Cervical cancer screening utilization among kidney transplant recipients, 2001-2018.

BACKGROUND: Kidney transplant recipients (KTRs) have elevated risks of cervical pre-cancers and cancers, and guidelines recommend more frequent cervical cancer screening exams. However, little is known about current trends in cervical cancer screening in this unique population. We described patterns in the uptake of cervical cancer screening exams among female KTRs and identified factors associated with screening utilization. METHODS: This retrospective cohort study included female KTRs between 20-65 years old, with Texas Medicare fee-for-service coverage, who received a transplant between January 1, 2001, and December 31, 2017. We determined the cumulative incidence of receiving cervical cancer screening post-transplant using ICD-9, ICD-10, and CPT codes and assessed factors associated with screening utilization, using the Fine and Gray model to account for competing events. Subdistribution hazards models were used to assess factors associated with screening uptake. RESULTS: Among 2,653 KTRs meeting the inclusion and exclusion criteria, the 1-, 2-, and 3-year cumulative incidences of initiating a cervical cancer screening exam post-transplant were 31.7% (95% confidence interval (CI), 30.0-33.6%), 48.0% (95% CI, 46.2-49.9%), and 58.5% (95% CI, 56.7-60.3%), respectively. KTRs who were 55-64 years old (vs. <45 years old) and those with a higher Charlson Comorbidity Score post-transplant were less likely to receive cervical cancer screening post-transplant. CONCLUSIONS: Cervical cancer screening uptake is low in the years immediately following a kidney transplant. IMPACT: Our findings highlight a need for interventions to improve cervical cancer screening utilization among KTRs.

The Survival Benefit of Re-abstinence After Harmful Alcohol Use Following Early Liver Transplant for Severe Alcohol-Associated Hepatitis: A Multi-Center ACCELERATE Study.

BACKGROUND AND AIMS: Early (i.e. without mandated period of abstinence) liver transplant (LT) for alcohol-associated hepatitis (AH) is the fastest growing indication for LT in the US and Europe. Harmful alcohol use post-LT is associated with poor outcomes but the distinction of establishing abstinence after return to drinking (i.e. re-abstinence) is understudied. This study aims to characterize the survival outcomes of achieving re-abstinence after post-LT harmful alcohol use. METHODS: We analyzed early LT recipients from 12 US LT centers between 2006-2021. Post-LT alcohol use was characterized as harmful using criteria of "binge" (>5 [men] or >4 [women] drinks in < 24 hours) or "frequent" (>4 days in one week) by interview or phosphatidylethanol >20ng/mL. Re-abstinence was defined as >12 consecutive months without harmful alcohol use following harmful alcohol use. RESULTS: Among 347 LT recipients (64% male, median age 43, median MELD-Na 38) with median post-LT follow-up of 2.2 years (IQI 1.1 - 3.6), 276 (80%) recipients had no evidence of harmful alcohol use, 35 (10%) recipients had re-abstinence, and 36 (10%) recipients had continued harmful alcohol use without re-abstinence. Five-year predicted survival, adjusted for age, sex, MELD-Na score, was lowest among LT recipients with continued harmful alcohol use (77%), but similar among those with no harmful use (93%) and re-abstinence (94%). CONCLUSIONS: Achieving re-abstinence after post-LT harmful alcohol use is associated with similar five-year post-LT survival compared to those without evidence of post-LT harmful alcohol use. Our findings highlight the importance of early detection and treatment of post-LT alcohol use.

Temporal Trends in Treatment and Outcomes of Endometrial Carcinoma in the United States, 2005-2020.

Endometrial cancer has continued to see a rising incidence in the US over the years. The main aim of this study was to assess current trends in patients' characteristics and outcomes of treatment for endometrial carcinoma over 16 years. A dataset from the National Cancer Database (NCDB) for patients diagnosed with endometrial carcinoma from 2005 to 2020 was used in this retrospective, case series study. The main outcomes and measures of interest included tumor characteristics, hospitalization, treatments, mortality, and overall survival. Then, 569,817 patients who were diagnosed with endometrial carcinoma were included in this study. The mean (SD) age at diagnosis was 62.7 (11.6) years, but 66,184 patients (11.6%) were younger than 50 years, indicating that more patients are getting diagnosed at younger ages. Of the patients studied, 37,079 (6.3%) were Hispanic, 52,801 (9.3%) were non-Hispanic Black, 432,058 (75.8%) were non-Hispanic White, and 48,879 (8.6%) were other non-Hispanic. Patients in the 4th period from 2017 to 2020 were diagnosed more with stage IV (7.1% vs. 5.2% vs. 5.4% vs. 5.9%; p < 0.001) disease compared with those in the other three periods. More patients with severe comorbidities (Charlson Comorbidity Index score of three) were seen in period 4 compared to the first three periods (3.9% vs. ≤1.9%). Systemic chemotherapy use (14.1% vs. 17.7% vs. 20.4% vs. 21.1%; p < 0.001) and immunotherapy (0.01% vs. 0.01% vs. 0.2% vs. 1.1%; p < 0.001) significantly increased from period 1 to 4. The use of laparotomy decreased significantly from 42.1% in period 2 to 16.7% in period 4, while robotic surgery usage significantly increased from 41.5% in period 2 to 64.3% in period 4. The 30-day and 90-day mortality decreased from 0.6% in period 1 to 0.2% in period 4 and 1.4% in period 1 to 0.6% in period 4, respectively. Over the period studied, we found increased use of immunotherapy, chemotherapy, and minimally invasive surgery for the management of endometrial cancer. Overall, the time interval from cancer diagnosis to final surgery increased by about 6 days. The improvements observed in the outcomes examined can probably be associated with the treatment trends observed.

Cost-Effectiveness of Population-Based Multigene Testing for Breast and Ovarian Cancer Prevention.

Importance: The current method of BRCA testing for breast and ovarian cancer prevention, which is based on family history, often fails to identify many carriers of pathogenic variants. Population-based genetic testing offers a transformative approach in cancer prevention by allowing for proactive identification of any high-risk individuals and enabling early interventions. Objective: To assess the lifetime incremental effectiveness, costs, and cost-effectiveness of population-based multigene testing vs family history-based testing. Design, Setting, and Participants: This economic evaluation used a microsimulation model to assess the cost-effectiveness of multigene testing (BRCA1, BRCA2, and PALB2) for all women aged 30 to 35 years compared with the current standard of care that is family history based. Carriers of pathogenic variants were offered interventions, such as magnetic resonance imaging with or without mammography, chemoprevention, or risk-reducing mastectomy and salpingo-oophorectomy, to reduce cancer risk. A total of 2000 simulations were run on 1 000 000 women, using a lifetime time horizon and payer perspective, and costs were adjusted to 2022 US dollars. This study was conducted from September 1, 2020, to December 15, 2023. Main Outcomes and Measures: The main outcome measure was the incremental cost-effectiveness ratio (ICER), quantified as cost per quality-adjusted life-year (QALY) gained. Secondary outcomes included incremental cost, additional breast and ovarian cancer cases prevented, and excess deaths due to coronary heart disease (CHD). Results: The study assessed 1 000 000 simulated women aged 30 to 35 years in the US. In the base case, population-based multigene testing was more cost-effective compared with family history-based testing, with an ICER of $55 548 per QALY (95% CI, $47 288-$65 850 per QALY). Population-based multigene testing would be able to prevent an additional 1338 cases of breast cancer and 663 cases of ovarian cancer, but it would also result in 69 cases of excess CHD and 10 excess CHD deaths per million women. The probabilistic sensitivity analyses show that the probability that population-based multigene testing is cost-effective was 100%. When the cost of the multigene test exceeded $825, population-based testing was no longer cost-effective (ICER, $100 005 per QALY; 95% CI, $87 601-$11 6323). Conclusions and Relevance: In this economic analysis of population-based multigene testing, population-based testing was a more cost-effective strategy for the prevention of breast cancer and ovarian cancer when compared with the current family history-based testing strategy at the $100 000 per QALY willingness-to-pay threshold. These findings support the need for more comprehensive genetic testing strategies to identify pathogenic variant carriers and enable informed decision-making for personalized risk management.

One dose versus two doses of COVID-19 vaccine for the prevention of breakthrough infections among people previously infected with SARS-Cov-2.

Studies have suggested the effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 reinfection among those previously infected. However, it is not yet clear if one dose of the vaccine is enough to prevent breakthrough infections compared to two doses. Using data from Optum deidentified COVID-19 Electronic Health Record (EHR) data set, we assessed breakthrough infection risks in individuals previously infected, comparing those with one vaccine dose to those with two doses. Propensity scores were applied to mitigate confounding factors. Follow-up spanned 6 months, beginning 2 weeks postvaccination. Among 213 845 individuals, those receiving one vaccine dose had a significantly higher breakthrough infection risk than the two-dose group (HR 1.69, 95% CI 1.54-1.85). This pattern was observed across genders, racial/ethnic groups, age categories, and vaccine types. This study reveals a substantial disparity in the risk of breakthrough infections between individuals receiving one versus two doses of the COVID-19 vaccine, suggesting that a single dose may not provide adequate protection against reinfection.

Randomized controlled trial of remote ischemic preconditioning in children having cardiac surgery.

BACKGROUND: Children undergoing cardiac surgery are at risk for acute kidney injury (AKI) and cardiac dysfunction. Opportunity exists in protecting end organ function with remote ischemic preconditioning. We hypothesize this intervention lessens kidney and myocardial injury. METHODS: We conducted a randomized, double blind, placebo controlled trial of remote ischemic preconditioning in children undergoing cardiac surgery. Pre-specified end points are change in creatinine, estimated glomerular filtration rate, development of AKI, B-type natriuretic peptide and troponin I at 6, 12, 24, 48, 72 h post separation from bypass. RESULTS: There were 45 in the treatment and 39 patients in the control group, median age of 3.5 and 3.8 years, respectively. There were no differences between groups in creatinine, cystatin C, eGFR at each time point. There was a trend for a larger rate of decrease, especially for cystatin C (p = 0.042) in the treatment group but the magnitude was small. AKI was observed in 21 (54%) of control and 16 (36%) of treatment group (p = 0.094). Adjusting for baseline creatinine, the odds ratio for AKI in treatment versus control was 0.31 (p = 0.037); adjusting for clinical characteristics, the odds ratio was 0.34 (p = 0.056). There were no differences in natriuretic peptide or troponin levels between groups. All secondary end points of clinical outcomes were not different. CONCLUSIONS: There is suggestion of RIPC delivering some kidney protection in an at-risk pediatric population. Larger, higher risk population studies will be required to determine its efficacy. Trial registration and date: Clinicaltrials.gov NCT01260259; 2021.

Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review.

In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma (HCC) risk after viral clearance is an important consideration when evaluating the CHIM. We estimate HCC risk in spontaneously cleared HCV and in noncirrhosis after sustained virological response (SVR) to HCV treatment in a systematic review and using data from 3 cohorts: German anti-D, Taiwan, and US Veterans Affairs (VA). For noncirrhosis SVR, the overall HCC rate is 0.33 per 100 patient-years in meta-analysis. HCC rates for the German, Taiwan, and US Veterans Affairs cohorts are 0, 0.14, and 0.02 per 100 patient-years, respectively. Past hepatitis B virus exposure was not accounted for in the Taiwan cohort, while VA patients were likely tested based on liver disease/risk factors, which may confound HCC outcomes. The German cohort with no HCC after 44 years is most comparable to the CHIM participants. Although it is difficult to precisely estimate HCC risk from an HCV CHIM, the data suggest the risk to be very low or negligible.

Hepatocellular Carcinoma Surveillance among Individuals with Cirrhosis: Trends by Payer, Etiology, and Calendar Year, from a Statewide, Multi-Payer Dataset, 2010-2018.

BACKGROUND: Hepatocellular carcinoma (HCC) surveillance is underutilized, with <25% of individuals with cirrhosis receiving surveillance exams as recommended. The epidemiology of cirrhosis and HCC in the United States has also shifted in recent years, but little is known about recent trends in surveillance utilization. We characterized patterns of HCC surveillance by payer, cirrhosis etiology, and calendar year in insured individuals with cirrhosis. METHODS: We conducted a retrospective cohort study of individuals with cirrhosis using claims data from Medicare, Medicaid, and private insurance plans in North Carolina. We included individuals ≥ 18 years with a first occurrence of an ICD-9/10 code for cirrhosis between January 1, 2010, and June 30, 2018. The outcome was HCC surveillance by abdominal ultrasound, CT, or MRI. We estimated 1- and 2-year cumulative incidences for HCC surveillance and assessed longitudinal adherence to surveillance by computing the proportion of time covered (PTC). RESULTS: Among 46,052 individuals, 71% were enrolled through Medicare, 15% through Medicaid, and 14% through private insurance. The overall 1-year cumulative incidence of HCC surveillance was 49% and the 2-year cumulative incidence was 55%. For those with an initial screen in the first 6 months of their cirrhosis diagnosis, the median 2-year PTC was 67% (Q1, 38%; Q3, 100%). CONCLUSIONS: HCC surveillance initiation after cirrhosis diagnosis remains low, though it has improved slightly over time, particularly among individuals with Medicaid. IMPACT: This study provides insight into recent trends in HCC surveillance and highlights areas to target for future interventions, particularly among patients with nonviral etiologies.

Incomplete HPV Vaccination among Individuals Aged 27-45 Years in the United States: A Mixed-Effect Analysis of Individual and Contextual Factors.

Background: In the United States, the human papillomavirus (HPV) vaccine is approved for use in individuals up to age 45. Individuals 15 years and older require three doses of the vaccine to complete the recommended dosing series. Incomplete HPV vaccination rates (i.e., one or two doses) among those over age 26, however, remain high. This study examined the independent effects of individual- and neighborhood-level factors on incomplete HPV vaccination rates in the United States (U.S.) among those aged 27-45 years. Methods: This retrospective cohort study used administrative data from Optum's de-identified Clinformatics® Data Mart Database to identify individuals aged 27-45 years who received one or more doses of HPV vaccine between July 2019 and June 2022. Multilevel multivariable logistic regression models were applied to the data on 7662 individuals identified as being fully or partially vaccinated against HPV, nested within 3839 neighborhoods across the U.S. Results: Approximately half of the patients in this study (52.93%) were not completely vaccinated against HPV. After adjusting for all other covariates in the final model, being older than 30 years old decreased the odds of not completing the HPV vaccine series. Participants living in South-region neighborhoods of the U.S. had enhanced odds of not completing the vaccine series compared with those residing in Northeast-region neighborhoods (aOR 1.21; 95% CrI 1.03-1.42). There was significant clustering of incomplete HPV vaccination rates at the neighborhood level. Conclusions: This study revealed that individual- and neighborhood-level factors were associated with the risk of not completing the HPV vaccine series among individuals aged 27-45 years in the U.S. Interventions to improve HPV vaccination series completion rates for this age group should take into consideration both individual and contextual factors.

Incidence of human papillomavirus-related cancers among males and females aged 15-34 years in the United States.

Postmarket surveillance of the incidence of human papillomavirus (HPV)-related cancers is essential to monitor the effectiveness of HPV vaccines. We directly compared HPV-related cancer incidences during the pre- and postvaccine era to assess the effects of HPV vaccination among vaccine-eligible age groups in the United States using data from the US Cancer Statistics database. The 5-year average annual incidence rates for HPV-related cancers decreased in 2015-2019 compared with 2002-2006 among females aged 15-24 years and 25-34 years. Overall, a decrease in young males was not observed, whereas males aged 25-34 years experienced a slight decline in oropharyngeal squamous cell carcinoma between 2005-2009 and 2015-2019. Incidence rates for HPV-related cancers statistically significantly decreased in the vaccine era compared with the prevaccine era among females aged 15-34 years, suggesting the potential early effects of the introduction of HPV vaccination in the United States.

Multicentered study of patient outcomes after declined for early liver transplantation in severe alcohol-associated hepatitis.

BACKGROUND: Early liver transplantation for alcohol-associated hepatitis is controversial in part because patients may recover, and obviate the need for liver transplantation. METHODS: In this retrospective study among 5 ACCELERATE-AH sites, we randomly sampled patients evaluated and then declined for liver transplantation for alcohol-associated hepatitis. All had Model of End-Stage Liver Disease (MELD) >20 and <6 months of abstinence. Recompensation was defined as MELD <15 without variceal bleeding, ascites, or overt HE requiring treatment. Multilevel mixed effects linear regression was used to calculate probabilities of recompensation; multivariable Cox regression was used for mortality analyses. RESULTS: Among 145 patients [61% men; median abstinence time and MELD-Na was 33 days (interquartile range: 13-70) and 31 (interquartile range: 26-36), respectively], 56% were declined for psychosocial reasons. Probability of 30-day, 90-day, 6-month, and 1-year survival were 76% (95% CI, 68%-82%), 59% (95% CI, 50%-66%), 49% (95% CI, 40%-57%), and 46% (95% CI, 37%-55%), respectively. Probability of 1-year recompensation was low at 10.0% (95% CI, 4.5%-15.4%). Among patients declined because of clinical improvement, 1-year probability of recompensation was 28.0% (95% CI, 5.7%-50.3%). Among survivors, median MELD-Na at 30 days, 90 days, and 1-year were 29 (interquartile range: 22-38), 19 (interquartile range : 14-29), and 11 (interquartile range : 7-17). Increased MELD-Na (adjusted HR: 1.13, p <0.001) and age (adjusted HR: 1.03, p <0.001) were associated with early (≤90 d) death, and only history of failed alcohol rehabilitation (adjusted HR: 1.76, p =0.02) was associated with late death. CONCLUSIONS: Liver recompensation is infrequent among severe alcohol-associated hepatitis patients declined for liver transplantation. Higher MELD-Na and age were associated with short-term mortality, whereas only history of failed alcohol rehabilitation was associated with long-term mortality. The distinction between survival and liver recompensation merits further attention.

Oral Fluorescein Angiography for the Diagnosis of Papilledema Versus Pseudopapilledema in Children.

PURPOSE: To evaluate the accuracy and safety of oral fluorescein angiography (OFA) in differentiating papilledema from pseudopapilledema in pediatric patients. DESIGN: Retrospective evaluation of a diagnostic test. METHODS: We retrospectively reviewed medical records of all children ≤18 years of age who presented to the Arkansas Children's Hospital between May 2018 and August 2021 with suspected optic disc (OD) swelling that had OFA and images >30 minutes after oral ingestion. Two masked specialists interpreted the images as either OD leakage, no leakage, or borderline leakage. Optic disc swelling was graded clinically according to the Frisen grading scale (0-5). We compared OFA images to the final clinical diagnosis and calculated the accuracy of the test as follows: (number of eyes correctly identified as papilledema [true positive] + number of eyes correctly identified as pseudopapilledema [true negative]) / (total number of eyes) × 100%. RESULTS: Forty-five patients (90 eyes) were included, 11 patients with papilledema and 34 with pseudopapilledema. The mean age was 14.1 ± 3.5 years; 66.7% were female. The accuracy of OFA was 62% for reviewer 1 and 69% for reviewer 2. No ocular or systemic side effects after OFA were observed. There was substantial agreement (k = 0.779) between both reviewers in grading the OFA images. CONCLUSION: OFA cannot definitively distinguish papilledema from pseudopapilledema in children and should be interpreted in conjunction with other clinical findings.

Alcohol-associated liver disease predicts increased post-liver transplant opioid use.

BACKGROUND: Alcohol-associated liver disease (ALD) is a rising indication for liver transplantation (LT). Prolonged opioid use after LT leads to increased graft loss and mortality. The aim is to determine if patients transplanted with a primary diagnosis of ALD had higher risk of post-LT opioid use (p-LTOU) compared to non-ALD patients. METHODS: This is a retrospective study of patients who underwent LT between 2015 and 2018 at Medstar Georgetown Transplant Institute. Patients with prolonged hospitalization post-LT (>90 days), death within 90 days post-LT, and re-transplants were excluded. RESULTS: Two hundred and ninety seven patients were transplanted, among 29% for indications of ALD. ALD patients were younger (52 vs. 56 years), more likely to be male (76% vs. 61%), Caucasian (71% vs. 44%), have higher MELD (28.8±8.8 vs. 25±8.8), and psychiatric disease than non-ALD patients (P < .05). There was no difference in pre-LT use of opioids, tobacco, marijuana, or illicit drugs between ALD and non-ALD patients. Pre-LT opioid use (OR = 11.7, P < .001), ALD (OR = 2.5, P = .01), and MELD score (OR = .95, P = .02) independently predicted 90-day p-LTOU. CONCLUSIONS: ALD, pre-LT opioid use, and MELD score independently predict p-LTOU. Special attention should be paid to identify post-LT prolonged opioid use in ALD patients.

Early Liver Transplantation for Severe Alcohol-Associated Hepatitis and a History of Prior Liver Decompensation.

INTRODUCTION: In the published studies of early liver transplantation (LT) for alcohol-associated hepatitis (AH), patients with a prior liver decompensation are excluded. The appropriateness of this criteria is unknown. METHODS: Among 6 American Consortium of Early Liver Transplantation for Alcohol-Associated Hepatitis sites, we included consecutive early LT for clinically diagnosed AH between 2007 and 2020. Patients were stratified as first vs prior history of liver decompensation, with the latter defined as a diagnosis of ascites, hepatic encephalopathy, variceal bleeding, or jaundice, and evidence of alcohol use after this event. Adjusted Cox regression assessed the association of first (vs prior) decompensation with post-LT mortality and harmful (i.e., any binge and/or frequent) alcohol use. RESULTS: A total of 241 LT recipients (210 first vs 31 prior decompensation) were included: median age 43 vs 38 years ( P = 0.23), Model for End-Stage Liver Disease Sodium score of 39 vs 39 ( P = 0.98), and follow-up after LT 2.3 vs 1.7 years ( P = 0.08). Unadjusted 1- and 3-year survival among first vs prior decompensation was 93% (95% confidence interval [CI] 89%-96%) vs 86% (95% CI 66%-94%) and 85% (95% CI 79%-90%) vs 78% (95% CI 57%-89%). Prior (vs first) decompensation was associated with higher adjusted post-LT mortality (adjusted hazard ratio 2.72, 95% CI 1.61-4.59) and harmful alcohol use (adjusted hazard ratio 1.77, 95% CI 1.07-2.94). DISCUSSION: Prior liver decompensation was associated with higher risk of post-LT mortality and harmful alcohol use. These results are a preliminary safety signal and validate first decompensation as a criterion for consideration in early LT for AH patients. However, the high 3-year survival suggests a survival benefit for early LT and the need for larger studies to refine this criterion. These results suggest that prior liver decompensation is a risk factor, but not an absolute contraindication to early LT.

Iron overload disorders.

Iron overload disorders represent a variety of conditions that lead to increased total body iron stores and resultant end-organ damage. An elevated ferritin and transferrin-iron saturation can be commonly encountered in the evaluation of elevated liver enzymes. Confirmatory homeostatic iron regulator (HFE) genetic testing for C282Y and H63D, mutations most encountered in hereditary hemochromatosis, should be pursued in evaluation of hyperferritinemia. Magnetic resonance imaging with quantitative assessment of iron content or liver biopsy (especially if liver disease is a cause of iron overload) should be used as appropriate. A secondary cause for iron overload should be considered if HFE genetic testing is negative for the C282Y homozygous or C282Y/H63D compound heterozygous mutations. Differential diagnosis of secondary iron overload includes hematologic disorders, iatrogenic causes, or chronic liver diseases. More common hematologic disorders include thalassemia syndromes, myelodysplastic syndrome, myelofibrosis, sideroblastic anemias, sickle cell disease, or pyruvate kinase deficiency. If iron overload has been excluded, evaluation for causes of hyperferritinemia should be pursued. Causes of hyperferritinemia include chronic liver disease, malignancy, infections, kidney failure, and rheumatic conditions, such as adult-onset Still's disease or hemophagocytic lymphohistiocytosis. In this review, we describe the diagnostic testing of patients with suspected hereditary hemochromatosis, the evaluation of patients with elevated serum ferritin levels, and signs of secondary overload and treatment options for those with secondary iron overload.

Artificial intelligence to identify harmful alcohol use after early liver transplant for alcohol-associated hepatitis.

Early liver transplantation (LT) for alcohol-associated hepatitis (AH) is the fastest growing indication for LT, but prediction of harmful alcohol use post-LT remains limited. Among 10 ACCELERATE-AH centers, we examined psychosocial evaluations from consecutive LT recipients for AH from 2006 to 2017. A multidisciplinary panel used content analysis to develop a maximal list of psychosocial variables. We developed an artificial intelligence model to predict post-LT harmful alcohol use. The cohort included training (N = 91 among 8 centers) and external validation (N = 25 among 2 centers) sets, with median follow-up of 4.4 (IQR 3.0-6.0) years post-LT. In the training set, AUC was 0.930 (95%CI 0.862-0.998) with positive predictive value of 0.891 (95%CI 0.620-1.000), internally validated through fivefold cross-validation. In the external validation set, AUC was 0.692 (95%CI 0.666-0.718) with positive predictive value of 0.82 (95%CI 0.625-1.000). The model identified specific variables related to social support and substance use as highly important to predict post-LT harmful alcohol use. We retrospectively developed and validated a model that identified psychosocial profiles at LT predicting harmful alcohol use post-LT for AH. This preliminary model may inform selection and post-LT management for AH and warrants prospective evaluation in larger studies among all alcohol-associated liver disease being considered for early LT.

Safety and Pharmacokinetic Assessment of Oral Proglumide in Those with Hepatic Impairment.

Proglumide is an orally administered cholecystokinin receptor antagonist that was found to improve nonalcoholic steatohepatitis, reverse liver fibrosis, and decrease incidence of hepatocellular carcinoma (HCC) in animal models. The current investigation aimed to test the pharmacokinetics and safety of proglumide in subjects with hepatic impairment compared with healthy controls. In this translational study, subjects with confirmed cirrhosis, Child-Pugh stage A or B, or healthy controls were recruited for a single-dosing study. Baseline urine and blood samples were obtained before administration of proglumide and also collected after ingestion up to 24 h. Drug concentrations measured by mass spectroscopy revealed peak plasma concentrations (Cmax) of 7847, 9721, and 10,635 ng/mL at about 1 h (Tmax) for healthy controls, subjects with Child-Pugh A, and B cirrhosis, respectively. The serum elimination half time was 3 h. Maximum urine drug concentration (Cmax = ~411 µg/mL) was observed at 3 h, and urinary drug concentration declined at 5 h. There were no adverse events reported, and follow-up liver panels in cirrhosis subjects were unchanged or improved. This investigation demonstrated that proglumide is safe and has similar pharmacokinetic properties in subjects with cirrhosis as in healthy controls; therefore, it will be safe to test the efficacy of proglumide as a therapeutic agent in those subjects with cirrhosis or HCC.

Patterns of Alcohol Use After Early Liver Transplantation for Alcoholic Hepatitis.

BACKGROUND & AIMS: Early liver transplantation (LT) for alcoholic hepatitis (AH) is lifesaving but concerns regarding return to harmful alcohol use remain. We sought to identify distinct patterns of alcohol use post-LT to inform pre-LT candidate selection and post-LT addiction care. METHODS: Detailed post-LT alcohol use data was gathered retrospectively from consecutive patients with severe AH at 11 ACCELERATE-AH sites from 2006-2018. Latent class analysis identified longitudinal patterns of alcohol use post-LT. Logistic and Cox regression evaluated associations between patterns of alcohol use with pre-LT variables and post-LT survival. A microsimulation model estimated the effect of selection criteria on overall outcomes. RESULTS: Of 153 LT recipients, 1-, 3-, and 5-year survival were 95%, 88% and 82%. Of 146 LT recipients surviving to home discharge, 4 distinct longitudinal patterns of post-LT alcohol use were identified: Pattern 1 [abstinent](n = 103; 71%), pattern 2 [late/non-heavy](n = 9; 6.2%), pattern 3 [early/non-heavy](n = 22; 15%), pattern 4 [early/heavy](n = 12; 8.2%). One-year survival was similar among the 4 patterns (100%), but patients with early post-LT alcohol use had lower 5-year survival (62% and 53%) compared to abstinent and late/non-heavy patterns (95% and 100%). Early alcohol use patterns were associated with younger age, multiple prior rehabilitation attempts, and overt encephalopathy. In simulation models, the pattern of post-LT alcohol use changed the average life-expectancy after early LT for AH. CONCLUSIONS: A significant majority of LT recipients for AH maintain longer-term abstinence, but there are distinct patterns of alcohol use associated with higher risk of 3- and 5-year mortality. Pre-LT characteristics are associated with post-LT alcohol use patterns and may inform candidate selection and post-LT addiction care.

Toxoplasma Neuroretinitis.

Neuroretinitis is an inflammatory condition with rapid unilateral vision loss, optic disc edema, and macular star formation. While neuroretinitis is commonly due to infectious causes such as Bartonella henselae, neuroretinitis due to toxoplasmosis is uncommon. A 29-year-old male presents to our neuro-ophthalmology clinic on December 7, 2021, at the University of Arkansas for Medical Sciences with symptoms of left eye pain and blurred vision. Subsequent workup led to the diagnosis and treatment of toxoplasma neuroretinitis. The fundus exam eventually demonstrated a notable macular star. Treatment was well tolerated, and the patient regained total visual acuity in the affected eye. Toxoplasma neuroretinitis is known for a characteristic appearance of optic disc edema prior to appearance of stellate maculopathy with vitreous inflammation and peripheral chorioretinal scars. Although loss of vision due to toxoplasmosis is rare, it should be included as part of the differential diagnosis with pertinent history.

Polypharmacy and medication use by cancer history in a nationally representative group of adults in the USA, 2003-2014.

PURPOSE: This study examines polypharmacy and prescription drug use patterns in cancer survivors, a growing population at risk for cancer sequelae and side effects from treatment, which can arise months or even years following diagnosis. Survivors may experience greater medication burden than the general population, increasing concerns for polypharmacy and subsequent risks of drug interactions and non-adherence. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2014, we examined the association between a cancer history and presence of polypharmacy (5+ medications). We estimated prevalence ratios and prevalence differences for polypharmacy comparing those with and without a cancer history using binomial regression models and propensity score (PS) weighting to account for baseline differences between groups. RESULTS: We identified 32,238 adults aged 20 years or older; 1899 had cancer (excluding non-melanoma skin) at least 1 year before the survey. Overall, polypharmacy prevalence was 13% and 35% in those with and without a cancer history, respectively. After PS weighting, the polypharmacy prevalence was 1.26 times higher among those with versus without a cancer history (weighted prevalence ratio, 1.26; 95% CI, 1.18, 1.35). In sub-group analyses, the weighted prevalence ratio was largest for those 20-39 years old at survey (2.78; 95% CI, 1.71, 4.53), and the weighted prevalence difference was largest for those 40-64 years old at survey (9.35%; 95% CI, 5.70%, 13.01%). CONCLUSIONS/IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors of all ages take more medications than those without cancer history and may benefit from discussions with providers about age-tailored medication use management.