Modern glucose-lowering drugs in liver transplant recipients: improvement in weight, glycemic control, and potentially allograft steatosis.

Introduction: Recurrent allograft steatosis occurs in one-third of transplanted livers. Antidiabetic agents like glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter type-2 (SGLT2) inhibitors are effective in the management of obesity and hepatic steatosis in the general population; however, there is limited evidence supporting their use in allograft steatosis. We aimed to evaluate their effects on steatosis, body weight, and glycemic control in liver transplant recipients at our institution. Methods: In this single-center retrospective cohort study of liver transplant recipients currently on a GLP1RA or SGLT2 inhibitor (transplanted 2015-2022), we compared clinical and radiological data before medication use and at follow-up. Differences were compared using Wilcoxon signed-rank test. Results: Thirty-seven liver transplant recipients were taking the agents. Diabetes was the most common indication (n = 33) followed by obesity (n = 4). Median follow up was 427 days (301,798). Among those with documented steatosis (n = 21), steatosis improved in 5, worsened in 4, remained unchanged in 1, and change could not be evaluated in 11 due to lack of comparable pre and post imaging. Average weight loss was 3.2 kg (p < 0.001) and BMI decreased by 1.2 kg/m2 (p < 0.001). Hemoglobin A1c decreased by 0.6 mmol/mol (p = 0.0014), insulin requirement reduced by 7 units/day (p = 0.02), and there was no change in additional antidiabetic medications. Discussion: GLP1RA and SGLT-2 inhibitors are tolerated in transplant patients and result in weight loss and better glycemic control. They are promising agents to treat recurrent or de-novo liver allograft steatosis, but further research is needed to evaluate long-term outcomes in liver transplant recipients.

Advances in personalized medicine and noninvasive diagnostics in solid organ transplantation.

Personalized medicine has been a mainstay and in practice in transplant pharmacotherapy since the advent of the field. Decisions pertaining to the diagnosis, selection, and monitoring of transplant pharmacotherapy are aimed toward the individual, the allograft, and the overall immunologic needs of the patient. Recent advances in pharmacogenomics, noninvasive biomarkers, and artificial intelligence (AI) technologies have the promise of transforming the way we individualize treatment and monitor allograft function. Pharmacogenomic testing can provide clinicians with additional data that can minimize toxicity and maximize therapeutic dosing in high-risk patients, leading to more informed decisions that may decrease the risk of rejection and adverse outcomes related to immunosuppressive therapies. Development of noninvasive strategies to monitor allograft function may offer safer and more convenient methods to detect allograft injury. Cell free DNA and gene expression profiling offer the potential to serve as "liquid biopsies" minimizing the risk to patients and providing clinicians with useful molecular data that may help individualize immunosuppression and rejection treatment. Use of big data in transplant and novel AI platforms, such as the iBox, hold tremendous promise in providing clinicians a "glimpse into the future" thereby allowing for a more individualized approach to immunosuppressive therapy that may minimize future adverse outcomes. Advances in diagnostics, laboratory science, and AI have made the application of personalized medicine even more tailored for solid organ transplant recipients. In this perspective, we summarize the current and emerging tools available, literature supporting use, and the horizon for future personalization of transplantation.

Safety of intravenous push thiamine administration at a tertiary academic medical center.

OBJECTIVES: Intravenous (IV) thiamine, administered using both diluted solution for infusion and undiluted solution for IV push, is used to correct low levels of thiamine. Although thiamine has a good safety profile, its IV administration is associated with rare cases of anaphylaxis. The objective of this analysis was to evaluate the incidence of anaphylaxis and IV site reactions associated with IV push thiamine. DESIGN: A single-center, retrospective chart review was performed using electronic health records. SETTING AND PARTICIPANTS: All adult patients who received undiluted IV push thiamine between June 1, 2015, and July 31, 2017, were included. Patient demographics, IV access site, allergy history, and antihistaminic medication use before thiamine administration were collected. OUTCOME MEASURES: Anaphylaxis was assessed while infiltration and phlebitis were evaluated using a standardized institutional grading system. All documented adverse events were adjudicated with the Naranjo Nomogram for adverse drug reaction assessment. RESULTS: A total of 8606 administrations in 2595 patients were evaluated; 5560 doses were administered peripherally, 1643 doses were administered centrally, and the line of administration was not documented for the remaining doses. Administrations included 7605 doses of 100 mg, 433 of 200 mg, 549 of 250 mg, and 19 of 500 mg. No anaphylactic or anaphylactoid reactions were observed. A total of 26 injection site reactions (0.30%) were noted in 19 patients (phlebitis, 12 events and infiltration, 14 events). Assessment with the Naranjo Nomogram classified 18 reactions to have a possible likelihood and 8 reactions to have a probable likelihood of being caused by IV push thiamine administration. CONCLUSION: Administration of IV push thiamine was not associated with any anaphylactic event and had a low incidence of IV site reactions. IV push thiamine in doses up to 250 mg appeared to be safe. There may be an indication for its safe administration with doses up to 500 mg, although more research is needed.