Myocarditis, Myositis, and Myasthenia Gravis Overlap Syndrome Associated with Immune Checkpoint Inhibitors: A Systematic Review.

Immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment, but their use is linked to immune-related adverse events (irAEs), including the rare ICI-associated myocarditis, myositis, and myasthenia gravis (MMM) overlap syndrome. This systematic review aims to highlight MMM's clinical implications in emergency departments. PubMed and Embase were searched using a specific search strategy. Reports were eligible for inclusion if all three conditions were present and associated with the use of an ICI. Data were extracted by independent reviewers using the Rayyan web application for systematic reviews. Descriptive statistics and qualitative synthesis were used to summarize demographic, clinical, and treatment data for the reported cases. Among 50 cases, predominantly associated with melanoma, lung cancer, and renal cancer, the in-hospital mortality rate was 38.0%. The most commonly presenting symptoms were ptosis (58%), dyspnea (48%), diplopia (42%), or myalgia (36%). The median time from ICI initiation to MMM presentation was 21 days (interquartile range: 15-28 days). Corticosteroids were the primary treatment for the irAEs. MMM, a rare but potentially fatal complication of ICI therapy, requires prompt recognition in emergency settings. Corticosteroids should be initiated if suspected, without waiting for confirmation. Multidisciplinary collaboration is vital for diagnosis and treatment planning. Research on MMM's link to specific cancers and ICIs is imperative for better risk assessment and interventions.

Immune-related adverse event in the emergency department: methodology of the immune-related emergency disposition index (IrEDi).

For many cancer patients, immune checkpoint inhibitors (ICIs) can be life-saving. However, the immune-related adverse events (irAEs) from ICIs can be debilitating and can quickly become severe or even be fatal. Often, irAEs will precipitate visits to the emergency department (ED). Therefore, early recognition and the decision to admit, observe, or discharge these patients from the ED can be key to a cancer patient's morbidity and mortality. ED clinicians typically make their decision for disposition (admit, observe, or discharge) within 2-6 h from their patient's ED presentation. However, irAEs are particularly challenging in the ED because of atypical presentations, the absence of classic symptoms, the delayed availability of diagnostic tests during the ED encounter, and the fast pace in the ED setting. At present, there is no single sufficiently large ED data source with clinical, biological, laboratory, and imaging data that will allow for the development of a tool that will guide early recognition and appropriate ED disposition of patients with potential irAEs. We describe an ongoing federally funded project that aims to develop an immune-related emergency disposition index (IrEDi). The project capitalizes on a multi-site collaboration among 4 members of the Comprehensive Oncologic Emergency Research Network (CONCERN): MD Anderson Cancer Center, Ohio State University, Northwestern University, and University of California San Diego. If the aims are achieved, the IrEDi will be the first risk stratification tool derived from a large racial/ethnically and geographically diverse population of cancer patients. The future goal is to validate irEDi in general EDs to improve emergency care of cancer patients on ICIs.

Influence of oral microbiome on longitudinal patterns of oral mucositis severity in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: This study investigated the influence of oral microbial features on the trajectory of oral mucositis (OM) in patients with squamous cell carcinoma of the head and neck. METHODS: OM severity was assessed and buccal swabs were collected at baseline, at the initiation of cancer treatment, weekly during cancer treatment, at the termination of cancer treatment, and after cancer treatment termination. The oral microbiome was characterized via the 16S ribosomal RNA V4 region with the Illumina platform. Latent class mixed-model analysis was used to group individuals with similar trajectories of OM severity. Locally estimated scatterplot smoothing was used to fit an average trend within each group and to assess the association between the longitudinal OM scores and longitudinal microbial abundances. RESULTS: Four latent groups (LGs) with differing patterns of OM severity were identified for 142 subjects. LG1 has an early onset of high OM scores. LGs 2 and 3 begin with relatively low OM scores until the eighth and 11th week, respectively. LG4 has generally flat OM scores. These LGs did not vary by treatment or clinical or demographic variables. Correlation analysis showed that the abundances of Bacteroidota, Proteobacteria, Bacteroidia, Gammaproteobacteria, Enterobacterales, Bacteroidales, Aerococcaceae, Prevotellaceae, Abiotrophia, and Prevotella_7 were positively correlated with OM severity across the four LGs. Negative correlation was observed with OM severity for a few microbial features: Abiotrophia and Aerococcaceae for LGs 2 and 3; Gammaproteobacteria and Proteobacteria for LGs 2, 3, and 4; and Enterobacterales for LGs 2 and 4. CONCLUSIONS: These findings suggest the potential to personalize treatment for OM. PLAIN LANGUAGE SUMMARY: Oral mucositis (OM) is a common and debilitating after effect for patients treated for squamous cell carcinoma of the head and neck. Trends in the abundance of specific microbial features may be associated with patterns of OM severity over time. Our findings suggest the potential to personalize treatment plans for OM via tailored microbiome interventions.

Cardiovascular events after cancer immunotherapy as oncologic emergencies: Analyses of 610 head and neck cancer patients treated with immune checkpoint inhibitors.

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.

Attempts to Understand Oral Mucositis in Head and Neck Cancer Patients through Omics Studies: A Narrative Review.

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).

Premature senescence and cardiovascular disease following cancer treatments: mechanistic insights.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, especially among the aging population. The "response-to-injury" model proposed by Dr. Russell Ross in 1999 emphasizes inflammation as a critical factor in atherosclerosis development, with atherosclerotic plaques forming due to endothelial cell (EC) injury, followed by myeloid cell adhesion and invasion into the blood vessel walls. Recent evidence indicates that cancer and its treatments can lead to long-term complications, including CVD. Cellular senescence, a hallmark of aging, is implicated in CVD pathogenesis, particularly in cancer survivors. However, the precise mechanisms linking premature senescence to CVD in cancer survivors remain poorly understood. This article aims to provide mechanistic insights into this association and propose future directions to better comprehend this complex interplay.

An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis.

BACKGROUND: ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and inflammation. We aimed to investigate how ERK5 reprograms myeloid cells to the proinflammatory senescent phenotype, subsequently leading to atherosclerosis. METHODS: A ERK5 S496A (dephosphorylation mimic) knock in (KI) mouse model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9), and atherosclerosis was characterized by hypercholesterolemia induction. The plaque phenotyping in homozygous ERK5 S496A KI and wild type (WT) mice was studied using imaging mass cytometry. Bone marrow-derived macrophages were isolated from hypercholesterolemic mice and characterized using RNA sequencing and functional in vitro approaches, including senescence, mitochondria reactive oxygen species, and inflammation assays, as well as by metabolic extracellular flux analysis. RESULTS: We show that atherosclerosis was inhibited in ERK5 S496A KI mice. Furthermore, ERK5 S496 phosphorylation mediates both senescence-associated secretory phenotype and senescence-associated stemness by upregulating AHR (aryl hydrocarbon receptor) in plaque and bone marrow-derived macrophages isolated from hypercholesterolemic mice. We also discovered that ERK5 S496 phosphorylation could induce NRF2 (NFE2-related factor 2) SUMOylation at a novel K518 site to inhibit NRF2 transcriptional activity without altering ERK5 catalytic activity and mediates oxidized LDL (low-density lipoprotein)-induced senescence-associated secretory phenotype. Specific ERK5 kinase inhibitors (AX15836 and XMD8-92) also inhibited ERK5 S496 phosphorylation, suggesting the involvement of ERK5 S496 phosphorylation in the anti-inflammatory effects of these ERK5 kinase inhibitors. CONCLUSIONS: We discovered a novel mechanism by which the macrophage ERK5-NRF2 axis develops a unique senescence-associated secretory phenotype/stemness phenotype by upregulating AHR to engender atherogenesis. The finding of senescence-associated stemness phenotype provides a molecular explanation to resolve the paradox of senescence in proliferative plaque by permitting myeloid cells to escape the senescence-induced cell cycle arrest during atherosclerosis formation.

Emergency department use by patients who received chimeric antigen receptor T cell infusion therapy.

Background: Chimeric antigen receptor T cell infusion (CAR T) therapy has revolutionized the treatment of hematologic malignancies, but treatment-related 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.

Long COVID in cancer patients: preponderance of symptoms in majority of patients over long time period.

Background: An increasing number of observational studies have reported the persistence of symptoms following recovery from acute COVID-19 disease in non-cancer patients. The long-term consequences of COVID-19 are not fully understood particularly in the cancer patient population. The purpose of this study is to assess post-acute sequelae of SARS-CoV-2 infection (PASC) in cancer patients following acute COVID-19 recovery. Methods: We identified cancer patients at MD Anderson Cancer Center who were diagnosed with COVID-19 disease between March 1, 2020, and September 1, 2020, and followed them till May 2021. To assess PASC, we collected patients reported outcomes through questionnaires that were sent to patients daily for 14 days after COVID-19 diagnosis then weekly for 3 months, and then monthly thereafter. We also reviewed patients' electronic medical records to capture the persistence or emergence of new COVID19-related symptoms reported during any clinic or hospital encounter beyond 30 days of the acute illness and up to 14 months. Results: We included 312 cancer patients with a median age of 57 years (18-86). The majority of patients had solid tumors (75%). Of the 312 patients, 188 (60%) reported long COVID-19 symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis. The most common symptoms reported included fatigue (82%), sleep disturbances (78%), myalgias (67%), and gastrointestinal symptoms (61%), followed by headache, altered smell or taste, dyspnea (47%), and cough (46%). A higher number of females reported a persistence of symptoms compared to males (63% vs. 37%; p=0.036). Cancer type, neutropenia, lymphocytopenia, and hospital admission during acute COVID-19 disease were comparable in both groups. Among the 188 patients with PASC, only 16 (8.5%) were re-admitted for COVID-related reasons. Conclusions: More than one out of two cancer patients, and more likely females, report PASC that may persist beyond 6 months and even 1 year. The most common symptoms are non-respiratory and consist of fatigue, sleep disturbance, myalgia, and gastrointestinal symptoms. Most of the cancer patients with PASC were managed on outpatient basis with only 8.5% requiring a COVID-19-related re-admission. Funding: This research is supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672, which supports the MD Anderson Cancer Center Clinical Trials Office. The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.

MyTPill: study protocol for a cross-over randomised controlled trial comparing novel strategies to monitor antiretroviral adherence among HIV+ prescription opioid users.

INTRODUCTION: Adherence to HIV antiretroviral therapy (ART) remains the cornerstone of HIV treatment. For individuals with suboptimal adherence, electronic adherence monitoring (EAM) technologies have become an important component of multimodal adherence support strategies. Most EAM technologies detect pillbox opening, and therefore, assume but cannot verify actual ingestion of oral medication. In contrast, a digital pill system (ID-capsule manufactured by etectRX, here named My/Treatment/Pill) measures directly ingestion of medications. Identifying the superior method to measure ART adherence would improve virological suppression by enabling the delivery of real-time interventions to support ART adherence, particularly in high-risk populations. METHODS AND ANALYSIS: Cross-over, randomised trial with 1:1 variable block size randomisation comparing two EAM systems in prescription opioid-using HIV+patient on once daily oral bictegravir, emtricitabine and tenofovir alafenamide regimens and detectable viral load >200 copies/mL within 30 days of screening (n=80). The primary outcome is once daily ART adherence measurement efficacy as assessed by comparing the accuracy of each EAM system as measured by concordance of the respective EAM systems to dried blood spot ART concentrations. Secondary outcomes are the identification of multilevel factors that are prevalent in the target population most closely linked to ART non-adherence and EAM non-adherence. ETHICS AND DISSEMINATION: This protocol was approved by the institutional review boards of participating sites (The Ohio State University, The Fenway Institute and the University of Miami). Data will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03978793.

International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship.

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03). Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality. Funding: National Cancer Institute and National Institutes of Health.

Radiation therapy induces immunosenescence mediated by p90RSK.

Radiation therapy (RT) to the chest increases the patients' risk of cardiovascular disease (CVD). A complete understanding of the mechanisms by which RT induces CVD could lead to specific preventive, therapeutic approaches. It is becoming evident that both genotoxic chemotherapy agents and radiation induce mitochondrial dysfunction and cellular senescence. Notably, one of the common phenotypes observed in cancer survivors is accelerated senescence, and immunosenescence is closely related to both cancer risk and CVD development. Therefore, suppression of immunosenescence can be an ideal target to prevent cancer treatment-induced CVD. However, the mechanism(s) by which cancer treatments induce immunosenescence are incompletely characterized. We isolated peripheral blood mononuclear cells (PBMCs) before and 3 months after RT from 16 thoracic cancer patients. We characterized human immune cell lineages and markers of senescence, DNA damage response (DDR), efferocytosis, and determinants of clonal hematopoiesis of indeterminant potential (CHIP), using mass cytometry (CyTOF). We found that the frequency of the B cell subtype was decreased after RT. Unsupervised clustering of the CyTOF data identified 138 functional subsets of PBMCs. Compared with baseline, RT increased TBX21 (T-bet) expression in the largest B cell subset of Ki67-/DNMT3a+naïve B cells, and T-bet expression was correlated with phosphorylation of p90RSK expression. CD38 expression was also increased in naïve B cells (CD27-) and CD8+ effector memory CD45RA T cells (TEMRA). In vitro, we found the critical role of p90RSK activation in upregulating (1) CD38+/T-bet+ memory and naïve B, and myeloid cells, (2) senescence-associated ß-gal staining, and (3) mitochondrial reactive oxygen species (ROS) after ionizing radiation (IR). These data suggest the crucial role of p90RSK activation in immunosenescence. The critical role of p90RSK activation in immune cells and T-bet induction in upregulating atherosclerosis formation has been reported. Furthermore, T-bet directly binds to the CD38 promoter region and upregulates CD38 expression. Since both T-bet and CD38 play a significant role in the process of immunosenescence, our data provide a cellular and molecular mechanism that links RT-induced p90RSK activation and the immunosenescence with T-bet and CD38 induction observed in thoracic cancer patients treated by RT and suggests that targeting the p90RSK/T-bet/CD38 pathway could play a role in preventing the radiation-associated CVD and improving cancer prognosis by inhibiting immunosenescence.

"Triple Threat" Conditions Predict Mortality Among Patients With Advanced Cancer Who Present to the Emergency Department.

BACKGROUND: Delirium, poor performance status, and dyspnea predict short survival in the palliative care setting. OBJECTIVE: Our goal was to determine whether these three conditions, which we refer to as a "triple threat," also predict mortality among patients with advanced cancers in the emergency department (ED). METHODS: The study sample included 243 randomly selected, clinically stable patients with advanced cancer who presented to our ED. The analysis included patients who had delirium (Memorial Delirium Assessment Scale score ≥ 7), poor performance status (Eastern Cooperative Oncology Group performance status score of 3 or 4), or dyspnea as a presenting symptom. We obtained survival data from medical records. We calculated predicted probability of dying within 30 days and association with number of symptoms after the ED visit using logistic regression analysis. RESULTS: Twenty-eight patients died within 30 days after presenting to the ED. Death within 30 days occurred in 36% (16 of 44) of patients with delirium, 28% (17 of 61) of patients with poor performance status, and 14% (7 of 50) of patients with dyspnea, with a predicted probability of 30-day mortality of 0.38 (95% confidence interval [CI] 0.25-0.53), 0.28 (95% CI 0.18-0.40), and 0.15 (95% CI 0.07-0.29), respectively. The predicted probability of death within 30 days for patients with two or three of the conditions was 0.49 (95% CI 0.34-0.66) vs. 0.05 (95% CI 0.02-0.09) for patients with none or one of the conditions. CONCLUSIONS: Patients with advanced cancers who present to the ED and have at least two triple threat conditions have a high probability of death within 30 days.

International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship.

Background: In this international multicenter study we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were more likely to be pancytopenic, and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding two weeks (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms (p≤0.01). By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who did not (5.9% vs 17.6%; p=0.03). Conclusions: Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality. Condensed Abstract: In this large multicenter worldwide study of 4015 patients with COVID-19 that included 1115 patients with cancer, we found that cancer is an independent risk factor for increased 30-day all-cause mortality. Remdesivir is a promising treatment modality to reduce 30-day all-cause mortality.

Neuropathic pain prevalence and risk factors in head and neck cancer survivors.

BACKGROUND: Neuropathic pain (NP) is a debilitating symptom among head and neck cancer (HNC) survivors although few large studies report its prevalence and associated risk factors. METHODS: A cross-sectional survey assessing demographic, behavioral, and clinical risk factors for NP. NP was assessed using the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS). RESULTS: Forty-five percent (227/505) reported having pain including 13.7% (69/505) who were positive for S-LANSS. Reported pain sites were in the regions of the head and oral cavity (46.2%) and neck and throat (41.5%). Despite a higher self-reported use of analgesic medication (NP+ = 41.2%; NP- = 27.4%; p = 0.020) and alternative pain therapies (NP+ = 19.1%; NP- = 8.4%; p = 0.009), severe pain was more prevalent among those with NP (N+ = 23.2%; NP- = 13.3%; p = 0.004). Adjusted for opioid medications, ethnicity/race, age, surgery, depression, and comorbidities were risk factors for NP. CONCLUSION: NP remains prevalent in HNC survivors highlighting the importance of routine pain surveillance.

Cancer treatment-induced NAD+ depletion in premature senescence and late cardiovascular complications.

Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. Senescence-associated secretory phenotype (SASP) can be induced by telomere dysfunction. Telomeric DNA damage response induced by some cancer treatments can persist for months, possibly accounting for long-term sequelae of cancer treatments. Telomeric DNA damage-induced mitochondrial dysfunction and increased reactive oxygen species production are hallmarks of premature senescence. Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family that is not only a kinase but also a transcriptional co-activator) were vital signaling events that played crucial roles in linking mitochondrial dysfunction, nuclear telomere dysfunction, persistent SASP induction, and atherosclerosis. In this review, we will discuss the role of NAD+ depletion in instigating SASP and its downstream signaling and regulatory mechanisms that lead to the premature onset of atherosclerotic cardiovascular diseases in cancer survivors.

Characterization of older adults with cancer seeking acute emergency department care: A prospective observational study.

INTRODUCTION: Disparities in care of older adults in cancer treatment trials and emergency department (ED) use exist. This report provides a baseline description of older adults ≥65 years old who present to the ED with active cancer. MATERIALS AND METHODS: Planned secondary analysis of the Comprehensive Oncologic Emergencies Research Network observational ED cohort study sponsored by the National Cancer Institute. Of 1564 eligible adults with active cancer, 1075 patients were prospectively enrolled, of which 505 were ≥ 65 years old. We recruited this convenience sample from eighteen participating sites across the United States between February 1, 2016 and January 30, 2017. RESULTS: Compared to cancer patients younger than 65 years of age, older adults were more likely to be transported to the ED by emergency medical services, have a higher Charlson Comorbidity Index score, and be admitted despite no significant difference in acuity as measured by the Emergency Severity Index. Despite the higher admission rate, no significant difference was noted in hospitalization length of stay, 30-day mortality, ED revisit or hospital admission within 30 days after the index visit. Three of the top five ED diagnoses for older adults were symptom-related (fever of other and unknown origin, abdominal and pelvic pain, and pain in throat and chest). Despite this, older adults were less likely to report symptoms and less likely to receive symptomatic treatment for pain and nausea than the younger comparison group. Both younger and older adults reported a higher symptom burden on the patient reported Condensed Memorial Symptom Assessment Scale than to ED providers. When treating suspected infection, no differences were noted in regard to administration of antibiotics in the ED, admissions, or length of stay ≤2 days for those receiving ED antibiotics. DISCUSSION: We identified several differences between older (≥65 years old) and younger adults with active cancer seeking emergency care. Older adults frequently presented for symptom-related diagnoses but received fewer symptomatic interventions in the ED suggesting that important opportunities to improve the care of older adults with cancer in the ED exist.

Palliative Care Needs and Clinical Outcomes of Patients with Advanced Cancer in the Emergency Department.

Background: Older adults with cancer use the emergency department (ED) for acute concerns. Objectives: Characterize the palliative care needs and clinical outcomes of advanced cancer patients in the ED. Design: A planned secondary data analysis of the Comprehensive Oncologic Emergencies Research Network (CONCERN) data. Settings/Subjects: Cancer patients who presented to the 18 CONCERN affiliated EDs in the United States. Measurements: Survey included demographics, cancer type, functional status, symptom burden, palliative and hospice care enrollment, and advance directive code status. Results: Of the total (674/1075, 62.3%) patients had advanced cancer and most were White (78.6%) and female (50.3%); median age was 64 (interquartile range 54-71) years. A small proportion of them were receiving palliative (6.5% [95% confidence interval; CI 3.0-7.6]; p = 0.005) and hospice (1.3% [95% CI 1.0-3.2]; p = 0.52) care and had a higher 30-day mortality rate (8.3%, [95% CI 6.2-10.4]). Conclusions: Patients with advanced cancer continue to present to the ED despite recommendations for early delivery of palliative care.

A modified emergency severity index level is associated with outcomes in cancer patients with COVID-19.

OBJECTIVE: To evaluate a modified emergency severity index (mESI)-based triage of cancer patients with coronavirus disease 2019 (COVID-19) in the emergency department (ED) and determine the associations between mESI level and ED disposition, hospital length of stay, and overall survival. METHODS: Medical records were retrospectively reviewed for all patients who presented to our institution's ED between March 22, 2020, and March 12, 2021, and tested positive for SARS-CoV-2. RESULTS: A total of 306 cancer patients tested positive for SARS-CoV-2, with 45% of patients triaged to level 2 (emergent) and 55% to level 3 (urgent). Among all patients, 61.8% were admitted to the hospital, 15.7% were admitted to the intensive care unit, 2.9% were sent for observation, and 19.6% were discharged. Although demographic and clinical characteristics did not significantly vary by triage level, we observed significant differences in ED length of stay (urgent = 6.67 h, emergent = 5.97 h; p < 0.01). Hospital and intensive care unit admission rates were also significantly higher among emergent patients than among urgent patients (p < 0.05). There were 75 deaths (urgent = 32; emergent = 43), and the 30-day mortality rate was significantly higher among emergent patients (urgent = 8%, emergent = 15%; p < 0.05). The mESI level persisted as a significant factor associated with overall survival (hazard ratio = 1.7, 95% confidence interval = 1.09-2.81) in multivariable analysis. CONCLUSION: The mESI level is associated with ED disposition, ED length of stay, and overall survival in cancer patients presenting with COVID-19. These results indicate that the mESI triage tool can be effectively used in cancer patients with COVID-19, whose condition can rapidly deteriorate.