Falsely Elevated Tacrolimus (FK506) Trough Levels in a Liver Transplant Recipient.

Antibody-conjugated magnetic immunoassay (ACMIA) for tacrolimus (FK506) may detect falsely elevated tacrolimus trough levels, a commonly underreported event. We report a case of falsely elevated whole-blood tacrolimus levels in a patient post-orthotopic liver transplantation. A 71-year-old male patient underwent liver transplantation in 2012. Post-transplantation, the patient was immediately started on tacrolimus for maintenance immunosuppression. His most recent dose was 0.5 mg four times weekly. During monitoring, trough levels were at 25.9 ng/mL using ACMIA. After this result, a decision was made to hold tacrolimus. After holding tacrolimus for seven days, detected trough levels were still continually greater than 20 ng/mL. Upon suspicion of falsely elevated results, liquid chromatography with mass spectroscopy (LC-MS) was used to check tacrolimus trough levels. Results showed normal trough levels of 7.6 ng/mL. Because of its narrow therapeutic window, tacrolimus levels need to be carefully monitored throughout treatment. When high tacrolimus levels are detected using ACMIA without a correlating clinical scenario, trough levels should be re-confirmed using LC-MS to prevent clinical decisions from being made based on falsely elevated results.

Understanding healthcare workers' knowledge and attitudes regarding the coronavirus disease 2019 (COVID-19) vaccine: Overcoming gaps to improve public health response.

Vaccines serve as a major tool against the coronavirus disease 2019 (COVID-19) pandemic, but vaccine hesitancy remains a major concern in the United States. Healthcare workers (HCWs) strongly influence a patient's decision to get vaccinated. We evaluated HCW knowledge and attitudes regarding the COVID-19 vaccine.

SIRT3 is required for liver regeneration but not for the beneficial effect of nicotinamide riboside.

Liver regeneration is critical to survival after traumatic injuries, exposure to hepatotoxins, or surgical interventions, yet the underlying signaling and metabolic pathways remain unclear. In this study, we show that hepatocyte-specific loss of the mitochondrial deacetylase SIRT3 drastically impairs regeneration and worsens mitochondrial function after partial hepatectomy. Sirtuins, including SIRT3, require NAD as a cosubstrate. We previously showed that the NAD precursor nicotinamide riboside (NR) promotes liver regeneration, but whether this involves sirtuins has not been tested. Here, we show that despite their NAD dependence and critical roles in regeneration, neither SIRT3 nor its nuclear counterpart SIRT1 is required for NR to enhance liver regeneration. NR improves mitochondrial respiration in regenerating WT or mutant livers and rapidly increases oxygen consumption and glucose output in cultured hepatocytes. Our data support a direct enhancement of mitochondrial redox metabolism as the mechanism mediating improved liver regeneration after NAD supplementation and exclude signaling via SIRT1 and SIRT3. Therefore, we provide the first evidence to our knowledge for an essential role for a mitochondrial sirtuin during liver regeneration and insight into the beneficial effects of NR.