PURPOSE The risk of immune checkpoint inhibitor therapy–related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors. PATIENTS AND METHODS We performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events. RESULTS Of the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn’s disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P < .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event–related deaths were recorded. Anti–cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively). CONCLUSION Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.

BACKGROUND. Checkpoint inhibitor pneumonitis (CIP) is a highly morbid complication of immune checkpoint immunotherapy (ICI), one which precludes the continuation of ICI. Yet, the mechanistic underpinnings of CIP are unknown. METHODS. To better understand the mechanism of lung injury in CIP, we prospectively collected bronchoalveolar lavage (BAL) samples in ICI-treated patients with (n = 12) and without CIP (n = 6), prior to initiating first-line therapy for CIP (high-dose corticosteroids). We analyzed BAL immune cell populations using a combination of traditional multicolor flow cytometry gating, unsupervised clustering analysis, and BAL supernatant cytokine measurements. RESULTS. We found increased BAL lymphocytosis, predominantly CD4 + T cells, in patients with CIP. Specifically, we observed increased numbers of BAL central memory T cells, evidence of type I polarization, and decreased expression of cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1 in BAL Tregs, suggesting both activation of proinflammatory subsets and an attenuated suppressive phenotype. CIP BAL myeloid immune populations displayed enhanced expression of IL-1β and decreased expression of counterregulatory interleukin-1 receptor antagonist. We observed increased levels of T-cell chemoattractants in the BAL supernatant, consistent with our proinflammatory, lymphocytic cellular landscape. CONCLUSION. We observe several immune cell subpopulations that are dysregulated in CIP, which may represent possible targets that could lead to therapeutics for this morbid immune-related adverse event.

BackgroundImmune-checkpoint inhibitor (ICI)-pneumonitis that does not improve or resolve with corticosteroids and requires additional immunosuppression is termed steroid-refractory ICI-pneumonitis. Herein, we report the clinical features, management and outcomes for patients treated with intravenous immunoglobulin (IVIG), infliximab, or the combination of IVIG and infliximab for steroid-refractory ICI-pneumonitis.MethodsPatients with steroid-refractory ICI-pneumonitis were identified between January 2011 and January 2020 at a tertiary academic center. ICI-pneumonitis was defined as clinical or radiographic lung inflammation without an alternative diagnosis, confirmed by a multidisciplinary team. Steroid-refractory ICI-pneumonitis was defined as lack of clinical improvement after high-dose corticosteroids for 48 hours, necessitating additional immunosuppression. Serial clinical, radiologic (CT imaging), and functional features (level-of-care, oxygen requirement) were collected preadditional and postadditional immunosuppression.ResultsOf 65 patients with ICI-pneumonitis, 18.5% (12/65) had steroid-refractory ICI-pneumonitis. Mean age at diagnosis of ICI-pneumonitis was 66.8 years (range: 35–85), 50% patients were male, and the majority had lung carcinoma (75%). Steroid-refractory ICI-pneumonitis occurred after a mean of 5 ICI doses from PD-(L)1 start (range: 3–12 doses). The most common radiologic pattern was diffuse alveolar damage (DAD: 50%, 6/12). After corticosteroid failure, patients were treated with: IVIG (n=7), infliximab (n=2), or combination IVIG and infliximab (n=3); 11/12 (91.7%) required ICU-level care and 8/12 (75%) died of steroid-refractory ICI-pneumonitis or infectious complications (IVIG alone=3/7, 42.9%; infliximab alone=2/2, 100%; IVIG + infliximab=3/3, 100%). All five patients treated with infliximab (5/5; 100%) died from steroid-refractory ICI-pneumonitis or infectious complications. Mechanical ventilation was required in 53% of patients treated with infliximab alone, 80% of those treated with IVIG + infliximab, and 25.5% of those treated with IVIG alone.ConclusionsSteroid-refractory ICI-pneumonitis constituted 18.5% of referrals for multidisciplinary irAE care. Steroid-refractory ICI-pnuemonitis occurred early in patients’ treatment courses, and most commonly exhibited a DAD radiographic pattern. Patients treated with IVIG alone demonstrated an improvement in both level-of-care and oxygenation requirements and had fewer fatalities (43%) from steroid-refractory ICI-pneumonitis when compared to treatment with infliximab (100% mortality).

PURPOSE: Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs). The proportion of patients who are hospitalized for irAEs and their spectrum, management, and outcomes are not well described. METHODS: We report the proportion of hospitalized patients in an academic center who were treated with ICIs from May to December 2017. Patient characteristics, toxicities, management, and outcomes for confirmed irAE admissions are reported. Associations between patient features and irAE hospitalizations are examined. RESULTS: Twenty-three percent (n = 100) of 443 patients who were admitted to an academic oncology center over 6 months had ever received ICIs. Of these patients, 41% were admitted for suspected irAEs and 23% were confirmed irAEs. IrAEs accounted for 5% of all oncology hospitalizations (n = 23). Ninety-one percent of patients with confirmed irAEs prompted a medicine subspecialist consultation, most commonly gastroenterology (22%). Fifteen patients (65%) had their irAEs improve/resolve, seven (30%) had worsening irAEs, and three (13%) died of their irAEs. The majority of patients (n = 20; 87%) discontinued ICIs after discharge. Among ICI-treated patients who required admission, an increased likelihood of irAE-related hospitalization was associated with patient age older than 65 years (odds ratio, 5.4; 95% CI, 1.6 to 17.8) and receipt of combination immunotherapy (OR, 6.8; 95% CI, 2.0 to 23.2). CONCLUSION: A notable proportion of ICI-treated patients are hospitalized for irAEs, and these patients have a high demand for multidisciplinary management. Older age and combination ICI treatment were associated with an increased risk of irAE-related hospitalization. Whereas these data are from an academic center and include patients in clinical trials, with expanding use of ICIs, these data have important implications for inpatient service planning and risk stratification.

138 Background: Immune checkpoint inhibitors (ICIs) are anti-cancer agents now in routine clinical practice, and may cause immune-related adverse events (irAEs). The proportion of inpatient admissions for irAEs, spectrum of toxicities, management and outcomes are not well described. Methods: Patients with solid tumors admitted to the inpatient oncology service at a tertiary academic center over 3 months, were identified. Patient demographics, treatment details, irAE event and management data, were collected for those who received ICIs, in an IRB-approved database. The diagnosis of irAEs was confirmed by the treating physician and oncologist. Associations between clinical details and irAEs were evaluated using Fisher's exact test. Results: We identified 240 inpatient oncology patients: 53 (22.1%) had received ICIs, and 25% (13/53) were admitted for irAEs. The majority of irAEs requiring admission were high grade (CTCAE grade 1-2: 6/13, 46%; grade 3+: 7/13, 54%), and included: colitis (31%), pneumonitis (23%), skin rash (8%), fever (8%), pancreatitis (8%), fatigue (8%), and renal transplant rejection (8%). Treatment for irAEs included: ICI withhold (2/13, 15%), oral/IV corticosteroids (10/13, 76%), and infliximab (1/13, 8%); with 85% of patients requiring subspecialty consultations. Those with irAEs had a shorter median length of stay vs. other inpatients (5 vs. 6 days). Most irAEs resolved/improved (11/13, 85%), while 15% worsened (1/13) or resulted in patient death (1/13). There was a numerically higher risk of any/grade3+ irAEs for those: treated with combination vs monotherapy (33% vs 23%; 100% vs 40%), age > 65 vs < 65 (33% vs 15%; 56% vs 50%), and former/current vs. never smokers (31% vs 19%; 63% vs 40%), however differences were not statistically significant. Conclusions: Patients with irAEs constitute a notable proportion of inpatient oncology admissions, with a higher incidence than in reported clinical trials. Initial data suggest that patients treated with combination ICIs, aged > 65, and former/current smokers may be more likely to be admitted for irAEs. The majority of irAE admissions require subspecialty consultations, signifying a growing need for multidisciplinary irAE management.

PURPOSE The risk of immune checkpoint inhibitor therapy-related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors. PATIENTS AND METHODSWe performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events. RESULTSOf the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn's disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P , .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event-related deaths were recorded. Anti-cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively).CONCLUSION Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.

Background The COVID-19 pandemic has brought about sweeping change in health care delivery, which has shifted from in-person consultations to a web-based format. Few medical schools provide web-based medicine or telemedicine training to their learners, though this is likely to be important for future medical practice. Objective This tutorial communicates a framework for incorporating medical students into primary care telemedicine clinics. Methods A third-year medical student and internal medicine attending physician from the Johns Hopkins University completed telemedicine clinic visits in April 2020 by using a variety of video platforms and via telephone calls. Results Nine telemedicine visits were completed over 4 clinic days. Our patients were, on average, aged 68 years. The majority of patients were female (6/9, 67%), and most appointments were completed via a video platform (6/9, 67%). Additionally, our experience is summarized and describe (1) practical tips for how to prepare for a telehealth visit; (2) technology considerations; (3) recommendations for participation during a telehealth visit; (4) debriefing and feedback; (5) challenges to care; and (6) student, care provider, and patient reactions to telemedicine visits. Conclusions Telemedicine clinics have been successfully used for managing patients with chronic conditions, those who have attended low-risk urgent care visits, and those with mental health concerns. Patients have reported high patient satisfaction scores for telemedicine visits, and the majority of patients are comfortable with having medical students as part of their care team. Moving forward, telemedicine will remain a popular method for receiving health care. This study has highlighted that medical students can successfully be integrated into telemedicine clinics and that they should be exposed to telehealth whenever possible prior to residency.

Methadone use for opioid use disorder and chronic pain has increased since the start of the century with about 4.4 million dispensed prescriptions in 2009. With increased use of methadone, there has been increasing reporting of less commonly reported side effects (ie, hypoglycaemia). Here, we describe a woman in her 70s with history of opioid use disorder on methadone, stage 4 chronic kidney disease and prior hypoglycaemic episodes who initially presented with perforated gastric ulcer requiring surgical repair. Her perioperative course was complicated by profound hyperinsulinaemic hypoglycaemia. Given concern for methadone-induced hypoglycaemia, methadone was discontinued with monitoring of subsequent blood glucose, insulin, C peptide, proinsulin, β-hydroxybutyrate and blood methadone levels. As the serum methadone levels decreased, insulin levels substantially decreased in parallel. After 21 days off methadone, dextrose infusion was discontinued with restoration of euglycaemia. In a patient with hyperinsulinaemic hypoglycaemia and methadone use, it is important to consider discontinuing methadone and re-evaluate fasting glucose levels prior to an extensive and invasive insulinoma workup.