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Simple Summary: As more cancer patients with advanced disease present to the emergency department (ED), data on outcomes of cardiopulmonary resuscitation (CPR) are needed to help counsel patients before and during an acute event. We investigated the characteristics of cancer patients who required CPR, their outcomes, and how prior advanced care planning (ACP) influenced these outcomes. Few studies have specifically looked at these data in an emergency department, where medical history is limited and the need for acute intervention often precludes discussion of therapeutic limitations. We found cardiopulmonary resuscitation of cancer patients to be rare in the ED. Although the return of spontaneous circulation (ROSC) is often attained, very few patients survive to discharge. Patient characteristics, resuscitation success, overall mortality, and the cost of care did not differ between patients with and without ACP. However, patients with ACP had shorter hospital and intensive care unit (ICU) stays and higher rates of conversion to do-not-resuscitate (DNR) status post-resuscitation. Cardiopulmonary resuscitation (CPR) outcomes vary for patients with cancer. Here, we characterized cancer patients who underwent CPR in the emergency department (ED), their outcomes, and the effects of advanced care planning (ACP). The hospital databases and electronic medical records of cancer patients at a comprehensive cancer center who underwent CPR in the ED from 6 March 2016 to 31 December 2022 were reviewed for patient characteristics, return of spontaneous circulation (ROSC), conversion to do-not-resuscitate (DNR) status afterward, hospital and intensive care unit (ICU) length of stay, mortality, cost of hospitalization, and prior GOC discussions. CPR occurred in 0.05% of all ED visits. Of the 100 included patients, 67 patients achieved ROSC, with 15% surviving to hospital discharge. The median survival was 26 h, and the 30-day mortality rate was 89%. Patients with and without prior ACP had no significant differences in demographics, metastatic involvement, achievement of ROSC, or in-hospital mortality, but patients with ACP were more likely to change their code status to DNR and had shorter stays in the ICU or hospital. In conclusion, few cancer patients undergo CPR in the ED. Whether this results from an increase in terminally ill patients choosing DNR status requires further study. ACP was associated with increased conversion to DNR after resuscitation and decreased hospital or ICU stays without an increase in overall mortality. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases (BMs), the most common type of cerebral tumor, are primarily associated with lung cancer, breast cancer, and melanoma. Patients typically present to the emergency department (ED) with insidious symptoms such as headaches, focal neurological deficits, seizures, and signs of increased intracranial pressure. Key symptomatic treatment in the ED includes corticosteroids to manage peritumoral edema, and carefully selected antiepileptic medications for tumor-related epileptic conditions. After stabilization, the treatment philosophy for BMs should prioritize effective yet minimally toxic options to maximize quality of life. Surgery is recommended for accessible BMs in patients with good performance status. Radiation therapy and systemic treatments, including chemotherapy, targeted therapy, and immunotherapy, are available options for managing disease progression. Given that over half of patients with BMs in the ED are admitted, a better understanding of avoidable hospitalizations is essential to differentiate those who can be safely discharged from those needing observation or hospitalization. Brain metastases (BMs) are the most prevalent type of cerebral tumor, significantly affecting survival. In adults, lung cancer, breast cancer, and melanoma are the primary cancers associated with BMs. Symptoms often result from brain compression, and patients may present to the emergency department (ED) with life-threatening conditions. The goal of treatment of BMs is to maximize survival and quality of life by choosing the least toxic therapy. Surgical resection followed by cavity radiation or definitive stereotactic radiosurgery remains the standard approach, depending on the patient's condition. Conversely, whole brain radiation therapy is becoming more limited to cases with multiple inoperable BMs and is less frequently used for postoperative control. BMs often signal advanced systemic disease, and patients usually present to the ED with poorly controlled symptoms, justifying hospitalization. Over half of patients with BMs in the ED are admitted, making effective ED-based management a challenge. This article reviews the epidemiology, clinical manifestations, and current treatment options of patients with BMs. Additionally, it provides an overview of ED management and highlights the challenges faced in this setting. An improved understanding of the reasons for potentially avoidable hospitalizations in cancer patients with BMs is needed and could help emergency physicians distinguish patients who can be safely discharged from those who require observation or hospitalization. [ABSTRACT FROM AUTHOR]

Obesity is associated with an increased risk of developing breast cancer and is also associated with worse clinical prognosis. The mechanistic link between obesity and breast cancer progression remains unclear, and there has been no development of specific treatments to improve the outcome of obese cancer patients. Here we show that obesity-associated NLRC4 inflammasome activation/ interleukin (IL)-1 signalling promotes breast cancer progression. The tumour microenvironment in the context of obesity induces an increase in tumour-infiltrating myeloid cells with an activated NLRC4 inflammasome that in turn activates IL-1β, which drives disease progression through adipocyte-mediated vascular endothelial growth factor A (VEGFA) expression and angiogenesis. Further studies show that treatment of mice with metformin inhibits obesity-associated tumour progression associated with a marked decrease in angiogenesis. This report provides a causal mechanism by which obesity promotes breast cancer progression and lays out a foundation to block NLRC4 inflammasome activation or IL-1β signalling transduction that may be useful for the treatment of obese cancer patients.

Oral mucositis (OM) is a common and clinically impactful side effect of cytotoxic cancer treatment, particularly in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy with or without concomitant chemotherapy. The etiology and pathogenic mechanisms of OM are complex, multifaceted and elicit both direct and indirect damage to the mucosa. In this narrative review, we describe studies that use various omics methodologies (genomics, transcriptomics, microbiomics and metabolomics) in attempts to elucidate the biological pathways associated with the development or severity of OM. Integrating different omics into multi-omics approaches carries the potential to discover links among host factors (genomics), host responses (transcriptomics, metabolomics), and the local environment (microbiomics). [ABSTRACT FROM AUTHOR]

The mammalian constitutive photomorphogenesis 9 (COP9) signalosome (CSN), a protein complex involved in embryonic development, is implicated in cell cycle regulation and the DNA damage response. Its role in tumor development, however, remains unclear. Here, we have shown that the COP9 subunit 6 (CSN6) gene is amplified in human breast cancer specimens, and the CSN6 protein is upregulated in human breast and thyroid tumors. CSN6 expression positively correlated with expression of murine double minute 2 (MDM2), a potent negative regulator of the p53 tumor suppressor. Expression of CSN6 appeared to prevent MDM2 autoubiquitination at lysine 364, resulting in stabilization of MDM2 and degradation of p53. Mice in which Csn6 was deleted died early in embryogenesis (E7.5). Embryos lacking both Csn6 and p53 survived to later in embryonic development (E10.5), which suggests that loss of p53 could partially rescue the effect of loss of Csn6. Mice heterozygous for Csn6 were sensitized to γ-irradiation--induced, p53-dependent apoptosis in both the thymus and the developing CNS. These mice were also less susceptible than wild-type mice to γ-irradiation--induced tumorigenesis. These results suggest that loss of CSN6 enhances p53-mediated tumor suppression in vivo and that CSN6 plays an important role in regulating DNA damage--associated apoptosis and tumorigenesis through control of the MDM2-p53 signaling pathway., Introduction The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) was originally identified from Arabidopsis mutants that mimic light-induced seedling development when grown in the dark (1). The mammalian COP9 contains 8 [...]

The article examines pain among non-Hispanic Black and non-Hispanic white patients with cancer visiting emergency departments (ED) with Comprehensive Oncologic Emergencies Research Network (CONCERN). Topics include encourage research into any racial or socioeconomic gaps in the treatment of pain in ED cancer patients; and patient self report and compared using Pearson chi-square with assessed cell residuals.

Abstract Mammalian constitutive photomorphogenic 1 (COP1) is a p53 E3 ubiquitin ligase involved in regulating p53 protein level. In plants, the dynamic cytoplasm/nucleus distribution of COP1 is important for its function in terms of catalyzing the degradation of target proteins. In mammalian cells, the biological consequence of cytoplasmic distribution of COP1 is not well characterized. Here, we show that DNA damage leads to the redistribution of COP1 to the cytoplasm and that 14-3-3σ, a p53 target gene product, controls COP1 subcellular localization. Investigation of the underlying mechanism suggests that COP1 S387 phosphorylation is required for COP1 to bind 14-3-3σ. Significantly, upon DNA damage, 14-3-3σ binds to phosphorylated COP1 at S387, resulting in COP1's accumulation in the cytoplasm. Cytoplasmic COP1 localization leads to its enhanced ubiquitination. We also show that N-terminal 14-3-3σ interacts with COP1 and promotes COP1 nuclear export through its NES sequence. Further, we show that COP1 is important in causing p53 nuclear exclusion. Finally, we demonstrate that 14-3-3σ targets COP1 for nuclear export, thereby preventing COP1-mediated p53 nuclear export. Together, these results define a novel, detailed mechanism for the subcellular localization and regulation of COP1 after DNA damage and provide a mechanistic explanation for the notion that 14-3-3σ's impact on the inhibition of p53 E3 ligases is an important step for p53 stabilization after DNA damage.

Background: The impact of noncancerous factors on the morbidity and mortality of glioblastoma multiforme (GBM) has not been well studied. Using a large surgical cohort, we examined the association between multiple clinical characteristics and postoperative morbidities and survival in patients with GBM. Materials and Methods: The study included 404 consecutive GBM patients who underwent initial tumor resection at MD Anderson Cancer Center between January 1, 2010, and December 31, 2014. Data about clinical characteristics, treatments, and postoperative complications were collected. The associations between clinical parameters and postoperative complications and survival were analyzed. Results: Charlson Comorbidity Index was positively related to a higher incidence of postoperative total (odds ratio [OR] = 1.20; p = .002) and neurological (OR = 1.18; p = .011) complications. Preoperative systolic blood pressure (SBp) over 140 mmHg was associated with a higher incidence of postoperative intracranial hemorrhage (OR = 4.42; p = .039) and longer hospital stay (OR = 2.48; p = .015). Greater postoperative fluctuation of SBp (OR = 1.14; p = .025) and blood glucose (mmol/L; OR = 1.48; p = .023) were related to a higher incidence of neurological complications, whereas higher postoperative blood glucose (OR = 0.64; p < .001) was related to a lower incidence. Long‐term lower SBp (<124 mmHg; hazard ratio [HR] = 1.47; p = .010) and higher blood glucose (HR = 1.12; p < .001) were associated with shorter survival. Long‐term serum albumin level (g/dL; HR = 0.32; p < .001) was positively associated with survival. Conclusion: Short‐term SBp and blood glucose levels and fluctuations are associated with postoperative complications in GBM patients. Their long‐term optimization may impact survival of these patients. Future clinical trials are needed to confirm the benefit of optimizing medical comorbidities on GBM patients' outcomes. Implications for Practice: Glioblastoma multiforme (GBM) is one of the most feared cancer diagnoses because of its limited survival and treatment. This study revealed significant associations of noncancerous factors on the morbidity and mortality of GBM. The complexity of medical comorbidities, as well as short‐term postoperative levels and fluctuations of blood pressure and blood glucose, was associated with postoperative complications, but not overall survival. However, long‐term levels of these common clinical parameters were significantly associated with survival. Optimization of medical conditions may be critical for reducing the morbidity and mortality of GBM patients. Future clinical trials are needed to validate the observed associations in an independent cohort. Glioblastoma multiforme (GBM) is the most lethal primary brain tumor. This article examines the effect of medical comorbidities and their stability on postoperative complications and overall survival in GBM patients at a single large cancer institute. [ABSTRACT FROM AUTHOR]