Case Report: Cardiac Toxicity Associated With Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) have now emerged as a mainstay of treatment for various cancer. Along with the development of ICIs, immune-related adverse effects (irAEs) have been the subject of wide attention. The cardiac irAE, a rare but potentially fatal and fulminant effect, have been reported recently. This article retrospectively reviewed 10 cases from our hospital with cardiac irAEs, with severity ranging from asymptomatic troponin-I elevations to cardiac conduction abnormalities and even fulminant myocarditis. In our series, all the cases were solid tumors and lung cancer was the most frequent cancer type (4,40%). In total, three (30.0%) patients experienced more than one type of life-threatening complication. A systemic corticosteroid was given to nine patients (90.0%). The majority of cases (7, 70%) were performed at an initial dose of 1–2 mg/kg/day. Two (20.0%) patients were admitted to ICU, three (30.0%) patients were put on mechanical ventilation, two (20.0%) patients received the plasma exchange therapy, and one patient was implanted with a pacemaker. Two (20.0%) of the patients succumbed and died, with a median duration of 7.5 days (IQR5.0–10.0) from diagnosis of cardiac irAE to death. Based on these results, we recommend that clinicians be alert to cardiac irAEs, including performing cardiovascular examinations before ICI treatment to accurately diagnose suspected myocarditis, enabling immediate initiation of immunosuppressive therapy to improve prognosis.

Does Frailty influence Inhospital Management and Outcomes of COVID-19 in Older Adults in the US?

Older age has been consistently associated with adverse COVID-19 outcomes. Frailty, a syndrome characterized by declining function across multiple body systems is common in older adults and may increase vulnerability to adverse outcomes among COVID-19 patients. However, the impacts of frailty on COVID-19 management, severity, or outcomes have not been well characterized in a large, representative US population. Using the National COVID Cohort Collaborative, a multi-institutional US repository for COVID-19 research, we calculated the Hospital Frailty Risk Score (HFRS), a validated EHR-based frailty score, among COVID-19 inpatients age ≥ 65. We examined patient demographics and comorbidities, length of stay (LOS), systemic corticosteroid and remdesivir use, ICU admission, and inpatient mortality across subgroups by HFRS score. Among 58,964 inpatients from 53 institutions (51% male, 65% White, 18% Black, 9% Hispanic, mean age 75, mean Charlson comorbidity count 3.0, and median LOS 7 days), 38,692 (66%), 4,180 (7%), 3,531 (6%), 3,525 (6%) and 7,862 (13%) had HFRS scores of 0-1, 2, 3, 4, and >=5 , respectively. Frailty was only moderately correlated with age and comorbidity (□=0.178 and 0.348, respectively, p<0.001). Overall, 34% received systemic corticosteroid and 19% received remdesivir. We observed 4% ICU admissions and 16% inpatient death. Among non-ICU admissions, after adjusting for demographics and comorbidities, frailty (HFRS ≥ 2) was associated with 79% greater systemic corticosteroid use and 22% greater remdesivir use, whereas a higher HRFS score was marginally associated with higher rates of severe COVID disease, inpatient death, or ICU admission.

Clinical Outcomes of COVID-19 and Impact on Disease Course in Patients with Inflammatory Bowel Disease

Background and Aims. The impact of COVID-19 has been of great concern in patients with inflammatory bowel disease (IBD) worldwide, including an increased risk of severe outcomes and/or possible flare of IBD. This study aims to evaluate prevalence, outcomes, the impact of COVID-19 in patients with IBD, and risk factors associated with severe COVID-19 or flare of IBD activity. Methods. A consecutive cohort of IBD patients who were diagnosed with COVID-19 infection and followed up at the McGill University Health Care Centre was obtained between March 1, 2020, and April 30, 2021. Demographics, comorbidities, IBD (type, treatments, pre- and post-COVID-19 clinical activity, biomarkers, and endoscopic activity), and COVID-19-related outcomes (pneumonia, hospitalization, death, and flare of IBD disease) were analyzed. Results. A cohort of 3,516 IBD patients was included. 82 patients (2.3%) were diagnosed with COVID-19 infection (median age: 39.0 (IQR 27.8–48.0), 77% with Crohn’s disease, 50% were female). The prevalence of COVID-19 infection in IBD patients was significantly lower compared to the general population in Canada and Quebec (3.5% versus 4.3%, p < 0.001 ). Severe COVID-19 occurred in 6 patients (7.3%); 2 patients (2.4%) died. A flare of IBD post-COVID-19 infection was reported in 8 patients (9.8%) within 3 months. Biologic therapy was held during active COVID-19 infection in 37% of patients. Age ≥55 years (odds ratio (OR): 11.1, 95% CI: 1.8–68.0), systemic corticosteroid use (OR: 4.6, 95% CI: 0.7–30.1), active IBD (OR: 3.8, 95% CI: 0.7–20.8), and comorbidity (OR: 4.9, 95% CI: 0.8–28.6) were factors associated with severe COVID-19. After initial infection, 61% of IBD patients received COVID-19 vaccinations. Conclusion. The prevalence of COVID-19 infection among patients with IBD was lower than that in the general population in Canada. Severe COVID-19, mortality, and flare of IBD were relatively rare, while a large proportion of patients received COVID-19 vaccination. Older age, comorbidities, active IBD disease, and systemic corticosteroid, but not immunosuppressive or biological therapy, were associated with severe COVID-19 infection.

Clinical Reasoning: A 31-Year-Old Man With Sequential Vision Loss

A 31-year-old healthy white male experienced painless sequential vision loss. Brain imaging and laboratory investigations for infectious, inflammatory, and nutritional conditions, in addition to targeted genetic testing for Leber hereditary optic neuropathy (LHON), were all normal or negative. Despite systemic corticosteroid therapy and plasma exchange, vision continued to worsen. Eventually, mitochondrial whole genome sequencing was performed, which demonstrated a mutation at the 13513G>A position confirming the diagnosis of LHON. Three primary mutations (11778G>A, 14484T>C and 3460G>A) account for 90% of LHON cases, therefore it is important to consider whole genome mitochondrial sequencing in cases with a high index of clinical suspicion.

P.162 Effects of Systemic Corticosteroid Treatment on Pseudotumoral Hemicerebellitis

Background: Pseudotumoral hemicerebellitis is an acute, unilateral inflammation of the cerebellum that typically affects the pediatric population. The etiology remains to be elucidated, however frequently is attributed to post-infectious inflammation. Though it tends to be self-resolving, treatment may reduce the time to symptomatic recovery. Systemic corticosteroid therapy has been proposed as a mechanism for improving outcomes and time to symptomatic recovery. Methods: We present a case report of a 12-year-old male with pseudotumoral hemicerebellitis and unilateral cerebellar dysfunction. Additionally, we briefly review the additional 35 reported cases of pseudotumoural hemicerebellitis with respect to length of time to symptomatic recovery with or without systemic corticosteroid treatment. Results: 30 cases reported length of time to symptomatic recovery. Including our case, the mean time to recovery for those treated with systemic corticosteroids (n=20) was 48.05 days(SE=16.3). The mean time to recovery for those treated without (n=10) was 86.7 days(SE=29.3). Conclusions: Treatment with systemic corticosteroids was associated with a faster time to symptomatic recovery compared to without. Regardless of etiology, reducing inflammation and mass effect involved in pseudotumoral hemicerebellitis may be integral to a more rapid return to neurological baseline.