Intermittent Versus Continuous Infusion Dosing of Intravenous Proton Pump Inhibitors for Upper Gastrointestinal Bleeding.

BACKGROUND: Proton pump inhibitor (PPI) continuous infusions or intermittent boluses are used for the treatment of upper gastrointestinal bleeding (UGIB). Intermittent boluses are easier to give and are of lower cost without affecting clinical outcomes. OBJECTIVE: To compare the rate of rebleeding between intermittent bolus and continuous infusion PPI therapy. METHODS: We performed a retrospective, multicenter review of patients with UGIB receiving either continuous or intermittent PPI therapy. During the study period, due to drug and supply shortages, each institution implemented policies preferring intermittent PPI bolus therapy. We performed bivariate and multivariable comparisons of the 2 treatment strategies, with the primary outcome of interest being incidence of rebleeding. Additional variables of interest included intensive care unit (ICU) and hospital lengths of stay, discharge disposition, and in-hospital mortality. RESULTS: Compared with intermittent bolus dosing (n = 209), patients receiving continuous infusion PPI (n = 237) were associated with a higher rate of rebleeding (33.8% vs 23.0%; P = 0.012); however, no difference was detected in multivariable analysis: adjusted odds ratio, 1.50 (95% confidence interval, 0.91-2.50). There was no difference in median hospital or ICU length of stay, discharge disposition, or in-hospital mortality. Correlatively, patients receiving continuous infusion therapy were more likely to have liver disease (29.1% vs 20.1%; P = 0.028), alcohol use disorder (28.3% vs 16.3.%; P = 0.003), history of lower gastrointestinal bleeding (6.4% vs 1.9%; P = 0.021), variceal bleeding (6.3 vs 2.4%, P = 0.045), and be admitted to the ICU (65.0% vs 32.5%, P = 0.00). CONCLUSIONS: Introduction of intermittent PPI bolus UGIB treatment via change in hospital policy was not associated with higher rates of rebleeding. However, continuous PPI therapy may have been perceived as more effective as it was used more commonly in high-risk patients.

A Severe Case of Diabetic Ketoacidosis and New-Onset Type 1 Diabetes Mellitus Associated with Anti-Glutamic Acid Decarboxylase Antibodies Following Immunotherapy with Pembrolizumab.

BACKGROUND Immune checkpoint inhibitors (ICIs) are a novel class of antibodies, which have been increasingly utilized in cancer immunotherapies. Pembrolizumab is a humanized IgG4 monoclonal antibody, which acts against programmed cell death (PD)-1 receptors to help restore the body's T-cell and immune response. CASE REPORT In this case, we present a 51-year-old woman with a past medical history of lung adenocarcinoma and triple-positive breast cancer who was actively receiving therapy with pembrolizumab. Following her second chemotherapy cycle, she developed a severe case of diabetic ketoacidosis (DKA), with concern for new-onset autoimmune type 1 diabetes mellitus (T1DM), secondary to her recent ICI therapy. The patient was initiated on a high-dose insulin infusion for rapid glycemic control and was successfully transitioned to a subcutaneous regimen approximately 24 h after presentation. She additionally developed other autoimmune-related complications, including hepatoxicity, duodenitis, and a maculopapular rash, which all resolved upon discontinuation of the ICI treatment. Her laboratory test results were consistent with positive anti-glutamic acid decarboxylase (anti-GAD) antibodies and undetectable c-peptides, illustrating the uniqueness of an ICI potentially precipitating an autoimmune T1DM. CONCLUSIONS Immune-related adverse events from ICI therapy warrant further investigation to acknowledge the risk of potentially life-threatening adverse reactions, such as the development of DKA. Patients receiving ICI therapy should be educated on signs and symptoms of hyperglycemia, and routine measurements of blood glucose levels should be completed during each chemotherapy cycle. Future research in assessing potential biomarkers of beta cell dysfunction, such as anti-GAD antibodies and c-peptides, is of interest, particularly for patients receiving ICI therapies.

An overview of current and emerging antifungal pharmacotherapy for invasive fungal infections.

Introduction: Invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality despite significant advancements in currently available therapy. With a flush pipeline of investigational antifungals, the clinician must identify appropriate roles of currently available therapies, potential advantages of emerging antifungals, and shortcomings in the evolving clinical evidence.Areas covered: Standard and developing treatment approaches for IFIs with currently available antifungals are summarized with a focus on invasive candidiasis and invasive aspergillosis. Emerging investigational antifungals are discussed in depth, including mechanisms of action, fungal activity, clinical evidence, and ongoing research. An opinion on the impact and potential role of therapy for emerging antifungals of interest is also provided.Expert opinion: Despite advances and clinical studies optimizing antifungal use, current therapies fall short in preventing IFI morbidity and mortality. Further optimization of currently available antifungals may improve outcomes; however, novel agents are required for historically difficult-to-treat infections, transitions to oral treatment, minimizing adverse drug effects, decreasing drug interactions, and ultimately improving patient quality of life. Emerging antifungals may positively revolutionize the treatment of IFIs.