Purpose: Cancer treatment for those nearing death has become increasingly aggressive over time despite evidence that less aggressive approaches are associated with better quality of life and sometimes longer survival. Chemotherapy administration in the last 14 days of life is one of the proposed benchmarks for quality of cancer care. The purpose of our study is to evaluate factors associated with aggressive cancer treatment in patients who died within 2 weeks of receiving chemotherapy. Methods: This retrospective cohort study evaluated adult patients who died between 1 February 2018 and 1 March 2019 after receiving cancer treatment in the preceding 14 days at the Prisma Health Cancer Institute. This project was approved by our institutional review board. Data was obtained by review of electronic medical records and analyzed using commercial software. Results: We identified 92 patients who met inclusion criteria for the study. Of those who were staged, 57% had metastatic disease. A majority received treatments with only palliative intent (54%). These patients overwhelmingly died in the hospital (62%). Few had documented advanced directives (28%) or dedicated palliative care for longer than 1 week (28%). Overall, this cohort reflects a rate of 11.7% of patients who received cancer treatment during the study time period. Significance of Results: Patients receiving aggressive cancer treatment at the end of life elucidate significant gaps in quality cancer care, particularly the early involvement of dedicated palliative care. Systematic review helped identify multiple gaps and assisted in implementing interventions to improve this outcome.
Prostate transmembrane protein androgen induced 1 (PMEPA1) has been reported to promote cancer progression, but the potential role of PMEPA1 in bladder cancer (BLCA) remains elusive. We assess the role of PMEPA1 in BLCA, via a publicly available database and in vitro study. PMEPA1 was identified from 107 differentially expressed genes (DEGs) to have prognostic value. GO, KEGG, and GSEA analysis indicated that PMEPA1 was involved in cancer progression and the tumor microenvironment (TME). Then bioinformatical analysis in TCGA, GEO, TIMER, and TISIDB show a positive correlation with the inflammation and infiltration levels of three tumor-infiltrating immune cells (TAMs, CAFs, and MDSCs) and immune/stromal scores in TME. Moreover, in vitro study revealed that PMEPA1 promotes bladder cancer cell malignancy. Immunohistochemistry and survival analysis shed light on PMEPA1 potential to be a novel biomarker in predicting tumor progression and prognosis. At last, we also analyzed the role of PMEPA1 in predicting the molecular subtype and the response to several treatment options in BLCA. We found that PMEPA1 may be a novel potential biomarker to predict the progression, prognosis, and molecular subtype of BLCA.
Introduction Religion and spirituality play important roles in the lives of many, including healthcare providers and their patients. The purpose of this study was to examine the relationships between religion, spirituality, and cultural competence of healthcare providers. Methods Physicians, residents, and medical students were recruited through social platforms to complete an electronically delivered survey, gathering data regarding demographics, cultural competency, religiosity, and spirituality. Four composite variables were created to categorize cultural competency: Patient Care Knowledge, Patient Care Skills/Abilities, Professional Interactions, and Systems Level Interactions. Study participants (n = 144) were grouped as Christian (n = 95)/non-Christian (n = 49) and highly religious (n = 62)/not highly religious (n = 82); each group received a score in the four categories. Wilcoxon rank sum and Chi-square tests were used for analysis of continuous and discrete variables. Results A total of 144 individuals completed the survey with the majority having completed medical school (n = 87), identifying as women (n = 108), white (n = 85), Christian (n = 95), and not highly religious (n = 82). There were no significant differences amongst Christian versus non-Christian groups or highly religious versus not highly religious groups when comparing their patient care knowledge (p = .563, p = .457), skills/abilities (p = .423, p = .51), professional interactions (p = .191, p = .439), or systems level interaction scores (p = .809, p = .078). Nevertheless, participants reported decreased knowledge of different healing traditions (90%) and decreased skills inquiring about religious/spiritual and cultural beliefs that may affect patient care (91% and 88%). Providers also reported rarely referring patients to religious services (86%). Conclusions Although this study demonstrated no significant impact of healthcare providers’ religious/spiritual beliefs on the ability to deliver culturally competent care, it did reveal gaps around how religion and spirituality interact with health and healthcare. This suggests a need for improved cultural competence education.
The majority of diffuse large B-cell lymphoma (DLBCL) patients develop relapsed or refractory disease after standard ruxolitinib, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, which is partly related to a dysregulated tumor immune microenvironment. However, how the infiltration of immune cells is appropriately regulated is poorly understood. Herein, we show that the E3 ubiquitin ligase Trim35 is expressed at low levels in human DLBCL tissues. We also show that overexpression of Trim35 suppresses DLBCL cell proliferation and correlates with inferior survival in DLBCL patients. Our mechanistic study shows that Trim35 functions as an E3 ligase to mediate the ubiquitination and degradation of CLOCK, a key regulator of circadian rhythmicity. High expression of Trim35 correlates with NK cell infiltration in DLBCL, partly due to the degradation of CLOCK. Consistently, patients with high expression of CLOCK show poor overall survival. Overall, these findings suggest that Trim35 suppresses the progression of DLBCL by modulating the tumor immune microenvironment, indicating that it may be a promising diagnostic and prognostic biomarker in DLBCL.
We apply a multiresolution Gaussian process model (Lattice Kriging) to combine satellite observations, ground‐based observations, and an empirical auroral model, to produce the assimilation of auroral energy flux and mean energy over high‐latitude regions. Compared to a simple padding, the assimilation coherently combines various data inputs leading to continuous transitions between different datasets. The multiresolution modeling capability is achieved by allocating multiple layers of basis functions with different resolutions. Higher‐resolution fitting results capture more mesoscale (10–100 s km) structures such as auroral arcs, than the low‐resolution ones and the empirical model. To better reconcile different datasets, two preprocessing steps, temporal interpolation of satellite data and spatial down‐sampling of low‐fidelity data, are implemented. The inherent smoothing effect of the fitting, which causes an unrealistic spreading of the aurora, is mitigated by a post processing step: the K Nearest Neighbor (KNN) algorithm. KNN identifies the probability of a region with significant aurora and thereby eliminates those regions with low values. Thereby, this methodology can be used to maintain realistic and mesoscale auroral structures without boundary issues. We then run the Thermosphere Ionosphere Electrodynamics General Circulation Model (TIEGCM) driven by the high‐ and low‐resolution auroral assimilations and compare total electron contents (TECs). TIEGCM driven by data assimilation produces enhanced TECs by a factor of ∼2 than the one driven by the empirical aurora, and high‐resolution results show mesoscale structures. Our study shows the value of incorporating realistic auroral inputs via assimilation to drive ionosphere‐thermosphere models for better understanding the consequences of mesoscale phenomena.
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