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.

Current gaps in emergency medicine core content education for oncologic emergencies: A targeted needs assessment.

Objective: The core content of emergency medicine (EM) residency training includes the management of oncologic emergencies; however, documented knowledge gaps continue to exist in this subtopic. This study represents a targeted needs assessment as indicated by Step 2 of Kern's curriculum design to determine the specific training gaps to be addressed within the oncologic EM curriculum. Methods: A multi-institutional cross-sectional survey of oncologists (surgical and medical) and emergency physicians (attendings and residents) was conducted during 2023 at five institutions. The voluntary survey consisted of general and specialty-specific questions exploring gaps in oncologic emergency-specific training/education topics. Descriptive statistics reported responses as frequencies and percentages. Results: Of the 833 surveys sent across the five sites, 302 (36.3%) were accessed by link; of these, 271 (89.7%) surveys were completed. There were no differences in the responses between early and later respondents and no differences in the characteristics of respondents between sites. A vast majority of the oncologist and EM groups (91.2% and 83.0%, respectively) reported a belief that emergency physicians would benefit from additional oncologic emergency training. Our survey identified 16 important topics for inclusion in an oncologic EM curriculum, including five topics not present on the 2022 Model of Clinical Practice of Emergency Medicine. Conclusions: Based on this needs assessment, an oncologic EM curriculum should include the topics listed under oncologic emergencies in the 2022 Model of the Clinical Practice of Emergency Medicine along with our respondent-identified topics of radiation therapy adverse effects, stem cell transplant complications, and the management of cancer-specific postsurgical complications, pain, and common diseases in patients with cancer.

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.

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.

Evaluation and management of acute high-grade immunotherapy-related neurotoxicity.

Immune checkpoint inhibitor monoclonal antibodies allow the host's immune system to attack tumors, which has revolutionized cancer care over the last decade. As the use of immune checkpoint inhibitors has expanded, so have autoimmune-like complications known as immune-related adverse events. These include the infrequent but increasingly more common, potentially deadly neurological immune related adverse events. When feeling acutely ill, patients will often seek care not from their oncologist but from their family physician, clinics, emergency, and urgent care sites, or other available providers. Thus, while assessing acutely ill cancer patients who are experiencing neurological symptoms, non-oncologists should be prepared to recognize, diagnose, and treat neurological immune related adverse events in addition to more familiar conditions. This narrative review is designed to update acute care clinicians on current knowledge and to present a symptom-based framework for evaluating and treating neurological immune related adverse events based on the leading immunotoxicity organizations' latest recommendations.

Characteristics and Outcomes of Patients with Cancer Pain Placed in an Emergency Department Observation Unit.

Pain remains an undertreated complication of cancer, with poor pain control decreasing patients' quality of life. Traditionally, patients presenting to an emergency department with pain have only had two dispositions available to them: hospitalization or discharge. A third emerging healthcare environment, the emergency department observation unit (EDOU), affords patients access to a hospital's resources without hospitalization. To define the role of an EDOU in the management of cancer pain, we conducted a retrospective study analyzing patients placed in an EDOU with uncontrolled cancer pain for one year. Patient characteristics were summarized using descriptive statistics and predictors of disposition from the EDOU and were identified with univariate and multivariate analyses. Most patients were discharged home, and discharged patients had low 72-hour revisit and 30-day mortality rates. Significant predictors of hospitalization were initial EDOU pain score (odds ratio (OR) = 1.12; 95% CI 1.06−1.19; p < 0.001) and supportive care (OR = 2.04; 95% CI 1.37−3.04; p < 0.001) or pain service (OR = 2.67; 95% CI 1.63−4.40; p < 0.001) consultations. We concluded that an EDOU appears to be the appropriate venue to care for a subsegment of patients presenting to an emergency department with cancer pain, with patients receiving safe care as well as appropriate consultation and admission when indicated.

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.

Characteristics and predictors of venous thrombosis recurrence in patients with cancer and catheter-related thrombosis.

Background: Central venous catheters raise the risk of catheter-related thrombosis (CRT) in patients with cancer, typically affecting the upper extremity. Management of CRT involves catheter removal and anticoagulation. However, robust evidence is lacking on the optimal timing of anticoagulation relative to catheter removal. Objectives: Our goal is to provide a better understanding of the factors that increase the risk of recurrent venous thromboembolism (VTE) in these patients. Patients and Methods: We conducted a retrospective chart review of all consecutive patients with cancer in our hospital affected by CRT between January 1, 2015, and December 31, 2017. We measured recurrence of VTE as thrombosis in any vascular bed or pulmonary embolism, for up to 2 years after diagnosis. Logistic and competing risk regression analyses were used to determine the association between different clinical factors and any VTE recurrence in patients with cancer and CRT. Results: Of the 257 individuals meeting the inclusion criteria, 80.2% had their catheter removed; of these, 50.5% did not receive anticoagulation before the removal. Patients who did not receive anticoagulation before the removal had increased 3-month and 1-year risks of recurrent VTE (odds ratio, 5.07 [95% confidence interval [CI], 1.53-23.18]; and hazard ratio, 3.47 [95% CI, 1.34-9.01]), respectively. Conclusions: Our study supports the use of anticoagulants before catheter removal in patients with CRT. Randomized clinical trials are recommended to establish stronger evidence pertaining to the long-term risk of VTE recurrence and the effect of catheter reinsertion.

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.