease of methionine metabolism, and the increase of activated Th17 cells were related to the severity of radiochemotherapy-induced intestinal injury. Ten new strains of Lactobacillus were isolated, cultured, and identified from the feces of matched normal people. Among them, Lactobacillus rhamnosus DY801 had a resistance to acid and bile salt, and has the strongest ability to treat radiochemotherapy-induced intestinal injury. In vivo and in vitro experiments suggest that Lactobacillus rhamnosus DY801 inhibited the proinflammatory Th17 cells through methionine, a production of metB gene, and significantly improve acute intestinal injury. Conclusions: Lactobacillus rhamnosus DY801 regulated methionine metabolism and inhibited Th17 cells in the treatment of the acute radiochemotherapy-induced intestinal injury.
Beyond the “teachable moment”: Smoking cessation during cancer treatment remains challenging despite high motivation to quit.
Authors: Rieth Katherine , Cupertino Ana Paula , Kadambi Sindhuja G , Janelsins Michelle Christine , Morrow Gary R. , Peppone Luke Joseph 
Published: June 2024

e24141 Background: Continued smoking throughout cancer treatment, including surgery, is associated with treatment-related complications and a higher total symptom burden during treatment. This can lead to interruptions and delays in therapy that can compromise treatment efficacy and survival. Approximately 1 in 3 patients smoke at or around time of cancer diagnosis. Despite this “teachable moment” for smoking cessation, at least half of patients with cancer are unsuccessful in their attempts, and relapse rates for post-surgical cancer patients are high. Better understanding of quit motivation among these patients can help guide tobacco treatment interventions in the post-operative and adjuvant treatment time periods. Methods: This is an analysis of a longitudinal nationwide multicenter study of 1003 patients through the University of Rochester Cancer Center NCI Community Oncology Research Program (URCC NCORP) that assessed treatment type, treatment-related symptoms, smoking status, and motivation to quit smoking for patients with a new diagnosis of cancer. Patients supplied demographic and clinical information at enrollment with assessments at two weeks pre- adjuvant treatment, post adjuvant treatment, and 6 months. Chi-square, multinomial logistic regression, and ANOVA were used to analyze the difference between smokers and nonsmokers, and those with previous surgical treatment. Results: The majority of patients had surgery as part of their cancer treatment (n = 718, 71.6%). Of these (n = 222, 30.9%) had a diagnosis of a tobacco-associated cancer, which was associated with smoking status at pre-treatment (p < 0.05). For those with previous surgery, n = 90 (68.7%, p < 0.001) were current smokers before starting adjuvant treatment. Post-surgical patients who smoke had both higher total symptom burden ( M= 23.7 vs M= 17.0; p < 0.05) and higher symptom severity ( M =1.97 vs M= 1.42; p < 0.001) pre-adjuvant treatment and at 6 month follow up [( M =31.3 vs M= 22.2; p < 0.05);( M= 2.6 vs M= 1.8; p < 0.05)] compared to post-surgical patients who were not smokers. Motivation to quit was sustained among current smokers between the pre- and post- adjuvant treatment periods (p < 0.001), as well as for those that had previous surgery (p < 0.05). Despite motivation to quit among 64.4% of current smokers with previous surgery, 15.4% reported being able to quit by post-adjuvant treatment with 50% relapsing to smoking at 6-month follow up. Conclusions: For patients that continue to smoke after surgical treatment, cessation rates are much lower than motivation to quit with high rates of relapse. Early intervention around the time of surgery presents an ideal opportunity to optimize the “teachable moment” by providing longitudinal tobacco treatment as part of cancer care to improve treatment-related symptoms, as well as overall survival.