Endocrine Toxicity and Outcomes in Patients With Metastatic Malignancies Treated With Immune Checkpoint Inhibitors.

CONTEXT: Immune checkpoint inhibitors (ICIs) have gained a revolutionary role in management of many advanced malignancies. However, immune-related endocrine events (irEEs), have been associated with their use. irEEs have nonspecific clinical presentations and variable timelines, making their early diagnosis challenging. OBJECTIVE: To identify risk factors, timelines, and prognosis associated with irEEs development. DESIGN AND SETTING: Retrospective observational study within the Cleveland Clinic center. PATIENTS: Metastatic cancer adult patients who received ICIs were included. METHODS: 570 charts were reviewed to obtain information on demographics, ICIs used, endocrine toxicities, cancer response to treatment with ICI, and overall survival. MAIN OUTCOME MEASURES: Incidence of irEEs, time to irEEs development and overall survival of patients who develop irEEs. RESULTS: The final cohort included 551 patients. The median time for the diagnosis of irEEs was 9 weeks. Melanoma was associated with the highest risk for irEEs (31.3%). Ipilimumab appeared to have the highest percentage of irEEs (29.4%), including the highest risk of pituitary insufficiency (11.7%), the most severe (Grade 4 in 60%) and irreversible (100%) forms of irEEs. Forty-five percent of patients with irEEs had adequate cancer response to ICI compared to 28.3% of patients without irEEs (P = 0.002). Patients with irEEs had significantly better survival compared to patients without irEEs (P < 0.001). CONCLUSIONS: In the adult population with metastatic cancer receiving treatment with ICI, irEEs development may predict tumor response to immunotherapy and a favorable prognosis. Ipilimumab use, combination ICI therapy, and melanoma are associated with a higher incidence of irEEs.

Causes of diabetic ketoacidosis among adults with type 1 diabetes mellitus: insulin pump users and non-users.

INTRODUCTION: Insulin pumps are increasingly being used as a method of insulin delivery in patients with type 1 diabetes mellitus (T1DM). Diabetic ketoacidosis (DKA) is a serious complication of T1DM. This study aims to identify the causes of DKA in patients with T1DM on continuous subcutaneous insulin infusion (CSII) and to compare these with patients with T1DM on multiple daily insulin injections (MDIIs). RESEARCH DESIGN AND METHODS: This is a prospective observational study between January and June 2019 at the Cleveland Clinic Fairview Hospital. Demographic, clinical, and biochemical data were obtained from chart review. A questionnaire to explore additional clinical data relating to DKA was administered, with additional items for patients on the insulin pump. RESULTS: Seventy-four patients were admitted with a diagnosis of DKA between the period of January and June 2019. Of these, 45 met the inclusion criteria and 43 consented. These were divided into two groups: group 1 included patients on MDII and group 2 included CSII. Overall, the most common precipitating factor for developing DKA was insulin non-adherence, seen in 51.2% of the cases. The most common cause of DKA in group 2 was pump/tubing related to 55% of the cases. CONCLUSION: Despite non-adherence being common in both CSII and MDII, a combination of social factors, education and insulin pump malfunction, such as pump/tubing problems, might be playing a pivotal role in DKA etiology in young adults with T1DM, especially in CSII users. Continued education on pump use may reduce the rate of DKA in pump users.

CLINICAL CHARACTERISTICS OF PATIENTS WITH TYPE 2 DIABETES MELLITUS CONTINUED ON ORAL ANTIDIABETES MEDICATIONS IN THE HOSPITAL.

Objective: Basal/basal-bolus insulin with discontinuation of home oral antidiabetes medications (OADs) is the preferred method to achieve glycemic control in many hospitalized patients. We hypothesized that a subset of patients with type 2 diabetes mellitus (T2DM) can achieve an acceptable level of blood sugar control without cessation of their OADs when hospitalized. Methods: A retrospective chart review was conducted on patients with T2DM who were only on OADs at home, admitted to Fairview Hospital, a community hospital in the Cleveland Clinic Health System. We divided patients into those whose OADs were continued (group 1) and those whose OADs were discontinued (group 2), with or without the addition of insulin in the hospital. Blood glucose (BG) levels and patient characteristics were compared. Results: There were 175 patients, 73 in group 1 and 102 in group 2. The percentage of patients achieving all BG values within 100 to 180 mg/dL was the same between group 1 (21.9%) and group 2 (23.8%) (P = .78). Mean BG was similar between group 1 and group 2 (146.1 ± 41.4 mg/dL versus 152.1 ± 38.9 mg/dL; P = .33), with no significant difference in terms of percentage of patients with hyperglycemia or hypoglycemia. A greater proportion of patients in group 1 had an uninterrupted feeding status, nonintensive care unit admission and no contrast dye exposure, and a shorter length of stay. Conclusion: Our study shows that patients with certain characteristics could achieve an acceptable level of glycemic control without cessation of their home OADs. Abbreviations: BG = blood glucose; DPP-4 = dipeptidyl dipeptidase 4; GFR = glomerular filtration rate; HbA1c = hemoglobin A1c; ICU = intensive care unit; LOS = length of stay; NPO = nil per os; OAD = oral antidiabetes medication; POC = point of care; T2DM = type 2 diabetes mellitus.