Evolution of pretransplant cardiac risk factor burden and major adverse cardiovascular events in liver transplant recipients over time.

Major adverse cardiovascular events (MACEs) are the leading cause of early (<1 y) complications after liver transplantation (LT). NASH, the leading indication for waitlisting for LT, is associated with high cardiac risk factor burden. The contemporary prevalence and temporal trends in pretransplant cardiac risk factor burden and post-LT MACE among LT recipients (LTRs) with and without NASH are unknown. The aim of this study was to evaluate (1) the evolution of post-LT cardiac risk factors in LTRs over time and (2) post-LT MACE over time, stratified by NASH status. This is a retrospective cohort of 1775 adult LTRs at a single transplant center (2003-2020). MACE was defined as death or hospitalization from myocardial infarction, revascularization, stroke, heart failure during the first post-LT year. Between 2003 and 2020, there was a significant increase in pre-LT NASH ( ptrend <0.05). There was also a significant increase in pre-LT obesity, atherosclerotic cardiovascular (CV) disease, and older age (≥65 y old) ( ptrend <0.05 for all). There was no significant change in the proportion of LTRs with diabetes, chronic kidney disease, or heart failure. Unexpectedly, there were no changes in the rate of post-LT MACE over the study period (-0.1% per year, ptrend =0.44). The lack of change in MACE despite an increase in CV risk factor prevalence may reflect advancement in the identification and management of CV risk factors in LTRs. With projected continued increase in cardiac risk burden and the proportion of patients transplanted for NASH, it is critical for LT programs to develop and implement quality improvement efforts to optimize CV care in LTRs.

Alloimmune versus autoimmune hepatitis following liver transplantation.

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Noninvasive biomarkers for the diagnosis and management of autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a rare disease of unclear etiology characterized by loss of self-tolerance that can lead to liver injury, cirrhosis, and acute liver failure. First-line treatment consists of systemic corticosteroids, or budesonide, and azathioprine, to which most patients are initially responsive, although predictors of response are lacking. Relapses are very common, correlate with histological activity despite normal serum transaminases, and increase hepatic fibrosis. Furthermore, current regimens lead to adverse effects and reduced quality of life, whereas medication titration is imprecise. Biomarkers that can predict the clinical course of disease, identify patients at elevated risk for relapse, and improve monitoring and medication dosing beyond current practice would have high clinical value. Herein, we review novel candidate biomarkers in adult and pediatric AIH based on prespecified criteria, including gene expression profiles, proteins, metabolites, and immune cell phenotypes in different stages of AIH. We also discuss biomarkers relevant to AIH from other immune diseases. We conclude with proposed future directions in which biomarker implementation into clinical practice could lead to advances in personalized therapeutic management of AIH.

Biomarkers of rejection in liver transplantation.

PURPOSE OF REVIEW: Liver transplantation is a lifesaving therapy for thousands of individuals with end-stage liver disease across the world. Allograft rejection, which is traditionally detected through an invasive graft biopsy, is a major complication for liver transplant recipients in the postoperative period. Biomarkers represent a relatively newer and safer means of detecting and predicting transplant rejection when compared with the current standard of care: liver biopsy. This review serves to compile recent progress in the field of biomarker discovery in liver allograft rejection. RECENT FINDINGS: Several promising biomarkers exist in the field of liver transplant rejection. Recent developments include blood genomic assays measuring miRNA, mRNA and donor-derived cell-free DNA. Additionally, serum levels of cytokines, proteoforms, donor-specific antibodies and immunophenotyping have shown promising results in predicting rejection pre and/or posttransplant. SUMMARY: Biomarkers represent a novel method of predicting the risk of developing allograft rejection. The findings discussed in the studies outlined in this review are promising in the potential to improve patient management, reduce complications from over- or under-immunosuppression, and ultimately enhance outcomes.

Poor Practitioner Adherence to Clinical Tobacco Use Guidelines in Liver Transplant Recipients.

Tobacco use is a modifiable risk factor for cardiovascular events (CVEs) in liver transplant recipients (LTRs), but there is a paucity of data about practitioner adherence to tobacco cessation guidelines for LTRs. We sought to assess adherence to these guidelines as a predictor of CVEs after liver transplant. METHODS: We conducted a retrospective, observational, cohort study of adult LTRs from 2010 to 2016 at a large urban, tertiary care transplant network. RESULTS: Of 572 LTRs (mean age' 56.9; 64.1% male), 325 (56.8%) were never, 191 (33.4%) were former, and 56 (9.8%) were current tobacco users before liver transplant. Most LTRs (59%) had their tobacco use assessed annually by transplant providers. Among current users, documented tobacco cessation interventions decreased over time' and <25% were offered pharmacologic treatment or referral to counseling. There was no difference in CVEs between tobacco users who received cessation interventions compared with those who did not. CONCLUSIONS: This single-center study suggests that although tobacco use cessation counseling and interventions were not associated with a decrease in CVEs, evidence-based interventions for tobacco use were under utilized in this high cardiac risk population. These findings underscore missed opportunities for transplant practitioners to provide tobacco use cessation interventions to LTRs, which potentially could reduce CVEs.

What are the differences in protective characteristics of orthodontic mouthguards? An in vitro study.

BACKGROUND: Orthodontic patients wearing fixed appliances are susceptible to traumatic dental injuries during contact-sport. This laboratory study investigated the protective qualities of orthodontic mouthguards using impact-testing to a typodont fitted with a fixed appliance through peak load transfer and retention of the mouthguard. METHODS: Seven orthodontic mouthguards [three custom-made (Medium-CM, Heavy-CM, Heavy-pro-CM); three commercially-available mouth-formed (Shock-Doctor® Ultra Braces, Opro® Ortho-Gold Braces, Opro® Ortho-Bronze Braces) and a Shock-Doctor® Instant-Fit] were fitted to a maxillary arch typodont bonded with a fixed appliance and impact-tested using 0.5 or 1 Joule (J) energy via hockey-ball, cricket-ball or steel-ball projectile. A load-cell recorded peak load transfer through mouthguard to typodont with retention scored in a binary manner dependent upon any displacement following impact. Differences across mouthguards were calculated with ANOVA or Kruskal-Wallis test for normal and non-normal data, respectively. Post hoc comparisons across mouthguards were conducted via Dunnett's test with Sidak correction. RESULTS: Only the three custom-made and Opro® Ortho-Gold Braces were not displaced by impact-testing. For these, Opro® Ortho-Gold Braces transferred the smallest load for 3/6 impact-tests, followed by Medium-CM. Heavy-pro-CM performed poorly, ranking penultimate or worst for all impact-tests. Significant differences were found between mouthguards for cricket-ball and steel-ball set-ups. The Opro® Ortho-Gold Braces performed better than the Heavy and Heavy-pro-CM for 0.5 J cricket-ball impact-test (P < 0.05), whilst Medium-CM performed better than Heavy-pro-CM. For 1 J cricket-ball, there were significant differences between Medium-CM and Heavy-pro-CM (P < 0.05). For 0.5 J steel-ball, the Medium-CM performed significantly better than both Heavy-pro-CM and Opro® Ortho-Gold Braces (P < 0.05), whilst Heavy-CM performed better than the Heavy-pro-CM (P < 0.05). For the 1 J steel-ball, Medium and Heavy-CM performed better than Opro® Ortho-Gold Braces (P < 0.05). CONCLUSIONS: Opro® Ortho-Gold and Medium-CM mouthguards offer the best protection for low-impact sports, whilst Medium or Heavy-CM mouthguards are recommended for high-impact sport.

Wearability and preference of mouthguard during sport in patients undergoing orthodontic treatment with fixed appliances: a randomized clinical trial.

BACKGROUND: Orthodontic patients wearing fixed appliances are susceptible to traumatic dental injuries during a wide range of sporting activities. This randomized clinical trial investigated wearability and preference of mouthguards during sporting activities in patients undergoing orthodontic treatment with fixed appliances. METHODS: A prospective three-arm crossover randomized clinical trial conducted in the UK. Thirty patients in active orthodontic treatment with fixed appliances undertaking at least 120 minutes of contact sport per 6-8-week observation period were randomly assigned to one of six mouthguard allocation sequences consisting of three mouthguard types: (MG1) custom-made laboratory constructed, (MG2) mouth-formed OPRO® Gold Braces, and (MG3) pre-fabricated Shock Doctor® Single Brace. Patients completed a nine-outcome 100-mm visual analogue scale (VAS) questionnaire relating to mouthguard wearability during sport. Once feedback was completed, subjects were allocated the next mouthguard in the sequence. At study-end, subjects were asked to identify their preferred mouthguard. RESULTS: Twenty-four patients (median age = 13; inter-quartile range 12-14.5 years) completed n = 72 follow-up questionnaires with most playing rugby union or field hockey. Considering VAS score as a continuous variable, for comfort, stability, hardness, ability to breathe, ability to not cause nausea, and inclination to chew, MG2 performed better than MG3. For categorization of VAS score into low (less than 80 mm) or high (at least 80 mm) wearability, for comfort, stability, ability to not cause nausea, and inclination to chew, MG1 and MG2 also rated superior to MG3. Patients preferred MG1 overall. CONCLUSIONS: This randomized clinical trial found that during contact sport patients in fixed appliances reported superior wearability for custom-made and mouth-formed mouthguards in comparison to pre-fabricated. Overall, patients preferred custom-made mouthguards. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT04588831.

Advances in Rejection Management: Prevention and Treatment.

Extended survival of liver transplant recipients has brought rejection management to the forefront of liver transplant research. This article discusses T-cell-mediated rejection, antibody-mediated rejection, and chronic rejection. We focus on the prevention and then discuss treatment options. Future directions of rejection management include biomarkers of rejection, which may allow for monitoring of patients who are considered high risk for rejection and detection of rejection before there is any clinical evidence to improve graft and patient survival. With improved graft life and survival of liver transplant recipients, the new frontier of rejection management focuses on immunosuppression minimization, withdrawal, and personalization.

A retrospective analysis of dentofacial deformities and orthognathic surgeries using the index of orthognathic functional treatment need (IOFTN).

OBJECTIVES: To assess the functional needs of orthognathic cases treated in Northampton General Hospital using the index of orthognathic functional treatment need (IOFTN). MATERIALS AND METHODS: A retrospective study was conducted on 78 subjects (54 female and 24 males, 10-54 years, mean (SD) age=21.88 (6.98) years) who had orthognatic surgery in Northampton General Hospital or were in preparation for it (5 case). The sample represents a period between February 1997 and December 2014. The components of IOFTN and Dental Health Component (DHC) of the Index of Orthodontic Treatment Need (IOTN) as well as Malocclusion type were recorded. RESULTS: Class III malocclusion/skeletal pattern was the most prevalent type (approximately 49%). There were 1, 36, 3, and 38 subjects with Class I, Class II Division I, Class II Division II, and Class III malocclusions, respectively. In terms of sagittal skeletal relationship, there were 2, 37, and 39 subjects with Class I, Class II, and Class III skeletal bases, respectively. The most prevalent IOFTN score in our sample was the 5.2 (29.5%), followed by 5.3 (15.5%), 4.2 (13%), 4.3 (11.5%). Overall, 92.3% were classified as in great and very great functional needs according to the IOFTN. Similarly, 84.6% scored as grade 4 or 5, according to the IOTN (DHC). The bimaxillary type osteotomy was the most prevalent type (61.5%). CONCLUSIONS: Using IOFTN, 92.3% of our sample were classified as having great and very great functional needs. IOFTN is a simple and reliable tool to identify patients in need of orthognathic surgery and can be used in resource allocation for patients with highest functional needs.

Toward improved statistical reporting in the journal of consulting and clinical psychology.

Philip Kendall's (1997) editorial encouraged authors in the Journal of Consulting and Clinical Psychology (JCCP) to report effect sizes and clinical significance. The present authors assessed the influence of that editorial--and other American Psychological Association initiatives to improve statistical practices--by examining 239 JCCP articles published from 1993 to 2001. For analysis of variance, reporting of means and standardized effect sizes increased over that period, but the rate of effect size reporting for other types of analyses surveyed remained low. Confidence interval reporting increased little, reaching 17% in 2001. By 2001, the percentage of articles considering clinical (not only statistical) significance was 40%, compared with 36% in 1996. In a follow-up survey of JCCP authors (N=62), many expressed positive attitudes toward statistical reform. Substantially improving statistical practices may require stricter editorial policies and further guidance for authors on reporting and interpreting measures.