tbuckley/cabot-search huggingface dataset:
OS09.7.A Quality of life outcomes in patients with incidental and operated meningiomas: the QUALMS study
Authors: S M Keshwara, A I Islim, C P Millward, C S Gillespie, G E Richardson, M A Mustafa, A M George, S J Mills, A R Brodbelt, M D Jenkinson
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Long-term Health-Related Quality of Life (HRQoL) is an important measure of patient wellbeing. There is a paucity of studies evaluating HRQoL in meningioma patients. MATERIAL AND METHODS Cross-sectional study of adult patients with an incidental or symptomatic intracranial meningioma. Patients with less than 5 years of follow-up, a history of craniospinal radiation or neurofibromatosis type 2 were excluded. HRQoL was evaluated with SF-36, EORTC QLQ-C30 and EORTC QLQ-BN20 questionnaires. Outcome determinants were evaluated using a multi-variable linear regression analysis, adjusted for patient, tumour and treatment characteristics, and duration of follow-up. RESULTS 699 patients were invited to participate and 246 responded: 118 (48%) had an incidental meningioma. Mean age at diagnosis was 56.8 years (SD=13) and 81% were female. Median time from diagnosis to completion of questionnaire was 8.5 years (IQR 6.8–11.5). During follow-up, 158 patients (64.2%) had at least one operation for their meningioma and 47 patients (19.1%) had radiotherapy. Of those operated, 126 (79.7%) had WHO grade 1 and 24 (15.2%) had grade 2 meningiomas. Compared to normative population values, meningioma patients reported a worse SF-36 general health score (mean 61.9 vs 56.5, P=0.003) but a similar QLQ-C30 global health score (mean 62.3 vs 65.8, P=0.039), worse SF-36 and QLQ-C30 physical functioning scores (mean 74.1 vs 64.6, P&amp;lt;0.001 and mean 81.8 vs 76.5, P=0.007) and similar SF-36 and QLQ-C30 emotional health scores (mean 72.2 vs 70.9, P=0.367 and mean 71.0 vs 71.9, P=0.960). QLQ-C30 cognitive functioning was worse (mean 80.5 vs 71.4, P&amp;lt;0.001). Compared to the meningioma literature, QLQ-BN20 seizure burden was similar (mean 2.0 vs 1.6, P=0.760). A worse performance status at diagnosis was associated with an inferior QLQ-C30 global health score (β-coefficient=-4.9 [95% CI -9.1-(-)0.6] P=0.024). Number of surgeries was significantly associated with a worse QLQ-C30 cognitive functioning score (β-coefficient=-7.0 [95% CI -13.2-(-)0.9], P=0.025). Anti-epileptic drug use was associated with a significantly worse QLQ-C30 emotional health score (β-coefficient=-10.9 [95% CI -21.7-(-)0.01], P=0.050). CONCLUSION Meningioma patients have long-term HRQoL impairments affecting their physical and cognitive functions. An understanding that multiple surgeries affects cognitive function, and the need for anti-epileptic drugs equate to poorer emotional health, could help target appropriate therapies and support in the future.
Digital intervention increases influenza vaccination rates for people with diabetes in a decentralized randomized trial
Authors: J. L. Lee, L. Foschini, S. Kumar, J. Juusola, J. Liska, M. Mercer, C. Tai, R. Buzzetti, M. Clement, X. Cos, L. Ji, N. Kanumilli, D. Kerr, E. Montanya, D. Müller-Wieland, C. G. Ostenson, N. Skolnik, V. Woo, N. Burlet, M. Greenberg, S. I. Samson
Journal: npj Digital Medicine (2021)

Abstract People with diabetes (PWD) have an increased risk of developing influenza-related complications, including pneumonia, abnormal glycemic events, and hospitalization. Annual influenza vaccination is recommended for PWD, but vaccination rates are suboptimal. The study aimed to increase influenza vaccination rate in people with self-reported diabetes. This study was a prospective, 1:1 randomized controlled trial of a 6-month Digital Diabetes Intervention in U.S. adults with diabetes. The intervention group received monthly messages through an online health platform. The control group received no intervention. Difference in self-reported vaccination rates was tested using multivariable logistic regression controlling for demographics and comorbidities. The study was registered at clinicaltrials.gov: NCT03870997. A total of 10,429 participants reported influenza vaccination status (5158 intervention, mean age (±SD) = 46.8 (11.1), 78.5% female; 5271 control, Mean age (±SD) = 46.7 (11.2), 79.4% female). After a 6-month intervention, 64.2% of the intervention arm reported influenza vaccination, vers us 61.1% in the control arm (diff = 3.1, RR = 1.05, 95% CI [1.02, 1.08], p = 0.0013, number needed to treat = 33 to obtain 1 additional vaccination). Completion of one or more intervention messages was associated with up to an 8% increase in vaccination rate (OR 1.27, 95% CI [1.17, 1.38], p &lt; 0.0001). The intervention improved influenza vaccination rates in PWD, suggesting that leveraging new technology to deliver knowledge and information can improve influenza vaccination rates in high-risk populations to reduce public health burden of influenza. Rapid cycle innovation could maximize the effects of these digital interventions in the future with other populations and vaccines.
Ectopic activation of the miR-200c–EpCAM axis enhances antitumor T cell responses in models of adoptive cell therapy
Authors: Minggang Zhang, Zeguo Zhao, Yuri Pritykin, Margaret Hannum, Andrew C. Scott, Fengshen Kuo, Viraj Sanghvi, Timothy A. Chan, Venkatraman Seshan, Hans-Guido Wendel, Andrea Schietinger, Michel Sadelain, Morgan Huse
Journal: Science Translational Medicine (2021)

Up-regulation of the miR-200c–EpCAM axis promotes the engraftment, persistence, and antitumor activity of transferred T cells in murine models.
P-137 Patient baseline characteristics in the PROMETCO study: A real-world, prospective longitudinal cohort on the continuum of care of metastatic colorectal cancer
Authors: M. Koopman, C. Pinto, G. Bodoky, F. Marti Marti, H. Chrostek, A. Raimond-Thibaut, R. Fougeray, R. Garcia-Carbonero, J. Bachet
Journal: Annals of Oncology (2021)
Transcription factor FOXF1 identifies compartmentally distinct mesenchymal cells with a role in lung allograft fibrogenesis
Authors: Russell R. Braeuer, Natalie M. Walker, Keizo Misumi, Serina Mazzoni-Putman, Yoshiro Aoki, Ruohan Liao, Ragini Vittal, Gabriel G. Kleer, David S. Wheeler, Jonathan Z. Sexton, Carol F. Farver, Joshua D. Welch, Vibha N. Lama
Journal: Journal of Clinical Investigation (2021)

In this study, we demonstrate that forkhead box F1 (FOXF1), a mesenchymal transcriptional factor essential for lung development, was retained in a topographically distinct mesenchymal stromal cell population along the bronchovascular space in an adult lung and identify this distinct subset of collagen-expressing cells as key players in lung allograft remodeling and fibrosis. Using Foxf1-tdTomato BAC (Foxf1-tdTomato) and Foxf1-tdTomato Col1a1-GFP mice, we show that Lin-Foxf1+ cells encompassed the stem cell antigen 1+CD34+ (Sca1+CD34+) subset of collagen 1-expressing mesenchymal cells (MCs) with a capacity to generate CFU and lung epithelial organoids. Histologically, FOXF1-expressing MCs formed a 3D network along the conducting airways; FOXF1 was noted to be conspicuously absent in MCs in the alveolar compartment. Bulk and single-cell RNA-Seq confirmed distinct transcriptional signatures of Foxf1+ and Foxf1- MCs, with Foxf1-expressing cells delineated by their high expression of the transcription factor glioma-associated oncogene 1 (Gli1) and low expression of integrin α8 (Itga), versus other collagen-expressing MCs. FOXF1+Gli1+ MCs showed proximity to Sonic hedgehog-expressing (Shh-expressing) bronchial epithelium, and mesenchymal expression of Foxf1 and Gli1 was found to be dependent on paracrine Shh signaling in epithelial organoids. Using a murine lung transplant model, we show dysregulation of epithelial-mesenchymal SHH/GLI1/FOXF1 crosstalk and expansion of this specific peribronchial MC population in chronically rejecting fibrotic lung allografts.
Disparities in clinical trials participation in a vertically integrated care delivery system.
Authors: Ahmed Megahed, Gary L Buchschacher, Ngoc J. Ho, Reina Haque, Robert Michael Cooper
Journal: Journal of Clinical Oncology (2021)

128 Background: Sparse data exists on the diversity clinical trial enrollment in community settings. This information is important to ensure equity of care and generalizability of results. Methods: We conducted a retrospective cohort study of members of an integrated healthcare system diagnosed with invasive malignancies (excluding non-melanoma skin cancers) between 2013-2017 to examine demographics of the oncology population compared to those who enrolled in a clinical trial. Logistic regression was used to assess correlates of clinical trial participation, comparing general and screened samples to enrolled sample. Odds ratios were adjusted for gender, geocoded median household income, cancer type, and stage. Results: Of the 84,977 patients with a cancer diagnosis, N = 2606 were screened for clinical trial participation and consented, and of those N = 1372 enrolled. The percent of Latinx (25.8% vs 24.0%; OR 0.9? CI 0.72-1.05) and African American/Black (10.9% vs 11.1%; OR 0.92 CI 0.75-1.11) clinical trial participation mirrored that of the general oncology population, respectively using Non-Hispanic Whites as reference. Asian/Pacific Islander had equal odds of clinical trial enrollment (OR 1.08 CI 0.92-1.27). The enrolled population was younger than the general oncology population. Conclusions: This study suggests that in an integrated healthcare system with equal access to care, the clinical trials population is well representative of its general oncology population.[Table: see text]
Potential Implications of Expanded US Food and Drug Administration Labeling for Sacubitril/Valsartan in the US
Authors: Muthiah Vaduganathan, Brian L. Claggett, Stephen J. Greene, Rahul Aggarwal, Ankeet S. Bhatt, John J. V. McMurray, Gregg C. Fonarow, Scott D. Solomon
Journal: JAMA Cardiology (2021)

The US Food and Drug Administration (FDA) expanded labeling for sacubitril/valsartan for use in individuals with chronic heart failure (HF) with left ventricular ejection fraction (LVEF) lower than normal. The population-level implications of implementation of sacubitril/valsartan at higher LVEF ranges is unknown. While the Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction (PARAGON-HF) trial did not meet its primary end point, the trial may provide useful information in projecting expected clinical events among treated individuals.To quantify newly eligible treatment candidates for sacubitril/valsartan under the expanded FDA labeling and to apply treatment effects and the number needed to treat (NNT) to prevent 1 worsening HF event derived from subgroups of the PARAGON-HF trial who fall under the revised FDA label.Newly eligible treatment candidates were estimated by mapping the LVEF distribution from 559 520 adult patients hospitalized between 2014 and 2019 in the Get With The Guidelines-Heart Failure registry to adults self-identifying with HF in the National Health and Nutrition Examination Survey (2015 to 2018). The NNT with 3 years of treatment for 3 end points of interest (total HF hospitalizations, total HF hospitalizations and cardiovascular death, and total HF hospitalizations and urgent HF visits and cardiovascular death) were estimated from the PARAGON-HF trial. Data were analyzed from February to June 2021.Number of worsening HF events prevented or postponed if eligible patients were treated with sacubitril/valsartan for 3 years.Of an estimated 4 682 098 adults, the mean (SE) age was 66.3 (0.8) years, 1 995 037 (42.6%) were women, and 748 045 (16.0%) were Black. The potential number of adults projected to be newly eligible varied by the definition of FDA labeling of lower than normal LVEF from 643 161 (95% CI, 534 433-751 888; LVEF of 41% to 50%) to 1 838 756 (95% CI, 1 527 911-2 149 601; LVEF of 41% to 60%). In the PARAGON-HF trial, the NNT to prevent a worsening HF event (range, 7 to 12 patients) was consistent irrespective of specific LVEF range selected. Comprehensive implementation of sacubitril/valsartan among newly eligible patients was empirically estimated to prevent up to 69 268 (95% CI, 57 558-80 978) worsening HF events (LVEF of 41% to 50%) to 182 592 (95% CI, 151 725-213 460) worsening HF events (LVEF of 41% to 60%).The expanded FDA labeling is positioned to substantially increase the potential HF population eligible for sacubitril/valsartan by up to 1.8 million individuals and has the potential to prevent or postpone as many as 180 000 worsening HF events, depending on the definition of normal LVEF.
Paradoxical carbon dioxide embolism during laparoscopic nephrectomy
Authors: Chun Ma, Dan Xu
Journal: Intensive Care Medicine (2021)

A 64-year-old female underwent laparoscopic nephrectomy for a kidney carcinoma.Amid the operation, the end-tidal carbon dioxide dropped from 39 to 22 mmHg.The expected wake at the end of the procedure did not achieve.The magnetic resonance imaging demonstrated diffuse lesions with restricted diffusion localized in the intracerebral parenchyma (Fig. 1).Paradoxical carbon dioxide embolism was diagnosed.No signs of right-toleft shunting were detected by transesophageal echocardiography.The patient was given Rivaroxaban for anticoagulant therapy.The patient remained in a coma 20 days before she recovered.During the hospitalization, the patient developed acute appendicitis and lung infection.
Abstract P099: Association Between Arsenic And Heart Failure
Authors: Kalaivani Sivakumar, Demilade Adedinsewo, Anekwe Onwuanyi
Journal: Circulation (2016)

Background: Heart failure is a major contributor to morbidity and mortality in the United States. Arsenic, a ubiquitous element, found in drinking water, rice, flour and other grains, has been shown to play a role in the development of arrhythmias and coronary heart disease through vascular endothelial dysfunction and free radical injury. Studies have shown that arsenic induces interstitial myocardial fibrosis and we hypothesize that this may contribute to the development of heart failure. Methods: We conducted an analysis of the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Urinary arsenic was evaluated as a combination of inorganic arsenic, and methylated arsenic species (Monomethylarsonic acid and Dimethylarsinic acid) in microgram per gram of urine creatinine. We used a logistic regression model to evaluate the relationship between quartiles of urinary arsenic and heart failure while controlling for confounders. Analyses were conducted using SAS survey procedures and data evaluated at α=0.05. Results: The total number of study participants were 2065 adults with the mean age of 40.2 years, approximately half were male (48.8%) and 64.1% were white. There was no significant association between urinary arsenic measures and incidence of heart failure. Persons with high arsenic levels (&gt;75th percentile) were less likely to develop heart failure after controlling for confounders. Conclusion: Our results show a statistically significant decrease in the odds of developing heart failure among persons with high arsenic levels (&gt;24ug/g). This is in contrast to other studies, which have shown high arsenic levels to have a toxic effect on the heart. Limitations of our study include the inability to determine the chronicity of exposure and exclude persons with increased levels of organic arsenic from seafood, which are nontoxic. Additional observational and prospective studies are needed to further evaluate this association.
The next step in immorality: charging to create and cure disease
Authors: Kamran Abbasi
Journal: BMJ (2021)

Surrogate markers are seductive. In clinical trials and regulatory decisions, why not reach for something quick, convenient, and relatively cheap? Why stop patients receiving a treatment of plausible and potential benefit? That is the logic behind “accelerated pathways” for drug approval, such as the one used by the US Food and Drug Administration since the 1990s. But the FDA’s experience is worrying, a story of claims unproved and obligations avoided (doi:10.1136/bmj.n2059).1 Surrogate markers rank with subgroup analyses, composite outcomes, and secondary outcomes as great deceivers in clinical trial design and reporting. Their overuse is a triumph of commercial hype, playing on the hope of a treatment that anybody with an illness will, understandably, cling to.

The promise of …
PL03.1.A Surgery for glioblastomas in the elderly: an ANOCEF trial (CSA)
Authors: F Laigle-Donadey, P Metellus, J Guyotat, P Menei, F Proust, H Dufour, O Chinot, J Honnorat, T Faillot, P Paquis, P Peruzzi, E Emery, J S Guillamo, A Carpentier, M Wager, S Lebbah, D Hajage, J Y Delattre, P Cornu
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The role of surgery for the treatment of malignant gliomas in patients 70 years of age or older is unsettled. We conducted a randomized trial that compared surgical resection of the tumor and biopsy only, both followed by standard therapy, in such patients. MATERIAL AND METHODS Patients aged 70 years and older, with a KPS of at least 50, presenting with a radiological suspicion of an operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008–2017), with the adjunction of concomitant and adjuvant temozolomide when this regimen became standard (2017–2019). The primary end point was survival; secondary endpoints were progression free survival (PFS), cognitive status (MMS), autonomy (KPS), quality of life (EORTC QLQ C30 and BN20), and perioperative morbidity/ mortality. RESULTS From 2008 to 2019, 107 patients from 9 centers were enrolled in the study, of whom 101 were evaluable for analysis because the diagnosis of GBM was histologically confirmed (50 patients in the “surgery” arm and 51 patients in the “biopsy” arm). There was no statistically significant difference of median survival between the “surgery” arm (9.37 mo) and the “biopsy” arms (8.96 mo, p=0.36). However, the surgery group had increased PFS (5.06 mo vs 4.02 mo; p=0.034; p=0.002 on multivariate analysis) and better QOL (e.g. physical and cognitive functioning, motor dysfunction, fatigue) and KPS score evolution as compared to the “biopsy” group. Surgery was not associated with increased mortality or morbidity. CONCLUSION This study suggests that optimal debulking surgery does not provide a significant survival benefit in elderly patients suffering from newly diagnosed malignant glioma, but resection improves QOL and autonomy with a significant though modest improvement of PFS.
A qualitative study informing about barriers and facilitators associated to chemotherapy initiation among breast cancer patients: Next steps for an intervention.
Authors: Mariana Chavez Mac Gregor, Ashley Housten, Edna Paredes, Catalina Malinowski, Cassandra Harris, Sharon H. Giordano
Journal: Journal of Clinical Oncology (2021)

247 Background: (Neo)Adjuvant chemotherapy decreases the risk of recurrence and improves overall survival among breast cancer patients; however, delays in chemotherapy initiation are associated with adverse outcomes. The causes of delay are complex and include interrelated social, economic, cultural, environmental, and health system factors . Project Start was a qualitative study designed to assess and identify the multilevel factors contributing to the barriers and facilitators of chemotherapy initiation. Methods: English or Spanish-speaking women, ≥18 years, diagnosed with primary invasive breast cancer experiencing (neo)-adjuvant chemotherapy initiation delay ( ≥60 days) were included. Participants completed semi-structured interviews designed to explore perceptions about individual, community, and system-level barriers and facilitators contributing to chemotherapy initiation. Interviews were audio-recorded, transcribed verbatim, and coded using the Sort and Sift, Think and Shift qualitative approach to identify concepts and themes within and across transcripts. To supplement qualitative data, sociodemographic data and health literacy/numeracy, physician trust, and social support questionnaires were obtained. Results: Participants (n = 22) identified as: Latina (n = 8); Black (n = 5); and non-Latina White (n = 9). While the interview guide included questions addressing chemotherapy delays, explicit insight into chemotherapy delay was rare. Participants described barriers and facilitators at the patient, family, medical, and community levels. Barriers at the patient level included patient’s hesitancy to initiate chemo due to shock, fear, and denial. Within the family level, we learned of participant’s family roles (e.g., caregiving, income), treatment costs, and the need for emotional support (e.g., not shutting family members out). Participants sought out and relied heavily on support from their communities (e.g., churches, other patients, survivors). Patients described their reliance on the medical team for information, the trust needed to navigate their treatment process, and the challenge of managing information associated with their treatment. Participants described the importance of self-efficacy to take an active role in treatment. Conclusions: Project Start is informing the design of a pilot study aimed to test the acceptability and feasibility of a navigation intervention. Using facilitators and barriers identified from Project Start, we are developing a checklist that will serve as a tool to identify the support each patient needs. Once areas of need are identified, appropriate referrals will be made in a personalized and culturally sensitive way with the goal of increasing self-efficacy and activating patients to avoid treatment delays.
Long-Term Outcomes of Children Undergoing Dialysis-treated AKI: Some Opinions and Prospects
Authors: Shiyuan Wei
Journal: Journal of the American Society of Nephrology (2021)

In a recently published article in JASN , Robinson et al. [1][1] performed a retrospective study reporting the long-term kidney outcomes after childhood dialysis-treated AKI (DT-AKI). This topic is very important, and there is currently very limited evidence on this issue,[2][2],[3][3] especially in
Charge-reversal biodegradable MSNs for tumor synergetic chemo/photothermal and visualized therapy
Authors: Zimu Li, Yao Yang, Huaxuan Wei, Xiaoting Shan, Xuanzhi Wang, Meitong Ou, Qingyun Liu, Nansha Gao, Hongzhong Chen, Lin Mei, Xiaowei Zeng
Journal: Journal of Controlled Release (2021)