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Abstract Background Hepatitis C virus’ (HCV) chronic prevalence among pregnant women in the United States doubled nationally from 2009–2014 (~0.7%), yet many cases remain undiagnosed. Screening pregnant women is not recommended by the Society of Maternal-Fetal Medicine or the Centers for Disease Control and Prevention, despite new American Association For the Study of Liver Diseases (AASLD)/Infectious Diseases Society of America (IDSA) guidelines recommending screening for this group. We assessed the cost-effectiveness of HCV screening for pregnant women in the United States. Methods An HCV natural history Markov model was used to evaluate the cost-effectiveness of universal HCV screening of pregnant women, followed by treatment after pregnancy, compared to background risk-based screening from a health-care payer perspective. We assumed a HCV chronic prevalence of 0.73% among pregnant women, based on national data. We assumed no Medicaid reimbursement restrictions by fibrosis stage at baseline, but explored differing restrictions in sensitivity analyses. We assessed costs (in US dollars) and health outcomes (in quality-adjusted life-years [QALYs]) over a lifetime horizon, using new HCV drug costs of $25 000/treatment. We assessed mean incremental cost-effectiveness ratios (ICERs) under a willingness-to-pay threshold of $50 000/QALY gained. We additionally evaluated the potential population impact. Results Universal antenatal screening was cost-effective in all treatment eligibility scenarios (mean ICER <$3000/QALY gained). Screening remained cost-effective at a prevalence of 0.07%, which is the lowest estimated prevalence in the United States (in Hawaii). Screening the ~5.04 million pregnant women in 2018 could result in the detection and treatment of 33 000 women, based on current fibrosis restrictions. Conclusions Universal screening for HCV among pregnant women in the United States is cost-effective and should be recommended nationally. Despite increases in hepatitis C virus (HCV) rates among pregnant women, the Society of Maternal-Fetal medicine only recommends risk-based screening. HCV screening among pregnant women in the United States is cost-effective and should be recommended nationally by all societies.

BackgroundPatients who have undergone the Fontan operation for palliation of congenital heart disease with single-ventricle pathophysiology are at high risk for developing progressive liver fibrosis. Pathological assessment from percutaneous liver biopsy is central to the management of Fontan-associated liver disease, but liver biopsy in this vulnerable population poses unique challenges and potential risks.ObjectiveThis retrospective study describes our experience with percutaneous liver biopsy performed to assess changes of Fontan-associated liver disease, with particular regard to procedural outcomes.Materials and methodsData from liver biopsy procedure reports, pathology reports, cardiac angiography pressure measurements and laboratory values of patients with single ventricle heart disease after the Fontan operation who underwent ultrasound-guided percutaneous liver biopsy performed in interventional radiology at a pediatric tertiary care center during a 3-year period were retrospectively analyzed.ResultsSixty-eight liver biopsies were performed in 67 patients (mean age: 20.2 years, range: 7.2–39 years). The technical success rate was 100%, and tissue was adequate for assessing liver disease in 100% of the procedures, including biopsies performed with a single pass. Anticoagulation was routinely suspended before biopsy, and no cardiac complications were encountered due to this suspension. A coaxial biopsy system using an 18-gauge (G) full-core instrument through a 17-G introducer trocar was most commonly used, in 41/68 cases (60%). The most common trough length was 2.3 cm, used in 37 cases (54%). One pass was made in 27 procedures (40%) and two passes in 30 (44%); tract embolization with gelatin sponge was performed in 52 (76%). The only complication was hemorrhage, which occurred in 5/68 (7.4%) of the biopsies, minor in four (5.9%) and major in one (1.5%) -- similar to rates reported for liver biopsy in non-Fontan patients. Hemorrhage had a delayed presentation in three of these five cases. Immediate post-biopsy hemoglobin decrease of ≥2 mg/dL showed a low sensitivity for hemorrhage. The mean Fontan pressure measured during cardiac angiography was 13.8 mmHg, and shunt pressures were not associated with an increased risk of hemorrhage.ConclusionPercutaneous liver biopsy in Fontan patients can be performed safely with high technical success rates and without increased complication rates. Meticulous technique and close observation are recommended to reduce post-biopsy complications. The degree of right heart pressure elevation was not associated with hemorrhage.

Alagille syndrome (ALGS) is a rare, cholestatic, multisystemic disorder characterized by bile duct paucity. Cholestatic pruritus is a common, and often severe, symptom of ALGS and is the leading cause of liver transplantation. The treatment of cholestatic pruritus is challenging and involves medical and surgical options, such as surgical biliary diversion (SBD) for refractory cases. However, SBD is associated with medical/lifestyle challenges. Maralixibat, an ileal bile acid transporter inhibitor, is a recently approved treatment for cholestatic pruritus in patients with ALGS and is used as part of standard of care. We present cases of two patients with ALGS who initiated treatment with maralixibat: one before, with continuation after, reversal of SBD, and one after SBD reversal. In both cases, treatment with maralixibat was well‐tolerated and demonstrated marked improvements in cholestatic pruritus. This suggests that maralixibat is a pharmacological alternative for patients who would like to pursue reversal of SBD. What is Known Cholestatic pruritus is the most common and severe symptom of Alagille syndrome (ALGS). Treatment for cholestatic pruritus involves medical and surgical options. However, historical medical treatments are used off‐label and are ineffective at controlling symptoms, and surgical options, such as surgical biliary diversion (SBD), are associated with medical and lifestyle challenges. Maralixibat was approved for the treatment of cholestatic pruritus in patients with ALGS ≥3 months of age in the United States in 2021 and has since become the standard of care. What is New Maralixibat treatment was safe and demonstrated improvements in cholestatic pruritus in a patient with ALGS with an existing SBD and in a patient with ALGS who had SBD reversal. Treatment with maralixibat may be utilized in patients with ALGS who have undergone SBD.

The Fontan operation, although part of a life-saving surgical strategy, manifests a variety of end-organ complications and unique morbidities that are being recognised with increasing frequency as patients survive into their second and third decades of life and beyond. Liver fibrosis, protein-losing enteropathy and plastic bronchitis are consequences of a complex physiology involving circulatory insufficiency, inflammation and lymphatic derangement. These conditions are manifest in a chronic, indolent state. Management strategies are emerging, which shed some light on the origins of these complications. A better characterisation of the end-organ consequences of the Fontan circulation is necessary, which can then allow for development of specific methods for treatment. Ideally, the goal is to establish systematic strategies that might reduce or eliminate the development of these potentially life-threatening challenges.

BackgroundElevated spleen stiffness may be seen in patients with portal hypertension due to cirrhosis. In patients with Fontan physiology, elevated liver stiffness has been shown to correlate poorly with liver fibrosis. It is unknown whether spleen stiffness may instead serve as a surrogate marker of liver fibrosis in these patients.ObjectiveTo compare spleen stiffness determined by shear wave elastography (SWE) with histological findings of an ultrasound-guided liver biopsy in patients who had undergone Fontan palliation as a potential surrogate for Fontan-associated liver disease.Materials and methodsThis was an IRB-approved single-center, retrospective study. Patients with Fontan palliation who had undergone both a spleen SWE study and a percutaneous liver biopsy between 2016 and 2020 were included. Biopsy, performed during cardiac catheterization, within 3 months of the SWE was required for inclusion. Using Kruskal–Wallis tests, spleen stiffness was compared with three liver biopsy scoring methods: Ishak, METAVIR, and congestive hepatic fibrosis score (CHFS). When available, Pearson’s correlation was also used to compare collagen deposition determined using Sirius Red stain (%SR) with SWE values. A P-value < 0.05 was considered statistically significant.ResultsTwenty-two patients (15 males) were included in the study, with a median age of 17 years (IQR is 14.8–20.5 years; age range: 7 years to 30.2 years). The median spleen stiffness was 2.94 m/s (IQR: 2.57–3.61 m/s; range: 1.48–4.27 m/s). The median Fontan pressure was 11 mm Hg (IQR: 10–13.3 mm Hg; range: 7–19 mm Hg) obtained within a median of 10 days (IQR: 1–41 days) of SWE. Splenic stiffness did not correlate with the extent of fibrosis determined by histology (all P > 0.05). There was also no statistically significant correlation between the %SR staining and SWE-determined spleen stiffness (Pearson’s correlation of 0.165, P = 0.59, n = 13).ConclusionsIn this preliminary study, SWE spleen stiffness values did not correlate with biopsy-determined scoring of liver fibrosis in patients with Fontan physiology.

Importance Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. Objective To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. Design, Setting, and Participants This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. Exposures Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. Main Outcome and Measure Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-WhitneyUtest, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. Results The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. Conclusions and Relevance The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

Recent research has established that individuals with amnestic mild cognitive impairment (aMCI) have impaired prospective memory (PM); however, findings regarding differential deficits on time-based versus event-based PM have been less clear. Furthermore, the diagnostic utility of PM measures has received scant attention. Healthy older adults (n = 84) and individuals with aMCI (n = 84) were compared on the Cambridge Prospective Memory Test (CAMPROMPT) and two single-trial event-based PM tasks. The aMCI participants showed global impairment on all PM measures. Measures of retrospective memory and complex attention predicted both time and event PM performance for the aMCI group. Each of the PM measures was useful for discriminating aMCI from healthy older adults and the time- and event-based scales of the CAMPROMPT were equivalent in their discriminative ability. Surprisingly, the brief PM tasks were as good as more comprehensive measures of PM (CAMPROMPT) at predicting aMCI. Results indicate that single-trial PM measures, easily integrated into clinical practice, may be useful screening tools for identifying aMCI. As PM requires retrospective memory skills along with complex attention and executive skills, the interaction between these skills may explain the global PM deficits in aMCI and the good discriminative ability of PM for diagnosing aMCI. (JINS, 2012, 18, 295–304)

Rapid urbanization and shifting dietary patterns across Africa have contributed to a disconnect between younger generations and their culinary heritage. As Westernized, convenience-oriented foods become more common, essential cooking skills and traditional food practices are declining, driving consumers toward processed alternatives and away from local products. In South Africa, the limited consumption of locally produced pork—despite its global popularity—reflects broader challenges related to consumer perception, accessibility, and limited awareness of the value of local food systems. Addressing these gaps requires a clearer understanding of consumer priorities and the influence of food literacy on purchasing behavior. This study examined South African consumers’ prioritization of extrinsic product attributes in relation to local pork, with specific attention to the role of indigenous food literacy. Exploratory factor analysis identified nine dimensions: Clean Label Attributes, Ethical and Sustainable Farming Practices, Brand Strength, Engaging and Traceable Labeling, Food Safety and Shelf-Life Assurance, Product Presentation, Retailer Credibility, Affordability, and Product Origin. Product presentation (M = 4.07) and food safety assurance (M = 3.90) ranked highest, while origin (M = 2.78) and traceability (M = 3.09) were less influential. Significant differences across gender, population group, income, and education showed that women and lower-income, less formally educated respondents placed greater emphasis on transparency, affordability, and retailer trustworthiness—patterns linked to lower food literacy and higher risk aversion. These insights highlight opportunities to reposition local pork through transparent labeling, ethical production narratives, and culturally grounded marketing that support food literacy and local food systems.

When and how could technological advances undermine nuclear deterrence? This research uses an interdisciplinary approach to explore the technical, strategic, and social factors that propagate interest in emerging technologies like quantum sensing, and to assess the likely effects on strategic stability. Recent scholarship asserts that new remote sensing technologies may soon provide the capabilities needed to detect, track, and precisely target the delivery systems that constitute a nuclear-armed state’s second-strike capabilities. If true, this would have profound consequences for international security, nuclear force structure planning and arms control. Even if such predictions are not technically feasible, exaggerated expectations generated by strategic or social influences could still negatively impact acquisition and force structure decisions critical to strategic stability and arms control policy. This dissertation proposes an integrated, socio-technical analytical framework to examine the technical, strategic, and social factors that inform U.S. decision-making on new technologies with important military implications. The framework improves upon existing research in security studies literature by integrating technical projection methods and science and technology studies theories. Before applying the framework to the contemporary case of quantum sensing, the framework’s operability is demonstrated through five historical case studies: ballistic missile defense, hypersonics, satellite imagery, remote vision, and isomer weapons. These case studies illustrate the intricate interplay among technical, strategic, and social factors that has shaped prior U.S. decisions about pursuing technological innovations related to nuclear deterrence, often leading to over-investment as a strategy to hedge against technological surprise. The quantum sensing case study begins with a technical assessment to determine the realistic advances that can be expected, and the likelihood of disruption to a core feature of stable nuclear deterrence: confidence in the survivability of retaliatory forces. It surveys experimental results to identify sensitivities of current quantum sensor prototypes and theoretical literature to evaluate the likelihood of performance gains as R&D progresses. It then estimates how much these projected capabilities could improve submarine detection and missile accuracy applications in the next 10 years. It finds that quantum sensing will afford more evolutionary, rather than revolutionary, improvements in comparison to existing capabilities. The dissertation then surveys the types of strategic narratives and social dynamics that had important effects on prior decisions about efforts to innovate other strategically relevant technologies, highlighting how they also appear to be shaping debates and decisions about quantum sensing. By assessing competing claims about quantum sensing’s impact on second-strike vulnerability, this dissertation explores how diverging deterrence theories amplify disagreements over the impact of new technologies. It also evaluates the social factors that propagate expectations for quantum sensing across the respective social worlds of technologists and capability seekers, finding that realistic assessments are further frustrated by divides between technical and non-technical literatures and classified information barriers. Based on these findings, policymakers should anticipate continued pressure to pursue emerging technologies like quantum sensing, regardless of patent technical limitations, due to a combination of social dynamics and strategic narratives that support damage limitation deterrence postures. While a technology hedging strategy may seem like an innocuous way for policymakers to appease stakeholders with diverging viewpoints on the risks and benefits of emerging technologies, this dissertation suggests that hedging is likely to galvanize social, strategic, and technical momentum that ultimately signals innovation, fosters competition, and manifests strategic effects, regardless of the initial policy intent.