Search

BACKGROUND & AIMS: Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. METHODS: We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. RESULTS: In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40–65). Compared with no surveillance, surveillance detected 130 additional HCCs in ‘very early’/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40–50). Compared with no surveillance, surveillance detected 24 additional HCCs in ‘very early’/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. CONCLUSION: Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. LAY SUMMARY: Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

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.

The heart-liver axis is of growing importance. Previous studies have identified independent association of liver dysfunction and fibrosis with adverse cardiac outcomes, but mechanistic pathways remain uncertain. We sought to understand the relations between the degree of hepatic fibrosis identified by the Fibrosis-4 (Fib-4) risk score and comprehensive cardiac MRI (CMR) measures of subclinical cardiac disease. We conducted a retrospective single-center cohort study of patients between 2011 and 2021. We identified consecutive patients who underwent a comprehensive CMR imaging protocol including contrast enhanced with stress/rest perfusion, and lacked pre-existing cardiovascular disease or perfusion abnormalities on CMR. We examined the association of hepatic fibrosis, using the Fib-4 score, with subclinical cardiac disease on CMR while adjusting for cardiometabolic traits. Given known associations of hepatic disease and coronary microvascular dysfunction, we prioritized analyses with the myocardial perfusion reserve index (MPRI), a marker of coronary microvascular function. Of the 66 patients in our study cohort, 54 were female (81%) and the mean age was 53.7 ± 15.3 years. We found that higher Fib-4 was associated with reduction in the MPRI (β [SE] - 1.12 [0.46], P = 0.02), after adjusting for cardiometabolic risk factors. Importantly, Fib-4 was not significantly associated with any other CMR phenotypes including measures of cardiac remodeling, inflammation, fibrosis, or dysfunction. We found evidence that hepatic fibrosis associated with coronary microvascular dysfunction, in the absence of overt associations with any other subclinical cardiac disease measures. These findings highlight a potentially important precursor pathway leading to development of subsequent heart-liver disease.

Background: In a study from our institution, ultrasonic percutaneous tenotomy of the brevis and the common extensor tendon for recalcitrant lateral elbow tendinopathy showed excellent safety profiles, high tolerability, efficiency, sustained pain relief, functional improvement, and sonographic evidence of tissue healing in 20 patients at 3 years’ follow-up. Purpose: To explore the long-term clinical and sonographic results of ultrasonic percutaneous tenotomy of the brevis and the common extensor tendon. Study Design: Case series; Level of evidence, 4. Methods: The same cohort of 20 patients was recalled after 7 years, and visual analog scale (VAS) for pain and Disabilities of the Arm, Shoulder and Hand (DASH) scores, need for secondary intervention, and overall satisfaction were assessed. They were also reassessed using ultrasound imaging of the brevis and the common extensor tendon to evaluate tendon hypervascularity, tendon thickness, and the progress or the recurrence of the hypoechoic scar tissue. Results: We successfully scored 19 patients and performed ultrasound on 16 patients with a median follow-up of 90 months (range, 86-102 months). There were no adverse outcomes and satisfaction remained at 100% (6 patients, satisfied; 13 patients, very satisfied). No patient developed a recurrence of symptoms and signs of lateral elbow tendinopathy, and therefore no secondary intervention was required. The improvement from baseline and early term scores was sustained ( P < .001 for all). At 90 months, there was a significant improvement in VAS scores and DASH–Compulsory scores compared with preprocedure scores and all follow-up times until 3 months. There was no difference in VAS scores and DASH–Compulsory scores at 90 months compared with 6 and 36 months. For DASH–Work scores, there was a significant improvement at 90 months compared with preprocedure scores, but there was no difference between DASH–Work scores at 90 months and scores at all other points of follow-up. At 90 months, hypervascularity remained resolved in 79% of patients, while all patients had reduced tendon swelling and sustained resolution or reduction of the hypoechoic lesion. Conclusion: At the long-term follow-up of 90 months, ultrasonic percutaneous tenotomy of the brevis and the common extensor tendon, previously shown to enhance recovery of lateral elbow tendinopathy, demonstrated good durability of pain relief and functional recovery that was previously achieved. This was accompanied by sustained sonographic tissue healing with no significant deterioration.

Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality and has been increasing. To inform public health efforts to address the growing incidence of ALD, we assessed the association of geographic density of gastroenterologists with ALD-related mortality.National data were obtained for adults aged ≥25 years with state-level demographics and 2010-2019 mortality estimates by linking federally maintained registries (WONDER, NSSATS, BRFSS, HRSA, US Census Bureau). Multivariable linear regression was used to assess the association of state-level geographic density of gastroenterologists with ALD-related mortality, adjusting for age, sex, race/ethnicity, and other potential confounders.Among 50 states and the District of Columbia, the national mean geographic density of gastroenterologists was 4.6 per 100,000 population, and annual ALD-related mortality rate was 85.6 per 1,000,000 population. There was greater than 5-fold differences in geographic density of gastroenterologists and ALD-related mortality across states. In multivariable analysis, the geographic density of gastroenterologists was significantly associated with lower ALD-related mortality (9.0 [95% confidence interval, 1.3-16.7] fewer ALD-related deaths per 1,000,000 population for each additional gastroenterologist per 100,000 population). The association appeared to peak at a threshold of ≥7.5 gastroenterologists per 100,000 population. We estimated that differences in geographic density of gastroenterologists across states may potentially represent 40% of national ALD-related mortality. Exploratory analyses to assess for confounding by generalized subspecialty care, transplant access, alcohol taxation, and substance use or mental health services, including negative control analyses, did not affect primary results.State-level geographic density of gastroenterologists is associated with lower ALD-related mortality. These results may inform medical societies and health policymakers to address anticipated workforce gaps to address the growing epidemic of ALD.

This study characterized the prevalence, drinking patterns, and sociodemographic characteristics of U.S. adult subpopulations with distinct drinking trajectories during the COVID-19 pandemic's first 42 weeks.Adult respondents (n = 8130) in a nationally representative prospective longitudinal study completed 21 biweekly web surveys (March 2020 to January 2021). Past-week alcohol drinking frequency (drinking days [range: 0 to 7]) and intensity (binge drinking on usual past-week drinking day [yes/no]) were assessed at each timepoint. Growth mixture models identified multiple subpopulations with homogenous drinking trajectories based on mean drinking days or binge drinking proportional probabilities across time.Four drinking frequency trajectories were identified: Minimal/stable (72.8% [95% CI = 71.8 to 73.8]) with1 mean past-week drinking days throughout; Moderate/late decreasing (6.7% [95% CI = 6.2 to 7.3) with 3.13 mean March drinking days and reductions during summer, reaching 2.12 days by January 2021; Moderate/early increasing (12.9% [95% CI = 12.2 to 13.6) with 2.13 mean March drinking days that increased in April and then plateaued, ending with 3.20 mean days in January 2021; and Near daily/early increasing (7.6% [95% CI = 7.0 to 8.2]) with 5.58 mean March drinking days that continued increasing without returning to baseline. Four drinking intensity trajectories were identified: Minimal/stable (85.8% [95% CI = 85.0% to 86.5%]) with0.01 binge drinking probabilities throughout; Low-to-moderate/fluctuating (7.4% [95% CI = 6.8% to 8%]) with varying binge probabilities across timepoints (range:0.12 to 0.26); Moderate/mid increasing (4.2% [95% CI = 3.7% to 4.6%]) with 0.39 April binge drinking probability rising to 0.65 during August-September without returning to baseline; High/early increasing trajectory (2.7% [95% CI = 2.3% to 3%]) with 0.84 binge drinking probability rising to 0.96 by June without returning to baseline. Males, Whites, middle-aged/older adults, college degree recipients, those consistently working, and those above the poverty limit were overrepresented in various increasing (vs. minimal/stable) frequency trajectories. Males, Whites, nonmarried, those without college degree, 18 to 39-year-olds, and middle aged were overrepresented in increasing (vs. minimal/stable) intensity trajectories.Several distinct U.S. adult sociodemographic subpopulations appear to have acquired new drinking patterns during the pandemic's first 42 weeks. Frequent alcohol use assessment in the COVID-19 era could improve personalized medicine and population health efforts to reduce drinking.

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.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.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).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.

BACKGROUND & AIMS: Studies regarding acute-on-chronic liver failure (ACLF) among liver transplant (LT) candidates from the United Network for Organ Sharing (UNOS) database are being used to inform LT policy changes worldwide. We assessed the validity of identifying ACLF in UNOS. METHODS: We performed stratified random sampling among 3 US LT centers between 2013–2019 to obtain a representative patient sample across ACLF grades. We compared the concordance of ACLF classification by UNOS vs. blinded manual chart review, according to EASL-CLIF. RESULTS: Among 481 sampled LT registrants, 250 (52%) had no ACLF, 75 (16%) had ACLF grade 1, 79 (16%) had ACLF Grade 2, and 77 (16%) had ACLF Grade 3 per UNOS categorization. Concordance of ACLF grade by UNOS vs. chart review was: 72%, 64%, 56%, and 64% for no ACLF, Grade 1, Grade 2, and Grade 3, respectively, with overall Cohen’s kappa coefficient 0.48 (95%CI 0.42–0.54). Absence of acute decompensation was the most common reason for overestimation, and discordant brain and respiratory failure categorization were the most common reasons for underestimation of ACLF by UNOS. CONCLUSIONS: In this retrospective multi-center study, ACLF categorization by UNOS showed weak agreement with manual chart review. These findings are informative for ongoing allocation policy discussions, highlight the importance of prospective studies regarding ACLF in LT and should encourage UNOS reform. LAY SUMMARY: Acute-on-chronic-liver-failure (ACLF) is a specific and common form of liver failure with high death rates. Studies have been published using the United States transplant registry (UNOS) to identify and describe outcomes of transplant candidates and recipients with ACLF, and these data are driving policy changes for transplant allocation around the world, but nobody has shown whether these data are reliable. We found that UNOS was not categorizing ACLF in concordance or accurately when compared to chart review, which shows the need for UNOS reform and non-UNOS studies to appropriately inform policies in transplant with ACLF.

Background:The optimal choice for intervention for recalcitrant lateral elbow tendinopathy remains unclear as various treatment modalities have documented comparable results in the literature.Purpose:To explore the safety, tolerability, and early efficacy of a new minimally invasive mode of treatment that delivers focused, calibrated ultrasonic energy, effectively microresecting the pathological tendon and removing only pathological tissue.Study Design:Case series; Level of evidence, 4.Methods:Seven male and 13 female patients aged 33 to 65 years averaging 12.5 months (range, 4-48) of failed nonoperative therapy underwent the ultrasonic microresection procedure in an outpatient clinic setting. The procedure involved a sterile, ultrasound-guided percutaneous microresection with a proprietary device (TX1) performed through a stab incision under local anesthesia. The duration of the procedure and complications of the device or procedure were assessed. Outcome parameters included patient satisfaction; visual analog scale (VAS) pain scores; Disabilities of the Arm, Shoulder and Hand (DASH) scores at 1, 3, 6, and 12 months; and ultrasound assessment at 3 and 6 months.Results:The median duration for the sterile confirmatory ultrasound examination (phase 1) was 88.5 seconds (range, 39-211; SD, ±47.6), the median duration of the procedure proper (phase 2) was 10.1 minutes (range, 4.1-19.4; SD, ±3.7), and the median energy time (duration the TX1 device was activated) was 32.5 seconds (range, 18-58; SD, ±11.0). No complications were encountered. A significant improvement in VAS score (from 5.5 to 3.3; P < .001) occurred by 1 week, and significant improvements in both DASH-Compulsory (from 21.7 to 11.3; P = .001) and DASH-Work (from 25.0 to 6.3; P = .012) scores occurred by 1 month. The VAS scores further improved at 3, 6, and 12 months (from 2.0 to 1.0 to 0.50; P = .003 and .023). The DASH-Compulsory score improved significantly from 3 to 6 months (from 8.6 to 4.6; P = .003), and both the DASH-Compulsory and DASH-Work scores were sustained by 12 months. Sonographically reduced tendon thickness (19 patients), resolved or reduced hypervascularity (17 patients), and reduced hypoechoic area (18 patients) occurred by 6 months. Nineteen of the 20 patients (95%) expressed satisfaction with the procedure, with 9 patients being very satisfied with their overall experience at 6 months after the procedure, 10 patients somewhat satisfied, and 1 patient neutral.Conclusion:Ultrasonic microresection of diseased tissue with the TX1 device provides a focally directed, safe, specific, minimally invasive, and well-tolerated treatment for recalcitrant lateral elbow tendinopathy in an office-based or ambulatory surgical setting with good evidence of some level of efficacy in 19 of 20 patients (95%) that is sustained for at least 1 year.

Background: A previously published study found positive outcomes for a novel technique for ultrasound-guided percutaneous ultrasonic tenotomy, showing good tolerability, safety, and early efficacy within an office setting. Purpose: In this follow-up study, all 20 members of the original cohort were contacted after 3 years to explore the sustainability of symptomatic relief, functional improvement, and sonographic soft tissue response for percutaneous ultrasonic tenotomy. Study Design: Case series; Level of evidence, 4. Methods: All 20 subjects of the clinical trial that was performed from June to November 2011 were further assessed at 36 months after the procedure in terms of visual analog scale for pain, Disabilities of the Arm, Shoulder and Hand (DASH)–Compulsory/Work scores, need for adjunct procedures, and overall satisfaction. Importantly, all 20 were reassessed with ultrasound imaging at 36 months, and evidence of the common extensor tendon response was assessed in terms of tendon hypervascularity, tendon thickness, and the progress of the hypoechoic scar tissue. Results: A 100% clinical follow-up was achieved, inclusive of ultrasonographic assessment. None of the subjects required further treatment procedures, and 100% expressed satisfaction. Previous improvements in visual analog scale (current median ± SD, 0 ± 0.9; range, 0-3) and DASH-Work scores (current median, 0 ± 0) were sustained with conformity to a linear pattern on polynomial measures. There was further reduction in DASH-Compulsory scores to a median of 0 ± 0.644 (range, 0-2) with a significant decrease on repeated measures ( P = .008). Tendon hypervascularity was resolved in 94% of patients, and 100% had reduction in tendon thickness. Overall reduction in the hypoechoic scar tissue was observed in all subjects, with a 90% response achieved by 6 months. Between 6 and 36 months, further reduction in the scar was observed in around 60% of patients, with 20% of patients having complete resolution of the hypoechoic scar. Conclusion: Minimally invasive percutaneous ultrasonic tenotomy provided sustained pain relief and functional improvement for recalcitrant tennis elbow at 3-year follow-up. It is one of the few procedures to demonstrate positive sonographic evidence of tissue-healing response and is an attractive alternative to surgical intervention for definitive treatment of recalcitrant elbow tendinopathy.

The results of 102 consecutive primary and revision total hip arthroplasties performed with bone-grafting for acetabular bone deficiencies were reviewed at an average of 10.2 years (range, 4–18.6) after surgery. Ninety-one percent had structural bone defects and 57% had underlying developmental dysplasia of the hip. Overall acetabular revision rates for aseptic loosening were 8% at 5 years and 26% at 10 years. In addition, in the patients with developmental dysplasia who had primary hip arthroplasties, acetabular revision rates for aseptic loosening were 3 and 18% at 5 and 10 years, respectively. Ninety-six percent of all uninfected grafts incorporated. Bulk grafts fared better than particulate grafts. No difference in failure rate was noted between primary and revision hip arthroplasty, type of deficiency, or amount of graft coverage. Although early results are encouraging, acetabular failure increased significantly with longer follow-up evaluation; however, graft incorporation was successful and facilitated subsequent revision surgery.

Background. Extraskeletal osteosarcomas are rare malignancies that account for about 1% of all soft tissue sarcomas. Few large series have been reported. Methods. Clinical records and histologic slides of all patients with extraskeletal osteosarcomas treated at the Mayo Clinic between 1915 and 1988 were reviewed. Results. The study group consisted of 40 patients, most of whom presented in the sixth and seventh decades of life (mean age, 50.7 years). There was a male predominance (male-to-female ratio, 1.9:1). The lower limbs most commonly were involved (68%), usually the thigh and buttock regions. Ninety-three percent of tumors presented as an enlarging soft tissue mass, with a history of trauma in nine patients. In nine patients, the lesions were initially interpreted histologically as benign, most commonly as myositis ossificans. Histologically, all were high grade osteosarcomas. Multiple local recurrences (45%) are a feature of this tumor. All recurrences occurred within 3 years. Distant metastasis (65%) is also common and is usually to the lungs (81%). Radical resections appear to be the best option for local control, with resection of the pulmonary metastasis occasionally producing a cure. By univariate analysis of Kaplan-Meier survival curves, the patients with predominantly chondroblastic tumors fared better than those with predominantly osteoblastic tumors (P=0.03). Analysis of survival differences of the three main subtypes together (osteoblastic, chondroblastic, and fibroblastic) was not significant. A small-sized initial lesion did not equate with better survival. Seventy-three percent died of the disease, with a mean follow-up of 5.9 years. Conclusion. Extraskeletal osteosarcoma is a high grade malignant tumor associated with a 5-year survival rate of 37% (95% confidence interval, 28%–59%). Local recurrences and distant metastasis are common and usually occur by 3 years after excision. Patients with the chondroblastic subtype survive longer than those with the osteoblastic subtype. Cancer 1995; 76:2253–9.

Articular wear is considered to be a possible long-term complication of the use of stemmed, coupled elbow replacements with the capacity to correct deformity and restore function. There have been no reports on this topic, to our knowledge.A review of the results of 919 replacements with the semi-constrained linked Coonrad-Morrey total elbow implant, performed between 1981 and 2000, revealed that twelve patients (1.3%) had undergone an isolated exchange of the articular bushings as a result of polyethylene wear. The status of these patients was assessed clinically and radiographically.The mean age of the twelve patients at the time of the initial total elbow replacement was forty-four years compared with a mean age of sixty-two years in the overall group (p0.001). Seven of the twelve patients had posttraumatic arthritis, and five had rheumatoid arthritis. Nine patients had extensive deformity. The group consisted of seven women and five men, and ten patients had involvement of the right dominant elbow. The mean age at the bushing revision was fifty-two years, and the bushings were revised at an average of 7.9 years after implantation. All twelve patients reported pain, and five reported crepitus or a squeaking sound. None had extensive osteolysis. The mean duration of follow-up after the bushing exchange was sixty-five months. The mean arc of motion improved from 89 degrees before the surgery to 109 degrees after it. Three of the twelve patients underwent an additional articular revision at fifty-three, fifty-four, and 136 months after the initial bushing exchange. At the time of final follow-up, all twelve patients had functioning elbows.Isolated bushing exchange can be a successful revision procedure in patients with a semi-constrained linked total elbow prosthesis. Younger patients with a posttraumatic condition and/or severe pre-existing deformity are at greater risk for the development of excessive bushing wear. Patients should be cautioned against exceeding the recommended activity and lifting restrictions.