Publications by authors named "Watt K"

Entrustable professional activities (EPAs) are increasingly being adopted as an assessment tool by medicine and other health professions in a bid to enhance competency-based health professional education. EPAs are well-defined professional activities that can be entrusted to students to perform with varying levels of supervision. They were introduced to overcome some of the limitations of traditional assessment methods of competency such as individual skills assessment or Direct Observation of Procedures and Objective Structured Clinical Examinations.

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Introduction: Heplisav-B, a CpG-adjuvanted recombinant hepatitis B virus (HBV) vaccine, has a higher seroprotection rate and immunogenicity than the conventional HBV vaccine. This study aimed to identify the predictors of HBV seroprotection post-transplantation in thoracic organ transplant recipients who received Heplisav-B.

Methods: We conducted a retrospective study of adult thoracic organ (heart and lung) transplant recipients at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2020 and August 2023.

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Sotalol, a class III antiarrhythmic agent, is used to maintain sinus rhythm in patients with atrial fibrillation or atrial flutter (AFIB/AFL). Despite its efficacy, sotalol's use is limited by its potential to cause life-threatening ventricular arrhythmias due to QT interval prolongation. Traditionally, sotalol administration required hospitalization to monitor these risks.

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Posttransplant diabetes mellitus (PTDM) is associated with significant morbidity and mortality in liver transplant recipients (LTRs). We used the Organ Procurement and Transplantation Network (OPTN) database to compare the incidence of developing PTDM across the United States and develop a risk prediction model for new-onset PTDM using OPTN region as well as donor-related, recipient-related, and transplant-related factors. All US adult, primary, deceased donor, LTRs between January 1, 2007, and December 31, 2016, with no prior history of diabetes noted, were identified.

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Malignancy has a crucial impact on long-term survival after liver transplantation. There have been enhanced early detection rates with refined cancer screening and improved prognosis for many cancer diagnoses in the general population with the advent of targeted anticancer therapies. Similar advancements have not occurred in the transplant population over this same timeframe.

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Background: Milrinone is commonly prescribed to critically ill patients who need extracorporeal life support such as extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). Currently, the effect of ECMO and CRRT on the disposition of milrinone is unknown.

Methods: Ex vivo ECMO and CRRT circuits were primed with human blood and then dosed with milrinone to study drug extraction by the circuits.

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Background: Diagnostic uncertainty caused by the low positive predictive value of HEV-specific IgM antibody (Ab) testing in a low-prevalence setting. We investigated the utility of a two-step HEV IgM Ab testing approach for diagnosing HEV infection.

Methods: We retrospectively reviewed all adults who underwent HEV IgM Ab and/or HEV RNA testing from July 2013 through June 2023 at Mayo Clinic.

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Background: Azithromycin and methylprednisolone are two medications that are commonly used in patients who require ECMO support. Unfortunately, ECMO support can decrease drug concentrations through adsorption to circuit components. Such interactions have not been well described for either azithromycin or methylprednisolone.

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Protein synthesis plays a major role in homeostasis and when dysregulated leads to various pathologies including cancer. To this end, imbalanced expression of eukaryotic translation initiation factors (eIFs) is not only a consequence but also a driver of neoplastic growth. eIF3 is the largest, multi-subunit translation initiation complex with a modular assembly, where aberrant expression of one subunit generates only partially functional subcomplexes.

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We identified cord blood gentamicin concentrations that were higher than anticipated, and above clinical targets for immediate gentamicin re-dosing after birth. Incorporation of gentamicin levels at birth may aid in optimizing postnatal gentamicin dosing among infants exposed to intrapartum gentamicin.

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Article Synopsis
  • The study focuses on the frequency and risk factors of long-term complications in patients with primary sclerosing cholangitis (PSC) who underwent liver transplantation (LT) between 1984 and 2012.
  • A total of 293 patients were analyzed over a median follow-up period of 15 years, revealing complications such as hepatic artery thrombosis and biliary strictures, with the recurrence of PSC increasing significantly over time.
  • The findings suggest that factors like donor age influence complications, and emphasize the need for careful monitoring and early detection of issues post-transplant to improve patient outcomes.
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Background: Chronic kidney disease (CKD) is a well-recognized complication in patients undergoing liver transplantation (LT), particularly those with metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of cirrhosis in the modern era. This study sought to refine risk stratification for CKD events post-LT in cirrhosis patients with MASH by leveraging baseline renal function at transplant.

Methods: A total of 717 MASH cirrhosis patients who had LT (1997-2017) at 7 US centers (NailMASH Consortium) were analyzed.

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Article Synopsis
  • * Amiodarone is effective but poses dosing challenges due to its narrow therapeutic window and long half-life, especially in patients undergoing CRRT.
  • * An ex vivo study found that CRRT circuits significantly extract amiodarone, with only 23% remaining in plasma after 6 hours, indicating that dosage adjustments may be necessary to maintain effective drug concentrations.
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  • Intraductal papillary mucinous neoplasms (IPMNs) are common pancreatic cysts often found incidentally in liver transplant recipients, but their risk of progressing to cancer and the effects of immunosuppression are not well understood.
  • A study at Mayo Clinic over 13 years reviewed 146 liver transplant patients for suspected IPMNs and found only 7 cases of progression (2 with cancer and 5 with concerning features) during an average follow-up of 66.6 months.
  • Results indicated that the type of immunosuppression used did not influence IPMN progression, though factors like combined kidney-liver transplant and prior cholangiocarcinoma were associated, suggesting that larger studies are needed
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Extracorporeal life support (ECLS), including extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), are life-saving therapies for critically ill children. Despite this, these modalities carry frustratingly high mortality rates. One driver of mortality may be altered drug disposition due to a combination of underlying illness, patient-circuit interactions, and drug-circuit interactions.

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Objective: Dysregulation of hepatic cholesterol metabolism can contribute to elevated circulating cholesterol levels, which is a significant risk factor for cardiovascular disease. Cholesterol homeostasis in mammalian cells is tightly regulated by an integrated network of transcriptional and post-transcriptional signalling pathways. Whilst prior studies have identified many of the central regulators of these pathways, the extended supporting networks remain to be fully elucidated.

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Purpose: Regular exercise can reduce incidence and progression of breast cancer, but the mechanisms for such effects are not fully understood. The purpose of this study was to examine the mechanisms behind the protective effects of exercise.

Methods: We used a variety of rodent and human experimental model systems to determine whether exercise training can reduce tumor burden in breast cancer and to identify mechanism associated with any exercise training effects on tumor burden.

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  • This study focuses on developing a pharmacokinetic model for the drug anakinra in critically ill children undergoing extracorporeal life support (ECLS), which includes continuous renal replacement therapy (CRRT) and ECMO.
  • The model was initially created for healthy individuals and then adapted to account for the physiological changes and drug clearance activities related to ECLS in pediatric patients.
  • Results indicated that the model accurately predicted anakinra plasma concentrations in adolescents receiving ECLS, suggesting that the dosing recommendations could help improve pharmacotherapy in critically ill children.
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Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disorder in Western countries, with approximately 20%-30% of the MASLD patients progressing to severe stages. There is an urgent need for noninvasive, cost-effective, widely accessible, and precise biomarkers to evaluate liver steatosis. This study aims to assess and compare the diagnostic performance of a novel reference frequency method-based ultrasound attenuation coefficient estimation (ACE) in both fundamental (RFM-ACE-FI) and harmonic (RFM-ACE-HI) imaging for detecting and grading liver steatosis.

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Introduction: Hepatitis B virus (HBV) vaccination is recommended for solid organ transplant (SOT) candidates. However, there is a lack of data on the HBV vaccine compliance, serologic response, and durability of HBV seroprotection in thoracic organ transplantation recipients.

Methods: We conducted a retrospective study of adult thoracic organ (heart and lung) transplant candidates who received HBV vaccination at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023.

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Background: Patients supported with extracorporeal life support (ECLS) circuits such as ECMO and CRRT often require high doses of sedatives and analgesics, including ketamine and dexmedetomidine. Concentrations of many medications are affected by ECLS circuits through adsorption to the circuit components, dialysis, as well as the large volume of blood used to prime the circuits. However, the impact of ECLS circuits on ketamine and dexmedetomidine pharmacokinetics has not been well described.

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  • The study investigates the pharmacokinetics of oral clavulanic acid in neonates and infants, as existing data on this topic is limited.
  • It analyzes combined data from four datasets using a one-compartment model to determine dosing regimens and exposure levels based on age and body weight.
  • Findings indicate that an amoxicillin/clavulanic acid ratio of 4:1 is optimal, with significant differences in exposure levels based on varying threshold concentrations, laying groundwork for future research.
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  • Spectacle lenses with highly aspherical lenslets (HAL) have been shown to slow down the progress of myopia in children, and this study examined their impact on low hyperopic children.
  • A total of 108 Chinese children aged 6-9 were divided into two groups, one receiving HAL lenses and the other single vision lenses, with measurements taken over a year.
  • Results indicated that children in the HAL group experienced less axial length elongation, especially if they wore their lenses for over 30 hours a week, highlighting a correlation between lens wearing time and eye changes.
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