Vibration-Controlled Transient Elastography-Based Parameters Predict Clinical Outcomes in Liver Transplant Recipients.

BACKGROUND AND AIMS: Vibration-controlled transient elastography (VCTE) is used in clinical practice to risk-stratify liver transplant (LT) recipients; however, there are currently little data demonstrating the relationship between VCTE and clinical outcomes. METHODS: A total of 362 adult LT recipients with successful VCTE examination between 2015 and 2022 were included. Presence of advanced fibrosis was defined as liver stiffness measurement (LSM) ≥10.5 kPa and hepatic steatosis as controlled attenuation parameter (CAP) ≥270 dB/m. The outcomes of interest included all-cause mortality, myocardial infarction (MI), and graft cirrhosis using cumulative incidence analysis that accounted for the competing risks of these outcomes. RESULTS: The LSM was elevated in 64 (18%) and CAP in 163 (45%) LT recipients. The baseline LSM values were similar in patients with elevated vs normal CAP values. After a median follow-up of 65 (interquartile range, 20-140) months from LT to baseline VCTE, 66 (18%) patients died, 12 (3%) developed graft cirrhosis, and 18 (5%) experienced an MI. Baseline high LSM was independently associated with all-cause mortality (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.11-3.50; P = .02) and new onset cirrhosis (HR, 6.74; 95% CI, 2.08-21.79; P < .01). A higher CAP value was significantly and independently associated with increased risk of experiencing a MI over study follow-up (HR, 4.14; 95% CI, 1.29-13.27; P = .017). CONCLUSIONS: The VCTE-based parameters are associated with clinical outcomes and offer the potential to be incorporated into clinical risk-stratification strategies to improve outcomes among LT recipients.

Utility of scores to predict alcohol use after liver transplant (lt): take them with a grain of salt.

BACKGROUND AIMS: The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict return to alcohol use after liver transplant (LT) for alcohol associated liver disease (ALD). METHODS: A retrospective analysis of deceased donor LT 10/2018 to 4/2022 was performed. All patients (pts) underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. Post-LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol (PeTH) testing. Pts with ALD were stratified by < or > 6 month sobriety prior to listing. Those with <6 month were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict return to alcohol use (+PeTH) within 1 year after LT. RESULTS: Of the 365 LT, 86 had > 6 month sobriety and 85 had <6 month sobriety; 41 with AH and 44 non-AH. In those with AH, the mean time of abstinence to LT was 58 days, and 71% failed prior rehabilitation. Following LT, return to drinking was similar in the AH (24%) compared to <6M non-AH (15%) and >6M ALD (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict return to alcohol was low (accuracy 61-63%) with poor sensitivity (46% and 37%), specificity (67-68%), positive predictive value (22-26%) with moderate negative predictive value (NPV) (81-83%), respectively with higher NPVs (95%) in predicting return to heavy drinking. CONCLUSIONS: Both SALT and HRAR scores had good NPV in identifying patients at low risk for recidivism.

Burden of Portal Hypertension Complications Is Greater in Liver Transplant Wait-Listed Registrants with End-Stage Liver Disease and Type 2 Diabetes.

BACKGROUND AND AIMS: Impact of type 2 diabetes mellitus (T2DM) in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT) remains poorly defined. The objective of the present study is to evaluate the relationship between T2DM and clinical outcomes among patients with LT waitlist registrants. We hypothesize that the presence of T2DM will be associated with worse clinical outcomes. METHODS: 593 patients adult (age 18 years or older) who were registered for LT between 1/2010 and 1/2017 were included in this retrospective analysis. The impact of T2DM on liver-associated clinical events (LACE), survival, hospitalizations, need for renal replacement therapy, and likelihood of receiving LT were evaluated over a 12-month period. LACE was defined as variceal hemorrhage, hepatic encephalopathy, and ascites. Kaplan-Meier and Cox regression analysis were used to determine the association between T2DM and clinical outcomes. RESULTS: The baseline prevalence of T2DM was 32% (n = 191) and patients with T2DM were more likely to have esophageal varices (61% vs. 47%, p = 0.002) and history of variceal hemorrhage (23% vs. 16%, p = 0.03). The presence of T2DM was associated with increased risk of incident ascites (HR 1.91, 95% CI 1.11, 3.28, p = 0.019). Patients with T2DM were more likely to require hospitalizations (56% vs. 49%, p = 0.06), hospitalized with portal hypertension-related complications (22% vs. 14%; p = 0.026), and require renal replacement therapy during their hospitalization. Patients with T2DM were less likely to receive a LT (37% vs. 45%; p = 0.03). Regarding MELD labs, patients with T2DM had significantly lower bilirubin at each follow-up; however, no differences in INR and creatinine were noted. CONCLUSION: Patients with T2DM are at increased risk of clinical outcomes. This risk is not captured in MELD score, which may potentially negatively affect their likelihood of receiving LT.

Development of Clinical Algorithm Utilizing Vibration-Controlled Transient Elastography to Detect Advanced Hepatic Fibrosis in Liver Transplant Recipients.

INTRODUCTION: Vibration-controlled transient elastography (VCTE) based liver stiffness measurement (LSM) is an excellent 'rule-out' test for advanced hepatic fibrosis in liver transplant (LT) recipients, however, its ability to 'rule-in' the disease is suboptimal. The study aimed to improve diagnostic performance of LSM in LT recipients. METHODS: Adult LT recipients with a liver biopsy and VCTE were included (N = 150). Sequential covering analysis was performed to create rules to identify patients at low or high risk for advanced fibrosis (stage 3-4). RESULTS: Advanced hepatic fibrosis was excluded in patients with either LSM < 7.45 kPa (n = 72) or 7.45 ≤ LSM < 12.1 kPa and time from LT < 5.6 years (n = 25). Conversely, likelihood of advanced fibrosis was 95% if patients had LSM > 14.1 and controlled attenuation parameter > 279 dB/m (n = 21). Thus, 118 (79%) were correctly identified and 32 (21%) would have required a biopsy to establish the diagnosis. Compared to previously established LSM based cutoff values of 10.5 kPa (Youden index) and 13.3 kPa (maximized specificity), the false positive rates of sequential covering analysis was 1% compared to 16.5% with LSM ≥ 10.5 kPa and 8.3% with LSM ≥ 13.3 kPa. The true positive rates were comparable at 87% for sequential covering analysis, 93% for LSM ≥ 10.5 kPa and 83% for LSM ≥ 13.3 kPa. CONCLUSION: The proposed clinical sequential covering analysis allows for better risk stratification when evaluating for advanced fibrosis in LT recipients compared to LSM alone. Additional efforts are necessary to further reduce the number of patients with indeterminate results in whom a liver biopsy may be required.

Utility of Lille Score in Predicting 30-Day Survival in Steroid-Treated Alcohol-Associated Hepatitis.

BACKGROUND/AIMS: In alcohol-associated hepatitis (AH), the Lille score is used to assess futility of steroids. However, the ability of the Lille score to predict 30-day survival in AH is not well-defined. Our aim is to compare the utility of the Lille score in predicting 30-day survival in those with AH treated with steroids. METHODS: Retrospective chart review of 882 patients hospitalized with AH from January 1st, 2012 through December 30th, 2019 was performed. Of these, 201 patients with severe AH met the threshold to receive steroids. Those with data to calculate Lille score < 0.45 on day 4 (n = 29) or 7 (n = 89) who continued steroids were compared to 83 patients with Lille scores ≥ 0.45 on day 4 (n = 18) or 7 (n = 65) who stopped steroids. The primary outcome was 30-day survival. For comparison, a contemporaneous matched control group was also analyzed of 110 patients who were hospitalized with severe AH, but did not receive steroids. RESULTS: In patients with Lille score < 0.45, survival was higher at 30-day when compared to those with Lille score ≥ 0.45 (94.9% vs. 80.72%; p = 0.002). The sensitivity, specificity, positive predictive value and negative predictive value of Lille score (< 0.45) to predict 30-day survival was 95%, 19%, 63%, and 73%, respectively. CONCLUSIONS: In severe AH, those with Lille score < 0.45 at day 4 or 7 have improved 30-day survival compared to those with Lille score ≥ 0.45. In those receiving steroids, Lille score has excellent sensitivity to predict 30-day survival but poor specificity.

Physicians in ACOs report greater documentation burden.

OBJECTIVES: First, to analyze the relationship between value-based payment (VBP) program participation and documentation burden among office-based physicians. Second, to analyze the relationship between specific VBP programs (eg, accountable care organizations [ACOs]) and documentation burden. STUDY DESIGN: Retrospective analyses of US office-based physicians in 2019 and 2021. METHODS: We used cross-sectional data from the National Electronic Health Records Survey to measure VBP program participation and our outcomes of reported electronic health record (EHR) documentation burden. We used ordinary least squares regression models adjusting for physician and practice characteristics to estimate the relationship between participation in any VBP program and EHR burden outcomes. We also estimated the relationship between participation in 6 distinct VBP programs and our outcomes to decompose the aggregate relationship into program-specific estimates. RESULTS: In adjusted analyses, participation in any VBP program was associated with 10.5% greater probability of reporting more than 1 hour per day of after-hours documentation time (P = .01), which corresponded to an estimated additional 11 minutes per day (P = .03). Program-specific estimates illustrated that ACO participation drove the aggregate relationship, with ACO participants reporting greater after-hours documentation time (18 additional minutes per day; P < .001), more difficulty documenting (30.6% more likely; P < .001), and more inappropriateness of time spent documenting (21.7% more likely; P < .001). CONCLUSIONS: Office-based physicians participating in ACOs report greater documentation burden across several measures; the same is not true for other VBP programs. Although many ACOs relax documentation requirements for reimbursement, documentation for quality reporting and risk adjustment may lead to a net increase in burden, especially for physicians exposed to numerous programs and payers.

Psychometric validation of the FACE-Q Aesthetics Satisfaction with Temples scale in individuals seeking minimally invasive treatment to improve temple hollowing.

BACKGROUND: The FACE-Q Aesthetics is used extensively to measure patient reported outcomes for minimally invasive and surgical facial aesthetic treatments. We recently developed a new FACE-Q scale to assess satisfaction with the appearance of the temples. AIM: The aim of this study was to field test the FACE-Q Satisfaction with Temples scale to examine its psychometric properties. METHODS: The FACE-Q Satisfaction with Temples scale was administered to 171 adults (22 years or older) seeking minimally invasive treatment to improve temple hollowing as part of a clinical trial. The severity of temple hollowing was established through the clinician-reported Allergan Temple Hollowing scale (clinician-rated). The psychometric properties of the FACE-Q Satisfaction with Temples scale were established by testing Rasch Measurement Theory (RMT) assumptions and model fit; unidimensionality by principal component analysis; and construct validity by hypothesis testing. RESULTS: The study sample consisted of 171 adults (mean age 54.7 ± 9.9, range, 25-82 years). RMT analysis provided evidence for the scientific soundness of a 12-item Satisfaction with Temples scale. The data fit the Rasch model (χ2 = 20.47, df = 24, p = 0.67), all items had ordered thresholds, and good item fit. Scale reliability was high, with Person Separation Index and Cronbach alpha values with and without extremes ≥0.93. Principal component analysis revealed a single component with high factor coefficients. Construct validity was established as scores for the Satisfaction with Temples and Face Overall scales were correlated (r = 0.623, p < 0.001). CONCLUSION: The FACE-Q Satisfaction with Temples scale is a reliable and valid measure that can be used in clinical practice and research to measure outcomes following treatment for temple hollowing.

Discovery of novel anticancer flavonoids as potential HDAC2 inhibitors: virtual screening approach based on molecular docking, DFT and molecular dynamics simulations studies.

Virtual screening of a library of 329 flavonoids obtained from the NPACT database was performed to find out potential novel HDAC2 inhibitors. Eleven out of 329 selected flavonoids were screened based on molecular docking studies, as they have higher binding affinities than the standard drugs vorinostat and panobinostat. All screened compounds occupying the catalytic site of HDAC2 showed important molecular interaction with Zn2+ and other important amino acids in the binding pocket. The screened compounds were validated using ADMET filtration and bioactivity prediction from which we obtained six compounds, NPACT00270, NPACT00676, NPACT00700, NPACT001008, NPACT001054, and NPACT001407, which were analyzed using DFT studies. DFT studies were performed for all six screened flavonoids. In DFT studies, three flavonoids, NPACT00700, NPACT001008, and NPACT001407, were found to be better based on HOMO-LUMO and molecular electrostatic potential (MEP) analyses. Furthermore, MD simulations were performed for 100 ns for the three compounds. In the MD analysis, NPACT001407 was found to be more stable in the active site of HDAC2 as zinc formed a coordination bond with ASP181, HIS183, ASP269, and GLY305, along with two hydroxyl groups of the ligand. Our findings reveal that these flavonoids can interact as ligands with the active site of HDAC2. Because of the absence of a hydroxamate group in flavonoids, there are no possibilities for the formation of isocyanate. This suggests that the major drawback of current HDACs inhibitors may be solved. Further experimental validation is needed to understand the selectivity of flavonoids as HDAC2 inhibitors. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03912-5.

Primary Care Physicians' Satisfaction With Interoperable Health Information Technology.

Importance: Enabling widespread interoperability-the ability of health information technology systems to exchange information and to use that information without special effort-is a primary focus of public policy on health information technology. More information on clinicians' experience using that technology can serve as one measure of the impact of that policy. Objective: To assess primary care physician perspectives on the state of interoperability. Design, Setting, and Participants: A cross-sectional survey of family medicine physicians in the US was conducted from December 12, 2021, to October 12, 2022. A sample of family medicine physicians who completed the Continuous Certification Questionnaire (CCQ), a required part of the American Board of Family Medicine certification process, which has a 100% response rate, were invited to participate. Main Outcomes and Measures: Eighteen items on the CCQ assessed experience accessing and using various information from outside organizations, including medications, immunizations, and allergies. Results: A total of 2088 physicians (1053 women [50%]; age reported categorically as either ≥50 years or <50 years) completed the CCQ interoperability questions in 2022. Of these respondents, 35% practiced in hospital or health system-owned practices, while 27% practiced in independently owned practices. Eleven percent were very satisfied with their ability to electronically access all 10 types of information from outside organizations included on the questionnaire, and a mean of 70% were at least somewhat satisfied. A total of 23% of family medicine physicians reported information from outside organizations was very easy to use, and an additional 65% reported that information was somewhat easy to use. Only 8% reported that information from different electronic health record (EHR) developers' products was very easy to use compared with 38% who reported information from the same EHR developer's product was very easy to use. Conclusions and Relevance: This survey study of family medicine physicians found modest and uneven improvement in physicians' experience with interoperability. These findings suggest that substantial heterogeneity in satisfaction by information type, source of information, EHR, practice type, ownership, and patient population necessitates diverse policy and strategies to improve interoperability.

Impact of response bias in three surveys on primary care providers' experiences with electronic health records.

OBJECTIVE: To identify impacts of different survey methodologies assessing primary care physicians' (PCPs') experiences with electronic health records (EHRs), we compared three surveys: the 2022 Continuous Certification Questionnaire (CCQ) from the American Board of Family Medicine, the 2022 University of California San Francisco (UCSF) Physician Health IT Survey, and the 2021 National Electronic Health Records Survey (NEHRS). MATERIALS AND METHODS: We evaluated differences between survey pairs using Rao-Scott corrected chi-square tests, which account for weighting. RESULTS: CCQ received 3991 responses from PCPs (100% response rate), UCSF received 1375 (3.6% response rate), and NEHRS received 858 (18.2% response rate). Substantial, statistically significant differences in demographics were detected across the surveys. CCQ respondents were younger and more likely to work in a health system; NEHRS respondents were more likely to work in private practice; and UCSF respondents disproportionately practiced in larger academic settings. Many EHR experience indicators were similar between CCQ and NEHRS, but CCQ respondents reported higher documentation burden. DISCUSSION: The UCSF approach is unlikely to supply reliable data. Significant demographic differences between CCQ and NEHRS raise response bias concerns, and while there were similarities in some reported EHR experiences, there were important, significant differences. CONCLUSION: Federal EHR policy monitoring and maintenance require reliable data. This test of existing and alternative sources suggest that diversified data sources are necessary to understand physicians' experiences with EHRs and interoperability. Comprehensive surveys administered by specialty boards have the potential to contribute to these efforts, since they are likely to be free of response bias.

Loss of 3-O-sulfotransferase enzymes, Hs3st3a1 and Hs3st3b1, reduces kidney and glomerular size and disrupts glomerular architecture.

Heparan sulfate (HS) is an important component of the kidney anionic filtration barrier, the glomerular basement membrane (GBM). HS chains attached to proteoglycan protein cores are modified by sulfotransferases in a highly ordered series of biosynthetic steps resulting in immense structural diversity due to negatively charged sulfate modifications. 3-O-sulfation is the least abundant modification generated by a family of seven isoforms but creates the most highly sulfated HS domains. We analyzed the kidney phenotypes in the Hs3st3a1, Hs3st3b1 and Hs3st6 -knockout (KO) mice, the isoforms enriched in kidney podocytes. Individual KO mice show no overt kidney phenotype, although Hs3st3b1 kidneys were smaller than wildtype (WT). Furthermore, Hs3st3a1-/-; Hs3st3b1-/- double knockout (DKO) kidneys were smaller but also had a reduction in glomerular size relative to wildtype (WT). Mass spectrometry analysis of kidney HS showed reduced 3-O-sulfation in Hs3st3a1-/- and Hs3st3b1-/-, but not in Hs3st6-/- kidneys. Glomerular HS showed reduced HS staining and reduced ligand-and-carbohydrate engagement (LACE) assay, a tool that detects changes in binding of growth factor receptor-ligand complexes to HS. Interestingly, DKO mice have increased levels of blood urea nitrogen, although no differences were detected in urinary levels of albumin, creatinine and nephrin. Finally, transmission electron microscopy showed irregular and thickened GBM and podocyte foot process effacement in the DKO compared to WT. Together, our data suggest that loss of 3-O-HS domains disrupts the kidney glomerular architecture without affecting the glomerular filtration barrier and overall kidney function.