Immune checkpoint inhibitor-associated myasthenia gravis, myositis, and myocarditis overlap syndrome.

INTRODUCTION: Case reports of immune checkpoint inhibitor (ICI) overlap syndrome of myasthenia gravis, myositis and myocarditis, are increasing in the published literature. This is a potentially fatal adverse event of ICIs and emergency physicians need to be familiar with this triad when patients present to the emergency department (ED). METHODS: We performed a retrospective chart review of the electronic medical record between September 1, 2016 to March 9, 2020. We identified patients with the overlap syndrome who presented to our ED. RESULTS: Seven patients were identified. Most were female and treated with a programmed cell death-1 inhibitor. Most patients presented with abnormal vital signs and the most common symptoms were ptosis, diplopia, dyspnea and fatigue. Most required supplemental oxygen and had a prolonged length of stay. All received steroids in addition to other immunomodulators. Two patients died. DISCUSSION: Presence of one of the diagnosis should lead to evaluation for the others. Suspicion should be raised by patients presenting with ptosis, muscular weakness, fatigue and dyspnea. Early recognition of this triad can allow for early administration of high-dose glucocorticoids (1-2 mg/kg of prednisone or equivalent), which is the mainstay of treatment. However, it is likely that patients will need further immunomodulators and therefore, will need hospitalization. CONCLUSION: Emergency physicians should be aware of this potentially lethal triad in cancer patients receiving ICIs. The life-saving interventions in the ED include recognizing the triad, airway support, administration of high-dose glucocorticoids, and early involvement of a multidisciplinary team.

Cardiotoxicity associated with immune checkpoint inhibitors and CAR T-cell therapy.

INTRODUCTION: The expanding use of immunotherapy and the growing population of patients with cancer has led to an increase in the reporting of immune related adverse events (irAEs). The emergency clinician should be aware of these emerging toxicities, some of which can be fatal. In this review we discuss the cardiotoxic side effects of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR T-cell) therapy. DISCUSSION: Recognizing the possible presentations of cardiotoxic irAEs is of utmost important as the diagnosis of cardiotoxicity associated with ICI and CAR T-cell can be difficult to make in the emergency department. The emergency clinician will have to presume the diagnosis and treat it without final confirmation in most cases. For this reason, if the diagnosis is suspected, early involvement of the cardiologist and oncologist is important to help guide management. Most irAEs will be treated with glucocorticoids, but in the case of CAR T-cell cardiotoxicity, Tocilizumab should be used as first line. CONCLUSION: Although cardiotoxicity is rare, it is often life-threatening. Treatment should be initiated as soon as the diagnosis is suspected, and early involvement of the cardiologist and oncologist is imperative for optimal treatment.

Simulation-based curriculum development: lessons learnt in Global Health education.

BACKGROUND: Simulation based medical education (SBME) allows learners to acquire clinical skills without exposing patients to unnecessary risk. This is especially applicable to Emergency Medicine training programs where residents are expected to demonstrate proficiency in the management of time critical, low frequency, and highly-morbidity conditions. This study aims to describe the process through which a SBME curriculum was created, in a limited simulation resource setting at a 4-year Emergency Medicine (EM) residency program at the American University of Beirut Medical Center. METHODS: A case-based pilot simulation curriculum was developed following Kern's 6 step approach to curriculum design. The curricular objectives were identified through an anonymous survey of the program's residents and faculty. Curriculum outcomes were assessed, and the curriculum was revised to address curricular barriers. Evaluations of the revised curriculum were collected during the simulation sessions and through a whole revised curriculum evaluation at the end of the first year of its implementation. RESULTS: 14/20 residents (70%) and 8/8 faculty (100%) completed the needs assessment from which objectives for the pilot curriculum were developed and implemented through 6 2-h sessions over a 1-year period. Objectives were not met and identified barriers included cost, scheduling, resources, and limited faculty time. The revised curriculum addressed these barriers and 24 40-min sessions were successfully conducted during the following year. The sessions took place 3 at a time, in 2-h slots, using the same scenario to meet the objectives of the different learners' levels. 91/91 evaluations were collected from participants with overall positive results. The main differences between the pilot and the revised curricula included: a better understanding of the simulation center resources and faculty's capabilities. CONCLUSION: Simulation-based education is feasible even with limited-resources. However, understanding the resources available, and advocating for protected educator time are essential to implementing a successful EM simulation curriculum.

Adverse Events of Novel Therapies for Hematologic Malignancies: What Emergency Physicians Should Know.

In the past decade, rapid advances in therapeutic target discovery in hematologic malignancies have led to many clinical studies demonstrating efficacy of novel agents. Between 2014 and 2018, Food and Drug Administration approvals of new drugs and agents have increased, with greater than 2 dozen novel agents. Rapidly identifying the risk profiles of these cancer therapeutics that may present with acute toxicities and understanding the timing, sequence, duration, and treatment of disease processes are the most important challenges faced by practitioners in emergency medicine, even in nononcologic centers. The emergency medicine literature lags behind rapid advances in oncology, and guidelines for rapid recognition and management of these emerging entities are not familiar. In this Review Article, we discuss the most recent and clinically relevant developments in the arena of hematologic malignancies, further expanding on drug toxicities and their clinical presentations and offering suggestions for management. Specifically, we discuss immune-related adverse events after immune checkpoint inhibitor therapy (including myocarditis and hemophagocytic lymphohistiocytosis), chimeric antigen receptor-T cell therapy, cytokine release syndrome, chimeric antigen receptor-T cell-related encephalopathy syndrome, differentiation syndrome, sinusoid occlusion syndrome, QT-interval prolongation, and tumor lysis syndrome. Rapid advances in hematology and oncology will bring many new challenges for emergency health care providers in the near future; thus, the urgency to raise awareness among this community.

Acute ST Elevation Myocardial Infarction Due to Allergic Reaction, Kounis Syndrome.

Kounis syndrome is defined by the occurrence of an acute coronary syndrome (ACS) in the setting of an allergic, hypersensitivity or anaphylactic condition. Degranulation of mast cells and platelet activation leading to the release of multiple inflammatory mediators are thought to make the arterial circulation susceptible to acute cardiac events. It is an often underdiagnosed entity in the emergency setting, due to lack of awareness among emergency providers. Identifying Kounis syndrome is critical, since managing ACS differs from that of a classical acute myocardial infarction. We present the case of a 72-year old male patient with a history of stable coronary disease who presented to the emergency department with a diffuse pruritic rash and chest pain. Electrocardiogram showed ST elevation myocardial infarction. Urgent coronary angiography revealed total occlusion of the mid left anterior descending coronary artery which was treated with a drug eluting stent with an excellent outcome. The pruritic rash responded to treatment with intravenous corticosteroids and antihistamines; No allergens were identified. The patient's symptoms resolved and he had an uneventful hospitalization. The diagnosis of Kounis syndrome can complicate the management of acute allergic reactions. Special precautions should be taken by emergency physicians with regards to the administration of beta blockers, morphine and vasodilators, which may be detrimental in this setting.

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.

Characteristics of cancer patients with COVID-19 in a cancer hospital.

BACKGROUND: Cancer patients are vulnerable to the coronavirus disease (COVID-19) given their compromised immune system. The purpose of this study was to describe the presenting symptoms, inpatient stay trajectory, and survival outcomes, for cancer patients infected with COVID-19; who presented to the emergency department (ED) of a single center during the early months of the pandemic. METHODS: We reviewed the electronic medical records of all cancer patients diagnosed with COVID-19 at our institution for demographic information, clinical presentation, laboratory findings, treatment intervention and outcomes. All patients had at least 14 days of follow-up. We determined their survival outcomes as of August 5, 2020. RESULTS: Twenty-eight cancer patients were diagnosed with COVID-19, and 16 (57%) presented to the ED during the study period. The median age of patients who presented to the ED was 61 years, 69% were women, and the median length of hospitalization was 11 days. There was no difference between the groups (ED vs. no ED visit) for demographics, treatment status or solid tumor versus hematologic malignancies or treatments. Dyspnea was a significant symptom with 67% of ED patients experiencing it versus only 17% of those that did not come to the ED (P=0.009). Do not resuscitate orders were initiated in eight patients, as early as two days from ED presentation and two of these patients died, while 88% of patients were discharged alive. CONCLUSIONS: Most cancer patients with COVID-19 infection admitted though the ED experienced dyspnea and were discharged from the hospital. We did not notice a statistically significant difference between cancer types or type of therapy. A broad differential is of utmost importance when caring for cancer patients with COVID-19 due to the complexity of this population. Early goals of care discussion should be initiated in the ED.

Gastrointestinal adverse events associated with immune checkpoint inhibitor therapy.

Immunotherapy with checkpoint inhibitors has revolutionized cancer therapy and is now the standard treatment for several different types of cancer, supported by favorable outcomes and good tolerance. However, it is linked to multiple immune manifestations, referred to as immune-related adverse events (irAEs). These adverse events frequently affect the skin, colon, endocrine glands, lungs, and liver. The gastrointestinal system is one of the most commonly affected organ systems and is responsible for the most frequent emergency visits resulting from irAEs. However, because immune checkpoint inhibitors are a recent addition to our arsenal of cancer drugs, many health-care providers remain unfamiliar with the management of irAEs. Gastroenterologists involved in the treatment of oncology patients who have received checkpoint inhibitors are currently encountering cases of abdominal pain, diarrhea, and other nonspecific symptoms that may be challenging to manage. This article reviews the gastrointestinal, hepatic, and pancreatic toxicities of checkpoint inhibitors and provides an approach to their diagnosis and recommended workup. It also highlights the management of irAEs according to their toxicity grading and specifically discusses the instances in which corticosteroids should be administered and/or the immune checkpoint inhibitors should be withheld.

Diagnosis and management of immune-related adverse effects of immune checkpoint therapy in the emergency department.

Rapid advances in cancer immunotherapy using immune checkpoint inhibitors have led to significantly improved survival. Rapid identification of the toxicity syndromes associated with these therapeutic agents is very important for emergency physicians because the population of patients diagnosed with cancer is increasing and cancer therapies including immune checkpoint inhibitors have become the first-line treatment for more and more types of cancer. The emergency medicine literature lags behind rapid advances in oncology, and oncology guidelines for rapid recognition and management of these emerging toxicity syndromes are not familiar to emergency physicians. In this review article, we discuss the clinical presentation and management of immune-related adverse effects during the critical first hours of emergency care. We also suggest a workflow for the recognition and treatment of emergencies arising from serious immune-related adverse effects, including but not limited to colitis, adrenal crisis, myocarditis, pneumonitis, myasthenic crisis, diabetic ketoacidosis, bullous pemphigus, and hemophagocytic lymphohistiocytosis. Rapid advances in cancer therapy are bringing new diagnostic and therapeutic challenges to emergency providers, and therefore it is crucial to raise awareness and provide guidelines for the management of new treatment-related toxicities.

Epidemiology of burn patients presenting to a tertiary hospital emergency department in Lebanon.

BACKGROUND: The epidemiology of burns is well described in the United States, Europe and Asia. However, few studies address this topic in the Levant region. This study aims to describe characteristics of burn victims treated at the emergency department of a tertiary care center in Beirut, Lebanon and to report on factors that affect ED disposition. METHODS: A retrospective cohort study was conducted in the ED of a tertiary care hospital, in Beirut, Lebanon, between 2009 and 2013. Patients were recruited if their final ED diagnosis was burn. A descriptive analysis of patients' characteristics including burns was done, followed by a bivariate analysis to compare two groups (admitted vs discharged). Statistical analysis included the use of Student t-test and Pearson chi-square where appropriate. A multivariate analysis was then conducted to determine the predictors of hospital admission. RESULTS: A total of 366 patients had their charts queried. Age category distributions of the patients were 73 (19.9%) <5 years, 39 (10.7%) 5-14 years, 236 (64.5%) 15-65 years and 18 (4.9%) >65 years of age. Around half of the patients (47.3%) were males, with scalding being the most common mechanism of burn (53.9%), followed by contact with hot object (16.8%) and flame (11.9%). In terms of disposition from the ED, 58 (15.8%) patients were admitted to the hospital with 42 (72.4%) going to GPU, 12 (20.6%) to ICU and 4(6.9%) transferred to either another hospital or to an acute burn facility. Admitted patients tended to be at the extremes of ages (<5 years or ≥65 years), male dominant, more likely to be brought in by family, with higher proportions of more severe mechanisms of injury (flame, electric, chemical). Admitted patients also sustained higher degrees of burns with more TBSA injured. Predictors of hospital admission included the aforementioned factors with the strongest predictors of admission being full-thickness degree burn (OR 18.56 (4.67-73.72 CI95% p≤0.001)) and mechanism of injury such as electrical (OR 23.01 (3.23-163.89 CI95% p=0.002)) and chemical (OR 17.43 (2.33-130.14 CI95% p=0.003)). CONCLUSION: Characteristics of burn patients treated in an urban ED in Lebanon mirror those of burn victims in other international studies. Future larger epidemiologic studies are needed to better quantify the impact of burns in Lebanon.

Serum lactate is an independent predictor of hospital mortality in critically ill patients in the emergency department: a retrospective study.

BACKGROUND: Elevated lactate has been found to be associated with a higher mortality in a diverse patient population. The aim of the study is to investigate if initial serum lactate level is independently associated with hospital mortality for critically ill patients presenting to the Emergency Department. METHODS: Single-center, retrospective study at a tertiary care hospital looking at patients who presented to the Emergency Department (ED) between 2014 and 2016. A total of 450 patients were included in the study. Patients were stratified to lactate levels: <2 mmol/L, 2-4 mmol/L and >4 mmol/L. The primary outcome was in-hospital mortality. Secondary outcomes included 72-h hospital mortality, ED and hospital lengths of stay. RESULTS: The mean age was 64.87 ± 18.08 years in the <2 mmol/L group, 68.51 ± 18.01 years in the 2-4 mmol/L group, and 67.46 ± 17.67 years in the >4 mmol/L group. All 3 groups were comparable in terms of age, gender and comorbidities except for diabetes, with the 2-4 mmol/L and >4 mmol/L groups having a higher proportion of diabetic patients. The mean lactate level was 1.42 ± 0.38 (<2 mmol/L), 2.72 ± 0.55 (2-4 mmol/L) and 7.18 ± 3.42 (>4 mmol/L). In-hospital mortality was found to be 4 (2.7%), 18(12%) and 61(40.7%) patients in the low, intermediate and high lactate groups respectively. ED and hospital length of stay were longer for the >4 mmol/L group as compared to the other groups. While adjusting for all variables, patients with intermediate and high lactate had 7.13 (CI 95% 2.22-22.87 p = 0.001) and 29.48 (CI 95% 9.75-89.07 p = <0.001) greater odds of in-hospital mortality respectively. DISCUSSION: Our results showed that for all patients presenting to the ED, a rising lactate value is associated with a higher mortality. This pattern was similar regardless of patients' age, presence of infection or blood pressure at presentation. CONCLUSION: Higher lactate values are associated with higher hospital mortalities and longer ED and hospital lengths of stays. Initial ED lactate is a useful test to risk-stratify critically ill patients presenting to the ED.