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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.

Background: Cardio‐oncology and emergency medicine are closely collaborative, as many cardiac events in cancer patients require evaluation and treatment in the emergency department (ED). Immune checkpoint inhibitors (ICIs) have become a common treatment for patients with head and neck cancer (HNC). However, the immune‐related adverse events (irAEs) from ICIs can be clinically significant. Methods: We reviewed and analyzed cardiovascular diagnoses among HNC patients who received ICI during the period April 1, 2016–December 31, 2020 in a large tertiary cancer center. Demographics, clinical and cancer‐related data were abstracted, and billing databases were queried for cardiovascular disease (CVD)‐related diagnosis using International Classification of Disease‐version10 (ICD‐10) codes. We recorded receipt of care at the ED as one of the outcome variables. Results: A total of 610 HNC patients with a median follow‐up time of 12.3 months (median, interquartile range = 5–30 months) comprised our study cohort. Overall, 25.7% of patients had pre‐existing CVD prior to ICI treatment. Of the remaining 453 patients without pre‐existing CVD, 31.5% (n = 143) had at least one CVD‐related diagnosis after ICI initiation. Tachyarrhythmias (91 new events) was the most frequent CVD‐related diagnosis after ICI. The time to diagnosis of myocarditis from initiation of ICI occurred the earliest (median 2.5 months, 1.5–6.8 months), followed by myocardial infarction (3.7, 0.5–9), cardiomyopathy (4.5, 1.6–7.3), and tachyarrhythmias (4.9, 1.2–11.4). Patients with myocarditis and tachyarrhythmias mainly presented to the ED for care. Conclusion: The use of ICI in HNC is still expanding and the spectrum of delayed manifestation of ICI‐induced cardiovascular toxicities is yet to be fully defined in HNC survivors. [ABSTRACT FROM AUTHOR]

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]

Simple Summary: This review explores hemoptysis in cancer patients. It delves into risk factors, epidemiology and clinical consequences. The need for a mortality prediction score for cancer patients with hemoptysis-related variables is needed, and this tool could aid in risk assessment, optimize the control of bleeding with critical care, implement tracheobronchial or vascular interventions, and guide treatment planning. Managing hemoptysis in cancer patients requires addressing the underlying cause and providing supportive care for improved quality of life. Hemoptysis in cancer patients can occur for various reasons, including infections, tumors, blood vessel abnormalities and inflammatory conditions. The degree of hemoptysis is commonly classified according to the quantity of blood expelled. However, volume-based definitions may not accurately reflect the clinical impact of bleeding. This review explores a more comprehensive approach to evaluating hemoptysis by considering its risk factors, epidemiology and clinical consequences. In particular, this review provides insight into the risk factors, identifies mortality rates associated with hemoptysis in cancer patients and highlights the need for developing a mortality prediction score specific for cancer patients. The use of hemoptysis-related variables may help stratify patients into risk categories; optimize the control of bleeding with critical care; implement the use of tracheobronchial or vascular interventions; and aid in treatment planning. Effective management of hemoptysis in cancer patients must address the underlying cause while also providing supportive care to improve patients' quality of life. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor T cell infusion (CAR T) therapy has revolutionized the treatment of hematologic malignancies, but treatmentrelated toxicities are of concern. Understanding the timing and reasons for which patients present to the emergency department (ED) after CAR T therapy can assist with the early recognition and management of toxicities. Methods: A retrospective observational cohort study was conducted for patients who had undergone CAR T therapy in the past 6 months and visited the ED of The University of Texas MD Anderson Cancer Center between 04/01/2018 and 08/ 01/2022. The timing of presentation after CAR T product infusion, patient characteristics, and outcomes of the ED visit were examined. Survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates. Results: During the period studied, there were 276 ED visits by 168 unique patients. Most patients had diffuse large B-cell lymphoma (103/168; 61.3%), multiple myeloma (21/168; 12.5%), or mantle cell lymphoma (16/168; 9.5%). Almost all 276 visits required urgent (60.5%) or emergent (37.7%) care, and 73.5% of visits led to admission to the hospital or observation unit. Fever was the most frequent presenting complaint, reported in 19.6% of the visits. The 30- day and 90-day mortality rates after the index ED visits were 17.0% and 32.2%, respectively. Patients who had their first ED visit >14 days after CAR T product infusion had significantly worse overall survival (multivariable hazard ratio 3.27; 95% confidence interval 1.29–8.27; P=0.012) than patients who first visited the ED within 14 days of CAR T product infusion. Conclusion: Cancer patients who receive CAR T therapy commonly visit the ED, and most are admitted and/or require urgent or emergent care. During early ED visits patients mainly present with constitutional symptoms such as fever and fatigue, and these early visits are associated with better overall survival. [ABSTRACT FROM AUTHOR]

Background: The increasing use of computed tomography (CT) has identified many patients with incidental adrenal lesions. Further evaluation of these lesions is often dependent on the language used in the radiology report. Compared to the general population, patients with cancer have a higher risk for adrenal abnormalities, yet data on the prevalence and type of incidental adrenal lesions reported on radiologic reports in cancer patients is limited. In this study, we aimed to determine the prevalence and nature of adrenal abnormalities as an incidental finding reported on radiology reports of cancer patients evaluated for reasons other than suspected adrenal pathology. Methods: Radiology reports of patients who underwent abdominal CT within 30 days of presentation to a tertiary cancer center were reviewed and analyzed. We used natural language processing to perform a multi-class text classification of the adrenal reports. Patients who had CT for suspected adrenal mass including adrenal protocol CT were excluded. Three independent abstractors manually reviewed abnormal and questionable results, and we measured the interobserver agreement. Results: From June 1, 2006, to October 1, 2017, a total of 600,399 abdominal CT scans were performed including 66,478 scans obtained within 30 days of the patient's first presentation. Of these, 58,512 were eligible after applying the exclusion criteria. Adrenal abnormalities were identified in 7,817 (13.4%) reports, with adrenal nodularity (3,401 [43.5%]), adenomas (1,733 [22.2%]), and metastases (1,337 [17.1%]) being the most reported categories. Only 10 cases (0.1%) were reported as primary adrenal carcinomas and 2 as pheochromocytoma. Interobserver agreement using 300 reports yielded a Fleiss kappa of 0.893, implying almost perfect agreement between the abstractors. Conclusions: Incidental adrenal abnormalities are commonly reported in abdominal CT reports of cancer patients. As the terminology used by radiologists to describe these findings greatly determine the subsequent management plans, further studies are needed to correlate some of these findings to the actual confirmed diagnosis based on hormonal, histological and follow-up data and ascertain the impact of such reported findings on patients' outcomes. [ABSTRACT FROM AUTHOR]

Patients with advanced cancer generate 4 million visits annually to emergency departments (EDs) and other dedicated, high‐acuity oncology urgent care centers. Because of both the increasing complexity of systemic treatments overall and the higher rates of active therapy in the geriatric population, many patients experiencing acute decompensations are frail and acutely ill. This article comprehensively reviews the spectrum of oncologic emergencies and urgencies typically encountered in acute care settings. Presentation, underlying etiology, and up‐to‐date clinical pathways are discussed. Criteria for either a safe discharge to home or a transition of care to the inpatient oncology hospitalist team are emphasized. This review extends beyond familiar conditions such as febrile neutropenia, hypercalcemia, tumor lysis syndrome, malignant spinal cord compression, mechanical bowel obstruction, and breakthrough pain crises to include a broader spectrum of topics encompassing the syndrome of inappropriate antidiuretic hormone secretion, venous thromboembolism and malignant effusions, as well as chemotherapy‐induced mucositis, cardiomyopathy, nausea, vomiting, and diarrhea. Emergent and urgent complications associated with targeted therapeutics, including small molecules, naked and drug‐conjugated monoclonal antibodies, as well as immune checkpoint inhibitors and chimeric antigen receptor T‐cells, are summarized. Finally, strategies for facilitating same‐day direct admission to hospice from the ED are discussed. This article not only can serve as a point‐of‐care reference for the ED physician but also can assist outpatient oncologists as well as inpatient hospitalists in coordinating care around the ED visit. [ABSTRACT FROM AUTHOR]

Cancer vaccines critically rely on the availability of targetable immunogenic cancer‐specific neoepitopes. However, mutation‐based immunogenic neoantigens are rare or even non‐existent in subgroups of cancer types. To address this issue, we exploited a cancer‐specific aberrant transcription‐induced chimeric RNA, designated A‐PaschiRNA, as a possible source of clinically relevant and targetable neoantigens. A‐PaschiRNA encodes a recently discovered cancer‐specific chimeric protein that comprises full‐length astrotactin‐2 (ASTN2) C‐terminally fused in‐frame to the antisense sequence of the 18th intron of pregnancy‐associated plasma protein‐A (PAPPA). We used extracellular vesicles (EVs) from A‐PaschiRNA‐transfected dendritic cells (DCs) to produce the cell‐free anticancer vaccine DEXA‐P. Treatment of immunocompetent cancer‐bearing mice with DEXA‐P inhibited tumour growth and prolonged animal survival. In summary, we demonstrate for the first time that cancer‐specific transcription‐induced chimeric RNAs can be exploited to produce a cell‐free cancer vaccine that induces potent CD8+ T cell‐mediated anticancer immunity. Our novel approach may be particularly useful for developing cancer vaccines to treat malignancies with low mutational burden or without mutation‐based antigens. Moreover, this cell‐free anticancer vaccine approach may offer several practical advantages over cell‐based vaccines, such as ease of scalability and genetic modifiability as well as enhanced shelf life. [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.

Background: The Multinational Association for Supportive Care in Cancer (MASCC) risk index has been utilized to determine the risk for poor clinical outcomes in patients with febrile neutropenia (FN) in an emergency center (EC). However, this index comprises subjective elements and elaborated metrics limiting its use in ECs. We sought to determine whether procalcitonin (PCT) level (biomarker of bacterial infection) with or without lactate level (marker of inadequate tissue perfusion) offers a potential alternative to MASSC score in predicting the outcomes of patients with FN presenting to an EC. Methods: We retrospectively identified 550 cancer patients with FN who presented to our EC between April 2018, and April 2019, and had serum PCT and lactate levels measured. Results: Compared with patients with PCT levels <0.25 ng/ml, those with levels ≥0.25 ng/ml had a significantly higher 14‐day mortality rate (5.2% vs. 0.7%; p = 0.002), a higher bloodstream infection (BSI) rate, and a longer hospital length of stay (LOS). Logistic regression analysis showed that patients with PCT levels ≥0.25 ng/ml and lactate levels >2.2 mmol/L were more likely to be admitted and have an LOS >7 days, BSI, and 14‐day mortality than patients with lower levels. PCT level was a significantly better predictor of BSI than MASSC score (p = 0.003) or lactate level (p < 0.0001). Conclusions: Procalcitonin level is superior to MASCC index in predicting BSI. The combination of PCT and lactate levels is a good predictor of BSI, hospital admission, and 14‐day mortality and could be useful in identifying high‐risk FN patients who require hospital admission. [ABSTRACT FROM AUTHOR]

Background: Prior research has confirmed that persistent hypomagnesemia was predictive of shorter survival among patients with ovarian cancer who received carboplatin‐based chemotherapy. In the current retrospective study, the authors examined the association between hypomagnesemia and survival in patients with head and neck cancer who received concurrent chemoradiation with weekly infusions of cisplatin and/or carboplatin. Methods: Patients with head and neck cancers who had undergone chemoradiation with cisplatin and/or carboplatin between January 1, 2010, and December 31, 2014, were included. Patients were aged ≥18 years with pathology of squamous cell carcinoma of the larynx, oral cavity, or oropharynx who had received at least 30 fractions of radiotherapy with concurrent weekly cisplatin and/or carboplatin. Pathology features, laboratory results, Eastern Cooperative Oncology Group performance status, social histories, and survival were recorded. The association between hypomagnesemia and survival was analyzed controlling for known prognostic factors. Results: The final cohort consisted of 439 patients with a median age of 59 years. A greater frequency of hypomagnesemia during the treatment course was found to be significantly associated with shorter survival (hazard ratio [HR], 1.13; P =.033) independent of age (HR, 1.65; P =.042), cancer site (nonoropharynx vs oropharynx: HR, 2.15 [P =.003]), Eastern Cooperative Oncology Group performance status (>1 vs ≤1: HR, 2.64 [P <.001]), and smoking history (smoker vs nonsmoker: HR, 1.88 [P =.012]). In addition, more severe hypomagnesemia was associated with shorter survival compared with the milder form. Conclusions: The frequency and severity of hypomagnesemia during treatment are prognostic of survival for patients with head and neck cancers who are receiving concurrent chemoradiation with cisplatin and/or carboplatin. A prospective study is needed to investigate the impact of the prevention of hypomagnesemia on survival in this patient population. Persistent hypomagnesemia appears to be predictive of shorter survival in patients with head and neck cancer who receive primary, concurrent, platinum‐based chemoradiation. The prevention of hypomagnesemia may be an indispensable component of a comprehensive anticancer strategy to improve the clinical outcomes for these patients. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine whether hypomagnesemia predicts osteoradionecrosis development in patients with squamous cell carcinoma of the oropharynx and oral cavity who received platinum‐based concurrent chemoradiation with or without induction therapy. Methods: We reviewed data from patients with head and neck cancers who had undergone chemoradiation with weekly cisplatin/carboplatin between January 1, 2010 and December 31, 2014 at our institution. Pathologic features, laboratory test results, disease stage, and social histories were recorded. The association between hypomagnesemia and osteoradionecrosis was analyzed controlling for known confounding factors. Results: Hypomagnesemia during cancer treatment was associated with osteoradionecrosis development (HR = 2.72, P =.037) independent of total radiation dose (HR = 1.07, P =.260) and smoking history (HR = 2.05, P =.056) among the patients who received platinum‐based induction chemotherapy followed by concurrent chemoradiation. Conclusions: Hypomagnesemia was predictive of the development of osteoradionecrosis in patients with cancers of the oropharynx and oral cavity receiving platinum‐based induction followed by concurrent chemoradiation. [ABSTRACT FROM AUTHOR]

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: Oral mucositis (OM) is a debilitating sequela for patients treated for squamous cell carcinoma of the head and neck (HNSCC). This study investigated whether oral microbial features before treatment or during treatment are associated with the time to onset of severe OM in patients with HNSCC. Methods: This was a cohort study of newly diagnosed patients with locoregional HNSCC who received chemotherapy with or without radiotherapy from April 2016 to September 2017. OM was based on the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. The oral microbiome was characterized on the basis of the 16S ribosomal RNA V4 region with the Illumina platform. A mixture cure model was used to generate hazard ratios for the onset of severe OM. Results: Eighty‐six percent of the patients developed OM (n = 57 [33 nonsevere cases and 24 severe cases]) with a median time to onset of OM of 21 days. With adjustments for age, sex, and smoking status, genera abundance was associated with the hazard for the onset of severe OM as follows: 1) at the baseline (n = 66), Cardiobacterium (P =.03) and Granulicatella (P =.04); 2) immediately before the development of OM (n = 57), Prevotella (P =.03), Fusobacterium (P =.03), and Streptococcus (P =.01); and 3) immediately before the development of severe OM (n = 24), Megasphaera (P =.0001) and Cardiobacterium (P =.03). There were no differences in α‐diversity between the baseline samples and Human Microbiome Project data. Conclusions: Changes in the abundance of genera over the course of treatment were associated with the onset of severe OM. The mechanism and therapeutic implications of these findings need to be investigated in future studies. Oral mucositis is a debilitating sequela for patients treated for squamous cell carcinoma of the head and neck. Specific genera may be targeted for probiotic or antibiotic therapy for the prevention and treatment of oral mucositis. [ABSTRACT FROM AUTHOR]

Forkhead‐Box Class O 4 (FOXO4) is involved in critical biological functions, but its response to EGF‐PKB/Akt signal regulation is not well characterized. Here, it is reported that FOXO4 levels are downregulated in response to EGF treatment, with concurrent elevation of COP9 Signalosome subunit 6 (CSN6) and E3 ubiquitin ligase constitutive photomorphogenic 1 (COP1) levels. Mechanistic studies show that CSN6 binds and regulates FOXO4 stability through enhancing the E3 ligase activity of COP1, and that COP1 directly interacts with FOXO4 through a VP motif on FOXO4 and accelerates the ubiquitin‐mediated degradation of FOXO4. Metabolomic studies demonstrate that CSN6 expression leads to serine and glycine production. It is shown that FOXO4 directly binds and suppresses the promoters of serine‐glycine‐one‐carbon (SGOC) pathway genes, thereby diminishing SGOC metabolism. Evidence shows that CSN6 can regulate FOXO4‐mediated SGOC gene expression. Thus, these data suggest a link of CSN6‐FOXO4 axis and ser/gly metabolism. Further, it is shown that CSN6‐COP1‐FOXO4 axis is deregulated in cancer and that the protein expression levels of CSN6 and FOXO4 can serve as prognostic markers for cancers. The results illustrate a pathway regulation of FOXO4‐mediated serine/glycine metabolism through the function of CSN6‐COP1 axis. Insights into this pathway may be strategically designed for therapeutic intervention in cancers. [ABSTRACT FROM AUTHOR]

Background Diabetes mellitus type 2 (DM2) is a modifiable risk factor associated with pancreatic carcinogenesis and tumor progression on the basis of epidemiology studies, but the biological mechanisms are not completely understood. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating these epidemiologic phenomena. Our hypothesis is that DM2 accelerates pancreatic cancer growth and that metformin treatment has a beneficial impact. Methods To determine the effect of glucose and insulin in pancreatic cancer proliferation, we used conditioned media to mimic DM2 conditions. Also, we studied the effect of anti-diabetic drugs, particularly metformin and rosiglitazone on pancreatic cancer growth. We established orthotopic/syngeneic (Lepr db/db ) mouse cancer models to evaluate the effect of diabetes on pancreatic tumor growth and aggressiveness. Results Our results showed that diabetes promotes pancreatic tumor growth. Furthermore, enhanced tumor growth and aggressiveness (e.g. epithelial–mesenchymal transition) can be explained by functional transcriptomic and metabolomic changes in the mice with diabetes, namely via activation of the AKT/mTOR pathway. Metformin treatment suppressed the diabetes-induced AKT/mTOR pathway activation and tumor growth. The metabolic profile determined by mass spectrum showed important changes of metabolites in the pancreatic cancer derived from diabetic mice treated with metformin. Conclusions Diabetes mellitus type 2 has critical effects that promote pancreatic cancer progression via transcriptomic and metabolomic changes. Our animal models provide strong evidence for the causal relationship between diabetes and accelerated pancreatic cancers. This study sheds a new insight into the effects of metformin and its potential as part of therapeutic interventions for pancreatic cancer in diabetic patients. [ABSTRACT FROM AUTHOR]

Objective Knowledge about the impact of metabolic disturbances and parenteral nutrition (PN) characteristics on the survival of cancer patients receiving PN is limited. We aimed to assess the association between clinical and PN characteristics and survival in colorectal-cancer patients receiving PN support. Methods Our study included 572 consecutive colorectal-cancer patients who had received PN support between 2008 and 2013. Patient characteristics, body mass index, weight, medical/surgical history, indication for PN, PN data and survival were recorded. Associations between clinical and PN characteristics and survival were analysed with important confounding factors. Results The final cohort included 437 evaluable patients, with a mean age of 57 years. Eighty-one percent of the study population had advanced stage of colorectal cancer. Unstable weight (weight change ≥2.5%) prior to PN initiation [hazard ratio (HR) = 1.41, P  = 0.023] was adversely associated with survival after adjusting for multiple factors including cancer stage. Bowel obstruction (HR = 1.75, P  = 0.017) as a PN indication was associated with worse survival when compared with without bowel obstruction. Higher PN amino acid by ideal body weight (g•kg−1) (HR = 0.59, P  = 0.029) was associated with longer survival, whereas a higher percentage of non-PN intravenous calories (HR = 1.04, P  = 0.011) was associated with shorter survival independently of confounding factors. Conclusions Body mass index and weight stability can be useful nutritional indices for survival prediction in cancer patients receiving PN. PN planning should take into account of non-PN calories to achieve optimal energy support and balance. Future research is needed to define optimal PN amino-acid requirement and energy balance. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors confer significant clinical benefit by bolstering immune‐system activity, however, they also produce a spectrum of immune‐related adverse events (irAEs). Rapid recognition and timely treatment of these patients is essential for improved outcomes. Methods: We conducted a systematic review of English‐language articles in MEDLINE, EMBASE, Web of Science, PubMed, and Cochrane CENTRAL databases on patients with head and neck cancer treated with immune checkpoint inhibitors who developed treatment‐related adverse events. Results: Of 1715 unique citations, 11 studies met inclusion criteria. Eight patients with serious irAEs were reported from case reports and case series. Overall, 46 treatment‐related AEs were identified from the pooled 791 patients with at least 12 having potential relevance to irAEs. The most frequent AEs observed in patients receiving PD‐1 inhibitors involved the endocrine, cutaneous, and gastrointestinal systems. Conclusions: Characterizing irAEs in longitudinal studies is needed for developing strategies for their prompt recognition and management. [ABSTRACT FROM AUTHOR]

Background: The frequency of delirium among patients with cancer presenting to the emergency department (ED) is unknown. The purpose of this study was to determine delirium frequency and recognition by ED physicians among patients with advanced cancer presenting to the ED of The University of Texas MD Anderson Cancer Center.Methods: The study population was a random sample of English-speaking patients with advanced cancer who presented to the ED and met the study criteria. All patients were assessed with the Confusion Assessment Method (CAM) to screen for delirium and with the Memorial Delirium Assessment Scale (MDAS) to measure delirium severity (mild, ≤15; moderate, 16-22; and severe, ≥23). ED physicians were also asked whether their patients were delirious.Results: Twenty-two of the 243 enrolled patients (9%) had CAM-positive delirium, and their median MDAS score was 14 (range, 9-21 [30-point scale]). The median age of the enrolled patients was 62 years (range, 19-89 years). Patients with delirium had a poorer performance status than patients without delirium (P < .001); however, the 2 groups did not differ in other characteristics. Ten of the 99 patients who were 65 years old or older (10%) had CAM-positive delirium, whereas 12 of the 144 patients younger than 65 years (8%) did (P = .6). According to the MDAS scores, delirium was mild in 18 patients (82%) and moderate in 4 patients (18%). Physicians correctly identified delirium in 13 of the CAM-positive delirious patients (59%).Conclusions: Delirium is relatively frequent and is underdiagnosed by physicians in patients with advanced cancer who are visiting the ED. Further research is needed to identify the optimal screening tool for delirium in ED. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2918-2924. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose: Consultation to palliative care (PC) services in hospitalized patients is frequently late after admission to a hospital. The purpose of this study is to examine the association of in-hospital mortality and timing of palliative care consultation in cancer patients admitted through the emergency department (ED) of MD Anderson Cancer Center.Methods: Institutional databases were queried for unique medical admissions over a period of 1 year. Primary cancer type, ED versus direct admission, length of stay (LOS), presenting symptoms, and in-hospital mortality were reviewed; patient data were analyzed, and risk factors for in-hospital mortality were identified. The association of early palliative care consultation (within 3 days of admission) with these outcomes was studied. Descriptive statistics and multivariate logistic regression model were used.Results: Equal numbers of patients were admitted directly versus through the ED (7598 and 7538 respectively). However, of all patients who died in the hospital, 990 (88%) were admitted through the ED, compared with 137 admitted directly (P < 0.001). Patients who died in the hospital had longer median LOS compared with patients who were discharged alive (11 vs. 4 days, respectively, P < 0.001). Early palliative care consultation was associated with decreased mortality, compared with late consultation (P < 0.001). Chief complaints of respiratory problems, neurologic issues, or fatigue/weakness were significantly associated with in-hospital mortality.Conclusion: We found an association between ED admission and hospital mortality. Decedent cancer patients had a prolonged LOS, and early palliative care consultation for terminally ill symptomatic patients may prevent in-hospital mortality and improve quality of cancer care. [ABSTRACT FROM AUTHOR]

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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]

Background: Thromboembolism (TE) is a leading cause of death in cancer patients. Primary thromboprophylaxis (PTP) in ambulatory cancer patients receiving chemotherapy has been debated and considered to potentially improve survival by reducing TE occurrence. Objective: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in ambulatory lung cancer (LC) patients on chemotherapy to determine the benefit and risk of PTP with low-molecular-weight heparins (LMWHs). Method: A literature search using MEDLINE and EMBASE databases was performed through June 2016. RCTs with venous thromboembolism (VTE) reduction as primary or secondary endpoints were included. Mantel-Haenszel method was used to estimate the pooled event risk ratio as well as pooled absolute risk difference with 95% confidence interval (CI). Result: A total of 4315 LC patients from six studies were available for analysis. PTP lasted for 4 to 6 months. The venous thromboembolism (VTE) incidence was 4.0% and 7.9% in LMWH and control groups, respectively (risk ratio, 0.510 (95% CI, 0.397-0.654, P < 0.001). The absolute risk difference in VTE was -0.039 (95% CI, -0.053 to -0.025, P < 0.001), with an estimated number needed to treat (NNT) of 25 to prevent one VT Eevent. The pooled risk ratio for major bleeding was 1.468 (95% CI, 0.785-2.746, P = 0.229). The pooled risk ratio for overall survival was statistically nonsignificant at 1.020 (95% CI, 0.938-1.109, P = 0.648). Conclusion: Routine PTP for ambulatory LC patients receiving chemotherapy is not recommended and further studies are necessary to define a subset of ambulatory LC patients receiving chemotherapy who may benefit from PTP. [ABSTRACT FROM AUTHOR]

Background: Cancer chemotherapy-associated febrile neutropenia (FN) is a common condition that is deadly when bacteremia is present. Detection of bacteremia depends on culture, which takes days, and no accurate predictive tools applicable to the initial evaluation are available. We utilized metabolomics and transcriptomics to develop multivariable predictors of bacteremia among FN patients. Methods: We classified emergency department patients with FN and no apparent infection at presentation as bacteremic (cases) or not (controls), according to blood culture results. We assessed relative metabolite abundance in plasma, and relative expression of 2,560 immunology and cancer-related genes in whole blood. We used logistic regression to identify multivariable predictors of bacteremia, and report test characteristics of the derived predictors. Results: For metabolomics, 14 bacteremic cases and 25 non-bacteremic controls were available for analysis; for transcriptomics we had 7 and 22 respectively. A 5-predictor metabolomic model had an area under the receiver operating characteristic curve of 0.991 (95%CI: 0.972,1.000), 100% sensitivity, and 96% specificity for identifying bacteremia. Pregnenolone steroids were more abundant in cases and carnitine metabolites were more abundant in controls. A 3-predictor gene expression model had corresponding results of 0.961 (95%CI: 0.896,1.000), 100%, and 86%. Genes involved in innate immunity were differentially expressed. Conclusions: Classifiers derived from metabolomic and gene expression data hold promise as objective and accurate predictors of bacteremia among FN patients without apparent infection at presentation, and can provide insights into the underlying biology. Our findings should be considered illustrative, but may lay the groundwork for future biomarker development. [ABSTRACT FROM AUTHOR]